PARIS – A new bioabsorbable sutureless device provides operators with a safe, simple, and dependable option for fully percutaneous closure of the large, 12-24 French femoral arteriotomies created for transcatheter aortic valve replacement or endovascular abdominal aortic aneurysm repair, Arne Schwindt, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

He presented the 12-month follow-up results of the FRONTIER II study of the Vivasure PerQseal device. The device recently received European marketing approval on the strength of FRONTIER II but remains investigational in the United States.

The PerQseal device is deployed in less than 1 minute at the end of the primary procedure and achieves immediate hemostasis. It’s a simple three-step deployment process with essentially no learning curve, as evidenced by the fact that in FRONTIER II, the technical success rate starting from no experience was 97%, explained Dr. Schwindt of St. Franziskus Hospital in Muenster, Germany.

The large femoral arteriotomies created for TAVR or endovascular abdominal aortic aneurysm repair have typically required surgical cut down and sutured repair with a 3- to 5-cm incision. Vascular complications have been common. Indeed, the literature shows this method entails on average a 14.7% rate of major vascular complications up to 3 months post procedure, so that was the bar set in FRONTIER II: In order for the PerQseal to be deemed noninferior to surgical cut down and sutured repair, the rate of major complications directly related to the novel device at 3 months follow-up could be no greater than 14.7%. The current Valve Academic Research Consortium (VARC) 2 definition of major complications was used.

In fact, the vascular complication rate proved to be zero. Moreover, at 12 months of follow-up, no cases of groin fibrosis or scarring had been observed, Dr. Schwindt reported.

FRONTIER II was a single-arm, prospective, multicenter European study of 58 patients who received the PerQseal device for 66 closures. They were evaluated at discharge and 1, 3, and 12 months post procedure by Doppler ultrasound, with uniformly unremarkable findings.

PerQseal features a synthetic low-profile implant with over-the-wire delivery. The implant is loaded into a sheath, released by pulling back on the sheath, then pulled up against the arteriotomy from the inside. Blood pressure molds the device to the arterial wall and seals it. The device is fully absorbed in 180 days.

Session co-chair Dr. Ted E. Feldman was favorably impressed.

“This is really terrific. It’s very nice to see we’re finally making progress with large-bore closure devices,” commented Dr. Feldman, professor of medicine at Northwestern University, Chicago.

Dr. Schwindt reported receiving a research grant from Vivasure, which sponsored the FRONTIER II study. In addition, he serves as a consultant to a half dozen medical device companies.

[email protected]

PARIS – A new bioabsorbable sutureless device provides operators with a safe, simple, and dependable option for fully percutaneous closure of the large, 12-24 French femoral arteriotomies created for transcatheter aortic valve replacement or endovascular abdominal aortic aneurysm repair, Arne Schwindt, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

He presented the 12-month follow-up results of the FRONTIER II study of the Vivasure PerQseal device. The device recently received European marketing approval on the strength of FRONTIER II but remains investigational in the United States.

The PerQseal device is deployed in less than 1 minute at the end of the primary procedure and achieves immediate hemostasis. It’s a simple three-step deployment process with essentially no learning curve, as evidenced by the fact that in FRONTIER II, the technical success rate starting from no experience was 97%, explained Dr. Schwindt of St. Franziskus Hospital in Muenster, Germany.

The large femoral arteriotomies created for TAVR or endovascular abdominal aortic aneurysm repair have typically required surgical cut down and sutured repair with a 3- to 5-cm incision. Vascular complications have been common. Indeed, the literature shows this method entails on average a 14.7% rate of major vascular complications up to 3 months post procedure, so that was the bar set in FRONTIER II: In order for the PerQseal to be deemed noninferior to surgical cut down and sutured repair, the rate of major complications directly related to the novel device at 3 months follow-up could be no greater than 14.7%. The current Valve Academic Research Consortium (VARC) 2 definition of major complications was used.

In fact, the vascular complication rate proved to be zero. Moreover, at 12 months of follow-up, no cases of groin fibrosis or scarring had been observed, Dr. Schwindt reported.

FRONTIER II was a single-arm, prospective, multicenter European study of 58 patients who received the PerQseal device for 66 closures. They were evaluated at discharge and 1, 3, and 12 months post procedure by Doppler ultrasound, with uniformly unremarkable findings.

PerQseal features a synthetic low-profile implant with over-the-wire delivery. The implant is loaded into a sheath, released by pulling back on the sheath, then pulled up against the arteriotomy from the inside. Blood pressure molds the device to the arterial wall and seals it. The device is fully absorbed in 180 days.

Session co-chair Dr. Ted E. Feldman was favorably impressed.

“This is really terrific. It’s very nice to see we’re finally making progress with large-bore closure devices,” commented Dr. Feldman, professor of medicine at Northwestern University, Chicago.

Dr. Schwindt reported receiving a research grant from Vivasure, which sponsored the FRONTIER II study. In addition, he serves as a consultant to a half dozen medical device companies.

[email protected]

PARIS – A new bioabsorbable sutureless device provides operators with a safe, simple, and dependable option for fully percutaneous closure of the large, 12-24 French femoral arteriotomies created for transcatheter aortic valve replacement or endovascular abdominal aortic aneurysm repair, Arne Schwindt, MD, reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

He presented the 12-month follow-up results of the FRONTIER II study of the Vivasure PerQseal device. The device recently received European marketing approval on the strength of FRONTIER II but remains investigational in the United States.

The PerQseal device is deployed in less than 1 minute at the end of the primary procedure and achieves immediate hemostasis. It’s a simple three-step deployment process with essentially no learning curve, as evidenced by the fact that in FRONTIER II, the technical success rate starting from no experience was 97%, explained Dr. Schwindt of St. Franziskus Hospital in Muenster, Germany.

The large femoral arteriotomies created for TAVR or endovascular abdominal aortic aneurysm repair have typically required surgical cut down and sutured repair with a 3- to 5-cm incision. Vascular complications have been common. Indeed, the literature shows this method entails on average a 14.7% rate of major vascular complications up to 3 months post procedure, so that was the bar set in FRONTIER II: In order for the PerQseal to be deemed noninferior to surgical cut down and sutured repair, the rate of major complications directly related to the novel device at 3 months follow-up could be no greater than 14.7%. The current Valve Academic Research Consortium (VARC) 2 definition of major complications was used.

In fact, the vascular complication rate proved to be zero. Moreover, at 12 months of follow-up, no cases of groin fibrosis or scarring had been observed, Dr. Schwindt reported.

FRONTIER II was a single-arm, prospective, multicenter European study of 58 patients who received the PerQseal device for 66 closures. They were evaluated at discharge and 1, 3, and 12 months post procedure by Doppler ultrasound, with uniformly unremarkable findings.

PerQseal features a synthetic low-profile implant with over-the-wire delivery. The implant is loaded into a sheath, released by pulling back on the sheath, then pulled up against the arteriotomy from the inside. Blood pressure molds the device to the arterial wall and seals it. The device is fully absorbed in 180 days.

Session co-chair Dr. Ted E. Feldman was favorably impressed.

“This is really terrific. It’s very nice to see we’re finally making progress with large-bore closure devices,” commented Dr. Feldman, professor of medicine at Northwestern University, Chicago.

Dr. Schwindt reported receiving a research grant from Vivasure, which sponsored the FRONTIER II study. In addition, he serves as a consultant to a half dozen medical device companies.

[email protected]

Long-term follow-up from two randomized trials shows that the treatment advantage initially seen by adding radiotherapy to the CHOP regimen in patients with limited-stage diffuse large B-cell lymphoma disappeared over time.

After a median follow-up of nearly 18 years, there were no significant differences in either progression-free survival (PFS) or overall survival between patients who had received standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 8 cycles (CHOP8), or 3 cycles of CHOP with involved-field radiotherapy (CHOP3RT), reported Deborah M. Stephens, DO, of the University of Utah in Salt Lake City, and her colleagues.

The addition of rituximab to CHOP plus involved-field radiotherapy (IFRT) in a separate cohort did not appear to reduce the continued relapse risk, the investigators noted (J Clin Oncol. 2016 Jul. doi: 10.1200/JCO.2015.65.4582).

The findings suggest that long-term follow-up of patients enrolled in clinical trials may provide clinically important additional information, and that limited-stage diffuse large B-cell lymphoma (DLBCL) may have a biology that is distinctly different from that of advanced stage DLBCL, the investigators wrote.

Initial results from the SWOG (Southwest Oncology Group) Study 8736, published after a median follow-up of 4.4 years, showed that CHOP3RT was associated with significantly better 5-year PFS and OS rates, compared with patients treated with CHOP8.

A second trial, SWOG Study 0014, looked at the addition of rituximab (Rituxan) to CHOP plus IFRT in patients with high-risk DLBCL with at least one adverse feature of the stage-modified International Prognostic Index. In this trial, after a median follow-up of 5.3 years, 4-year PFS was 88%, and 4-year OS was 92%.

5 years not enough

Results of both trials were published around the 5-year follow-up mark. However, an analysis of 10-year follow-up data from the S8736 trial, published only as an abstract (Blood. 98:724a-725a, 2001; abstr 3024), showed that “the survival curves for CHOP8 and CHOP3RT, surprisingly, began to overlap,” Dr. Stephens and her colleagues wrote.

“Additionally, for both S8736 and S0014, no plateau had been reached in the PFS curves. These data contrasted the expected cure rates for advanced-stage DLBCL, leading to the hypothesis that limited-stage DLBCL may have a unique biology from its advanced-stage counterpart,” they added.

Although more than half of patients with advanced-stage diffuse large B-cell lymphoma (DLBCL) can be cured with anthracycline-based chemotherapy, cure rates are markedly lower among patients with limited-stage disease, defined as Ann Arbor stage I or II, confined to a single irradiation field. Limited-stage disease accounts for approximately one-third DLBCL cases.

To see whether the trends observed at 10 years continued, the investigators conducted a survival analysis from S8736 and compared the data from similar patients in the S0014 study.

They found that after a median follow-up of 17.7 years in S8736, median PFS was 12.0 years for patients treated with CHOP8, and 11.1 years for patients treated with CHOP3RT, a difference that was not statistically significant.

Median OS was 13.0 and 13.7 years, respectively, and was also not significant.

In S0014, after a median follow-up of 12 years, the 5-year OS rate was 82%, and 10-year rate was 67%. In this trial, the investigators observed “a persistent pattern of relapse despite the addition of rituximab.”

“The populations were not entirely identical; however, even the addition of rituximab as per S0014 to combined-modality therapy did not seem to mitigate the continued relapse risk, underscoring the value of prolonged observation of clinical trial patients and possible unique biology of limited-stage DLBCL,” Dr. Stephens and her associates wrote.

The study was sponsored by grants from the National Institutes of Health. Dr. Stephens reported having no financial disclosures. Several coauthors disclosed research funding, consulting, speakers’ bureau participation or travel expenses from various oncology drug makers.

Long-term follow-up from two randomized trials shows that the treatment advantage initially seen by adding radiotherapy to the CHOP regimen in patients with limited-stage diffuse large B-cell lymphoma disappeared over time.

After a median follow-up of nearly 18 years, there were no significant differences in either progression-free survival (PFS) or overall survival between patients who had received standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 8 cycles (CHOP8), or 3 cycles of CHOP with involved-field radiotherapy (CHOP3RT), reported Deborah M. Stephens, DO, of the University of Utah in Salt Lake City, and her colleagues.

The addition of rituximab to CHOP plus involved-field radiotherapy (IFRT) in a separate cohort did not appear to reduce the continued relapse risk, the investigators noted (J Clin Oncol. 2016 Jul. doi: 10.1200/JCO.2015.65.4582).

The findings suggest that long-term follow-up of patients enrolled in clinical trials may provide clinically important additional information, and that limited-stage diffuse large B-cell lymphoma (DLBCL) may have a biology that is distinctly different from that of advanced stage DLBCL, the investigators wrote.

Initial results from the SWOG (Southwest Oncology Group) Study 8736, published after a median follow-up of 4.4 years, showed that CHOP3RT was associated with significantly better 5-year PFS and OS rates, compared with patients treated with CHOP8.

A second trial, SWOG Study 0014, looked at the addition of rituximab (Rituxan) to CHOP plus IFRT in patients with high-risk DLBCL with at least one adverse feature of the stage-modified International Prognostic Index. In this trial, after a median follow-up of 5.3 years, 4-year PFS was 88%, and 4-year OS was 92%.

5 years not enough

Results of both trials were published around the 5-year follow-up mark. However, an analysis of 10-year follow-up data from the S8736 trial, published only as an abstract (Blood. 98:724a-725a, 2001; abstr 3024), showed that “the survival curves for CHOP8 and CHOP3RT, surprisingly, began to overlap,” Dr. Stephens and her colleagues wrote.

“Additionally, for both S8736 and S0014, no plateau had been reached in the PFS curves. These data contrasted the expected cure rates for advanced-stage DLBCL, leading to the hypothesis that limited-stage DLBCL may have a unique biology from its advanced-stage counterpart,” they added.

Although more than half of patients with advanced-stage diffuse large B-cell lymphoma (DLBCL) can be cured with anthracycline-based chemotherapy, cure rates are markedly lower among patients with limited-stage disease, defined as Ann Arbor stage I or II, confined to a single irradiation field. Limited-stage disease accounts for approximately one-third DLBCL cases.

To see whether the trends observed at 10 years continued, the investigators conducted a survival analysis from S8736 and compared the data from similar patients in the S0014 study.

They found that after a median follow-up of 17.7 years in S8736, median PFS was 12.0 years for patients treated with CHOP8, and 11.1 years for patients treated with CHOP3RT, a difference that was not statistically significant.

Median OS was 13.0 and 13.7 years, respectively, and was also not significant.

In S0014, after a median follow-up of 12 years, the 5-year OS rate was 82%, and 10-year rate was 67%. In this trial, the investigators observed “a persistent pattern of relapse despite the addition of rituximab.”

“The populations were not entirely identical; however, even the addition of rituximab as per S0014 to combined-modality therapy did not seem to mitigate the continued relapse risk, underscoring the value of prolonged observation of clinical trial patients and possible unique biology of limited-stage DLBCL,” Dr. Stephens and her associates wrote.

