ORLANDO – Uveal melanoma has little in common with it’s cutaneous namesake, and its distinct characteristics necessitated the development of specific guidelines for diagnosis and management, which were released earlier this year by the National Comprehensive Cancer Network (NCCN).

Unlike cutaneous melanoma, uveal melanoma is usually treated with radiotherapy rather than surgery, and primary treatment is based on tumor size, according to Christopher A. Barker, MD, a radiation oncologist and director of clinical investigations in the department of radiation at Memorial Sloan Kettering Cancer Center, New York.

Further, molecular testing aids in prognosis in uveal melanoma but not in predicting treatment response as it can in cutaneous disease, and recurrences of uveal melanoma are typically distant – usually occurring in the liver – rather than in the skin or lymph nodes as with cutaneous melanoma.

These and other diagnosis- and treatment-related issues are outlined in the new guidelines, which are the first developed by the NCCN for uveal melanoma.

Guidelines exist in several countries, including Australia, the United Kingdom, Canada, and the United States (published by The American Brachytherapy Society), but until now none have provided pathway-based strategies for the management of all stages of this rare disease that affects about 1 in 200,000 Americans, typically Caucasians in their 50s, 60s, or 70s, Dr. Barker, a member of the NCCN Melanoma guidelines panel and the uveal melanoma subcommittee, said at the NCCN’s annual meeting where he presented the guidelines.

The median age of diagnosis is 60 years, he noted.

The NCCN guidelines specifically address melanoma arising in the choroid and ciliary body of the uvea. The choroid is the predominant site of uveal melanoma origin, and tumors arising there may involve the ciliary body as well, although the latter is a rare site of melanoma origin. The iris is also a rare site of origin, and tumors arising there are typically indolent in nature and thus are not part of the new guidelines, he explained.

Risk factors include choroidal nevi, ocular melanocytosis, and familial uveal melanoma associated with germline BAP1 mutation, neurofibromatosis, or dysplastic nevus syndrome; cutaneous melanoma is not a risk factor, he said.

The guidelines address clinical presentation, diagnostic work-up, and staging; primary treatments; and metastatic risks and follow-up imaging.

Presentation, diagnosis, and staging

About two-thirds of patients with uveal melanoma present because of changes in their vision, and about a third present with no new symptoms and are diagnosed during routine evaluation, Dr. Barker said.

“History and physical exam, and specifically attention to any prior malignancies, is important,” he said. “A comprehensive eye examination is absolutely vital to the evaluation and staging of patients with uveal melanoma.”

Numerous additional testing options, including autofluorescence of the ocular fundus, retinal fluorescein angiography of the ocular fundus, and transillumination, among others, are listed in the guidelines, which note that MRI is sometimes needed to confirm diagnosis.

Biopsies, however, are generally only performed to confirm diagnosis if needed or for prognostic analysis for risk stratification.

Staging is determined mainly by tumor size, which is known to be associated with outcomes in patients with uveal melanoma, and is based on criteria from both the Collaborative Ocular Melanoma Study (COMS) staging system and the American Joint Committee on Cancer (AJCC) staging manual, Dr. Barker said.

The COMS system was developed based on separate studies of small, medium, and large tumors and helped define primary tumor management and establish existing standards of care. The AJCC system was developed subsequently and focuses more on tumor features that may improve clinical predictions.

 

Primary treatments

Options for primary treatment for small tumors (largest diameter 5-16 mm and thickness less than 2.5 mm) include plaque brachytherapy, partical beam radiation, and laser ablation in highly select patients. For medium tumors (18mm or less at largest diameter and thickness of 2.5-10 mm), they include plaque brachytherapy, particle beam radiation, and enucleation, according to the guidelines.

Large tumors can be treated with radiotherapy (preferably particle beam radiation, Dr. Barker said) or enucleation. Large tumors are those greater than 18mm with any thickness, those with thickness greater than 10mm with any diameter, and those with thickness greater than 8mm with optic nerve involvement.

In patients for whom surgical removal is selected, “ there are a few unusual situations where additional local adjuvant therapy might be considered,” Dr. Barker said, explaining, for example, that the presence of microscopically positive or close margins after enucleation without evidence of gross residual disease in the orbit may be observed or may warrant map biopsy and/or particle beam or photon beam radiotherapy to the orbit.

For visible extraocular tumors or suspicion of gross disease in the orbit, biopsy of the extraocular tissue is recommended when possible, along with either intraoperative cryotherapy, orbital exenteration, or particle beam or photon beam radiotherapy to the orbit, he added.

Metastatic risks and follow-up imaging

Recent studies, including Cancer Genome Atlas Research Network studies, have elucidated the genomics of both uveal and cutaneous melanomas, and they show “a completely different mutation spectrum” for uveal melanoma, Dr. Barker said.

These genomic studies demonstrate that cutaneous melanoma involves mutations that predict response to certain treatments, while those found in uveal melanoma do not, but they are, however, associated with the probability of metastasis, he said.

For example, various studies have shown that BRAF mutation in cutaneous melanoma predicts response to RAF or MEK inhibition and that the overall number of mutations in cutaneous melanoma may predict response to immunotherapy.

In uveal melanoma, alterations in ElFAX1, SF3B1, or BAP1 have been shown to indicate low, intermediate, and high risk of metastasis, respectively.

Other factors associated with the risk of metastasis after primary tumor treatment in uveal melanoma include clinical factors (tumor size, ciliary body involvement, and extraocular extension); histopathologic factors (spindle or epithelioid cell type); and cytogenetics (status of chromosomes 3, 6, and 8), he said.

An AJCC Ophthalmic Oncology Task Force study published in 2015, for example, showed that the 5-year metastasis-free survival was 97% for AJCC stage T1 disease, 85% for stage T2, 77% for stage T3, and 61% for stage T4. T-stage modifiers, which are based on particular tumor characteristics, such as ciliary body involvement (CBI) and extraocular extension (EXE), were also associated with the risk of distant metastasis: 5-year metastasis-free survival was 90%, 72%, 54% and 33% for AJCC T_a (no CBI or EXE), T_b (CBI only), T_c (EXE only), and T_d tumors (CBI and EXE), respectively.

Follow-up imaging after primary tumor treatment should be based on the most likely site of metastatic recurrence, which is the liver in 90% of uveal melanoma metastases.

“For this reason, surveillance of high-risk patients with uveal melanoma should include specific imaging of the liver,” Dr. Barker said, who noted that the NCCN risk stratification–based surveillance guidelines categorize patients as either low, medium, or high risk for metastasis based on the various characteristics that can affect risk.

“These risk groups help clinicians identify how often imaging should be performed in their surveillance strategy,” he said, adding that those who are high risk based on BAP1 mutation, PRAME mutation, CBI, or EXE, for example, should undergo imaging to evaluate signs or symptoms every 3-6 months for 5 years, every 6-12 months for 10 years, and then as clinically indicated thereafter.

The guideline calls for less stringent imaging for low- and medium-risk patients.

“Now, what happens when distant metastases are identified? Unfortunately there is no single systemic therapy that has proven to be most effective for uveal melanoma,” he said. “For this reason, the NCCN guideline encourages clinical trial participation whenever possible for patients who develop distant metastasis.”

This is because drugs effective for cutaneous melanoma are far less effective for uveal melanoma, but do elicit response in some patients and can be considered, he explained.

 

“Moreover, because the liver is the site of metastasis most often, and is often the exclusive site of metastasis, liver metastasis–directed therapy is considered part of the management of patients with uveal melanoma,” he said, adding that this can involve resection, ablation, chemo/radio embolization, or regional perfusion.”

The NCCN Uveal Melanoma Guidelines were developed by a panel of experts from various institutions based on the available evidence and on consensus; they are category 2A (based on lower-level evidence with uniform NCCN consensus that the intervention is appropriate).

Dr. Barker reported receiving clinical research support from Amgen, Bristol-Myers Squibb, Elekta, Merck, University of California San Francisco, and University of Florida Health Cancer Center Orlando, and serving as an advisor, consultant, or expert witness for Pfizer.

[email protected]

ORLANDO – Uveal melanoma has little in common with it’s cutaneous namesake, and its distinct characteristics necessitated the development of specific guidelines for diagnosis and management, which were released earlier this year by the National Comprehensive Cancer Network (NCCN).

