ACS Surgery News

In patients with moderate ischemic mitral regurgitation, adding mitral valve repair to coronary artery bypass graft did not significantly affect the extent of left ventricular remodeling at 2 years, according to a randomized multicenter trial.

Compared with revascularization alone, the combined procedure was associated with a two-thirds lower rate of moderate to severe mitral regurgitation at the end of year 2, reported Dr. Robert Michler at Albert Einstein College of Medicine, New York, together with his associates. But improved durability did not translate to better survival or lower rates of major adverse cardiac and cerebrovascular events, heart failure, or hospital readmissions, they said. Furthermore, adding mitral valve repair to CABG was linked to higher rates of postoperative neurologic events and supraventricular arrhythmias than for CABG alone, the investigators reported at the annual meeting of the American College of Cardiology and simultaneously online April 3 in the New England Journal of Medicine.

Surgeons have debated whether to add restrictive mitral annuloplasty to CABG in patients with moderate ischemic mitral regurgitation. The combined approach requires open-heart exposure and longer aortic cross-clamping and cardiopulmonary bypass time, all of which increase perioperative risk, the researchers noted. To explore the risk-benefit balance of these approaches, they randomly assigned 301 patients to either revascularization alone or to the combined procedure, and assessed clinical and echocardiographic outcomes over 2 years (New Engl. J. Med. 2016 April 3 doi: 10.1056/NEJMoa1602003).

At year 1, the arms resembled each other in terms of survival, rates of major adverse cardiac or cerebrovascular events (MACCEs), and left ventricular reverse remodeling, as measured by left ventricular end-systolic volume index (LVESVI), said the investigators. At year 2, the extent of remodeling remained similar between the arms, with mean LVESVIs of 41.2 mL (standard deviation, 20.0 mL) per square meter of body surface area in the CABG-only group and 43.2 mL (SD, 20.6 mL) in the combined procedure group, for a mean decrease from baseline of 14.1 and 14.6 mL, respectively. About two-thirds of improvements in LVESI occurred during year 1 regardless of procedure type, the researchers noted.

About a third of CABG-only patients had moderate to severe mitral regurgitation at 2 years, compared with only 11% of patients who underwent the combined procedure (P less than .001). Patients who had mild or no mitral regurgitation had more than twice the percentage improvement in the global wall motion index and in the inferior-posterior-lateral regional wall motion score, compared with patients with moderate to severe regurgitation. Although both groups improved on several quality-of-life indices, the combined-procedure group scored more than 5 points higher on the Duke Activity Status Index, which measures self-reported exercise capacity. That difference was not only clinically meaningful, but resembled the increase in peak myocardial oxygen consumption in a similar, smaller trial (New Engl. J. Med. 2016 Jan. 28 doi: 10.1056/NEJMoa151291), the investigators noted.

However, mortality rates were similar between the arms at 2 years – 10.6% for CABG only and 10% for the combined procedure, for a non-significant hazard ratio of 0.9. Likewise, rates of heart failure and other serious adverse events were similar between the arms, while the combined-procedure arm had more than three times more postoperative neurologic events and more than twice as many occurrences of supraventricular arrhythmia. Therefore, treatment choice requires “balancing the risks of adverse perioperative events against the uncertain benefits of a lower incidence of postoperative moderate or severe mitral regurgitation,” said the researchers. “Effective revascularization, as reflected in improved regional and global left ventricular function, plays an important role independent of mitral valve repair.”

The National Institutes of Health and the Canadian Institutes of Health Research funded the study. Disclosures were reported separately at nejm.org.

In patients with moderate ischemic mitral regurgitation, adding mitral valve repair to coronary artery bypass graft did not significantly affect the extent of left ventricular remodeling at 2 years, according to a randomized multicenter trial.

Compared with revascularization alone, the combined procedure was associated with a two-thirds lower rate of moderate to severe mitral regurgitation at the end of year 2, reported Dr. Robert Michler at Albert Einstein College of Medicine, New York, together with his associates. But improved durability did not translate to better survival or lower rates of major adverse cardiac and cerebrovascular events, heart failure, or hospital readmissions, they said. Furthermore, adding mitral valve repair to CABG was linked to higher rates of postoperative neurologic events and supraventricular arrhythmias than for CABG alone, the investigators reported at the annual meeting of the American College of Cardiology and simultaneously online April 3 in the New England Journal of Medicine.