The study was sponsored by grants from the National Institutes of Health. Dr. Stephens reported having no financial disclosures. Several coauthors disclosed research funding, consulting, speakers’ bureau participation or travel expenses from various oncology drug makers.

Long-term follow-up from two randomized trials shows that the treatment advantage initially seen by adding radiotherapy to the CHOP regimen in patients with limited-stage diffuse large B-cell lymphoma disappeared over time.

After a median follow-up of nearly 18 years, there were no significant differences in either progression-free survival (PFS) or overall survival between patients who had received standard CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 8 cycles (CHOP8), or 3 cycles of CHOP with involved-field radiotherapy (CHOP3RT), reported Deborah M. Stephens, DO, of the University of Utah in Salt Lake City, and her colleagues.

The addition of rituximab to CHOP plus involved-field radiotherapy (IFRT) in a separate cohort did not appear to reduce the continued relapse risk, the investigators noted (J Clin Oncol. 2016 Jul. doi: 10.1200/JCO.2015.65.4582).

The findings suggest that long-term follow-up of patients enrolled in clinical trials may provide clinically important additional information, and that limited-stage diffuse large B-cell lymphoma (DLBCL) may have a biology that is distinctly different from that of advanced stage DLBCL, the investigators wrote.

Initial results from the SWOG (Southwest Oncology Group) Study 8736, published after a median follow-up of 4.4 years, showed that CHOP3RT was associated with significantly better 5-year PFS and OS rates, compared with patients treated with CHOP8.

A second trial, SWOG Study 0014, looked at the addition of rituximab (Rituxan) to CHOP plus IFRT in patients with high-risk DLBCL with at least one adverse feature of the stage-modified International Prognostic Index. In this trial, after a median follow-up of 5.3 years, 4-year PFS was 88%, and 4-year OS was 92%.

5 years not enough

Results of both trials were published around the 5-year follow-up mark. However, an analysis of 10-year follow-up data from the S8736 trial, published only as an abstract (Blood. 98:724a-725a, 2001; abstr 3024), showed that “the survival curves for CHOP8 and CHOP3RT, surprisingly, began to overlap,” Dr. Stephens and her colleagues wrote.

“Additionally, for both S8736 and S0014, no plateau had been reached in the PFS curves. These data contrasted the expected cure rates for advanced-stage DLBCL, leading to the hypothesis that limited-stage DLBCL may have a unique biology from its advanced-stage counterpart,” they added.

Although more than half of patients with advanced-stage diffuse large B-cell lymphoma (DLBCL) can be cured with anthracycline-based chemotherapy, cure rates are markedly lower among patients with limited-stage disease, defined as Ann Arbor stage I or II, confined to a single irradiation field. Limited-stage disease accounts for approximately one-third DLBCL cases.

To see whether the trends observed at 10 years continued, the investigators conducted a survival analysis from S8736 and compared the data from similar patients in the S0014 study.

They found that after a median follow-up of 17.7 years in S8736, median PFS was 12.0 years for patients treated with CHOP8, and 11.1 years for patients treated with CHOP3RT, a difference that was not statistically significant.

Median OS was 13.0 and 13.7 years, respectively, and was also not significant.

In S0014, after a median follow-up of 12 years, the 5-year OS rate was 82%, and 10-year rate was 67%. In this trial, the investigators observed “a persistent pattern of relapse despite the addition of rituximab.”

“The populations were not entirely identical; however, even the addition of rituximab as per S0014 to combined-modality therapy did not seem to mitigate the continued relapse risk, underscoring the value of prolonged observation of clinical trial patients and possible unique biology of limited-stage DLBCL,” Dr. Stephens and her associates wrote.

The study was sponsored by grants from the National Institutes of Health. Dr. Stephens reported having no financial disclosures. Several coauthors disclosed research funding, consulting, speakers’ bureau participation or travel expenses from various oncology drug makers.

The proposed federal regulations to implement the MACRA health care reforms are too complex, too onerous on small and solo practices, lack opportunities for many to participate in alternative payment models, and should be delayed for a full year, at least.

That was the message that emerged from hundreds of comments regarding the proposed rule that were submitted by physician organizations and other stakeholders.

“The intent of [the Medicare Access and CHIP Reauthorization Act of 2015] was not to merely move the current incentive program into [the Merit-based Incentive Payment System], but to improve and simplify these programs into a single more unified approach,” the American Medical Association said in its comments, noting that “numerous changes” will be needed in the way cost and quality are measured.

AMA also called for a better, faster way for physicians to develop alternative payment models. “We strongly urge CMS to vigorously pursue this objective and establish a much more progressive and welcoming environment for the development and implementation of specialty-defined APMs than proposed in the [proposed rule].”

AMA also suggested that CMS provide more flexibility for solo and small practices, align the four components of MIPS so it operates as a single program, simplifying and lowering the financial risk for advanced APMs, and providing more timely feedback to physicians.

The organization also called for CMS to “create an initial transitional performance period from July 1, 2017, to December 31, 2017, to ensure the successful and appropriate implementation of the MACRA program. In future years, for all reporting requirements, CMS should allow physicians to select periods of less than a full calendar year to provide flexibility.”

In its comments, the American Medical Group Association questioned whether the proposed rule actually would lead to improved quality of care and reward value.

In the proposed rule, “CMS will measure and score quality and resource use or spending separately,” AMGA wrote in its comments. “CMS will not measure outcomes in relation to spending. CMS will not measure for value. If value is left unaddressed in the final rule, it will be difficult at best for the agency to meet MACRA and the [HHS] secretary’s overarching goals.”

While expressing support for MACRA conceptually, officials with the American Academy of Family Physicians wrote that they “see a strong and definite need and opportunity for CMS to step back and reconsider the approach to this proposed rule which we view as overly complex and burdensome to our members and indeed for all physicians. Given the significant complexity of the rule, we strongly encourage CMS to issue an interim final rule with comment period rather than to issue a final rule.”

Specifically, AAFP criticized the proposed rule for allowing small and solo practices to form “virtual groups” in order to earn bonuses, despite it being mandated by law.

Solo and small group practices who participate in MIPS to should “be eligible for positive payment updates if their performance yields such payments, but would be exempt from any negative payment update until such a time that the virtual group option is available,” AAFP officials wrote.

They also called for medical home delivery models to be included in APMs, in an effort to improve on the limited opportunities for family practices in particular to participate in alternative payment models.

The American College of Physicians also called for safe harbors for small and solo practices until virtual group options can be established.

ACP, like other groups, questioned that medical homes are not recognized as alternative payment models and argued that Congress intended medical homes to qualify as APMs “without bearing more than nominal financial risk.”

Despite the flexible approach to the overall quality payment program, CMS has “created a degree of complexity” and must “continue to seek ways to further streamline and simplify” the move to quality payments, according to comments from the American College of Cardiology.

The ACC also expressed concerns that the reporting requirements under MIPS and some of the APMs will limit the ability for cardiologists to report the most meaningful measures, particularly if they are part of a multi-specialty group, and suggested changes in scoring methodology or to allow more than one data file to be submitted in multi-specialty situations.

It also expressed concerns that the rule as proposed could adversely effect small practices, rural practices, and practices in health professional shortage areas, and “in the absence of other solutions such as virtual groups in 2017, CMS should monitor policies and provide effective practice assistance to these practices.”

The proposed rule provides no support for small practices, according to the American Gastroenterological Association.

“Upon release of the proposed rule, we were disappointed to see that not only will APMs be essentially closed off to small practices in the first years of implementation, but the MIPS program will significantly harm practices with less than 25 eligible clinicians,” AGA noted, citing data presented by CMS that 87% of solo practitioners will receive a negative adjustment with an aggregate negative impact of $300 million and for all practices with less than 25 eligible clinicians, the aggregate negative adjustment will total $649 million.

“Any system in which smaller practices are so heavily disadvantaged is unacceptable,” AGA said. CMS has previously stated that the regulatory impact statement would likely change and reflect a smaller impact for small and solo practices once more updated information can be modeled when the rule is final.

Additionally, AGA expressed concern over the limited engagement in APMs that will be possible under the proposed rule. “Given the importance of APM participation to both the practice and reimbursement of Medicare physicians, access to advanced APMs should be provided to all physicians.”

The association also expressed concern that the definition of APM is not broad enough and suggested that it be widened in scope so that it can capture payment models that have been created using the AGA’s Roadmap to the Future of GI Practice. It recommended a number of models be classified as APMs, including the colonoscopy bundled payment, gastroesophageal reflux disease episode payment, obesity bundled payment, Project Sonar (a chronic disease management program for IBD), and the Medical Home Neighbor.

The American College of Rheumatology called for a delay in the implementation of any final MACRA regulations, noting in its comments that with requirements set to begin in 2017, the current implementation schedule “does not provide enough time for providers to implement the required changes,” though ACR does not recommend a specific start time.

ACR also questioned how the criteria for APMs was set up, noting expressly that Physician Focused Payment Models may not meet the APM requirements. The group is seeking clarification on whether these models will qualify as an APM.

“Medical home APMs should also permit specialty physicians to participate, including small group and multispeciality groups, in keeping with the need for APMs to be flexible with their criteria and the role of specialty physicians in providing chronic care.

The American Academy of Dermatology Association echoed a number of concerns voiced across the medical profession and is calling for a delay in the implementation of MACRA’s regulations.

In particular, AADA noted that the regulations are not friendly for small and solo practices in general and little is contained within the proposal to “meaningfully engage specialist physicians in APMs.”

The association also is calling for broader mechanisms to allow for the development and recognition of APMs, including recognizing specialty-focused medical homes.

The group also is calling for pilot programs to test the validity of the measures that will form the basis of quality payment incentives and penalties.

In an effort to protect small and solo practices, AADA is calling for an exemption from MIPS or APM requirements until a virtual group option is developed, tested, and is fully operational.

The American Psychiatric Association echoed a number of broad concerns raised across the physician spectrum, including calling for a to the first year of implementation to July 1, 2017, and lasting through Dec. 31, 2017, as well as enabling the formation of virtual groups at the onset of implementation in its comments.

But APA also noted that mental health presents a variety of unique issues that need to be addressed.

For example, the association notes that psychiatrists work across a number of practice settings, including academic health centers, hospitals, clinics, nursing homes, and private practices, as well as offering services via telemedicine.

“This makes it difficult for psychiatrists to capture all the work they do, because of the combination of settings that utilize multiple, and potentially differing reporting programs and methods,” APA noted.

It added that psychiatrists generally have limited time and resources that can be devoted to Medicare quality reporting, which would make participation in MIPS and APMs more challenging, particularly because many operate in small or solo practices that do not own electronic health record systems, which would complicate reporting requirements to qualify for MIPS or APMs.

In addition to concerns with reporting in general, APA said that psychiatrists “also have limited choices in outcome quality measures.”

[email protected]

The proposed federal regulations to implement the MACRA health care reforms are too complex, too onerous on small and solo practices, lack opportunities for many to participate in alternative payment models, and should be delayed for a full year, at least.

That was the message that emerged from hundreds of comments regarding the proposed rule that were submitted by physician organizations and other stakeholders.

“The intent of [the Medicare Access and CHIP Reauthorization Act of 2015] was not to merely move the current incentive program into [the Merit-based Incentive Payment System], but to improve and simplify these programs into a single more unified approach,” the American Medical Association said in its comments, noting that “numerous changes” will be needed in the way cost and quality are measured.

AMA also called for a better, faster way for physicians to develop alternative payment models. “We strongly urge CMS to vigorously pursue this objective and establish a much more progressive and welcoming environment for the development and implementation of specialty-defined APMs than proposed in the [proposed rule].”

AMA also suggested that CMS provide more flexibility for solo and small practices, align the four components of MIPS so it operates as a single program, simplifying and lowering the financial risk for advanced APMs, and providing more timely feedback to physicians.

The organization also called for CMS to “create an initial transitional performance period from July 1, 2017, to December 31, 2017, to ensure the successful and appropriate implementation of the MACRA program. In future years, for all reporting requirements, CMS should allow physicians to select periods of less than a full calendar year to provide flexibility.”

In its comments, the American Medical Group Association questioned whether the proposed rule actually would lead to improved quality of care and reward value.

In the proposed rule, “CMS will measure and score quality and resource use or spending separately,” AMGA wrote in its comments. “CMS will not measure outcomes in relation to spending. CMS will not measure for value. If value is left unaddressed in the final rule, it will be difficult at best for the agency to meet MACRA and the [HHS] secretary’s overarching goals.”

While expressing support for MACRA conceptually, officials with the American Academy of Family Physicians wrote that they “see a strong and definite need and opportunity for CMS to step back and reconsider the approach to this proposed rule which we view as overly complex and burdensome to our members and indeed for all physicians. Given the significant complexity of the rule, we strongly encourage CMS to issue an interim final rule with comment period rather than to issue a final rule.”

Specifically, AAFP criticized the proposed rule for allowing small and solo practices to form “virtual groups” in order to earn bonuses, despite it being mandated by law.

Solo and small group practices who participate in MIPS to should “be eligible for positive payment updates if their performance yields such payments, but would be exempt from any negative payment update until such a time that the virtual group option is available,” AAFP officials wrote.

They also called for medical home delivery models to be included in APMs, in an effort to improve on the limited opportunities for family practices in particular to participate in alternative payment models.

The American College of Physicians also called for safe harbors for small and solo practices until virtual group options can be established.

ACP, like other groups, questioned that medical homes are not recognized as alternative payment models and argued that Congress intended medical homes to qualify as APMs “without bearing more than nominal financial risk.”

Despite the flexible approach to the overall quality payment program, CMS has “created a degree of complexity” and must “continue to seek ways to further streamline and simplify” the move to quality payments, according to comments from the American College of Cardiology.

The ACC also expressed concerns that the reporting requirements under MIPS and some of the APMs will limit the ability for cardiologists to report the most meaningful measures, particularly if they are part of a multi-specialty group, and suggested changes in scoring methodology or to allow more than one data file to be submitted in multi-specialty situations.