Unlike cutaneous melanoma, uveal melanoma is usually treated with radiotherapy rather than surgery, and primary treatment is based on tumor size, according to Christopher A. Barker, MD, a radiation oncologist and director of clinical investigations in the department of radiation at Memorial Sloan Kettering Cancer Center, New York.

Further, molecular testing aids in prognosis in uveal melanoma but not in predicting treatment response as it can in cutaneous disease, and recurrences of uveal melanoma are typically distant – usually occurring in the liver – rather than in the skin or lymph nodes as with cutaneous melanoma.

These and other diagnosis- and treatment-related issues are outlined in the new guidelines, which are the first developed by the NCCN for uveal melanoma.

Guidelines exist in several countries, including Australia, the United Kingdom, Canada, and the United States (published by The American Brachytherapy Society), but until now none have provided pathway-based strategies for the management of all stages of this rare disease that affects about 1 in 200,000 Americans, typically Caucasians in their 50s, 60s, or 70s, Dr. Barker, a member of the NCCN Melanoma guidelines panel and the uveal melanoma subcommittee, said at the NCCN’s annual meeting where he presented the guidelines.

The median age of diagnosis is 60 years, he noted.

The NCCN guidelines specifically address melanoma arising in the choroid and ciliary body of the uvea. The choroid is the predominant site of uveal melanoma origin, and tumors arising there may involve the ciliary body as well, although the latter is a rare site of melanoma origin. The iris is also a rare site of origin, and tumors arising there are typically indolent in nature and thus are not part of the new guidelines, he explained.

Risk factors include choroidal nevi, ocular melanocytosis, and familial uveal melanoma associated with germline BAP1 mutation, neurofibromatosis, or dysplastic nevus syndrome; cutaneous melanoma is not a risk factor, he said.

The guidelines address clinical presentation, diagnostic work-up, and staging; primary treatments; and metastatic risks and follow-up imaging.

Presentation, diagnosis, and staging

About two-thirds of patients with uveal melanoma present because of changes in their vision, and about a third present with no new symptoms and are diagnosed during routine evaluation, Dr. Barker said.

“History and physical exam, and specifically attention to any prior malignancies, is important,” he said. “A comprehensive eye examination is absolutely vital to the evaluation and staging of patients with uveal melanoma.”

Numerous additional testing options, including autofluorescence of the ocular fundus, retinal fluorescein angiography of the ocular fundus, and transillumination, among others, are listed in the guidelines, which note that MRI is sometimes needed to confirm diagnosis.

Biopsies, however, are generally only performed to confirm diagnosis if needed or for prognostic analysis for risk stratification.

Staging is determined mainly by tumor size, which is known to be associated with outcomes in patients with uveal melanoma, and is based on criteria from both the Collaborative Ocular Melanoma Study (COMS) staging system and the American Joint Committee on Cancer (AJCC) staging manual, Dr. Barker said.

The COMS system was developed based on separate studies of small, medium, and large tumors and helped define primary tumor management and establish existing standards of care. The AJCC system was developed subsequently and focuses more on tumor features that may improve clinical predictions.

 

Primary treatments

Options for primary treatment for small tumors (largest diameter 5-16 mm and thickness less than 2.5 mm) include plaque brachytherapy, partical beam radiation, and laser ablation in highly select patients. For medium tumors (18mm or less at largest diameter and thickness of 2.5-10 mm), they include plaque brachytherapy, particle beam radiation, and enucleation, according to the guidelines.

Large tumors can be treated with radiotherapy (preferably particle beam radiation, Dr. Barker said) or enucleation. Large tumors are those greater than 18mm with any thickness, those with thickness greater than 10mm with any diameter, and those with thickness greater than 8mm with optic nerve involvement.

In patients for whom surgical removal is selected, “ there are a few unusual situations where additional local adjuvant therapy might be considered,” Dr. Barker said, explaining, for example, that the presence of microscopically positive or close margins after enucleation without evidence of gross residual disease in the orbit may be observed or may warrant map biopsy and/or particle beam or photon beam radiotherapy to the orbit.

For visible extraocular tumors or suspicion of gross disease in the orbit, biopsy of the extraocular tissue is recommended when possible, along with either intraoperative cryotherapy, orbital exenteration, or particle beam or photon beam radiotherapy to the orbit, he added.

Metastatic risks and follow-up imaging

Recent studies, including Cancer Genome Atlas Research Network studies, have elucidated the genomics of both uveal and cutaneous melanomas, and they show “a completely different mutation spectrum” for uveal melanoma, Dr. Barker said.

These genomic studies demonstrate that cutaneous melanoma involves mutations that predict response to certain treatments, while those found in uveal melanoma do not, but they are, however, associated with the probability of metastasis, he said.

For example, various studies have shown that BRAF mutation in cutaneous melanoma predicts response to RAF or MEK inhibition and that the overall number of mutations in cutaneous melanoma may predict response to immunotherapy.

In uveal melanoma, alterations in ElFAX1, SF3B1, or BAP1 have been shown to indicate low, intermediate, and high risk of metastasis, respectively.

Other factors associated with the risk of metastasis after primary tumor treatment in uveal melanoma include clinical factors (tumor size, ciliary body involvement, and extraocular extension); histopathologic factors (spindle or epithelioid cell type); and cytogenetics (status of chromosomes 3, 6, and 8), he said.

An AJCC Ophthalmic Oncology Task Force study published in 2015, for example, showed that the 5-year metastasis-free survival was 97% for AJCC stage T1 disease, 85% for stage T2, 77% for stage T3, and 61% for stage T4. T-stage modifiers, which are based on particular tumor characteristics, such as ciliary body involvement (CBI) and extraocular extension (EXE), were also associated with the risk of distant metastasis: 5-year metastasis-free survival was 90%, 72%, 54% and 33% for AJCC T_a (no CBI or EXE), T_b (CBI only), T_c (EXE only), and T_d tumors (CBI and EXE), respectively.

Follow-up imaging after primary tumor treatment should be based on the most likely site of metastatic recurrence, which is the liver in 90% of uveal melanoma metastases.

“For this reason, surveillance of high-risk patients with uveal melanoma should include specific imaging of the liver,” Dr. Barker said, who noted that the NCCN risk stratification–based surveillance guidelines categorize patients as either low, medium, or high risk for metastasis based on the various characteristics that can affect risk.

“These risk groups help clinicians identify how often imaging should be performed in their surveillance strategy,” he said, adding that those who are high risk based on BAP1 mutation, PRAME mutation, CBI, or EXE, for example, should undergo imaging to evaluate signs or symptoms every 3-6 months for 5 years, every 6-12 months for 10 years, and then as clinically indicated thereafter.

The guideline calls for less stringent imaging for low- and medium-risk patients.

“Now, what happens when distant metastases are identified? Unfortunately there is no single systemic therapy that has proven to be most effective for uveal melanoma,” he said. “For this reason, the NCCN guideline encourages clinical trial participation whenever possible for patients who develop distant metastasis.”

This is because drugs effective for cutaneous melanoma are far less effective for uveal melanoma, but do elicit response in some patients and can be considered, he explained.

 

“Moreover, because the liver is the site of metastasis most often, and is often the exclusive site of metastasis, liver metastasis–directed therapy is considered part of the management of patients with uveal melanoma,” he said, adding that this can involve resection, ablation, chemo/radio embolization, or regional perfusion.”

The NCCN Uveal Melanoma Guidelines were developed by a panel of experts from various institutions based on the available evidence and on consensus; they are category 2A (based on lower-level evidence with uniform NCCN consensus that the intervention is appropriate).

Dr. Barker reported receiving clinical research support from Amgen, Bristol-Myers Squibb, Elekta, Merck, University of California San Francisco, and University of Florida Health Cancer Center Orlando, and serving as an advisor, consultant, or expert witness for Pfizer.

[email protected]

ORLANDO – Uveal melanoma has little in common with it’s cutaneous namesake, and its distinct characteristics necessitated the development of specific guidelines for diagnosis and management, which were released earlier this year by the National Comprehensive Cancer Network (NCCN).

Unlike cutaneous melanoma, uveal melanoma is usually treated with radiotherapy rather than surgery, and primary treatment is based on tumor size, according to Christopher A. Barker, MD, a radiation oncologist and director of clinical investigations in the department of radiation at Memorial Sloan Kettering Cancer Center, New York.

Further, molecular testing aids in prognosis in uveal melanoma but not in predicting treatment response as it can in cutaneous disease, and recurrences of uveal melanoma are typically distant – usually occurring in the liver – rather than in the skin or lymph nodes as with cutaneous melanoma.