Surgeons have debated whether to add restrictive mitral annuloplasty to CABG in patients with moderate ischemic mitral regurgitation. The combined approach requires open-heart exposure and longer aortic cross-clamping and cardiopulmonary bypass time, all of which increase perioperative risk, the researchers noted. To explore the risk-benefit balance of these approaches, they randomly assigned 301 patients to either revascularization alone or to the combined procedure, and assessed clinical and echocardiographic outcomes over 2 years (New Engl. J. Med. 2016 April 3 doi: 10.1056/NEJMoa1602003).

At year 1, the arms resembled each other in terms of survival, rates of major adverse cardiac or cerebrovascular events (MACCEs), and left ventricular reverse remodeling, as measured by left ventricular end-systolic volume index (LVESVI), said the investigators. At year 2, the extent of remodeling remained similar between the arms, with mean LVESVIs of 41.2 mL (standard deviation, 20.0 mL) per square meter of body surface area in the CABG-only group and 43.2 mL (SD, 20.6 mL) in the combined procedure group, for a mean decrease from baseline of 14.1 and 14.6 mL, respectively. About two-thirds of improvements in LVESI occurred during year 1 regardless of procedure type, the researchers noted.

About a third of CABG-only patients had moderate to severe mitral regurgitation at 2 years, compared with only 11% of patients who underwent the combined procedure (P less than .001). Patients who had mild or no mitral regurgitation had more than twice the percentage improvement in the global wall motion index and in the inferior-posterior-lateral regional wall motion score, compared with patients with moderate to severe regurgitation. Although both groups improved on several quality-of-life indices, the combined-procedure group scored more than 5 points higher on the Duke Activity Status Index, which measures self-reported exercise capacity. That difference was not only clinically meaningful, but resembled the increase in peak myocardial oxygen consumption in a similar, smaller trial (New Engl. J. Med. 2016 Jan. 28 doi: 10.1056/NEJMoa151291), the investigators noted.

However, mortality rates were similar between the arms at 2 years – 10.6% for CABG only and 10% for the combined procedure, for a non-significant hazard ratio of 0.9. Likewise, rates of heart failure and other serious adverse events were similar between the arms, while the combined-procedure arm had more than three times more postoperative neurologic events and more than twice as many occurrences of supraventricular arrhythmia. Therefore, treatment choice requires “balancing the risks of adverse perioperative events against the uncertain benefits of a lower incidence of postoperative moderate or severe mitral regurgitation,” said the researchers. “Effective revascularization, as reflected in improved regional and global left ventricular function, plays an important role independent of mitral valve repair.”

The National Institutes of Health and the Canadian Institutes of Health Research funded the study. Disclosures were reported separately at nejm.org.

In patients with moderate ischemic mitral regurgitation, adding mitral valve repair to coronary artery bypass graft did not significantly affect the extent of left ventricular remodeling at 2 years, according to a randomized multicenter trial.

Compared with revascularization alone, the combined procedure was associated with a two-thirds lower rate of moderate to severe mitral regurgitation at the end of year 2, reported Dr. Robert Michler at Albert Einstein College of Medicine, New York, together with his associates. But improved durability did not translate to better survival or lower rates of major adverse cardiac and cerebrovascular events, heart failure, or hospital readmissions, they said. Furthermore, adding mitral valve repair to CABG was linked to higher rates of postoperative neurologic events and supraventricular arrhythmias than for CABG alone, the investigators reported at the annual meeting of the American College of Cardiology and simultaneously online April 3 in the New England Journal of Medicine.

Surgeons have debated whether to add restrictive mitral annuloplasty to CABG in patients with moderate ischemic mitral regurgitation. The combined approach requires open-heart exposure and longer aortic cross-clamping and cardiopulmonary bypass time, all of which increase perioperative risk, the researchers noted. To explore the risk-benefit balance of these approaches, they randomly assigned 301 patients to either revascularization alone or to the combined procedure, and assessed clinical and echocardiographic outcomes over 2 years (New Engl. J. Med. 2016 April 3 doi: 10.1056/NEJMoa1602003).