It also expressed concerns that the rule as proposed could adversely effect small practices, rural practices, and practices in health professional shortage areas, and “in the absence of other solutions such as virtual groups in 2017, CMS should monitor policies and provide effective practice assistance to these practices.”

The proposed rule provides no support for small practices, according to the American Gastroenterological Association.

“Upon release of the proposed rule, we were disappointed to see that not only will APMs be essentially closed off to small practices in the first years of implementation, but the MIPS program will significantly harm practices with less than 25 eligible clinicians,” AGA noted, citing data presented by CMS that 87% of solo practitioners will receive a negative adjustment with an aggregate negative impact of $300 million and for all practices with less than 25 eligible clinicians, the aggregate negative adjustment will total $649 million.

“Any system in which smaller practices are so heavily disadvantaged is unacceptable,” AGA said. CMS has previously stated that the regulatory impact statement would likely change and reflect a smaller impact for small and solo practices once more updated information can be modeled when the rule is final.

Additionally, AGA expressed concern over the limited engagement in APMs that will be possible under the proposed rule. “Given the importance of APM participation to both the practice and reimbursement of Medicare physicians, access to advanced APMs should be provided to all physicians.”

The association also expressed concern that the definition of APM is not broad enough and suggested that it be widened in scope so that it can capture payment models that have been created using the AGA’s Roadmap to the Future of GI Practice. It recommended a number of models be classified as APMs, including the colonoscopy bundled payment, gastroesophageal reflux disease episode payment, obesity bundled payment, Project Sonar (a chronic disease management program for IBD), and the Medical Home Neighbor.

The American College of Rheumatology called for a delay in the implementation of any final MACRA regulations, noting in its comments that with requirements set to begin in 2017, the current implementation schedule “does not provide enough time for providers to implement the required changes,” though ACR does not recommend a specific start time.

ACR also questioned how the criteria for APMs was set up, noting expressly that Physician Focused Payment Models may not meet the APM requirements. The group is seeking clarification on whether these models will qualify as an APM.

“Medical home APMs should also permit specialty physicians to participate, including small group and multispeciality groups, in keeping with the need for APMs to be flexible with their criteria and the role of specialty physicians in providing chronic care.

The American Academy of Dermatology Association echoed a number of concerns voiced across the medical profession and is calling for a delay in the implementation of MACRA’s regulations.

In particular, AADA noted that the regulations are not friendly for small and solo practices in general and little is contained within the proposal to “meaningfully engage specialist physicians in APMs.”

The association also is calling for broader mechanisms to allow for the development and recognition of APMs, including recognizing specialty-focused medical homes.

The group also is calling for pilot programs to test the validity of the measures that will form the basis of quality payment incentives and penalties.

In an effort to protect small and solo practices, AADA is calling for an exemption from MIPS or APM requirements until a virtual group option is developed, tested, and is fully operational.

The American Psychiatric Association echoed a number of broad concerns raised across the physician spectrum, including calling for a to the first year of implementation to July 1, 2017, and lasting through Dec. 31, 2017, as well as enabling the formation of virtual groups at the onset of implementation in its comments.

But APA also noted that mental health presents a variety of unique issues that need to be addressed.

For example, the association notes that psychiatrists work across a number of practice settings, including academic health centers, hospitals, clinics, nursing homes, and private practices, as well as offering services via telemedicine.

“This makes it difficult for psychiatrists to capture all the work they do, because of the combination of settings that utilize multiple, and potentially differing reporting programs and methods,” APA noted.

It added that psychiatrists generally have limited time and resources that can be devoted to Medicare quality reporting, which would make participation in MIPS and APMs more challenging, particularly because many operate in small or solo practices that do not own electronic health record systems, which would complicate reporting requirements to qualify for MIPS or APMs.

In addition to concerns with reporting in general, APA said that psychiatrists “also have limited choices in outcome quality measures.”

[email protected]

The proposed federal regulations to implement the MACRA health care reforms are too complex, too onerous on small and solo practices, lack opportunities for many to participate in alternative payment models, and should be delayed for a full year, at least.

That was the message that emerged from hundreds of comments regarding the proposed rule that were submitted by physician organizations and other stakeholders.

“The intent of [the Medicare Access and CHIP Reauthorization Act of 2015] was not to merely move the current incentive program into [the Merit-based Incentive Payment System], but to improve and simplify these programs into a single more unified approach,” the American Medical Association said in its comments, noting that “numerous changes” will be needed in the way cost and quality are measured.

AMA also called for a better, faster way for physicians to develop alternative payment models. “We strongly urge CMS to vigorously pursue this objective and establish a much more progressive and welcoming environment for the development and implementation of specialty-defined APMs than proposed in the [proposed rule].”

AMA also suggested that CMS provide more flexibility for solo and small practices, align the four components of MIPS so it operates as a single program, simplifying and lowering the financial risk for advanced APMs, and providing more timely feedback to physicians.

The organization also called for CMS to “create an initial transitional performance period from July 1, 2017, to December 31, 2017, to ensure the successful and appropriate implementation of the MACRA program. In future years, for all reporting requirements, CMS should allow physicians to select periods of less than a full calendar year to provide flexibility.”

In its comments, the American Medical Group Association questioned whether the proposed rule actually would lead to improved quality of care and reward value.

In the proposed rule, “CMS will measure and score quality and resource use or spending separately,” AMGA wrote in its comments. “CMS will not measure outcomes in relation to spending. CMS will not measure for value. If value is left unaddressed in the final rule, it will be difficult at best for the agency to meet MACRA and the [HHS] secretary’s overarching goals.”

While expressing support for MACRA conceptually, officials with the American Academy of Family Physicians wrote that they “see a strong and definite need and opportunity for CMS to step back and reconsider the approach to this proposed rule which we view as overly complex and burdensome to our members and indeed for all physicians. Given the significant complexity of the rule, we strongly encourage CMS to issue an interim final rule with comment period rather than to issue a final rule.”

Specifically, AAFP criticized the proposed rule for allowing small and solo practices to form “virtual groups” in order to earn bonuses, despite it being mandated by law.

Solo and small group practices who participate in MIPS to should “be eligible for positive payment updates if their performance yields such payments, but would be exempt from any negative payment update until such a time that the virtual group option is available,” AAFP officials wrote.

They also called for medical home delivery models to be included in APMs, in an effort to improve on the limited opportunities for family practices in particular to participate in alternative payment models.

The American College of Physicians also called for safe harbors for small and solo practices until virtual group options can be established.

ACP, like other groups, questioned that medical homes are not recognized as alternative payment models and argued that Congress intended medical homes to qualify as APMs “without bearing more than nominal financial risk.”

Despite the flexible approach to the overall quality payment program, CMS has “created a degree of complexity” and must “continue to seek ways to further streamline and simplify” the move to quality payments, according to comments from the American College of Cardiology.

The ACC also expressed concerns that the reporting requirements under MIPS and some of the APMs will limit the ability for cardiologists to report the most meaningful measures, particularly if they are part of a multi-specialty group, and suggested changes in scoring methodology or to allow more than one data file to be submitted in multi-specialty situations.

It also expressed concerns that the rule as proposed could adversely effect small practices, rural practices, and practices in health professional shortage areas, and “in the absence of other solutions such as virtual groups in 2017, CMS should monitor policies and provide effective practice assistance to these practices.”

The proposed rule provides no support for small practices, according to the American Gastroenterological Association.

“Upon release of the proposed rule, we were disappointed to see that not only will APMs be essentially closed off to small practices in the first years of implementation, but the MIPS program will significantly harm practices with less than 25 eligible clinicians,” AGA noted, citing data presented by CMS that 87% of solo practitioners will receive a negative adjustment with an aggregate negative impact of $300 million and for all practices with less than 25 eligible clinicians, the aggregate negative adjustment will total $649 million.

“Any system in which smaller practices are so heavily disadvantaged is unacceptable,” AGA said. CMS has previously stated that the regulatory impact statement would likely change and reflect a smaller impact for small and solo practices once more updated information can be modeled when the rule is final.

Additionally, AGA expressed concern over the limited engagement in APMs that will be possible under the proposed rule. “Given the importance of APM participation to both the practice and reimbursement of Medicare physicians, access to advanced APMs should be provided to all physicians.”

The association also expressed concern that the definition of APM is not broad enough and suggested that it be widened in scope so that it can capture payment models that have been created using the AGA’s Roadmap to the Future of GI Practice. It recommended a number of models be classified as APMs, including the colonoscopy bundled payment, gastroesophageal reflux disease episode payment, obesity bundled payment, Project Sonar (a chronic disease management program for IBD), and the Medical Home Neighbor.

The American College of Rheumatology called for a delay in the implementation of any final MACRA regulations, noting in its comments that with requirements set to begin in 2017, the current implementation schedule “does not provide enough time for providers to implement the required changes,” though ACR does not recommend a specific start time.

ACR also questioned how the criteria for APMs was set up, noting expressly that Physician Focused Payment Models may not meet the APM requirements. The group is seeking clarification on whether these models will qualify as an APM.

“Medical home APMs should also permit specialty physicians to participate, including small group and multispeciality groups, in keeping with the need for APMs to be flexible with their criteria and the role of specialty physicians in providing chronic care.

The American Academy of Dermatology Association echoed a number of concerns voiced across the medical profession and is calling for a delay in the implementation of MACRA’s regulations.

In particular, AADA noted that the regulations are not friendly for small and solo practices in general and little is contained within the proposal to “meaningfully engage specialist physicians in APMs.”

The association also is calling for broader mechanisms to allow for the development and recognition of APMs, including recognizing specialty-focused medical homes.

The group also is calling for pilot programs to test the validity of the measures that will form the basis of quality payment incentives and penalties.

In an effort to protect small and solo practices, AADA is calling for an exemption from MIPS or APM requirements until a virtual group option is developed, tested, and is fully operational.

The American Psychiatric Association echoed a number of broad concerns raised across the physician spectrum, including calling for a to the first year of implementation to July 1, 2017, and lasting through Dec. 31, 2017, as well as enabling the formation of virtual groups at the onset of implementation in its comments.

But APA also noted that mental health presents a variety of unique issues that need to be addressed.

For example, the association notes that psychiatrists work across a number of practice settings, including academic health centers, hospitals, clinics, nursing homes, and private practices, as well as offering services via telemedicine.

“This makes it difficult for psychiatrists to capture all the work they do, because of the combination of settings that utilize multiple, and potentially differing reporting programs and methods,” APA noted.

It added that psychiatrists generally have limited time and resources that can be devoted to Medicare quality reporting, which would make participation in MIPS and APMs more challenging, particularly because many operate in small or solo practices that do not own electronic health record systems, which would complicate reporting requirements to qualify for MIPS or APMs.

In addition to concerns with reporting in general, APA said that psychiatrists “also have limited choices in outcome quality measures.”

[email protected]

T cells
Image from UNSW

Update: The hold on this trial has been lifted. Click here for additional details.

A trial of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 has been placed on clinical hold following 3 patient deaths.

The trial, known as ROCKET, is a phase 2 study of adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The US Food and Drug Administration (FDA) placed a hold on the trial after 3 patients died of cerebral edema.

All 3 patients had received conditioning with fludarabine, and Juno Therapeutics, the company developing JCAR015, believes this may have caused the patients’ deaths.

Patients enrolled on the ROCKET trial previously received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy.

The addition of fludarabine to conditioning had been shown to increase the efficacy of 2 of Juno’s other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials. 

“However, since adding fludarabine to the preconditioning on the ROCKET trial, we have seen an increase in the incidence of severe neurotoxicity, which has, unfortunately, included 2 patient deaths that occurred last week from cerebral edema that appeared to be treatment-related,” Hans Bishop, Juno’s president and chief executive officer, said in a conference call.

“After the first of these 2 deaths, we immediately paused the trial for an internal review and review with our Data Safety Monitoring Board [DSMB] and the FDA. There was also 1 previous death from cerebral edema on the trial in May. After a review of that event, we, along with the FDA and our DSMB, concluded there were confounding factors, and a change in our plans at the time was not warranted.”

After the more recent deaths, Juno investigated several factors that could have contributed, including the conditioning regimen, patient characteristics, toxicity management, product characteristics, and cell dose.

“Although more than 1 factor may have contributed, based on our review of the data available . . . , we believe the addition of fludarabine, when combined with JCAR015, is the most likely and the most appropriately modifiable factor,” Bishop said.

“Indeed, with cy[clophosphamide] alone, which we have used in the greatest number of patients treated in the ROCKET trial to date, there have not been any treatment-related deaths, and the incidence of severe neurotoxicity is within the range of what we expected in light of the Memorial Sloan-Kettering experience [phase 1 trial of JCAR015].”

Therefore, Juno has proposed continuing the ROCKET trial using conditioning with cyclophosphamide alone.

In response to this request, the FDA has requested that Juno submit:

• A revised patient informed consent form
• A revised investigator brochure
• A revised trial protocol
• A copy of a presentation the company made to the FDA.

The FDA said it will expedite the review of these documents and expects to complete the review within 30 days of receiving them.

If the clinical hold on the ROCKET trial is lifted, Juno plans to continue the trial. However, the hold will likely impact the company’s goal of gaining FDA approval for JCAR015 in 2017.

Juno’s trials and plans for its other CD19-directed CAR-T cell product candidates are not affected by the clinical hold placed on ROCKET.

ROCKET is not the first trial of JCAR015 to be placed on hold. The phase 1 trial of the therapy was placed on clinical hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

T cells
Image from UNSW

Update: The hold on this trial has been lifted. Click here for additional details.

A trial of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 has been placed on clinical hold following 3 patient deaths.

The trial, known as ROCKET, is a phase 2 study of adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The US Food and Drug Administration (FDA) placed a hold on the trial after 3 patients died of cerebral edema.

All 3 patients had received conditioning with fludarabine, and Juno Therapeutics, the company developing JCAR015, believes this may have caused the patients’ deaths.

Patients enrolled on the ROCKET trial previously received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy.

The addition of fludarabine to conditioning had been shown to increase the efficacy of 2 of Juno’s other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials. 