These and other diagnosis- and treatment-related issues are outlined in the new guidelines, which are the first developed by the NCCN for uveal melanoma.

Guidelines exist in several countries, including Australia, the United Kingdom, Canada, and the United States (published by The American Brachytherapy Society), but until now none have provided pathway-based strategies for the management of all stages of this rare disease that affects about 1 in 200,000 Americans, typically Caucasians in their 50s, 60s, or 70s, Dr. Barker, a member of the NCCN Melanoma guidelines panel and the uveal melanoma subcommittee, said at the NCCN’s annual meeting where he presented the guidelines.

The median age of diagnosis is 60 years, he noted.

The NCCN guidelines specifically address melanoma arising in the choroid and ciliary body of the uvea. The choroid is the predominant site of uveal melanoma origin, and tumors arising there may involve the ciliary body as well, although the latter is a rare site of melanoma origin. The iris is also a rare site of origin, and tumors arising there are typically indolent in nature and thus are not part of the new guidelines, he explained.

Risk factors include choroidal nevi, ocular melanocytosis, and familial uveal melanoma associated with germline BAP1 mutation, neurofibromatosis, or dysplastic nevus syndrome; cutaneous melanoma is not a risk factor, he said.

The guidelines address clinical presentation, diagnostic work-up, and staging; primary treatments; and metastatic risks and follow-up imaging.

Presentation, diagnosis, and staging

About two-thirds of patients with uveal melanoma present because of changes in their vision, and about a third present with no new symptoms and are diagnosed during routine evaluation, Dr. Barker said.

“History and physical exam, and specifically attention to any prior malignancies, is important,” he said. “A comprehensive eye examination is absolutely vital to the evaluation and staging of patients with uveal melanoma.”

Numerous additional testing options, including autofluorescence of the ocular fundus, retinal fluorescein angiography of the ocular fundus, and transillumination, among others, are listed in the guidelines, which note that MRI is sometimes needed to confirm diagnosis.

Biopsies, however, are generally only performed to confirm diagnosis if needed or for prognostic analysis for risk stratification.

Staging is determined mainly by tumor size, which is known to be associated with outcomes in patients with uveal melanoma, and is based on criteria from both the Collaborative Ocular Melanoma Study (COMS) staging system and the American Joint Committee on Cancer (AJCC) staging manual, Dr. Barker said.

The COMS system was developed based on separate studies of small, medium, and large tumors and helped define primary tumor management and establish existing standards of care. The AJCC system was developed subsequently and focuses more on tumor features that may improve clinical predictions.

 

Primary treatments

Options for primary treatment for small tumors (largest diameter 5-16 mm and thickness less than 2.5 mm) include plaque brachytherapy, partical beam radiation, and laser ablation in highly select patients. For medium tumors (18mm or less at largest diameter and thickness of 2.5-10 mm), they include plaque brachytherapy, particle beam radiation, and enucleation, according to the guidelines.

Large tumors can be treated with radiotherapy (preferably particle beam radiation, Dr. Barker said) or enucleation. Large tumors are those greater than 18mm with any thickness, those with thickness greater than 10mm with any diameter, and those with thickness greater than 8mm with optic nerve involvement.

In patients for whom surgical removal is selected, “ there are a few unusual situations where additional local adjuvant therapy might be considered,” Dr. Barker said, explaining, for example, that the presence of microscopically positive or close margins after enucleation without evidence of gross residual disease in the orbit may be observed or may warrant map biopsy and/or particle beam or photon beam radiotherapy to the orbit.

For visible extraocular tumors or suspicion of gross disease in the orbit, biopsy of the extraocular tissue is recommended when possible, along with either intraoperative cryotherapy, orbital exenteration, or particle beam or photon beam radiotherapy to the orbit, he added.

Metastatic risks and follow-up imaging

Recent studies, including Cancer Genome Atlas Research Network studies, have elucidated the genomics of both uveal and cutaneous melanomas, and they show “a completely different mutation spectrum” for uveal melanoma, Dr. Barker said.

These genomic studies demonstrate that cutaneous melanoma involves mutations that predict response to certain treatments, while those found in uveal melanoma do not, but they are, however, associated with the probability of metastasis, he said.

For example, various studies have shown that BRAF mutation in cutaneous melanoma predicts response to RAF or MEK inhibition and that the overall number of mutations in cutaneous melanoma may predict response to immunotherapy.

In uveal melanoma, alterations in ElFAX1, SF3B1, or BAP1 have been shown to indicate low, intermediate, and high risk of metastasis, respectively.

Other factors associated with the risk of metastasis after primary tumor treatment in uveal melanoma include clinical factors (tumor size, ciliary body involvement, and extraocular extension); histopathologic factors (spindle or epithelioid cell type); and cytogenetics (status of chromosomes 3, 6, and 8), he said.

An AJCC Ophthalmic Oncology Task Force study published in 2015, for example, showed that the 5-year metastasis-free survival was 97% for AJCC stage T1 disease, 85% for stage T2, 77% for stage T3, and 61% for stage T4. T-stage modifiers, which are based on particular tumor characteristics, such as ciliary body involvement (CBI) and extraocular extension (EXE), were also associated with the risk of distant metastasis: 5-year metastasis-free survival was 90%, 72%, 54% and 33% for AJCC T_a (no CBI or EXE), T_b (CBI only), T_c (EXE only), and T_d tumors (CBI and EXE), respectively.

Follow-up imaging after primary tumor treatment should be based on the most likely site of metastatic recurrence, which is the liver in 90% of uveal melanoma metastases.

“For this reason, surveillance of high-risk patients with uveal melanoma should include specific imaging of the liver,” Dr. Barker said, who noted that the NCCN risk stratification–based surveillance guidelines categorize patients as either low, medium, or high risk for metastasis based on the various characteristics that can affect risk.

“These risk groups help clinicians identify how often imaging should be performed in their surveillance strategy,” he said, adding that those who are high risk based on BAP1 mutation, PRAME mutation, CBI, or EXE, for example, should undergo imaging to evaluate signs or symptoms every 3-6 months for 5 years, every 6-12 months for 10 years, and then as clinically indicated thereafter.

The guideline calls for less stringent imaging for low- and medium-risk patients.

“Now, what happens when distant metastases are identified? Unfortunately there is no single systemic therapy that has proven to be most effective for uveal melanoma,” he said. “For this reason, the NCCN guideline encourages clinical trial participation whenever possible for patients who develop distant metastasis.”

This is because drugs effective for cutaneous melanoma are far less effective for uveal melanoma, but do elicit response in some patients and can be considered, he explained.

 

“Moreover, because the liver is the site of metastasis most often, and is often the exclusive site of metastasis, liver metastasis–directed therapy is considered part of the management of patients with uveal melanoma,” he said, adding that this can involve resection, ablation, chemo/radio embolization, or regional perfusion.”

The NCCN Uveal Melanoma Guidelines were developed by a panel of experts from various institutions based on the available evidence and on consensus; they are category 2A (based on lower-level evidence with uniform NCCN consensus that the intervention is appropriate).

Dr. Barker reported receiving clinical research support from Amgen, Bristol-Myers Squibb, Elekta, Merck, University of California San Francisco, and University of Florida Health Cancer Center Orlando, and serving as an advisor, consultant, or expert witness for Pfizer.

[email protected]

 

SAN DIEGO – In the first randomized, head-to-head trial of drug-releasing stents for above-the-knee femoropopliteal peripheral artery disease (PAD), Boston Scientific’s polymer-coated, paclitaxel-eluting stent outperformed Cook Medical’s polymer-free, paclitaxel-coated stent.

M. Alexander Otto

The IMPERIAL trial (NCT02574481), funded and conducted by Boston Scientific, randomized 309 patients with occlusive lesions of the superficial femoral and/or proximal popliteal arteries to the polymer-coated, paclitaxel-eluting Eluvia stent and 156 to the paclitaxel-eluting Zilver PTX, which is the only drug-releasing stent approved in the United States for the indication. Total lesion length was 30-140 mm, with a mean of 83 mm; subjects had moderate to severe claudication.