At year 1, the arms resembled each other in terms of survival, rates of major adverse cardiac or cerebrovascular events (MACCEs), and left ventricular reverse remodeling, as measured by left ventricular end-systolic volume index (LVESVI), said the investigators. At year 2, the extent of remodeling remained similar between the arms, with mean LVESVIs of 41.2 mL (standard deviation, 20.0 mL) per square meter of body surface area in the CABG-only group and 43.2 mL (SD, 20.6 mL) in the combined procedure group, for a mean decrease from baseline of 14.1 and 14.6 mL, respectively. About two-thirds of improvements in LVESI occurred during year 1 regardless of procedure type, the researchers noted.

About a third of CABG-only patients had moderate to severe mitral regurgitation at 2 years, compared with only 11% of patients who underwent the combined procedure (P less than .001). Patients who had mild or no mitral regurgitation had more than twice the percentage improvement in the global wall motion index and in the inferior-posterior-lateral regional wall motion score, compared with patients with moderate to severe regurgitation. Although both groups improved on several quality-of-life indices, the combined-procedure group scored more than 5 points higher on the Duke Activity Status Index, which measures self-reported exercise capacity. That difference was not only clinically meaningful, but resembled the increase in peak myocardial oxygen consumption in a similar, smaller trial (New Engl. J. Med. 2016 Jan. 28 doi: 10.1056/NEJMoa151291), the investigators noted.

However, mortality rates were similar between the arms at 2 years – 10.6% for CABG only and 10% for the combined procedure, for a non-significant hazard ratio of 0.9. Likewise, rates of heart failure and other serious adverse events were similar between the arms, while the combined-procedure arm had more than three times more postoperative neurologic events and more than twice as many occurrences of supraventricular arrhythmia. Therefore, treatment choice requires “balancing the risks of adverse perioperative events against the uncertain benefits of a lower incidence of postoperative moderate or severe mitral regurgitation,” said the researchers. “Effective revascularization, as reflected in improved regional and global left ventricular function, plays an important role independent of mitral valve repair.”

The National Institutes of Health and the Canadian Institutes of Health Research funded the study. Disclosures were reported separately at nejm.org.

Patients with severe aortic stenosis that puts them at increased risk for surgery continue to do better at 3 years after receiving a self-expanding transcatheter aortic valve replacement than do similar patients who have an open surgical valve replacement, according to new results from a randomized trial presented at the annual meeting of the American College of Cardiology.

Two-year follow-up results from the same trial cohort, the CoreValve U.S. Pivotal High Risk Trial, showed superior survival and stroke outcomes for TAVR compared with open surgery (J Am Coll Cardiol. 2015;66[2]:113-21). The difference in outcomes was thought to stem mainly from fewer postprocedural complications and faster recovery in the TAVR group.

The new study, presented at the meeting and simultaneously published online April 3 in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2016.03.506) aimed to determine whether the previously seen benefits extended into the third year and whether these were accompanied by differences in valve hemodynamics.

Dr. G. Michael Deeb, Herbert Sloan Collegiate Professor of Cardiac Surgery at the University of Michigan, Ann Arbor, and his colleagues evaluated three-year clinical and echocardiographic outcomes from the 391 patients who underwent TAVR and 359 who had SAVR. At baseline all patients had severe aortic stenosis and were considered to be at increased risk for SAVR, with an estimated 30-day mortality risk 15% or greater and a combined 30-day surgical mortality and major morbidity risk less than 50%.

At 3 years follow-up in the treated groups, combined all-cause mortality or stroke was significantly lower at 37% in TAVR patients as compared to nearly 47% in SAVR patients. All-cause mortality was 33% with TAVR and 39% with SAVR, a difference that did not reach statistical significance. Stroke rates were nearly 13% with TAVR and 19% with SAVR; major adverse cardiovascular or cerebrovascular events were 40% with TAVR and 48% for SAVR. Both were significant differences.

While mean aortic valve gradient measures were more favorable – 7.62 ± 3.57 mm Hg with TAVR and 11.40 ± 6.81 mm Hg with SAVR – regurgitation was significantly higher at nearly 7% with TAVR and no regurgitation with SAVR. Valve thrombosis and valve structural deterioration were not observed in either group.