“However, since adding fludarabine to the preconditioning on the ROCKET trial, we have seen an increase in the incidence of severe neurotoxicity, which has, unfortunately, included 2 patient deaths that occurred last week from cerebral edema that appeared to be treatment-related,” Hans Bishop, Juno’s president and chief executive officer, said in a conference call.

“After the first of these 2 deaths, we immediately paused the trial for an internal review and review with our Data Safety Monitoring Board [DSMB] and the FDA. There was also 1 previous death from cerebral edema on the trial in May. After a review of that event, we, along with the FDA and our DSMB, concluded there were confounding factors, and a change in our plans at the time was not warranted.”

After the more recent deaths, Juno investigated several factors that could have contributed, including the conditioning regimen, patient characteristics, toxicity management, product characteristics, and cell dose.

“Although more than 1 factor may have contributed, based on our review of the data available . . . , we believe the addition of fludarabine, when combined with JCAR015, is the most likely and the most appropriately modifiable factor,” Bishop said.

“Indeed, with cy[clophosphamide] alone, which we have used in the greatest number of patients treated in the ROCKET trial to date, there have not been any treatment-related deaths, and the incidence of severe neurotoxicity is within the range of what we expected in light of the Memorial Sloan-Kettering experience [phase 1 trial of JCAR015].”

Therefore, Juno has proposed continuing the ROCKET trial using conditioning with cyclophosphamide alone.

In response to this request, the FDA has requested that Juno submit:

• A revised patient informed consent form
• A revised investigator brochure
• A revised trial protocol
• A copy of a presentation the company made to the FDA.

The FDA said it will expedite the review of these documents and expects to complete the review within 30 days of receiving them.

If the clinical hold on the ROCKET trial is lifted, Juno plans to continue the trial. However, the hold will likely impact the company’s goal of gaining FDA approval for JCAR015 in 2017.

Juno’s trials and plans for its other CD19-directed CAR-T cell product candidates are not affected by the clinical hold placed on ROCKET.

ROCKET is not the first trial of JCAR015 to be placed on hold. The phase 1 trial of the therapy was placed on clinical hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

T cells
Image from UNSW

Update: The hold on this trial has been lifted. Click here for additional details.

A trial of the chimeric antigen receptor (CAR) T-cell therapy JCAR015 has been placed on clinical hold following 3 patient deaths.

The trial, known as ROCKET, is a phase 2 study of adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

The US Food and Drug Administration (FDA) placed a hold on the trial after 3 patients died of cerebral edema.

All 3 patients had received conditioning with fludarabine, and Juno Therapeutics, the company developing JCAR015, believes this may have caused the patients’ deaths.

Patients enrolled on the ROCKET trial previously received conditioning with cyclophosphamide alone, but investigators decided to add fludarabine in hopes of increasing efficacy.

The addition of fludarabine to conditioning had been shown to increase the efficacy of 2 of Juno’s other CAR T-cell therapies, JCAR014 and JCAR017, in phase 1/2 trials. 

“However, since adding fludarabine to the preconditioning on the ROCKET trial, we have seen an increase in the incidence of severe neurotoxicity, which has, unfortunately, included 2 patient deaths that occurred last week from cerebral edema that appeared to be treatment-related,” Hans Bishop, Juno’s president and chief executive officer, said in a conference call.

“After the first of these 2 deaths, we immediately paused the trial for an internal review and review with our Data Safety Monitoring Board [DSMB] and the FDA. There was also 1 previous death from cerebral edema on the trial in May. After a review of that event, we, along with the FDA and our DSMB, concluded there were confounding factors, and a change in our plans at the time was not warranted.”

After the more recent deaths, Juno investigated several factors that could have contributed, including the conditioning regimen, patient characteristics, toxicity management, product characteristics, and cell dose.

“Although more than 1 factor may have contributed, based on our review of the data available . . . , we believe the addition of fludarabine, when combined with JCAR015, is the most likely and the most appropriately modifiable factor,” Bishop said.

“Indeed, with cy[clophosphamide] alone, which we have used in the greatest number of patients treated in the ROCKET trial to date, there have not been any treatment-related deaths, and the incidence of severe neurotoxicity is within the range of what we expected in light of the Memorial Sloan-Kettering experience [phase 1 trial of JCAR015].”

Therefore, Juno has proposed continuing the ROCKET trial using conditioning with cyclophosphamide alone.

In response to this request, the FDA has requested that Juno submit:

• A revised patient informed consent form
• A revised investigator brochure
• A revised trial protocol
• A copy of a presentation the company made to the FDA.

The FDA said it will expedite the review of these documents and expects to complete the review within 30 days of receiving them.

If the clinical hold on the ROCKET trial is lifted, Juno plans to continue the trial. However, the hold will likely impact the company’s goal of gaining FDA approval for JCAR015 in 2017.

Juno’s trials and plans for its other CD19-directed CAR-T cell product candidates are not affected by the clinical hold placed on ROCKET.

ROCKET is not the first trial of JCAR015 to be placed on hold. The phase 1 trial of the therapy was placed on clinical hold in 2014, after 2 patients died of cytokine release syndrome.

That hold was lifted following changes to enrollment criteria and dosing. Results from this trial were presented at ASCO 2015 and ASCO 2016.

The prevalence of inherited mutations in DNA repair genes such as BRCA2 in men with metastatic prostate cancer may be as high as 12%, investigators in a multicenter study report.

The prevalence of presumably harmful mutations in men with metastatic disease was more than twice that of men with localized prostate cancer, and men with metastatic prostate cancer had a 3- to 19-fold higher risk for having mutations in individual DNA repair genes, compared with men without prostate cancer in a population-wide genetic sample, reported Colin C. Pritchard, MD, PhD, of the University of Washington in Seattle and colleagues.

©SilverV/Thinkstock.com

“Because the high frequency of DNA repair gene mutations is not exclusive to an early-onset phenotype and is associated with clinically and histologically aggressive disease, with compelling evidence for therapeutic relevance, it may be of interest to routinely examine all men with metastatic prostate cancer for the presence of germline mutations in DNA repair genes,” the investigators suggest (N Engl J Med. 2016 July. doi: 10.1056/NEJMoa1603144).

The findings point to possible therapeutic interventions for men with advanced prostate cancer with identified germline mutations in DNA repair genes, such as poly (ADP-ribose) polymerase (PARP) inhibitors or platinum compound–based chemotherapy,

To date, the only genetic factors known to be associated with aggressive prostate cancer and prostate cancer–specific mortality are mutations in DNA repair genes such as BRCA1 and BRCA2, CHEK2, and PALB2. The frequency of mutations in these genes among men with localized prostate cancer in general is relatively low, accounting for just a few percentage points of familial prostate cancer cases in a sample unselected for family predisposition, the authors noted.

To determine the frequency of mutations in advanced disease, the investigators reviewed genetic data on 692 men with metastatic prostate cancer who were enrolled in one of seven cases series and were unselected for family history of cancer or age at diagnosis.

They used multiplex genetic sequencing assays to look for mutation in 20 DNA repair genes that are associated with autosomal dominant cancer predisposition syndromes.

They found 84 presumably harmful mutations in 82 men, for an overall prevalence of 11.8%. In contrast, the frequency of germline DNA repair mutations among 499 men in the Cancer Genome Atlas prostate cancer study, including men with high-risk disease, was 4.6%, the authors noted.

The mutations occurred in 16 different genes, including, in order of prevalence, BRCA2, ATM, CHEL2, BRCA1, RAD51D and PALB2. There were no significant differences in mutation frequencies by either family history of prostate cancer or age at diagnosis.

The authors also estimated the prevalence of DNA repair gene mutations among the general population by looking at a sample of 53,105 persons without a known diagnosis of cancer who were included in the Exome Aggregation Consortium. Men with metastatic prostate cancer had a fivefold risk for having any deleterious DNA repair mutation, compared with the general population (P less than .001).

The relative risk of mutations in individual genes for men with metastatic disease, compared with men in the control sample, ranged from 3.1 for CHEK2 (P = .002) to 18.6 for BRCA2 (P less than .001).

The study was supported by a Stand Up To Cancer–Prostate Cancer Foundation (SU2C-PCF) International Prostate Cancer Dream Team Translational Cancer Research Grant and awards from the National Institutes of Health, Department of Defense, and prostate cancer foundation. Several authors reported receiving research fees, grants, honoraria, and/or travel expenses from various pharmaceutical companies.

[email protected]

The prevalence of inherited mutations in DNA repair genes such as BRCA2 in men with metastatic prostate cancer may be as high as 12%, investigators in a multicenter study report.

The prevalence of presumably harmful mutations in men with metastatic disease was more than twice that of men with localized prostate cancer, and men with metastatic prostate cancer had a 3- to 19-fold higher risk for having mutations in individual DNA repair genes, compared with men without prostate cancer in a population-wide genetic sample, reported Colin C. Pritchard, MD, PhD, of the University of Washington in Seattle and colleagues.

©SilverV/Thinkstock.com

“Because the high frequency of DNA repair gene mutations is not exclusive to an early-onset phenotype and is associated with clinically and histologically aggressive disease, with compelling evidence for therapeutic relevance, it may be of interest to routinely examine all men with metastatic prostate cancer for the presence of germline mutations in DNA repair genes,” the investigators suggest (N Engl J Med. 2016 July. doi: 10.1056/NEJMoa1603144).

The findings point to possible therapeutic interventions for men with advanced prostate cancer with identified germline mutations in DNA repair genes, such as poly (ADP-ribose) polymerase (PARP) inhibitors or platinum compound–based chemotherapy,

To date, the only genetic factors known to be associated with aggressive prostate cancer and prostate cancer–specific mortality are mutations in DNA repair genes such as BRCA1 and BRCA2, CHEK2, and PALB2. The frequency of mutations in these genes among men with localized prostate cancer in general is relatively low, accounting for just a few percentage points of familial prostate cancer cases in a sample unselected for family predisposition, the authors noted.

To determine the frequency of mutations in advanced disease, the investigators reviewed genetic data on 692 men with metastatic prostate cancer who were enrolled in one of seven cases series and were unselected for family history of cancer or age at diagnosis.

They used multiplex genetic sequencing assays to look for mutation in 20 DNA repair genes that are associated with autosomal dominant cancer predisposition syndromes.

They found 84 presumably harmful mutations in 82 men, for an overall prevalence of 11.8%. In contrast, the frequency of germline DNA repair mutations among 499 men in the Cancer Genome Atlas prostate cancer study, including men with high-risk disease, was 4.6%, the authors noted.

The mutations occurred in 16 different genes, including, in order of prevalence, BRCA2, ATM, CHEL2, BRCA1, RAD51D and PALB2. There were no significant differences in mutation frequencies by either family history of prostate cancer or age at diagnosis.

The authors also estimated the prevalence of DNA repair gene mutations among the general population by looking at a sample of 53,105 persons without a known diagnosis of cancer who were included in the Exome Aggregation Consortium. Men with metastatic prostate cancer had a fivefold risk for having any deleterious DNA repair mutation, compared with the general population (P less than .001).

The relative risk of mutations in individual genes for men with metastatic disease, compared with men in the control sample, ranged from 3.1 for CHEK2 (P = .002) to 18.6 for BRCA2 (P less than .001).

The study was supported by a Stand Up To Cancer–Prostate Cancer Foundation (SU2C-PCF) International Prostate Cancer Dream Team Translational Cancer Research Grant and awards from the National Institutes of Health, Department of Defense, and prostate cancer foundation. Several authors reported receiving research fees, grants, honoraria, and/or travel expenses from various pharmaceutical companies.

[email protected]

The prevalence of inherited mutations in DNA repair genes such as BRCA2 in men with metastatic prostate cancer may be as high as 12%, investigators in a multicenter study report.

The prevalence of presumably harmful mutations in men with metastatic disease was more than twice that of men with localized prostate cancer, and men with metastatic prostate cancer had a 3- to 19-fold higher risk for having mutations in individual DNA repair genes, compared with men without prostate cancer in a population-wide genetic sample, reported Colin C. Pritchard, MD, PhD, of the University of Washington in Seattle and colleagues.

©SilverV/Thinkstock.com

“Because the high frequency of DNA repair gene mutations is not exclusive to an early-onset phenotype and is associated with clinically and histologically aggressive disease, with compelling evidence for therapeutic relevance, it may be of interest to routinely examine all men with metastatic prostate cancer for the presence of germline mutations in DNA repair genes,” the investigators suggest (N Engl J Med. 2016 July. doi: 10.1056/NEJMoa1603144).

The findings point to possible therapeutic interventions for men with advanced prostate cancer with identified germline mutations in DNA repair genes, such as poly (ADP-ribose) polymerase (PARP) inhibitors or platinum compound–based chemotherapy,

To date, the only genetic factors known to be associated with aggressive prostate cancer and prostate cancer–specific mortality are mutations in DNA repair genes such as BRCA1 and BRCA2, CHEK2, and PALB2. The frequency of mutations in these genes among men with localized prostate cancer in general is relatively low, accounting for just a few percentage points of familial prostate cancer cases in a sample unselected for family predisposition, the authors noted.

To determine the frequency of mutations in advanced disease, the investigators reviewed genetic data on 692 men with metastatic prostate cancer who were enrolled in one of seven cases series and were unselected for family history of cancer or age at diagnosis.

They used multiplex genetic sequencing assays to look for mutation in 20 DNA repair genes that are associated with autosomal dominant cancer predisposition syndromes.

They found 84 presumably harmful mutations in 82 men, for an overall prevalence of 11.8%. In contrast, the frequency of germline DNA repair mutations among 499 men in the Cancer Genome Atlas prostate cancer study, including men with high-risk disease, was 4.6%, the authors noted.

The mutations occurred in 16 different genes, including, in order of prevalence, BRCA2, ATM, CHEL2, BRCA1, RAD51D and PALB2. There were no significant differences in mutation frequencies by either family history of prostate cancer or age at diagnosis.

The authors also estimated the prevalence of DNA repair gene mutations among the general population by looking at a sample of 53,105 persons without a known diagnosis of cancer who were included in the Exome Aggregation Consortium. Men with metastatic prostate cancer had a fivefold risk for having any deleterious DNA repair mutation, compared with the general population (P less than .001).