At 12 months, primary patency was 86.8% (231/266) in the Eluvia group, versus 81.5% (106/130) among those randomized to Zilver PTX. About 5% of Eluvia patients (14/273) and 9% of patients in the Zilver PTX arm (12/133) had a major adverse event, defined as death within a month or target limb amputation or revascularization through 12 months. Both outcomes were statistically significant at P less than .0001. Overall, 4.5% of Eluvia patients (13/287) required target lesion revascularization, compared with 9% of Zilver PTX patients (13/145).

“These data suggest the Boston Scientific product is superior. Unless there are big differences in cost or technical aspects of the procedure, I would foresee a fairly substantial shift to” Eluvia if it’s approved, which seems likely, said interventional cardiologist David Cohen, MD, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who comoderated the study presentation at the Transcatheter Cardiovascular Therapeutics annual meeting.

M. Alexander Otto

The different patency and revascularization rates might caused by the different way these stents deliver paclitaxel. The Zilver PTX is coated with the drug, so it’s released fairly quickly into surrounding tissues. The polymer coating on the Eluvia allows for slow release, “which is important considering that the observed peak of restenosis in the femoropopliteal arteries is at 10-12 months,” lead investigator William Gray, MD, a cardiologist at the Lankenau Heart Institute, Wynnewood, Pa., said at the meeting.

There were six cases of aneurysmal degeneration with Eluvia, but none with Zilver PTX. All six patients were patent at 1 year, without revascularization or stent thrombosis. It’s too early to know what to make of the finding. The planned 5-year follow-up should shed some light on the issue, Dr. Gray said.

At present, there’s no clear algorithm for above-the-knee PAD. Balloons and stents – both drug-releasing and bare – are all in play, and new devices are on the way. “With a head-to-head trial like this, we are staring to pare down all the noise in the market place. I think for long complicated lesions, I would be very surprised if we don’t start seeing more drug-eluting stents, because the results are so good. Drug-coated balloons are useful, but they take a little bit longer and a little more nuance,” especially when stent are used to touch up the results, he said.

 

M. Alexander Otto

“I was surprised at the results” of the IMPERIAL trial, coinvestigator and interventional cardiologist Michael Jaff, MD, said. “Even though the primary analysis says it met noninferiority, the secondary prespecified analysis of superiority was pretty impressive,” but whether people start shifting from Zilver PTX depends on price.

“If [Boston Scientific] prices this at a premium and my doctors come to me and say ‘You’ve got to let us buy this,’ it’s going to be a hard sell for me,” said Dr. Jaff, a professor of medicine at Harvard Medical School, Boston, and president of the nearby Newton-Wellesley Hospital in Newton, Mass.

As for shifting away from drug-coated balloons, which are an increasingly popular option, a head-to-head trial is in order. If it turns out Eluvia doesn’t “have a huge advantage, I’d start off with a drug-coated balloon. You leave yourself every option going down the road if it fails. If you have a stent that fails, it’s harder to work with,” he said.

 

About two-thirds of the subjects were men, and the mean age was about 68 years. Most patients in both arms had marked improvements in symptoms and walking ability after stent placement. Rates of stent thrombosis were low, at about 2% with Eluvia versus 4% with Zilver PTX, a statistically nonsignificant difference.

The IMPERIAL results were published online simultaneously with Dr. Gray’s presentation (Lancet. 2018 Sep 22. doi: 10.1016/S0140-6736[18]32262-1).

The work was funded and conducted by Boston Scientific. Dr. Gray and Dr. Jaffe are advisors to the company. Most of the other investigators disclosed financial ties to company, and one was an employee. Dr. Cohen wasn’t involved in the work. The TCT meeting was sponsored by the Cardiovascular Research Foundation.

[email protected]

 

SAN DIEGO – In the first randomized, head-to-head trial of drug-releasing stents for above-the-knee femoropopliteal peripheral artery disease (PAD), Boston Scientific’s polymer-coated, paclitaxel-eluting stent outperformed Cook Medical’s polymer-free, paclitaxel-coated stent.

M. Alexander Otto

The IMPERIAL trial (NCT02574481), funded and conducted by Boston Scientific, randomized 309 patients with occlusive lesions of the superficial femoral and/or proximal popliteal arteries to the polymer-coated, paclitaxel-eluting Eluvia stent and 156 to the paclitaxel-eluting Zilver PTX, which is the only drug-releasing stent approved in the United States for the indication. Total lesion length was 30-140 mm, with a mean of 83 mm; subjects had moderate to severe claudication.

At 12 months, primary patency was 86.8% (231/266) in the Eluvia group, versus 81.5% (106/130) among those randomized to Zilver PTX. About 5% of Eluvia patients (14/273) and 9% of patients in the Zilver PTX arm (12/133) had a major adverse event, defined as death within a month or target limb amputation or revascularization through 12 months. Both outcomes were statistically significant at P less than .0001. Overall, 4.5% of Eluvia patients (13/287) required target lesion revascularization, compared with 9% of Zilver PTX patients (13/145).

“These data suggest the Boston Scientific product is superior. Unless there are big differences in cost or technical aspects of the procedure, I would foresee a fairly substantial shift to” Eluvia if it’s approved, which seems likely, said interventional cardiologist David Cohen, MD, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who comoderated the study presentation at the Transcatheter Cardiovascular Therapeutics annual meeting.

M. Alexander Otto

The different patency and revascularization rates might caused by the different way these stents deliver paclitaxel. The Zilver PTX is coated with the drug, so it’s released fairly quickly into surrounding tissues. The polymer coating on the Eluvia allows for slow release, “which is important considering that the observed peak of restenosis in the femoropopliteal arteries is at 10-12 months,” lead investigator William Gray, MD, a cardiologist at the Lankenau Heart Institute, Wynnewood, Pa., said at the meeting.

There were six cases of aneurysmal degeneration with Eluvia, but none with Zilver PTX. All six patients were patent at 1 year, without revascularization or stent thrombosis. It’s too early to know what to make of the finding. The planned 5-year follow-up should shed some light on the issue, Dr. Gray said.

At present, there’s no clear algorithm for above-the-knee PAD. Balloons and stents – both drug-releasing and bare – are all in play, and new devices are on the way. “With a head-to-head trial like this, we are staring to pare down all the noise in the market place. I think for long complicated lesions, I would be very surprised if we don’t start seeing more drug-eluting stents, because the results are so good. Drug-coated balloons are useful, but they take a little bit longer and a little more nuance,” especially when stent are used to touch up the results, he said.

 

M. Alexander Otto

“I was surprised at the results” of the IMPERIAL trial, coinvestigator and interventional cardiologist Michael Jaff, MD, said. “Even though the primary analysis says it met noninferiority, the secondary prespecified analysis of superiority was pretty impressive,” but whether people start shifting from Zilver PTX depends on price.

“If [Boston Scientific] prices this at a premium and my doctors come to me and say ‘You’ve got to let us buy this,’ it’s going to be a hard sell for me,” said Dr. Jaff, a professor of medicine at Harvard Medical School, Boston, and president of the nearby Newton-Wellesley Hospital in Newton, Mass.

As for shifting away from drug-coated balloons, which are an increasingly popular option, a head-to-head trial is in order. If it turns out Eluvia doesn’t “have a huge advantage, I’d start off with a drug-coated balloon. You leave yourself every option going down the road if it fails. If you have a stent that fails, it’s harder to work with,” he said.

 

About two-thirds of the subjects were men, and the mean age was about 68 years. Most patients in both arms had marked improvements in symptoms and walking ability after stent placement. Rates of stent thrombosis were low, at about 2% with Eluvia versus 4% with Zilver PTX, a statistically nonsignificant difference.

The IMPERIAL results were published online simultaneously with Dr. Gray’s presentation (Lancet. 2018 Sep 22. doi: 10.1016/S0140-6736[18]32262-1).

The work was funded and conducted by Boston Scientific. Dr. Gray and Dr. Jaffe are advisors to the company. Most of the other investigators disclosed financial ties to company, and one was an employee. Dr. Cohen wasn’t involved in the work. The TCT meeting was sponsored by the Cardiovascular Research Foundation.

[email protected]

 

SAN DIEGO – In the first randomized, head-to-head trial of drug-releasing stents for above-the-knee femoropopliteal peripheral artery disease (PAD), Boston Scientific’s polymer-coated, paclitaxel-eluting stent outperformed Cook Medical’s polymer-free, paclitaxel-coated stent.