While the findings show sustained 3-year clinical benefit of self-expanding TAVR over SAVR in patients with aortic stenosis at increased risk for surgery, longer studies are needed to determine whether the crimping and re-crimping of the transcatheter valve would have an impact on long-term bioprosthesis durability.

The study was funded by the device manufacturer Medtronic, and 21 of its 28 authors disclosed financial relationships with Medtronic and/or other manufacturers; one is a Medtronic employee. Dr. Deeb disclosed serving as an unpaid advisor to Medtronic.

Patients with severe aortic stenosis that puts them at increased risk for surgery continue to do better at 3 years after receiving a self-expanding transcatheter aortic valve replacement than do similar patients who have an open surgical valve replacement, according to new results from a randomized trial presented at the annual meeting of the American College of Cardiology.

Two-year follow-up results from the same trial cohort, the CoreValve U.S. Pivotal High Risk Trial, showed superior survival and stroke outcomes for TAVR compared with open surgery (J Am Coll Cardiol. 2015;66[2]:113-21). The difference in outcomes was thought to stem mainly from fewer postprocedural complications and faster recovery in the TAVR group.

The new study, presented at the meeting and simultaneously published online April 3 in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2016.03.506) aimed to determine whether the previously seen benefits extended into the third year and whether these were accompanied by differences in valve hemodynamics.

Dr. G. Michael Deeb, Herbert Sloan Collegiate Professor of Cardiac Surgery at the University of Michigan, Ann Arbor, and his colleagues evaluated three-year clinical and echocardiographic outcomes from the 391 patients who underwent TAVR and 359 who had SAVR. At baseline all patients had severe aortic stenosis and were considered to be at increased risk for SAVR, with an estimated 30-day mortality risk 15% or greater and a combined 30-day surgical mortality and major morbidity risk less than 50%.

At 3 years follow-up in the treated groups, combined all-cause mortality or stroke was significantly lower at 37% in TAVR patients as compared to nearly 47% in SAVR patients. All-cause mortality was 33% with TAVR and 39% with SAVR, a difference that did not reach statistical significance. Stroke rates were nearly 13% with TAVR and 19% with SAVR; major adverse cardiovascular or cerebrovascular events were 40% with TAVR and 48% for SAVR. Both were significant differences.

While mean aortic valve gradient measures were more favorable – 7.62 ± 3.57 mm Hg with TAVR and 11.40 ± 6.81 mm Hg with SAVR – regurgitation was significantly higher at nearly 7% with TAVR and no regurgitation with SAVR. Valve thrombosis and valve structural deterioration were not observed in either group.

While the findings show sustained 3-year clinical benefit of self-expanding TAVR over SAVR in patients with aortic stenosis at increased risk for surgery, longer studies are needed to determine whether the crimping and re-crimping of the transcatheter valve would have an impact on long-term bioprosthesis durability.

The study was funded by the device manufacturer Medtronic, and 21 of its 28 authors disclosed financial relationships with Medtronic and/or other manufacturers; one is a Medtronic employee. Dr. Deeb disclosed serving as an unpaid advisor to Medtronic.

Patients with severe aortic stenosis that puts them at increased risk for surgery continue to do better at 3 years after receiving a self-expanding transcatheter aortic valve replacement than do similar patients who have an open surgical valve replacement, according to new results from a randomized trial presented at the annual meeting of the American College of Cardiology.

Two-year follow-up results from the same trial cohort, the CoreValve U.S. Pivotal High Risk Trial, showed superior survival and stroke outcomes for TAVR compared with open surgery (J Am Coll Cardiol. 2015;66[2]:113-21). The difference in outcomes was thought to stem mainly from fewer postprocedural complications and faster recovery in the TAVR group.

The new study, presented at the meeting and simultaneously published online April 3 in the Journal of the American College of Cardiology (doi: 10.1016/j.jacc.2016.03.506) aimed to determine whether the previously seen benefits extended into the third year and whether these were accompanied by differences in valve hemodynamics.