The relative risk of mutations in individual genes for men with metastatic disease, compared with men in the control sample, ranged from 3.1 for CHEK2 (P = .002) to 18.6 for BRCA2 (P less than .001).

The study was supported by a Stand Up To Cancer–Prostate Cancer Foundation (SU2C-PCF) International Prostate Cancer Dream Team Translational Cancer Research Grant and awards from the National Institutes of Health, Department of Defense, and prostate cancer foundation. Several authors reported receiving research fees, grants, honoraria, and/or travel expenses from various pharmaceutical companies.

[email protected]

An expansion of the Diabetes Prevention Program (DPP), announced July 7 in the proposed Medicare Physician Fee Schedule for 2017, would allow recognized suppliers to submit claims to the Centers for Medicare & Medicaid Services for payment beginning Jan. 1, 2018.

The proposed expansion would allow patients across the United States to access community-based intervention that curbs diabetes and keeps families healthy, according to Patrick Conway, MD, CMS chief medical officer.

“This is part of our efforts for better care, smarter spending, and healthier people,” Dr. Conway said in a statement. The “proposal is an exciting milestone for prevention and population health.”

The Diabetes Prevention Program started in 2011 as an Affordable Care Act pilot program awarded to the National Council of YMCAs of the United States of America (Y-USA). Medicare patients at high risk for diabetes attended 16 intensive educational sessions in a group-based, classroom-style setting and practical training in long-term dietary change, increased physical activity, and behavior change strategies for weight control.

The pilot resulted in savings of $2,650 per enrollee over 15 months, according to CMS, compared with costs associated with nonprogram beneficiaries – enough to cover the cost of the program. Program participants also were shown to lose an average of about 5% of their body weight.

In March 2016, the U.S. Health and Human Services Department announced that the CMS Office of the Actuary had certified the pilot Diabetes Prevention Program model as a cost savings program that reduced net Medicare spending. HHS determined that the program demonstrated the ability to improve the quality of patient care without limiting coverage or benefits.

In the fee schedule proposal, CMS is suggesting that each health care provider who offers services as part of a CDC-recognized organization delivering DPP services obtain a National Provider Identification number to provide Medicare DPP services, allowing supplier enrollment beginning as early as Jan. 1, 2017. In addition, CMS envisions a payment structure tying payment for Medicare DPP services to the number of sessions attended by patients and the achievement and maintenance of minimum weight loss. Claims for payment under the Medicare DPP would be submitted following the achievement of core session attendance and minimum weight loss, and following maintenance session attendance and maintenance of minimum weight loss, according to the proposal.

CMS has not decided whether the Medicare DPP should be expanded nationally in the first year of the program or whether it should be phased in.

The American College of Physicians expressed support for DPP expansion and said that organization leaders plan to provide comments on the basic framework.

Courtesy American College of Physicians

“As a practicing primary care internist myself, I am greatly encouraged that CMS is proposing substantial improvements to help me and my colleagues provide coordinated, patient-centered, high-value, and team-based care to our patients,” ACP President Nitin S. Damle, MD, said in a statement. “We look forward to providing CMS with detailed comments to support these improvements while recommending other changes to strengthen primary care.”

Robert E. Ratner, MD, chief scientific and medical officer for the American Diabetes Association agreed.

“Providing people with prediabetes with effective tools to prevent diabetes is a win for all of us,” Dr. Ratner said in a statement. “We appreciate HHS’s continued commitment to improving the nation’s health and helping us reduce the incidence and burden of diabetes across the country.”

Wanda Filer, MD, president of the American Academy of Family Physicians, said her organization was still analyzing the proposal, but that the expansion sounds positive for health care.

“We think the expansion is a great idea for patients,” she said in an interview, adding that it’s essential that doctors are reimbursed for preventive services. “Frankly, if you do the work, you need to get paid.”

CMS will accept comments on the proposed rule until Sept. 6. The proposed rule will appear in the July 15 Federal Register.

[email protected]

On Twitter @legal_med

An expansion of the Diabetes Prevention Program (DPP), announced July 7 in the proposed Medicare Physician Fee Schedule for 2017, would allow recognized suppliers to submit claims to the Centers for Medicare & Medicaid Services for payment beginning Jan. 1, 2018.

The proposed expansion would allow patients across the United States to access community-based intervention that curbs diabetes and keeps families healthy, according to Patrick Conway, MD, CMS chief medical officer.

“This is part of our efforts for better care, smarter spending, and healthier people,” Dr. Conway said in a statement. The “proposal is an exciting milestone for prevention and population health.”

The Diabetes Prevention Program started in 2011 as an Affordable Care Act pilot program awarded to the National Council of YMCAs of the United States of America (Y-USA). Medicare patients at high risk for diabetes attended 16 intensive educational sessions in a group-based, classroom-style setting and practical training in long-term dietary change, increased physical activity, and behavior change strategies for weight control.

The pilot resulted in savings of $2,650 per enrollee over 15 months, according to CMS, compared with costs associated with nonprogram beneficiaries – enough to cover the cost of the program. Program participants also were shown to lose an average of about 5% of their body weight.

In March 2016, the U.S. Health and Human Services Department announced that the CMS Office of the Actuary had certified the pilot Diabetes Prevention Program model as a cost savings program that reduced net Medicare spending. HHS determined that the program demonstrated the ability to improve the quality of patient care without limiting coverage or benefits.

In the fee schedule proposal, CMS is suggesting that each health care provider who offers services as part of a CDC-recognized organization delivering DPP services obtain a National Provider Identification number to provide Medicare DPP services, allowing supplier enrollment beginning as early as Jan. 1, 2017. In addition, CMS envisions a payment structure tying payment for Medicare DPP services to the number of sessions attended by patients and the achievement and maintenance of minimum weight loss. Claims for payment under the Medicare DPP would be submitted following the achievement of core session attendance and minimum weight loss, and following maintenance session attendance and maintenance of minimum weight loss, according to the proposal.

CMS has not decided whether the Medicare DPP should be expanded nationally in the first year of the program or whether it should be phased in.

The American College of Physicians expressed support for DPP expansion and said that organization leaders plan to provide comments on the basic framework.

Courtesy American College of Physicians

“As a practicing primary care internist myself, I am greatly encouraged that CMS is proposing substantial improvements to help me and my colleagues provide coordinated, patient-centered, high-value, and team-based care to our patients,” ACP President Nitin S. Damle, MD, said in a statement. “We look forward to providing CMS with detailed comments to support these improvements while recommending other changes to strengthen primary care.”

Robert E. Ratner, MD, chief scientific and medical officer for the American Diabetes Association agreed.

“Providing people with prediabetes with effective tools to prevent diabetes is a win for all of us,” Dr. Ratner said in a statement. “We appreciate HHS’s continued commitment to improving the nation’s health and helping us reduce the incidence and burden of diabetes across the country.”

Wanda Filer, MD, president of the American Academy of Family Physicians, said her organization was still analyzing the proposal, but that the expansion sounds positive for health care.

“We think the expansion is a great idea for patients,” she said in an interview, adding that it’s essential that doctors are reimbursed for preventive services. “Frankly, if you do the work, you need to get paid.”

CMS will accept comments on the proposed rule until Sept. 6. The proposed rule will appear in the July 15 Federal Register.

[email protected]

On Twitter @legal_med

An expansion of the Diabetes Prevention Program (DPP), announced July 7 in the proposed Medicare Physician Fee Schedule for 2017, would allow recognized suppliers to submit claims to the Centers for Medicare & Medicaid Services for payment beginning Jan. 1, 2018.

The proposed expansion would allow patients across the United States to access community-based intervention that curbs diabetes and keeps families healthy, according to Patrick Conway, MD, CMS chief medical officer.

“This is part of our efforts for better care, smarter spending, and healthier people,” Dr. Conway said in a statement. The “proposal is an exciting milestone for prevention and population health.”

The Diabetes Prevention Program started in 2011 as an Affordable Care Act pilot program awarded to the National Council of YMCAs of the United States of America (Y-USA). Medicare patients at high risk for diabetes attended 16 intensive educational sessions in a group-based, classroom-style setting and practical training in long-term dietary change, increased physical activity, and behavior change strategies for weight control.

The pilot resulted in savings of $2,650 per enrollee over 15 months, according to CMS, compared with costs associated with nonprogram beneficiaries – enough to cover the cost of the program. Program participants also were shown to lose an average of about 5% of their body weight.

In March 2016, the U.S. Health and Human Services Department announced that the CMS Office of the Actuary had certified the pilot Diabetes Prevention Program model as a cost savings program that reduced net Medicare spending. HHS determined that the program demonstrated the ability to improve the quality of patient care without limiting coverage or benefits.

In the fee schedule proposal, CMS is suggesting that each health care provider who offers services as part of a CDC-recognized organization delivering DPP services obtain a National Provider Identification number to provide Medicare DPP services, allowing supplier enrollment beginning as early as Jan. 1, 2017. In addition, CMS envisions a payment structure tying payment for Medicare DPP services to the number of sessions attended by patients and the achievement and maintenance of minimum weight loss. Claims for payment under the Medicare DPP would be submitted following the achievement of core session attendance and minimum weight loss, and following maintenance session attendance and maintenance of minimum weight loss, according to the proposal.

CMS has not decided whether the Medicare DPP should be expanded nationally in the first year of the program or whether it should be phased in.

The American College of Physicians expressed support for DPP expansion and said that organization leaders plan to provide comments on the basic framework.

Courtesy American College of Physicians

“As a practicing primary care internist myself, I am greatly encouraged that CMS is proposing substantial improvements to help me and my colleagues provide coordinated, patient-centered, high-value, and team-based care to our patients,” ACP President Nitin S. Damle, MD, said in a statement. “We look forward to providing CMS with detailed comments to support these improvements while recommending other changes to strengthen primary care.”

Robert E. Ratner, MD, chief scientific and medical officer for the American Diabetes Association agreed.

“Providing people with prediabetes with effective tools to prevent diabetes is a win for all of us,” Dr. Ratner said in a statement. “We appreciate HHS’s continued commitment to improving the nation’s health and helping us reduce the incidence and burden of diabetes across the country.”

Wanda Filer, MD, president of the American Academy of Family Physicians, said her organization was still analyzing the proposal, but that the expansion sounds positive for health care.

“We think the expansion is a great idea for patients,” she said in an interview, adding that it’s essential that doctors are reimbursed for preventive services. “Frankly, if you do the work, you need to get paid.”

CMS will accept comments on the proposed rule until Sept. 6. The proposed rule will appear in the July 15 Federal Register.

[email protected]

On Twitter @legal_med

Treatment-free remission attempts are safe and are achievable in most patients with chronic myeloid leukemia (CML) in chronic phase, Timothy P. Hughes, MD, and his colleagues in the international ENESTop trial reported at the annual meeting of the American Society of Clinical Oncology.

The conclusion is based on follow-up data on 126 patients who achieved a sustained deep molecular response (MR4.5) after switching from imatinib (Gleevec) to nilotinib (Tasigna) and discontinued nilotinib. So far, these are the largest prospective treatment-free remission data set in a population of patients who achieved a sustained deep molecular response after switching from imatinib to nilotinib, Dr. Hughes, head of hematology at the University of Adelaide and his colleagues wrote in a poster presentation.

Difu Wu/CC BY-SA 3.0

The ENESTop study is a single-arm, phase II study. Patients eligible for the study started treatment with imatinib when they were first diagnosed with CML, then switched to nilotinib for at least 2 years with the combined time on the drugs of at least 3 years and small amounts of leukemia cells remaining after the nilotinib treatment.

For the consolidation phase of the study, patients continued their nilotinib therapy for 1 year. Patients without confirmed loss of MR4.5 after 1 year were eligible to stop nilotinib. RQ-PCR (reverse transcriptase–polymerase chain reaction) was monitored every 12 weeks in the consolidation phase of the study and every 4 weeks during first 48 weeks of treatment-free remission. Nilotinib was restarted if patients had confirmed loss of deep molecular response (MR4 [consecutive BCR-ABL1IS greater than 0.01%]) or loss of major molecular response ([MMR] BCR-ABL1IS greater than 0.1%).

Of the 163 patients in the consolidation phase of the study, 126 entered treatment-free remission. Their median duration of tyrosine kinase inhibitor use prior to treatment-free remission was nearly 88 months, with a 53-month median duration of nilotinib therapy. At data cut-off, with median follow up of 50 weeks, 58% of the 126 patients were still in treatment-free remission at 48 weeks.

During treatment-free remission, 18 patients had confirmed loss of MR4 and 34 lost MMR. One patient had atypical transcript and came off the study. All but one of the 52 patients reinitiated nilotinib; 50 (98%) regained at least MMR by data cut-off, 48 (94%) regained MR4, and 47 (92%) regained MR4.5. One patient switched to another tyrosine kinase inhibitor at 22 weeks after restarting therapy.

Of those who restarted therapy, the median time was 12 weeks to regain MR4 and was 13 weeks to regain MR4.5. No new safety findings were observed on treatment.

The study is sponsored by Novartis, the maker of nilotinib (Tasigna). Dr. Hughes receives research support and honoraria from, and is a consultant or advisor to Novartis as well as Ariad and Bristol-Myers Squibb.

[email protected]

On Twitter @maryjodales

Treatment-free remission attempts are safe and are achievable in most patients with chronic myeloid leukemia (CML) in chronic phase, Timothy P. Hughes, MD, and his colleagues in the international ENESTop trial reported at the annual meeting of the American Society of Clinical Oncology.

The conclusion is based on follow-up data on 126 patients who achieved a sustained deep molecular response (MR4.5) after switching from imatinib (Gleevec) to nilotinib (Tasigna) and discontinued nilotinib. So far, these are the largest prospective treatment-free remission data set in a population of patients who achieved a sustained deep molecular response after switching from imatinib to nilotinib, Dr. Hughes, head of hematology at the University of Adelaide and his colleagues wrote in a poster presentation.