M. Alexander Otto

The IMPERIAL trial (NCT02574481), funded and conducted by Boston Scientific, randomized 309 patients with occlusive lesions of the superficial femoral and/or proximal popliteal arteries to the polymer-coated, paclitaxel-eluting Eluvia stent and 156 to the paclitaxel-eluting Zilver PTX, which is the only drug-releasing stent approved in the United States for the indication. Total lesion length was 30-140 mm, with a mean of 83 mm; subjects had moderate to severe claudication.

At 12 months, primary patency was 86.8% (231/266) in the Eluvia group, versus 81.5% (106/130) among those randomized to Zilver PTX. About 5% of Eluvia patients (14/273) and 9% of patients in the Zilver PTX arm (12/133) had a major adverse event, defined as death within a month or target limb amputation or revascularization through 12 months. Both outcomes were statistically significant at P less than .0001. Overall, 4.5% of Eluvia patients (13/287) required target lesion revascularization, compared with 9% of Zilver PTX patients (13/145).

“These data suggest the Boston Scientific product is superior. Unless there are big differences in cost or technical aspects of the procedure, I would foresee a fairly substantial shift to” Eluvia if it’s approved, which seems likely, said interventional cardiologist David Cohen, MD, of Saint Luke’s Mid America Heart Institute, Kansas City, Mo., who comoderated the study presentation at the Transcatheter Cardiovascular Therapeutics annual meeting.

M. Alexander Otto

The different patency and revascularization rates might caused by the different way these stents deliver paclitaxel. The Zilver PTX is coated with the drug, so it’s released fairly quickly into surrounding tissues. The polymer coating on the Eluvia allows for slow release, “which is important considering that the observed peak of restenosis in the femoropopliteal arteries is at 10-12 months,” lead investigator William Gray, MD, a cardiologist at the Lankenau Heart Institute, Wynnewood, Pa., said at the meeting.

There were six cases of aneurysmal degeneration with Eluvia, but none with Zilver PTX. All six patients were patent at 1 year, without revascularization or stent thrombosis. It’s too early to know what to make of the finding. The planned 5-year follow-up should shed some light on the issue, Dr. Gray said.

At present, there’s no clear algorithm for above-the-knee PAD. Balloons and stents – both drug-releasing and bare – are all in play, and new devices are on the way. “With a head-to-head trial like this, we are staring to pare down all the noise in the market place. I think for long complicated lesions, I would be very surprised if we don’t start seeing more drug-eluting stents, because the results are so good. Drug-coated balloons are useful, but they take a little bit longer and a little more nuance,” especially when stent are used to touch up the results, he said.

 

M. Alexander Otto

“I was surprised at the results” of the IMPERIAL trial, coinvestigator and interventional cardiologist Michael Jaff, MD, said. “Even though the primary analysis says it met noninferiority, the secondary prespecified analysis of superiority was pretty impressive,” but whether people start shifting from Zilver PTX depends on price.

“If [Boston Scientific] prices this at a premium and my doctors come to me and say ‘You’ve got to let us buy this,’ it’s going to be a hard sell for me,” said Dr. Jaff, a professor of medicine at Harvard Medical School, Boston, and president of the nearby Newton-Wellesley Hospital in Newton, Mass.

As for shifting away from drug-coated balloons, which are an increasingly popular option, a head-to-head trial is in order. If it turns out Eluvia doesn’t “have a huge advantage, I’d start off with a drug-coated balloon. You leave yourself every option going down the road if it fails. If you have a stent that fails, it’s harder to work with,” he said.

 

About two-thirds of the subjects were men, and the mean age was about 68 years. Most patients in both arms had marked improvements in symptoms and walking ability after stent placement. Rates of stent thrombosis were low, at about 2% with Eluvia versus 4% with Zilver PTX, a statistically nonsignificant difference.

The IMPERIAL results were published online simultaneously with Dr. Gray’s presentation (Lancet. 2018 Sep 22. doi: 10.1016/S0140-6736[18]32262-1).

The work was funded and conducted by Boston Scientific. Dr. Gray and Dr. Jaffe are advisors to the company. Most of the other investigators disclosed financial ties to company, and one was an employee. Dr. Cohen wasn’t involved in the work. The TCT meeting was sponsored by the Cardiovascular Research Foundation.

[email protected]

 

A combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the BRAF inhibitor vemurafenib appears safe for patients with advanced, BRAF-mutated, solid tumors that had progressed on BRAF and/or MEK therapy, investigators reported.

The combination provided partial responses in a variety of tumor types, and half of the patients achieved stable disease, reported Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center in Houston and his coauthors.

“Activation of alternative parallel signaling pathways such as the PI3K–mTOR pathway have been hypothesized to contribute to primary and acquired resistance to BRAF-targeted therapy,” the authors wrote in JCO Precision Oncology. Preclinical studies have supported this hypothesis, which led to the present study; it is the first to evaluate a combination of a BRAF inhibitor and an mTOR inhibitor.

The open-label, phase 1 trial included 20 patients with BRAF-mutated, advanced cancer that had progressed on BRAF and/or MEK therapy. Solid tumor types included melanoma (n = 7), glioma (n = 5), thyroid cancer (n = 4), appendiceal carcinoma (n = 1), colorectal cancer (n = 1), non–small cell lung cancer (NSCLC; n =1), and cancer of unknown primary (n = 1). More than half of the patients had already been treated with surgery, clinical trial therapy, radiation therapy, or chemotherapy. The median adult age was 64 years; two pediatric patients were aged 10 and 13 years.

Dose-escalation revealed a maximum-tolerated dose of everolimus 5 mg orally once a day and vemurafenib 720 mg orally twice a day. Across doses, the most common grade 3 adverse events were fatigue (20%) and rash (15%), followed distantly by anemia, thrombocytopenia, hyperglycemia, or hypertriglyceridemia, which occurred in one patient each.

 

Responses were evaluated in 18 patients. Of these, 22% had partial responses and 50% achieved stable disease. Partial responses occurred in patients with pleomorphic xanthoastrocytoma, optic nerve glioma, melanoma, and NSCLC.

“Our trial demonstrates that the combination of vemurafenib and everolimus can be tolerated in patients with advanced malignancies,” the authors concluded. “Our trial also demonstrates that the addition of an mTOR inhibitor to everolimus treatment is able to overcome resistance to BRAF and/or MEK inhibition in a subset of patients with BRAF-mutant advanced cancers.”

The authors reported affiliations with Baxter, Bayer, Novartis, Roche, Trovagene, and others.

SOURCE: Subbiah V et al. JCO Prec Oncol. 2018 Sep 13. doi: 10.1200/PO.18.00189.

 

A combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the BRAF inhibitor vemurafenib appears safe for patients with advanced, BRAF-mutated, solid tumors that had progressed on BRAF and/or MEK therapy, investigators reported.

The combination provided partial responses in a variety of tumor types, and half of the patients achieved stable disease, reported Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center in Houston and his coauthors.

“Activation of alternative parallel signaling pathways such as the PI3K–mTOR pathway have been hypothesized to contribute to primary and acquired resistance to BRAF-targeted therapy,” the authors wrote in JCO Precision Oncology. Preclinical studies have supported this hypothesis, which led to the present study; it is the first to evaluate a combination of a BRAF inhibitor and an mTOR inhibitor.

The open-label, phase 1 trial included 20 patients with BRAF-mutated, advanced cancer that had progressed on BRAF and/or MEK therapy. Solid tumor types included melanoma (n = 7), glioma (n = 5), thyroid cancer (n = 4), appendiceal carcinoma (n = 1), colorectal cancer (n = 1), non–small cell lung cancer (NSCLC; n =1), and cancer of unknown primary (n = 1). More than half of the patients had already been treated with surgery, clinical trial therapy, radiation therapy, or chemotherapy. The median adult age was 64 years; two pediatric patients were aged 10 and 13 years.

Dose-escalation revealed a maximum-tolerated dose of everolimus 5 mg orally once a day and vemurafenib 720 mg orally twice a day. Across doses, the most common grade 3 adverse events were fatigue (20%) and rash (15%), followed distantly by anemia, thrombocytopenia, hyperglycemia, or hypertriglyceridemia, which occurred in one patient each.

 

Responses were evaluated in 18 patients. Of these, 22% had partial responses and 50% achieved stable disease. Partial responses occurred in patients with pleomorphic xanthoastrocytoma, optic nerve glioma, melanoma, and NSCLC.

“Our trial demonstrates that the combination of vemurafenib and everolimus can be tolerated in patients with advanced malignancies,” the authors concluded. “Our trial also demonstrates that the addition of an mTOR inhibitor to everolimus treatment is able to overcome resistance to BRAF and/or MEK inhibition in a subset of patients with BRAF-mutant advanced cancers.”

The authors reported affiliations with Baxter, Bayer, Novartis, Roche, Trovagene, and others.

SOURCE: Subbiah V et al. JCO Prec Oncol. 2018 Sep 13. doi: 10.1200/PO.18.00189.

 

A combination of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the BRAF inhibitor vemurafenib appears safe for patients with advanced, BRAF-mutated, solid tumors that had progressed on BRAF and/or MEK therapy, investigators reported.

The combination provided partial responses in a variety of tumor types, and half of the patients achieved stable disease, reported Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center in Houston and his coauthors.

“Activation of alternative parallel signaling pathways such as the PI3K–mTOR pathway have been hypothesized to contribute to primary and acquired resistance to BRAF-targeted therapy,” the authors wrote in JCO Precision Oncology. Preclinical studies have supported this hypothesis, which led to the present study; it is the first to evaluate a combination of a BRAF inhibitor and an mTOR inhibitor.

The open-label, phase 1 trial included 20 patients with BRAF-mutated, advanced cancer that had progressed on BRAF and/or MEK therapy. Solid tumor types included melanoma (n = 7), glioma (n = 5), thyroid cancer (n = 4), appendiceal carcinoma (n = 1), colorectal cancer (n = 1), non–small cell lung cancer (NSCLC; n =1), and cancer of unknown primary (n = 1). More than half of the patients had already been treated with surgery, clinical trial therapy, radiation therapy, or chemotherapy. The median adult age was 64 years; two pediatric patients were aged 10 and 13 years.

Dose-escalation revealed a maximum-tolerated dose of everolimus 5 mg orally once a day and vemurafenib 720 mg orally twice a day. Across doses, the most common grade 3 adverse events were fatigue (20%) and rash (15%), followed distantly by anemia, thrombocytopenia, hyperglycemia, or hypertriglyceridemia, which occurred in one patient each.

 

Responses were evaluated in 18 patients. Of these, 22% had partial responses and 50% achieved stable disease. Partial responses occurred in patients with pleomorphic xanthoastrocytoma, optic nerve glioma, melanoma, and NSCLC.

“Our trial demonstrates that the combination of vemurafenib and everolimus can be tolerated in patients with advanced malignancies,” the authors concluded. “Our trial also demonstrates that the addition of an mTOR inhibitor to everolimus treatment is able to overcome resistance to BRAF and/or MEK inhibition in a subset of patients with BRAF-mutant advanced cancers.”

The authors reported affiliations with Baxter, Bayer, Novartis, Roche, Trovagene, and others.

SOURCE: Subbiah V et al. JCO Prec Oncol. 2018 Sep 13. doi: 10.1200/PO.18.00189.

 

ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.

M. Alexander Otto/MDedge News

Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.

They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.

To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.

The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.

That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.

Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.

Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.

A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.

The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.

Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.

There was no external funding, and the investigators had no disclosures.

 

[email protected]

 

ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.

M. Alexander Otto/MDedge News

Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.

They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.

To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.

The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.

That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.

Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.

Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.

A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.

The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.

Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.

There was no external funding, and the investigators had no disclosures.

 

[email protected]

 

ATLANTA – It took less than a year to curb overuse of intravenous antibiotics at the Cincinnati Children’s Hospital, according to a report given at the Pediatric Hospital Medicine meeting.

M. Alexander Otto/MDedge News

Overuse of IV antibiotics – continuing IV formulations when oral formulations would work just as well – is a widespread concern in hospital medicine. Patients can often be switched to an oral antibiotic after an initial IV course. It lowers costs, lessens the risk of antimicrobial resistance, and reduces IV complications, but timely transitions don’t always happen.

They certainly weren’t happening at Cincinnati Children’s. “Despite a strong antimicrobial stewardship program, we identified a problem with overuse of IV antibiotics. The majority of pediatric patients admitted to an in-hospital service were started on IV antibiotics regardless of diagnosis or condition. Conversion to enteral antibiotics was often not considered until the day of discharge, even if patients were taking other enteral medications earlier in the admission,” said project leader Sonya Girdwood, MD, a research fellow at the hospital.

To get a handle on the problem, her team focused on two common IV antibiotics, ampicillin and clindamycin, that have oral equivalents with equal bioavailability: amoxicillin in the case of ampicillin, and oral clindamycin. To further define the project, they zeroed in on two common indications: clindamycin for uncomplicated skin and soft-tissue infections, and ampicillin for community-acquired pneumonia, in children over 2 months old.

The team figured that, if patients were able to take other oral medications, they should also be able to take oral antibiotics, so the goal of the project was to increase the rate of antibiotics given orally in children who were taking other enteral medications.

That percentage was 44% at baseline, and increased to 80% by month 8, saving an estimated $30,000 annually. There was no increase in 30-day readmissions. Length of stay held steady overall at about a day and half, but Dr. Girdwood suspected it might have been reduced for cellulitis.

Improvement efforts focused on residents and started in January 2017. Among the first lessons was that IV ampicillin is about 21 times more expensive than amoxicillin and that IV clindamycin is about twice as expensive as its oral formulation.

Residents were tasked with forming a plan at admission to transition children to oral antibiotics as soon as possible and to discuss those plans with attending physicians in preround huddles. Often, “this led to [transition] orders being placed even before rounds started,” Dr. Girdwood said.

A time was set up during evening huddles – 10 p.m. – for residents working overnight to discuss transition timing with attending. Failures – patients still on IV clindamycin or ampicillin when they were taking oral meds – were identified and shared with resident teams.

The gains have been maintained for almost a year with little backsliding; residents are reminded weekly of transition goals.

Children with skin and soft-tissue infections with bone or eye involvement were excluded from the project, along with pneumonia patients with chest tubes or complex or loculated effusions requiring a surgery consult.

There was no external funding, and the investigators had no disclosures.

 

[email protected]

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.

An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.

Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.

There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.

However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.

The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.

Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.

 

“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”

However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.

“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.

The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.

The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.

An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.

Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.

There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.

However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.

The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.

Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.

 

“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”

However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.

“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.

The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.

The relationship between hypertension during pregnancy and sleep-disordered breathing may be partly mediated by obesity, new research suggests.

An article published in the Journal of Sleep Research details the results of a case-control study in 80 pregnant women – 40 normotensive and 40 with either gestational hypertension or preeclampsia – who were matched on body mass index.

Nearly half of the women in the study (45%) met the criteria for sleep-disordered breathing – defined as a respiratory disturbance index of 5 or above. The incidence was higher among women with hypertension (53%) than among women in the normotensive control group (38%), but the difference was not statistically significant.

There were also no significant differences in median respiratory disturbance index or apnea-hypopnea index between the hypertension and control groups.

However, the incidence of more severe sleep-disordered breathing – a respiratory disturbance index of at least 10 – was significantly greater in the hypertensive group (35% vs. 14%; P = .04). The women with pregnancy-related hypertension also had significantly higher respiratory disturbance index during non–rapid eye movement sleep and when they were sleeping on their back.

The severity of hypertensive disease did not affect the prevalence of sleep-disordered breathing.

Danielle L. Wilson of the Institute for Breathing and Sleep at Austin Health in Melbourne and her coauthors wrote that, while previous research has pointed to a link between hypertension in pregnancy and sleep-disordered breathing, this is the first study to explore the potential confounding role of obesity.

 

“We found SDB [sleep-disordered breathing] to be more common in our control group than in previous studies, confirming that BMI is an important covariate that requires evaluation in future studies exploring the relationship between SDB and HDP [hypertension during pregnancy],” they reported. “SDB may be a mechanism by which obesity and adverse perinatal outcomes are linked, but given the important contribution of obesity to both SDB and HDP, failing to adjust for this covariate will overestimate the strength of association between SDB and HDP.”

However, they acknowledged there was a significant association between moderate to severe sleep-disordered breathing and hypertension in pregnancy. They suggested this might be a means to increase women’s uptake of clinical review with a sleep physician, which was very low in the study despite it being offered to all women.

“Better engagement may be more likely for women with more severe disease if stronger links with adverse pregnancy outcome are demonstrated,” they wrote.

The study was supported by the Austin Medical Research Foundation and the Medical Research Foundation for Women and Babies. One author declared a scholarship from a research funding body, and two declared unrelated research support from private industry. No other conflicts of interest were declared.