Difu Wu/CC BY-SA 3.0

The ENESTop study is a single-arm, phase II study. Patients eligible for the study started treatment with imatinib when they were first diagnosed with CML, then switched to nilotinib for at least 2 years with the combined time on the drugs of at least 3 years and small amounts of leukemia cells remaining after the nilotinib treatment.

For the consolidation phase of the study, patients continued their nilotinib therapy for 1 year. Patients without confirmed loss of MR4.5 after 1 year were eligible to stop nilotinib. RQ-PCR (reverse transcriptase–polymerase chain reaction) was monitored every 12 weeks in the consolidation phase of the study and every 4 weeks during first 48 weeks of treatment-free remission. Nilotinib was restarted if patients had confirmed loss of deep molecular response (MR4 [consecutive BCR-ABL1IS greater than 0.01%]) or loss of major molecular response ([MMR] BCR-ABL1IS greater than 0.1%).

Of the 163 patients in the consolidation phase of the study, 126 entered treatment-free remission. Their median duration of tyrosine kinase inhibitor use prior to treatment-free remission was nearly 88 months, with a 53-month median duration of nilotinib therapy. At data cut-off, with median follow up of 50 weeks, 58% of the 126 patients were still in treatment-free remission at 48 weeks.

During treatment-free remission, 18 patients had confirmed loss of MR4 and 34 lost MMR. One patient had atypical transcript and came off the study. All but one of the 52 patients reinitiated nilotinib; 50 (98%) regained at least MMR by data cut-off, 48 (94%) regained MR4, and 47 (92%) regained MR4.5. One patient switched to another tyrosine kinase inhibitor at 22 weeks after restarting therapy.

Of those who restarted therapy, the median time was 12 weeks to regain MR4 and was 13 weeks to regain MR4.5. No new safety findings were observed on treatment.

The study is sponsored by Novartis, the maker of nilotinib (Tasigna). Dr. Hughes receives research support and honoraria from, and is a consultant or advisor to Novartis as well as Ariad and Bristol-Myers Squibb.

[email protected]

On Twitter @maryjodales

Treatment-free remission attempts are safe and are achievable in most patients with chronic myeloid leukemia (CML) in chronic phase, Timothy P. Hughes, MD, and his colleagues in the international ENESTop trial reported at the annual meeting of the American Society of Clinical Oncology.

The conclusion is based on follow-up data on 126 patients who achieved a sustained deep molecular response (MR4.5) after switching from imatinib (Gleevec) to nilotinib (Tasigna) and discontinued nilotinib. So far, these are the largest prospective treatment-free remission data set in a population of patients who achieved a sustained deep molecular response after switching from imatinib to nilotinib, Dr. Hughes, head of hematology at the University of Adelaide and his colleagues wrote in a poster presentation.

Difu Wu/CC BY-SA 3.0

The ENESTop study is a single-arm, phase II study. Patients eligible for the study started treatment with imatinib when they were first diagnosed with CML, then switched to nilotinib for at least 2 years with the combined time on the drugs of at least 3 years and small amounts of leukemia cells remaining after the nilotinib treatment.

For the consolidation phase of the study, patients continued their nilotinib therapy for 1 year. Patients without confirmed loss of MR4.5 after 1 year were eligible to stop nilotinib. RQ-PCR (reverse transcriptase–polymerase chain reaction) was monitored every 12 weeks in the consolidation phase of the study and every 4 weeks during first 48 weeks of treatment-free remission. Nilotinib was restarted if patients had confirmed loss of deep molecular response (MR4 [consecutive BCR-ABL1IS greater than 0.01%]) or loss of major molecular response ([MMR] BCR-ABL1IS greater than 0.1%).

Of the 163 patients in the consolidation phase of the study, 126 entered treatment-free remission. Their median duration of tyrosine kinase inhibitor use prior to treatment-free remission was nearly 88 months, with a 53-month median duration of nilotinib therapy. At data cut-off, with median follow up of 50 weeks, 58% of the 126 patients were still in treatment-free remission at 48 weeks.

During treatment-free remission, 18 patients had confirmed loss of MR4 and 34 lost MMR. One patient had atypical transcript and came off the study. All but one of the 52 patients reinitiated nilotinib; 50 (98%) regained at least MMR by data cut-off, 48 (94%) regained MR4, and 47 (92%) regained MR4.5. One patient switched to another tyrosine kinase inhibitor at 22 weeks after restarting therapy.

Of those who restarted therapy, the median time was 12 weeks to regain MR4 and was 13 weeks to regain MR4.5. No new safety findings were observed on treatment.

The study is sponsored by Novartis, the maker of nilotinib (Tasigna). Dr. Hughes receives research support and honoraria from, and is a consultant or advisor to Novartis as well as Ariad and Bristol-Myers Squibb.

[email protected]

On Twitter @maryjodales

The Food and Drug Administration placed Juno Therapeutics’ phase II ROCKET trial, involving CAR-T cell therapy, on clinical hold following two treatment-related patient deaths caused by excess fluid accumulation in the brain.

The ROCKET trial is a single-arm, multicenter phase II study treating adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia with an infusion of the patient’s own T cells that have been genetically modified to express a chimeric antigen receptor (CAR) that will bind to CD19-expressing leukemia cells. This treatment is referred to as JCAR015, and the ROCKET trial is only one of three current clinical trials testing its safety and efficacy.

Just before the ROCKET trial commenced, researchers added the chemotherapy drug fludarabine, which was successful in improving the performance of other immunotherapies, to the JCAR015 infusion. Researchers involved in the trial reported that the addition of this drug was likely the cause of the patient deaths.

Juno Therapeuticswill submit a revised trial protocol and patient consent form to the FDA before the hold is lifted, Juno reported in a written statement. The other trials led by Juno Therapeutics involving CAR-T cell product candidates are not affected.

[email protected]

On Twitter @jessnicolecraig

The Food and Drug Administration placed Juno Therapeutics’ phase II ROCKET trial, involving CAR-T cell therapy, on clinical hold following two treatment-related patient deaths caused by excess fluid accumulation in the brain.

The ROCKET trial is a single-arm, multicenter phase II study treating adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia with an infusion of the patient’s own T cells that have been genetically modified to express a chimeric antigen receptor (CAR) that will bind to CD19-expressing leukemia cells. This treatment is referred to as JCAR015, and the ROCKET trial is only one of three current clinical trials testing its safety and efficacy.

Just before the ROCKET trial commenced, researchers added the chemotherapy drug fludarabine, which was successful in improving the performance of other immunotherapies, to the JCAR015 infusion. Researchers involved in the trial reported that the addition of this drug was likely the cause of the patient deaths.

Juno Therapeuticswill submit a revised trial protocol and patient consent form to the FDA before the hold is lifted, Juno reported in a written statement. The other trials led by Juno Therapeutics involving CAR-T cell product candidates are not affected.

[email protected]

On Twitter @jessnicolecraig

The Food and Drug Administration placed Juno Therapeutics’ phase II ROCKET trial, involving CAR-T cell therapy, on clinical hold following two treatment-related patient deaths caused by excess fluid accumulation in the brain.

The ROCKET trial is a single-arm, multicenter phase II study treating adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia with an infusion of the patient’s own T cells that have been genetically modified to express a chimeric antigen receptor (CAR) that will bind to CD19-expressing leukemia cells. This treatment is referred to as JCAR015, and the ROCKET trial is only one of three current clinical trials testing its safety and efficacy.

Just before the ROCKET trial commenced, researchers added the chemotherapy drug fludarabine, which was successful in improving the performance of other immunotherapies, to the JCAR015 infusion. Researchers involved in the trial reported that the addition of this drug was likely the cause of the patient deaths.

Juno Therapeuticswill submit a revised trial protocol and patient consent form to the FDA before the hold is lifted, Juno reported in a written statement. The other trials led by Juno Therapeutics involving CAR-T cell product candidates are not affected.

[email protected]

On Twitter @jessnicolecraig

PARIS – What most interventional cardiologists and electrophysiologists do not know about their health risks due to occupational radiation exposure and how best to protect themselves could fill a book – or better still, make for an illuminating 2-hour expert panel discussion at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

“There’s a problem of lack of awareness on the part of interventional cardiologists, and also of institutional insensitivity to the problem,” declared Emanuela Piccaluga, MD, an investigator in the eye-opening Healthy Cath Lab study. This Italian national study showed that cardiac catheterization laboratory staff had radiation exposure duration–dependent increased risks of cataracts, cancers, and skin lesions, as well as other radiogenic noncancer effects: anxiety and depression, hypertension, and hyperlipidemia.

Bruce Jancin/Frontline Medical News

Cardiologists at some European hospitals have to pay for their own lead aprons and other protective gear. And even if the hospital does pick up the bill, administrators often balk at authorizing replacement of a lead apron that has developed microfractures and cracks. They view these imperfections as cosmetic defects, unaware that the damage renders the apron less protective, according to Dr. Piccaluga of Niguarda Ca’ Granda Hospital in Milan.

Ariel Roguin, MD, head of interventional cardiology at Rambam Medical Center in Haifa, Israel, said every cardiologist working with radiation should understand the three principles of radiation reduction, which he refers to in shorthand as “TDS,” for Time, Distance, and Shielding. Radiation is here to stay in cardiology, he said, but interventionalists can maximize their safety by keeping the fluoroscopy time and number of acquired images down, standing as far away as possible from both the radiation source and patient while still getting the job done well, and using appropriate shielding routinely.

Dr. Roguin gained notoriety with his report that 26 of 30 interventional cardiologists with glioblastoma multiforme or other brain malignancies had left-hemisphere cancers and 1 had a midline malignancy; only 3 were right-sided (Eur Heart J. 2014 Mar;35[10]:599-600). That distribution is highly unlikely to be due to play of chance, given that an interventional cardiologist’s left side is the side that’s usually exposed to more radiation.

Bruce Jancin/Frontline Medical News

“We should form a wall against radiation. Apart from the leaded aprons, for every procedure we all should also use lead skirts going from the table to the floor to block backscatter, ceiling-mounted overhead radiation shields, special glasses to protect against cataracts, and thyroid collars. And it’s very important to wear a dosimeter with sound; it helps increase awareness of our exposure,” he said.

Dr. Roguin has been a pioneer in the use of a thin, 0.5-mm lead shield draped across the patient’s abdomen from the umbilicus down during radial-access angiography. In a 322-patient randomized trial, he and his coinvestigators showed that this practice results in a threefold reduction in radiation to the operator, albeit at the cost of doubling the patient’s radiation exposure (Catheter Cardiovasc Interv. 2015 Jun;85[7]:1164-70).

“We now routinely do our radials with the lead apron across the patient’s abdomen. We’ve reached the conclusion that we work with radiation in the cath lab every day for many years and the patient is there only once or twice in a lifetime, hopefully,” the cardiologist explained.

With the growing popularity of radial-access interventions, audience members wanted to know if there is an advantage in terms of radiation exposure to left versus right radial artery access. The answer is no, according to Dr. Roguin.

“There are several studies showing no difference in radiation exposure. Left radial artery access is faster, but you’re leaning on the patient and getting more radiation as a result, while with right radial access you have to do more catheter manipulation, which takes longer. Both approaches involve more radiation to the operator than the transfemoral approach,” he said.

Dr. Piccaluga presented highlights from the Healthy Cath Lab study, sponsored by the Italian Society of Invasive Cardiology and the Italian National Research Council’s Institute of Clinical Physiology. The study involved detailed self-administered questionnaires completed by 218 interventional cardiologists and electrophysiologists, 191 nurses, and 57 technicians regularly exposed to ionizing radiation in the cardiac cath lab for a median of 10 years, along with 280 unexposed controls.

A variety of health problems were more frequent in the cath lab personnel regularly exposed to radiation. Rates were consistently highest in the cardiologists, followed next by the cath lab nurses, and then the radiation technicians.

Rates of health problems were highest in the 227 individuals with at least 13 years of cath lab radiation exposure. For example, their adjusted risks of cataracts, hypertension, hypercholesterolemia, and cancers were respectively 9-, 1.7-, 2.9-, and 4.5-fold fold greater than in unexposed controls, as detailed in a recent report (Circ Cardiovasc Interv. 2016 April. doi: 10.1161/CIRCINTERVENTIONS.115.003273).

Dr. Piccaluga also shared data from several other pertinent recent studies in which she was a coinvestigator. In one, 83 cardiologists and nurses working in cardiac catheterization laboratories and 83 matched radiation-nonexposed controls completed a neuropsychological test battery. The radiation-exposed group scored significantly lower on measures of delayed recall, visual short-term memory, and verbal fluency, all of which are skills located in left hemisphere structures of the brain – the side with more exposure to ionizing radiation during interventional procedures (J Int Neuropsychol Soc. 2015 Oct;21[9]:670-6).

In another study, Dr. Piccaluga and her coinvestigators had participants perform an odor-sniffing test. Olfactory discrimination in the cardiac cath lab staffers was significantly diminished in a pattern that has been identified in other studies as an early signal of impending clinical onset of Alzheimer’s and Parkinson’s diseases (Int J Cardiol. 2014 Feb 15;171[3]:461-3).

And in yet another study, Dr. Piccaluga and her coworkers found that left and right carotid intima-media thickness as measured by ultrasound in cardiac cath lab personnel having high lifetime radiation exposure was significantly greater than in those with low exposure and in nonexposed controls. In the left carotid artery, but not the right, intimal-medial thickness was significantly correlated with a total occupational radiologic risk score.

Moreover, the Italian investigators found a significant reduction in leukocyte telomere length – a biomarker for accelerated vascular aging – in cardiac cath lab staff regularly exposed to ionizing radiation, compared with controls (JACC Cardiovasc Interv. 2015 Apr 20;8[4]:616-27).

All of these findings, she stressed, make a persuasive case for interventional cardiologists doing everything they can to protect themselves from unnecessary radiation exposure at all times.

How to best go about accomplishing this was the territory covered by Alaide Chieffo, MD, of San Raffaele Scientific Institute in Milan.

The patient-related factors germane to radiation dose – procedure complexity and body thickness – are outside physician control. But there are plenty of operator-dependent factors, including, for starters, procedural experience. In one classic study, Dr. Chieffo noted, Greek investigators showed that interventional cardiologists’ radiation exposure dose was 60% greater in their first year of practice than in their second year.