SOURCE: Wilson D et al. J Sleep Research. 2018 Oct;27(5):e12656.

MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.

Bruce Jancin/MDedge News

That’s because a new secondary analysis of COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies), a randomized trial that included 27,395 patients with stable coronary or peripheral artery disease followed for a mean of 23 months at more than 600 centers in 33 countries, identified a strong association between early bleeding in rivaroxaban-treated patients and subsequent early diagnosis of new GI cancer. Ditto for rivaroxaban-associated genitourinary bleeding and subsequent GU cancer.

“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.

These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.

“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).

This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.

This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.

 

As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.

A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.

The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.

Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.

 

In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.

“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.

Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.

“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.

Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.

 

He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).

“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.

 

[email protected]

MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.

Bruce Jancin/MDedge News

That’s because a new secondary analysis of COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies), a randomized trial that included 27,395 patients with stable coronary or peripheral artery disease followed for a mean of 23 months at more than 600 centers in 33 countries, identified a strong association between early bleeding in rivaroxaban-treated patients and subsequent early diagnosis of new GI cancer. Ditto for rivaroxaban-associated genitourinary bleeding and subsequent GU cancer.

“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.

These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.

“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).

This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.

This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.

 

As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.

A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.

The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.

Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.

 

In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.

“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.

Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.

“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.

Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.

 

He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).

“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.

 

[email protected]

MUNICH – The increased risk of major GI bleeding documented with dual-antiplatelet therapy using rivaroxaban and aspirin when compared with aspirin alone for vascular protection in the previously reported massive COMPASS trial may turn out to be a blessing in disguise.

Bruce Jancin/MDedge News

That’s because a new secondary analysis of COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies), a randomized trial that included 27,395 patients with stable coronary or peripheral artery disease followed for a mean of 23 months at more than 600 centers in 33 countries, identified a strong association between early bleeding in rivaroxaban-treated patients and subsequent early diagnosis of new GI cancer. Ditto for rivaroxaban-associated genitourinary bleeding and subsequent GU cancer.

“Among COMPASS patients with vascular disease receiving long-term antithrombotic therapy, more than 1 in 5 new diagnoses of cancer are preceded by bleeding. GI and GU bleeding are powerful and relatively specific predictors of new GI and GU cancer diagnoses, respectively, and more than 75% of these cancers diagnosed after bleeding are diagnosed within 6 months of the bleed,” John W. Eikelboom, MD, reported at the annual congress of the European Society of Cardiology.

These findings strongly suggest that rivaroxaban (Xarelto), a direct-acting oral anticoagulant (DOAC), may be unmasking occult GI and GU cancers earlier than the malignancies would otherwise have declared themselves.

“Although overall cancer rates were similar in the three treatment groups [rivaroxaban at 2.5 mg twice daily plus aspirin at 100 mg/day, rivaroxaban monotherapy at 5 mg twice daily, or aspirin alone at 100 mg/day], the early increase in GI bleeding with rivaroxaban-based therapy resulted in earlier diagnosis of GI cancer in these patients. By reducing major cardiovascular events and mortality, the combination of rivaroxaban and aspirin already produces a clear net benefit, and by unmasking GI cancers at an earlier stage, the combination could potentially lead to the added benefit of improved GI cancer outcomes,” commented Dr. Eikelboom, a hematologist at McMaster University in Hamilton, Ont., and lead investigator of the previously published COMPASS trial (N Engl J Med. 2017 Oct 5;377[14]:1319-30).

This possibility that unmasking of occult GI cancer might result in improved survival deserves to be a high research priority in light of the enormous death toll caused by colorectal cancer. Planned longer-term follow-up of the COMPASS participants should be helpful in this regard, he added.

This new COMPASS finding effectively makes a silk purse out of a sow’s ear. When the primary outcomes of COMPASS were announced, many physicians reasoned that if the other commercially available DOACs also outperform warfarin but don’t pose a significantly increased threat of serious bleeding events, why not preferentially turn to them rather than rivaroxaban in patients with high HAS-BLED scores? But now rivaroxaban’s increased GI bleeding risk has begun to look like a potentially important advantage.

 

As previously reported, COMPASS participants on rivaroxaban plus aspirin had a 3.1% major bleeding rate as defined according to modified International Society on Thrombosis and Hemostasis criteria, for a statistically significant 70% increase in risk, compared with the 1.9% rate in patients on aspirin alone. Rivaroxaban monotherapy also was associated with increased bleeding risk. Of note, most of the excess in bleeding involved GI bleeding, and it was front-loaded during the first year of the trial. Also, reassuringly, there was no increased incidence of intracranial or fatal bleeding in patients on rivaroxaban.

A total of 1,082 patients were diagnosed with a new cancer during 23 months of follow-up. Nearly a quarter (23%) of the new GI cancers and 45% of the new GU cancers were diagnosed after bleeding from those sites.

The incidence of GI cancer diagnosed after GI bleeding was 7.8%, whereas patients with no prior GI bleeding had a mere 0.9% rate of newly diagnosed GI cancer during the study period. Thus, roughly 1 out of every 12 cases of GI bleeding was associated with diagnosis of a new GI cancer, and GI bleeding was associated with a 13-fold increased risk of subsequent GI cancer diagnosis. Put another way, the number of cases of GI bleeding occurring in patients on rivaroxaban that needed to be investigated in order to find one new GI cancer was 12.

Similarly, 13% of COMPASS participants who developed GU bleeding were subsequently diagnosed with a new GU cancer, compared with just 0.3% of subjects without GU bleeding. That translates into an 83.4-fold increased risk of GU cancer in patients with GU bleeding.

 

In contrast, the incidence of non-GI cancer following a GI bleed was 1.5%, while the rate was 1.0% in patients with no prior GI bleeding.

“That relationship was much weaker, with an odds ratio of 1.77, indicating that the relationship between GI bleeding and GI cancer is not only very strong but it’s rather specific,” according to Dr. Eikelboom.

Of GI cancers associated with a prior major GI bleed, 77% were diagnosed within 6 months following the bleed, as were nearly 89% of GU cancers. Another 9%-10% were diagnosed 6-12 months after the bleeding event.

“The implication for clinical practice is certainly that in patients who have GI or GU bleeding while receiving antithrombotic therapy, we should conduct a vigorous search for underlying cancer in the same organ system,” he concluded.

Discussant Lars C. Wallentin, MD, concurred. He called it a wake-up call for cardiologists to broaden their horizons and recognize that their elderly patients with vascular disease also are at substantial competing risk for major noncardiovascular diseases – and that his colleagues may have an important role to play in earlier cancer diagnoses.

 

He and his coinvestigators in the RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy) study made a similar point in their investigation of 18,113 patients with atrial fibrillation on oral anticoagulation for stroke protection. In that randomized trial of dabigatran (Pradaxa) versus warfarin, roughly 1 in 12 major GI bleeding events was found to be related to an occult colorectal or gastric cancer (Clin Gastroenterol Hepatol. 2017 May;15[5]:682-90).

“The data are very consistent. The message to cardiologists is that no bleeding should be disregarded in patients on oral anticoagulation,” declared Dr. Wallentin, professor of cardiology at Uppsala (Sweden) University.

COMPASS was sponsored by Bayer. Dr. Eikelboom reported receiving research grants from that company and more than half a dozen others.

 

[email protected]

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

 

Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.

There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.

Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.

Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.

 

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

 

Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.

There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.

Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.

Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.

 

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

Drug-eluting stents (DESs) and less-expensive bare-metal stents (BMSs) performed equally well in patients with failed saphenous vein grafts after coronary artery bypass graft surgery, based on an analysis of patients in the DIVA trial.

The findings run counter to those of previous clinical trials, which had found drug-eluting stents perform better than bare-metal stents in these situations. “The study results have important economic implications in countries with high DES prices, such as the USA, because they suggest that the lower-cost BMS can be used in SVG [saphenous vein graft] lesions without compromising either safety or efficacy,” lead author Emmanouil S. Brilakis, MD, PhD, of Minneapolis Heart Institute and his coauthors said in reporting the results for the DIVA trial investigators in the Lancet.

The DIVA trial was a randomized, double-blind, controlled trial done at 25 U.S. Department of Veterans Affairs centers. Researchers randomly assigned 599 patients who had previous coronary artery bypass surgery to either the DES or BMS groups, and the study reported data from 597 patients. The combined endpoint comprised cardiac death, target vessel MI, or target vessel revascularization at 12 months and then over the entire length of follow-up, which ranged from 2 to 7 years. Operators used the DES or BMS of their choice.

While BMSs are presumed to be less expensive than DESs, the study authors did not provide prices or price ranges for the stents. Dr. Brilakis and his coauthors acknowledged that the financial implications depend on local stent pricing practices.

The cost-effectiveness of using DESs vs. BMSs has been controversial, with many studies reporting that BMS are cost-effective over the long-term because of the lower incidence of revascularization and later hospitalization. These studies did not differentiate between SVG and native vessels, however. Multiple studies have reported that the overall costs, including the cost for reintervention, are lower for DESs than for BMSs in native vessels. A Wake Forest study reported the average per procedure cost was $1,846 higher for a DES but the cost was offset after 3 years by lower revascularization rates (Circ Cardiovasc Qual Outcomes. 2011. doi: 10.1161/CIRCOUTCOMES.110.960187)

A recent Korean study found the total cost of DESs was about 5% higher (Yonsei Med J. 2014 Nov;55[6]:1533-41). A French study reported BMSs resulted in a cost reduction $217 per case (Open Heart. 2016 Aug 25;3[2]:e000445). But few, if any, studies have directly compared prices hospitals pay for DESs and BMSs.

 

Pricing aside, Dr. Brilakis and his coauthors reported no statistical differences in terms of outcomes between the DES and BMS groups. Baseline characteristics of both groups were similar, and the vessel failure rates were 17% in the DES group and 19% in the BMS group after 12 months of follow-up. After 2-7 years, “target vessel failure occurred in approximately one in three patients, with no difference between the bare-metal and drug-eluting stents,” Dr. Brilakis and his coauthors said.

There was no significant difference in cardiac death rates – 5% for DES patients and 4% for BMS patients – or in rates of target lesion revascularization, at 9% and 8%, respectively. Postprocedure medication rates were also similar between the two groups. For example, the rates of patients on P2Y12 inhibitors were 89% for both groups at 12 months and, among those who had follow-up at 36 months, 48% for DES and 44% for BMS.

Among the limitations of the study that Dr. Brilakis and his coauthors noted was the high proportion of men in the VA population – only two women, both in the DES group, participated in the study – and the interventionists doing the index SVG intervention were not masked to the type of stent used.

Dr. Brilakis disclosed relationships with Abbott Vascular, Amgen, Asahi, Boston Scientific, Cardinal Health, CSI, Elsevier, GE Healthcare, Medicure, Medtronic, Nitiloop, InfraRedx, and Osprey.

 

SOURCE: Brilakis ES et al. Lancet. 2018 May 19;391(10134);1997-2007.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

 

“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.

“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.

The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”

SOURCE: AUA Annual Meeting, Abstract PD07-04.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

 

“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.

“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.

The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”

SOURCE: AUA Annual Meeting, Abstract PD07-04.

SAN FRANCISCO – Partial nephrectomy for localized renal cell carcinomas (RCCs) is on the rise, but the procedure is still less commonly performed than radical nephrectomy and more commonly performed at high-volume surgical centers.

About half of localized renal tumors are excised through partial nephrectomy, based on results from a new analysis of The National Cancer Database. The study also indicated that patient mortality rates were lower at high volume centers, those in the top 10 percentile of treatment volume, said David Cahn, DO, who presented the results at the annual meeting of the American Urological Association.

The study looked at surgeries among 142,000 patients with pT1a-T2b RCCs (no involvement of lymph nodes or metastases) who underwent procedures during 2004-2014.

Overall, 41% of patients had partial nephrectomies, 58% had radical nephrectomies, and 1% received ablative therapy. The frequency of partial nephrectomies rose markedly over the course of the study, increasing from 24% of cases in 2004 to 53% in 2014. The vast majority of partial nephrectomies, 81%, were performed for pT1a tumors; 24% of pT1b tumors also were excised using partial nephrectomy.

Compared with the reference point of T1a tumors, T1b tumors (odds ratio, 0.22; P less than .0001), T2a (OR, 0.06; P less than .0001), and T2b tumors (OR, 0.03; P less than .0001) were progressively less likely to be treated with partial nephrectomy. A multivariate analysis showed that patients at a high volume center were significantly more likely to undergo partial nephrectomy (OR, 1.89; P less than .0001). Overall mortality was lower at high volume centers (hazard ratio, 0.92; P = .012).

 

“I think that regionalization of care has ... some benefits to patients, but it comes with many challenges as well. This study really did help show that increased numbers [of procedures performed] makes you more comfortable and willing to offer partial nephrectomy,” said Dr. Cahn, of Fox Chase Cancer Center, Philadelphia.

“Volume tends to show better outcomes. But the concern is: Are you overloading systems? Are you making patients travel farther, and how does that work in terms of follow-up care?” Dr. Cahn said. He cited the example of a patient who may have to travel several hours to get surgery but then returns home and develops a postoperative complication that must be treated in a different facility. That raises issues of transfer of medical records and coordination of care.

The solution, he said, is for some of the procedures and practices common at high-volume centers to be transferred to smaller centers. “For the routine partial nephrectomy ... we need to have well-trained physicians who can offer those all over the country. I think it’s too hard in terms of feasibility to push those patients just towards certain high volume centers.”

SOURCE: AUA Annual Meeting, Abstract PD07-04.

Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.

After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.

About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.

“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.

Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”

The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.

Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.

 

Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).

The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.

Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.

 

Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.

“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.

Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.

SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.

Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.

After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.

About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.

“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.

Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”

The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.

Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.

 

Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).

The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.

Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.

 

Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.

“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.

Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.

SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.

Ulipristal acetate reduces breakthrough bleeding in women with etonogestrel implants, according to new findings.

After 30 days, patients treated with ulipristal were more satisfied with their bleeding profiles than were those given placebo, reported Rachel E. Zigler, MD, of the department of obstetrics and gynecology at Washington University in St. Louis and her colleagues.

About half of women experience unscheduled bleeding within the first 6 months of etonogestrel implantation, causing many to discontinue treatment. The etiology of this phenomenon is poorly understood.

“One leading theory is that sustained exposure to a progestin can lead to endometrial angiogenesis disruption, resulting in the development of a dense venous network that is fragile and prone to bleeding,” the researchers wrote in Obstetrics & Gynecology.

Ulipristal acetate is a selective progesterone receptor modulator approved for emergency contraception in the United States. Outside the United States, it is used to treat abnormal uterine bleeding in cases of uterine leiomyoma. Ulipristal acts directly upon myometrial and endometrial tissue and “may also displace local progestin within the uterus to counteract bleeding secondary to … a dense, fragile venous network.”

The double-blind, placebo-controlled study included 65 women aged 18-45 years with etonogestrel implants. Eligibility required that implants be in place for more than 90 days and less than 3 years and that participants experienced more than one bleeding episode over a 24-day time frame.

Patients received either 15 mg ulipristal (n = 32) or placebo (n = 33) daily for 7 days. From the first day of treatment until 30 days, patients self-reported bleeding events. Weekly phone questionnaires also were conducted to determine satisfaction with medication and side effects.

 

Ten days after starting treatment, bleeding resolved in 34% of patients treated with ulipristal versus 10% of patients given placebo (P = .03).

The ulipristal group reported a median of 5 fewer bleeding days, compared with the placebo group, over the month-long evaluation (7 vs. 12; P = .002). Treatment satisfaction rates were also better in the ulipristal group, with nearly three-quarters (72%) “very happy” with results versus about one-quarter (27%) of women who received placebo.

Consequently, more ulipristal patients desired to keep their implants, compared with placebo patients. All patients receiving ulipristal would consider ulipristal for breakthrough bleeding in the future, compared with two-thirds of patients in the placebo group.

 

Side effects were uncommon for both groups; the most common side effect was headache, reported in 9% in the ulipristal group and 19% in the placebo group.

“Increased satisfaction with the etonogestrel implant may lead to a decrease in discontinuation rates and potentially a decrease in unintended pregnancy rates in this population,” the researchers wrote.

Study funding was provided by the Society of Family Planning Research Fund, the Washington University Institute of Clinical and Translational Sciences, and the National Center for Advancing Translational Sciences. The authors reported financial disclosures related to Bayer and Merck.

SOURCE: Zigler RE et al. Obstet Gynecol. 2018;132:888-94.