Distance from the patient is crucial, she observed, since the patient is the greatest source of radiation to the operator. If the operator is 35 cm from the patient, the radiation exposure is fourfold greater than at a distance of 70 cm. At a distance of 17.5 cm, the exposure intensity is 16-fold greater than at a 70-cm distance. And at 8.8 cm of distance, it’s 64 times greater.

Image acquisition is another key variable within the interventionalist’s control. Cine images entail 12- to 20-times greater radiation doses than those of fluoroscopy, so don’t resort to cine when fluoroscopy will do. Also, reducing the fluoroscopy frame rate from 15 to 7.5 frames per second significantly decreases the amount of radiation released while providing images of adequate quality for many procedures. Tight collimation, the use of manually inserted wedge filters, and thoughtful selection of tube angulations result in less radiation for both patient and physician. It has been shown that tube angulations that expose a patient to intense radiation levels increase the operator’s radiation exposure exponentially. The least-irradiating tube angulations are caudal posteroanterior 0°/30°– angulation for the left coronary main stem, cranial posteroanterior 0°/30°+ for the left anterior descending coronary artery bifurcation, and right anterior oblique views of 40° or more. Left anterior oblique projections are the most radiation intensive, according to a comprehensive study (J Am Coll Cardiol. 2004 Oct 6;44[7]:1420-8), Dr. Chieffo continued.

Panelist Ghada Mikhail, MD, of Imperial College London, said there is some relatively new operator protective gear available. She cited lightweight protective caps, for example, but an audience show of hands indicated almost no one uses them.

“Protectors for the breasts and gonads are available. You can wear them underneath the lead. The extra time to put them on is worthwhile,” she said.

“I think the risk of radiation is completely underestimated,” Dr. Mikhail added. “We have a responsibility to young trainees to teach them about radiation protection, which a lot of institutions and supervisors don’t do. That’s partly because a lot of them don’t know the details.”

All of the speakers indicated they had no financial conflicts regarding their presentations.

[email protected]

PARIS – What most interventional cardiologists and electrophysiologists do not know about their health risks due to occupational radiation exposure and how best to protect themselves could fill a book – or better still, make for an illuminating 2-hour expert panel discussion at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

“There’s a problem of lack of awareness on the part of interventional cardiologists, and also of institutional insensitivity to the problem,” declared Emanuela Piccaluga, MD, an investigator in the eye-opening Healthy Cath Lab study. This Italian national study showed that cardiac catheterization laboratory staff had radiation exposure duration–dependent increased risks of cataracts, cancers, and skin lesions, as well as other radiogenic noncancer effects: anxiety and depression, hypertension, and hyperlipidemia.

Bruce Jancin/Frontline Medical News

Cardiologists at some European hospitals have to pay for their own lead aprons and other protective gear. And even if the hospital does pick up the bill, administrators often balk at authorizing replacement of a lead apron that has developed microfractures and cracks. They view these imperfections as cosmetic defects, unaware that the damage renders the apron less protective, according to Dr. Piccaluga of Niguarda Ca’ Granda Hospital in Milan.

Ariel Roguin, MD, head of interventional cardiology at Rambam Medical Center in Haifa, Israel, said every cardiologist working with radiation should understand the three principles of radiation reduction, which he refers to in shorthand as “TDS,” for Time, Distance, and Shielding. Radiation is here to stay in cardiology, he said, but interventionalists can maximize their safety by keeping the fluoroscopy time and number of acquired images down, standing as far away as possible from both the radiation source and patient while still getting the job done well, and using appropriate shielding routinely.

Dr. Roguin gained notoriety with his report that 26 of 30 interventional cardiologists with glioblastoma multiforme or other brain malignancies had left-hemisphere cancers and 1 had a midline malignancy; only 3 were right-sided (Eur Heart J. 2014 Mar;35[10]:599-600). That distribution is highly unlikely to be due to play of chance, given that an interventional cardiologist’s left side is the side that’s usually exposed to more radiation.

Bruce Jancin/Frontline Medical News

“We should form a wall against radiation. Apart from the leaded aprons, for every procedure we all should also use lead skirts going from the table to the floor to block backscatter, ceiling-mounted overhead radiation shields, special glasses to protect against cataracts, and thyroid collars. And it’s very important to wear a dosimeter with sound; it helps increase awareness of our exposure,” he said.

Dr. Roguin has been a pioneer in the use of a thin, 0.5-mm lead shield draped across the patient’s abdomen from the umbilicus down during radial-access angiography. In a 322-patient randomized trial, he and his coinvestigators showed that this practice results in a threefold reduction in radiation to the operator, albeit at the cost of doubling the patient’s radiation exposure (Catheter Cardiovasc Interv. 2015 Jun;85[7]:1164-70).

“We now routinely do our radials with the lead apron across the patient’s abdomen. We’ve reached the conclusion that we work with radiation in the cath lab every day for many years and the patient is there only once or twice in a lifetime, hopefully,” the cardiologist explained.

With the growing popularity of radial-access interventions, audience members wanted to know if there is an advantage in terms of radiation exposure to left versus right radial artery access. The answer is no, according to Dr. Roguin.

“There are several studies showing no difference in radiation exposure. Left radial artery access is faster, but you’re leaning on the patient and getting more radiation as a result, while with right radial access you have to do more catheter manipulation, which takes longer. Both approaches involve more radiation to the operator than the transfemoral approach,” he said.

Dr. Piccaluga presented highlights from the Healthy Cath Lab study, sponsored by the Italian Society of Invasive Cardiology and the Italian National Research Council’s Institute of Clinical Physiology. The study involved detailed self-administered questionnaires completed by 218 interventional cardiologists and electrophysiologists, 191 nurses, and 57 technicians regularly exposed to ionizing radiation in the cardiac cath lab for a median of 10 years, along with 280 unexposed controls.

A variety of health problems were more frequent in the cath lab personnel regularly exposed to radiation. Rates were consistently highest in the cardiologists, followed next by the cath lab nurses, and then the radiation technicians.

Rates of health problems were highest in the 227 individuals with at least 13 years of cath lab radiation exposure. For example, their adjusted risks of cataracts, hypertension, hypercholesterolemia, and cancers were respectively 9-, 1.7-, 2.9-, and 4.5-fold fold greater than in unexposed controls, as detailed in a recent report (Circ Cardiovasc Interv. 2016 April. doi: 10.1161/CIRCINTERVENTIONS.115.003273).

Dr. Piccaluga also shared data from several other pertinent recent studies in which she was a coinvestigator. In one, 83 cardiologists and nurses working in cardiac catheterization laboratories and 83 matched radiation-nonexposed controls completed a neuropsychological test battery. The radiation-exposed group scored significantly lower on measures of delayed recall, visual short-term memory, and verbal fluency, all of which are skills located in left hemisphere structures of the brain – the side with more exposure to ionizing radiation during interventional procedures (J Int Neuropsychol Soc. 2015 Oct;21[9]:670-6).

In another study, Dr. Piccaluga and her coinvestigators had participants perform an odor-sniffing test. Olfactory discrimination in the cardiac cath lab staffers was significantly diminished in a pattern that has been identified in other studies as an early signal of impending clinical onset of Alzheimer’s and Parkinson’s diseases (Int J Cardiol. 2014 Feb 15;171[3]:461-3).

And in yet another study, Dr. Piccaluga and her coworkers found that left and right carotid intima-media thickness as measured by ultrasound in cardiac cath lab personnel having high lifetime radiation exposure was significantly greater than in those with low exposure and in nonexposed controls. In the left carotid artery, but not the right, intimal-medial thickness was significantly correlated with a total occupational radiologic risk score.

Moreover, the Italian investigators found a significant reduction in leukocyte telomere length – a biomarker for accelerated vascular aging – in cardiac cath lab staff regularly exposed to ionizing radiation, compared with controls (JACC Cardiovasc Interv. 2015 Apr 20;8[4]:616-27).

All of these findings, she stressed, make a persuasive case for interventional cardiologists doing everything they can to protect themselves from unnecessary radiation exposure at all times.

How to best go about accomplishing this was the territory covered by Alaide Chieffo, MD, of San Raffaele Scientific Institute in Milan.

The patient-related factors germane to radiation dose – procedure complexity and body thickness – are outside physician control. But there are plenty of operator-dependent factors, including, for starters, procedural experience. In one classic study, Dr. Chieffo noted, Greek investigators showed that interventional cardiologists’ radiation exposure dose was 60% greater in their first year of practice than in their second year.

Distance from the patient is crucial, she observed, since the patient is the greatest source of radiation to the operator. If the operator is 35 cm from the patient, the radiation exposure is fourfold greater than at a distance of 70 cm. At a distance of 17.5 cm, the exposure intensity is 16-fold greater than at a 70-cm distance. And at 8.8 cm of distance, it’s 64 times greater.

Image acquisition is another key variable within the interventionalist’s control. Cine images entail 12- to 20-times greater radiation doses than those of fluoroscopy, so don’t resort to cine when fluoroscopy will do. Also, reducing the fluoroscopy frame rate from 15 to 7.5 frames per second significantly decreases the amount of radiation released while providing images of adequate quality for many procedures. Tight collimation, the use of manually inserted wedge filters, and thoughtful selection of tube angulations result in less radiation for both patient and physician. It has been shown that tube angulations that expose a patient to intense radiation levels increase the operator’s radiation exposure exponentially. The least-irradiating tube angulations are caudal posteroanterior 0°/30°– angulation for the left coronary main stem, cranial posteroanterior 0°/30°+ for the left anterior descending coronary artery bifurcation, and right anterior oblique views of 40° or more. Left anterior oblique projections are the most radiation intensive, according to a comprehensive study (J Am Coll Cardiol. 2004 Oct 6;44[7]:1420-8), Dr. Chieffo continued.

Panelist Ghada Mikhail, MD, of Imperial College London, said there is some relatively new operator protective gear available. She cited lightweight protective caps, for example, but an audience show of hands indicated almost no one uses them.

“Protectors for the breasts and gonads are available. You can wear them underneath the lead. The extra time to put them on is worthwhile,” she said.

“I think the risk of radiation is completely underestimated,” Dr. Mikhail added. “We have a responsibility to young trainees to teach them about radiation protection, which a lot of institutions and supervisors don’t do. That’s partly because a lot of them don’t know the details.”

All of the speakers indicated they had no financial conflicts regarding their presentations.

[email protected]

PARIS – What most interventional cardiologists and electrophysiologists do not know about their health risks due to occupational radiation exposure and how best to protect themselves could fill a book – or better still, make for an illuminating 2-hour expert panel discussion at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

“There’s a problem of lack of awareness on the part of interventional cardiologists, and also of institutional insensitivity to the problem,” declared Emanuela Piccaluga, MD, an investigator in the eye-opening Healthy Cath Lab study. This Italian national study showed that cardiac catheterization laboratory staff had radiation exposure duration–dependent increased risks of cataracts, cancers, and skin lesions, as well as other radiogenic noncancer effects: anxiety and depression, hypertension, and hyperlipidemia.

Bruce Jancin/Frontline Medical News

Cardiologists at some European hospitals have to pay for their own lead aprons and other protective gear. And even if the hospital does pick up the bill, administrators often balk at authorizing replacement of a lead apron that has developed microfractures and cracks. They view these imperfections as cosmetic defects, unaware that the damage renders the apron less protective, according to Dr. Piccaluga of Niguarda Ca’ Granda Hospital in Milan.

Ariel Roguin, MD, head of interventional cardiology at Rambam Medical Center in Haifa, Israel, said every cardiologist working with radiation should understand the three principles of radiation reduction, which he refers to in shorthand as “TDS,” for Time, Distance, and Shielding. Radiation is here to stay in cardiology, he said, but interventionalists can maximize their safety by keeping the fluoroscopy time and number of acquired images down, standing as far away as possible from both the radiation source and patient while still getting the job done well, and using appropriate shielding routinely.

Dr. Roguin gained notoriety with his report that 26 of 30 interventional cardiologists with glioblastoma multiforme or other brain malignancies had left-hemisphere cancers and 1 had a midline malignancy; only 3 were right-sided (Eur Heart J. 2014 Mar;35[10]:599-600). That distribution is highly unlikely to be due to play of chance, given that an interventional cardiologist’s left side is the side that’s usually exposed to more radiation.

Bruce Jancin/Frontline Medical News

“We should form a wall against radiation. Apart from the leaded aprons, for every procedure we all should also use lead skirts going from the table to the floor to block backscatter, ceiling-mounted overhead radiation shields, special glasses to protect against cataracts, and thyroid collars. And it’s very important to wear a dosimeter with sound; it helps increase awareness of our exposure,” he said.

Dr. Roguin has been a pioneer in the use of a thin, 0.5-mm lead shield draped across the patient’s abdomen from the umbilicus down during radial-access angiography. In a 322-patient randomized trial, he and his coinvestigators showed that this practice results in a threefold reduction in radiation to the operator, albeit at the cost of doubling the patient’s radiation exposure (Catheter Cardiovasc Interv. 2015 Jun;85[7]:1164-70).

“We now routinely do our radials with the lead apron across the patient’s abdomen. We’ve reached the conclusion that we work with radiation in the cath lab every day for many years and the patient is there only once or twice in a lifetime, hopefully,” the cardiologist explained.

With the growing popularity of radial-access interventions, audience members wanted to know if there is an advantage in terms of radiation exposure to left versus right radial artery access. The answer is no, according to Dr. Roguin.

“There are several studies showing no difference in radiation exposure. Left radial artery access is faster, but you’re leaning on the patient and getting more radiation as a result, while with right radial access you have to do more catheter manipulation, which takes longer. Both approaches involve more radiation to the operator than the transfemoral approach,” he said.

Dr. Piccaluga presented highlights from the Healthy Cath Lab study, sponsored by the Italian Society of Invasive Cardiology and the Italian National Research Council’s Institute of Clinical Physiology. The study involved detailed self-administered questionnaires completed by 218 interventional cardiologists and electrophysiologists, 191 nurses, and 57 technicians regularly exposed to ionizing radiation in the cardiac cath lab for a median of 10 years, along with 280 unexposed controls.

A variety of health problems were more frequent in the cath lab personnel regularly exposed to radiation. Rates were consistently highest in the cardiologists, followed next by the cath lab nurses, and then the radiation technicians.

Rates of health problems were highest in the 227 individuals with at least 13 years of cath lab radiation exposure. For example, their adjusted risks of cataracts, hypertension, hypercholesterolemia, and cancers were respectively 9-, 1.7-, 2.9-, and 4.5-fold fold greater than in unexposed controls, as detailed in a recent report (Circ Cardiovasc Interv. 2016 April. doi: 10.1161/CIRCINTERVENTIONS.115.003273).

Dr. Piccaluga also shared data from several other pertinent recent studies in which she was a coinvestigator. In one, 83 cardiologists and nurses working in cardiac catheterization laboratories and 83 matched radiation-nonexposed controls completed a neuropsychological test battery. The radiation-exposed group scored significantly lower on measures of delayed recall, visual short-term memory, and verbal fluency, all of which are skills located in left hemisphere structures of the brain – the side with more exposure to ionizing radiation during interventional procedures (J Int Neuropsychol Soc. 2015 Oct;21[9]:670-6).

In another study, Dr. Piccaluga and her coinvestigators had participants perform an odor-sniffing test. Olfactory discrimination in the cardiac cath lab staffers was significantly diminished in a pattern that has been identified in other studies as an early signal of impending clinical onset of Alzheimer’s and Parkinson’s diseases (Int J Cardiol. 2014 Feb 15;171[3]:461-3).

And in yet another study, Dr. Piccaluga and her coworkers found that left and right carotid intima-media thickness as measured by ultrasound in cardiac cath lab personnel having high lifetime radiation exposure was significantly greater than in those with low exposure and in nonexposed controls. In the left carotid artery, but not the right, intimal-medial thickness was significantly correlated with a total occupational radiologic risk score.

Moreover, the Italian investigators found a significant reduction in leukocyte telomere length – a biomarker for accelerated vascular aging – in cardiac cath lab staff regularly exposed to ionizing radiation, compared with controls (JACC Cardiovasc Interv. 2015 Apr 20;8[4]:616-27).

All of these findings, she stressed, make a persuasive case for interventional cardiologists doing everything they can to protect themselves from unnecessary radiation exposure at all times.

How to best go about accomplishing this was the territory covered by Alaide Chieffo, MD, of San Raffaele Scientific Institute in Milan.

The patient-related factors germane to radiation dose – procedure complexity and body thickness – are outside physician control. But there are plenty of operator-dependent factors, including, for starters, procedural experience. In one classic study, Dr. Chieffo noted, Greek investigators showed that interventional cardiologists’ radiation exposure dose was 60% greater in their first year of practice than in their second year.

Distance from the patient is crucial, she observed, since the patient is the greatest source of radiation to the operator. If the operator is 35 cm from the patient, the radiation exposure is fourfold greater than at a distance of 70 cm. At a distance of 17.5 cm, the exposure intensity is 16-fold greater than at a 70-cm distance. And at 8.8 cm of distance, it’s 64 times greater.

Image acquisition is another key variable within the interventionalist’s control. Cine images entail 12- to 20-times greater radiation doses than those of fluoroscopy, so don’t resort to cine when fluoroscopy will do. Also, reducing the fluoroscopy frame rate from 15 to 7.5 frames per second significantly decreases the amount of radiation released while providing images of adequate quality for many procedures. Tight collimation, the use of manually inserted wedge filters, and thoughtful selection of tube angulations result in less radiation for both patient and physician. It has been shown that tube angulations that expose a patient to intense radiation levels increase the operator’s radiation exposure exponentially. The least-irradiating tube angulations are caudal posteroanterior 0°/30°– angulation for the left coronary main stem, cranial posteroanterior 0°/30°+ for the left anterior descending coronary artery bifurcation, and right anterior oblique views of 40° or more. Left anterior oblique projections are the most radiation intensive, according to a comprehensive study (J Am Coll Cardiol. 2004 Oct 6;44[7]:1420-8), Dr. Chieffo continued.

Panelist Ghada Mikhail, MD, of Imperial College London, said there is some relatively new operator protective gear available. She cited lightweight protective caps, for example, but an audience show of hands indicated almost no one uses them.

“Protectors for the breasts and gonads are available. You can wear them underneath the lead. The extra time to put them on is worthwhile,” she said.

“I think the risk of radiation is completely underestimated,” Dr. Mikhail added. “We have a responsibility to young trainees to teach them about radiation protection, which a lot of institutions and supervisors don’t do. That’s partly because a lot of them don’t know the details.”

All of the speakers indicated they had no financial conflicts regarding their presentations.

[email protected]

Combination chemotherapy with bendamustine, gemcitabine, and vinorelbine can induce high complete response rates among patients with relapsed or refractory Hodgkin lymphoma (HL) who are candidates for autologous stem cell transplantation, final results of a phase II study show.

Among 59 patients enrolled in the multicenter study, 49 (83%) had responses, including 43 (73%) who achieved a complete response (CR), and 6 (10%) who had a partial response after 4 cycles of chemotherapy with bendamustine (Treanda), gemcitabine (Gemzar), and vinorelbine (BeGEV).

Of the 49 patients with responses, 43 went on to autologous stem cell transplant (ASCT), reported Armando Santoro, MD, from the Humanitas Cancer Center in Rozzano, Italy.

“These findings provide a strong rationale for further development of the BeGEV regimen,” the investigators wrote in a study published online in the Journal of Clinical Oncology (2016 Jul 5. doi: 10.1200/JCO.2016.66.4466).

The investigators had previously shown that a regimen of ifosfamide, gemcitabine, and vinorelbine (IEGV) as salvage chemotherapy prior to ASCT was associated with an 81% overall response rate (ORR) 54% CR rate.

Because bendamustine has shown good activity as monotherapy against relapsed/refractory HL, they conducted a phase II study with an IEGV-like regimen in which bendamustine would be substituted for ifosfamide, to determine whether the substitution could improve response rates.

They enrolled 59 consecutive patients aged 18 years and older with HL that had relapsed or was refractory to one previous line of chemotherapy. Patients were treated with gemcitabine 800 mg/m² on days 1 and 4, vinorelbine 20 mg/m² on day 1, and bendamustine 90 mg/m² on days 2 and 3. Patients also received prednisolone 100 mg/day for days 1 to 4. The patients were treated for four 21-day cycles.

Patients who achieved either a complete or partial response after completion of the four planned cycles then underwent myeloablative therapy with carmustine or fotemustine plus etoposide, cytarabine, and melphalan, followed by reinfusion of mobilized CD34-positive circulating stem cells.

Grade 3 or 4 hematologic toxicities included thrombocytopenia and neutropenia, which occurred in eight patients each. Fifty-five of 57 total evaluable patients had successful mobilization and harvesting of CD34-positive cells, and, as noted before, 43 went on to ASCT.

After a median follow-up of 29 months, the 2-year progression-free survival (PFS) rate for the total population was 62%, and the overall survival rates was nearly 78%. For patients who went on to ASCT, the 2-year PFS rate was 81%, and the 2-year survival rate was 89%.

The authors noted that BeGV was associated with higher CR rates than IEGV, and with “excellent” stem cell mobilization activity and engraftment. Additionally, BeGV has a favorable toxicity profile, because of the absence of ifosfamide which is known to significantly increase risk for hemorrhagic cystitis.

“Because the number of novel agents that may be added in the pretransplantation therapy setting is growing, direct comparisons of combinations incorporating novel agents with BeGEV and other regimens will be necessary to identify the best salvage strategy for relapsed and refractory HL,” the authors wrote.

The study was supported in part by a grant from Mundipharma Pharmaceuticals. Two coauthors disclosed consulting/advisory roles and travel accommodations and expenses from the company.

Combination chemotherapy with bendamustine, gemcitabine, and vinorelbine can induce high complete response rates among patients with relapsed or refractory Hodgkin lymphoma (HL) who are candidates for autologous stem cell transplantation, final results of a phase II study show.

Among 59 patients enrolled in the multicenter study, 49 (83%) had responses, including 43 (73%) who achieved a complete response (CR), and 6 (10%) who had a partial response after 4 cycles of chemotherapy with bendamustine (Treanda), gemcitabine (Gemzar), and vinorelbine (BeGEV).

Of the 49 patients with responses, 43 went on to autologous stem cell transplant (ASCT), reported Armando Santoro, MD, from the Humanitas Cancer Center in Rozzano, Italy.

“These findings provide a strong rationale for further development of the BeGEV regimen,” the investigators wrote in a study published online in the Journal of Clinical Oncology (2016 Jul 5. doi: 10.1200/JCO.2016.66.4466).

The investigators had previously shown that a regimen of ifosfamide, gemcitabine, and vinorelbine (IEGV) as salvage chemotherapy prior to ASCT was associated with an 81% overall response rate (ORR) 54% CR rate.

Because bendamustine has shown good activity as monotherapy against relapsed/refractory HL, they conducted a phase II study with an IEGV-like regimen in which bendamustine would be substituted for ifosfamide, to determine whether the substitution could improve response rates.

They enrolled 59 consecutive patients aged 18 years and older with HL that had relapsed or was refractory to one previous line of chemotherapy. Patients were treated with gemcitabine 800 mg/m² on days 1 and 4, vinorelbine 20 mg/m² on day 1, and bendamustine 90 mg/m² on days 2 and 3. Patients also received prednisolone 100 mg/day for days 1 to 4. The patients were treated for four 21-day cycles.

Patients who achieved either a complete or partial response after completion of the four planned cycles then underwent myeloablative therapy with carmustine or fotemustine plus etoposide, cytarabine, and melphalan, followed by reinfusion of mobilized CD34-positive circulating stem cells.

Grade 3 or 4 hematologic toxicities included thrombocytopenia and neutropenia, which occurred in eight patients each. Fifty-five of 57 total evaluable patients had successful mobilization and harvesting of CD34-positive cells, and, as noted before, 43 went on to ASCT.

After a median follow-up of 29 months, the 2-year progression-free survival (PFS) rate for the total population was 62%, and the overall survival rates was nearly 78%. For patients who went on to ASCT, the 2-year PFS rate was 81%, and the 2-year survival rate was 89%.

The authors noted that BeGV was associated with higher CR rates than IEGV, and with “excellent” stem cell mobilization activity and engraftment. Additionally, BeGV has a favorable toxicity profile, because of the absence of ifosfamide which is known to significantly increase risk for hemorrhagic cystitis.

“Because the number of novel agents that may be added in the pretransplantation therapy setting is growing, direct comparisons of combinations incorporating novel agents with BeGEV and other regimens will be necessary to identify the best salvage strategy for relapsed and refractory HL,” the authors wrote.

The study was supported in part by a grant from Mundipharma Pharmaceuticals. Two coauthors disclosed consulting/advisory roles and travel accommodations and expenses from the company.

Combination chemotherapy with bendamustine, gemcitabine, and vinorelbine can induce high complete response rates among patients with relapsed or refractory Hodgkin lymphoma (HL) who are candidates for autologous stem cell transplantation, final results of a phase II study show.

Among 59 patients enrolled in the multicenter study, 49 (83%) had responses, including 43 (73%) who achieved a complete response (CR), and 6 (10%) who had a partial response after 4 cycles of chemotherapy with bendamustine (Treanda), gemcitabine (Gemzar), and vinorelbine (BeGEV).

Of the 49 patients with responses, 43 went on to autologous stem cell transplant (ASCT), reported Armando Santoro, MD, from the Humanitas Cancer Center in Rozzano, Italy.

“These findings provide a strong rationale for further development of the BeGEV regimen,” the investigators wrote in a study published online in the Journal of Clinical Oncology (2016 Jul 5. doi: 10.1200/JCO.2016.66.4466).

The investigators had previously shown that a regimen of ifosfamide, gemcitabine, and vinorelbine (IEGV) as salvage chemotherapy prior to ASCT was associated with an 81% overall response rate (ORR) 54% CR rate.

Because bendamustine has shown good activity as monotherapy against relapsed/refractory HL, they conducted a phase II study with an IEGV-like regimen in which bendamustine would be substituted for ifosfamide, to determine whether the substitution could improve response rates.

They enrolled 59 consecutive patients aged 18 years and older with HL that had relapsed or was refractory to one previous line of chemotherapy. Patients were treated with gemcitabine 800 mg/m² on days 1 and 4, vinorelbine 20 mg/m² on day 1, and bendamustine 90 mg/m² on days 2 and 3. Patients also received prednisolone 100 mg/day for days 1 to 4. The patients were treated for four 21-day cycles.

Patients who achieved either a complete or partial response after completion of the four planned cycles then underwent myeloablative therapy with carmustine or fotemustine plus etoposide, cytarabine, and melphalan, followed by reinfusion of mobilized CD34-positive circulating stem cells.

Grade 3 or 4 hematologic toxicities included thrombocytopenia and neutropenia, which occurred in eight patients each. Fifty-five of 57 total evaluable patients had successful mobilization and harvesting of CD34-positive cells, and, as noted before, 43 went on to ASCT.

After a median follow-up of 29 months, the 2-year progression-free survival (PFS) rate for the total population was 62%, and the overall survival rates was nearly 78%. For patients who went on to ASCT, the 2-year PFS rate was 81%, and the 2-year survival rate was 89%.

The authors noted that BeGV was associated with higher CR rates than IEGV, and with “excellent” stem cell mobilization activity and engraftment. Additionally, BeGV has a favorable toxicity profile, because of the absence of ifosfamide which is known to significantly increase risk for hemorrhagic cystitis.

“Because the number of novel agents that may be added in the pretransplantation therapy setting is growing, direct comparisons of combinations incorporating novel agents with BeGEV and other regimens will be necessary to identify the best salvage strategy for relapsed and refractory HL,” the authors wrote.

The study was supported in part by a grant from Mundipharma Pharmaceuticals. Two coauthors disclosed consulting/advisory roles and travel accommodations and expenses from the company.