Dr. G. Michael Deeb, Herbert Sloan Collegiate Professor of Cardiac Surgery at the University of Michigan, Ann Arbor, and his colleagues evaluated three-year clinical and echocardiographic outcomes from the 391 patients who underwent TAVR and 359 who had SAVR. At baseline all patients had severe aortic stenosis and were considered to be at increased risk for SAVR, with an estimated 30-day mortality risk 15% or greater and a combined 30-day surgical mortality and major morbidity risk less than 50%.

At 3 years follow-up in the treated groups, combined all-cause mortality or stroke was significantly lower at 37% in TAVR patients as compared to nearly 47% in SAVR patients. All-cause mortality was 33% with TAVR and 39% with SAVR, a difference that did not reach statistical significance. Stroke rates were nearly 13% with TAVR and 19% with SAVR; major adverse cardiovascular or cerebrovascular events were 40% with TAVR and 48% for SAVR. Both were significant differences.

While mean aortic valve gradient measures were more favorable – 7.62 ± 3.57 mm Hg with TAVR and 11.40 ± 6.81 mm Hg with SAVR – regurgitation was significantly higher at nearly 7% with TAVR and no regurgitation with SAVR. Valve thrombosis and valve structural deterioration were not observed in either group.

While the findings show sustained 3-year clinical benefit of self-expanding TAVR over SAVR in patients with aortic stenosis at increased risk for surgery, longer studies are needed to determine whether the crimping and re-crimping of the transcatheter valve would have an impact on long-term bioprosthesis durability.

The study was funded by the device manufacturer Medtronic, and 21 of its 28 authors disclosed financial relationships with Medtronic and/or other manufacturers; one is a Medtronic employee. Dr. Deeb disclosed serving as an unpaid advisor to Medtronic.

CHICAGO – Transcatheter aortic-valve replacement performed as well as surgical-valve replacement in patients with an intermediate mortality risk in a prospective, randomized trial with more than 2,000 patients followed for 2 years, the first randomized trial to compare the efficacy and safety of transcatheter aortic-valve replacement against surgical replacement in patients who did not have a high mortality risk.

The results “support TAVR [transcatheter aortic-valve replacement] as an alternative to surgery in intermediate-risk patients similar to those included in this trial,” said Dr. Craig R. Smith at the annual meeting of the American College of Cardiology. The findings from the Placement of Aortic Transcatheter Valves (PARTNER) 2 cohort A trial “will increase use of TAVR,” predicted Dr. Smith, professor and chairman of surgery at New York–Presbyterian Hospital/Columbia University in New York.

Mitchel L. Zoler/Frontline Medical News

Until now, TAVR had been compared with surgical aortic-valve replacement in two prospective, randomized trials that both enrolled either high-risk or inoperable patients with severe aortic stenosis, the PARTNER 1 trial that tested the original Sapien TAVR system, and the U.S. CoreValve High-Risk Study that tested the original CoreValve system (often now called CoreValve classic). The average Society of Thoracic Surgeons (STS) operative risk score of high-risk patients enrolled in PARTNER 1 was 11.8%, and the average risk score in patients enrolled in the CoreValve study was 7.3%. In contrast, the design of PARTNER 2A specified that enrolled patients have a STS risk score of 4%-8%, a criterion actually met by 81% of the enrolled patients, and the average STS risk score of all patients enrolled in PARTNER 2A was 5.8%.

Although U.S. labeling for both the Sapien valve and its later iterations, Sapien XT and S3, and for CoreValve and its later iteration, Evolut R, specify that treated patients should have a STS risk score of at least 8%, the labeling also gives the heart teams that perform TAVR the latitude to treat patients with risk scores below 8% when the heart teams identify other patient factors that confer high risk such as frailty or comorbidities. U.S. and European TAVR registries have documented that many patients with STS risk scores below 8% have undergone TAVR since these systems received regulatory approval. The new results from PARTNER 2A may change that by leading to revised labeling that cuts the STS risk-score threshold.

“These findings might lead to a labeling change that would avoid a lot of the patient-evaluation gymnastics that have been used to justify” TAVR treatment, noted Dr. Smith. New labeling like this “would sanction what is already going on” in terms of which patients undergo TAVR.

Others who heard these results at the meeting agreed they were an important milestone in TAVR development and its expanding use.

Mitchel L. Zoler/Frontline Medical News

The new results “make a huge difference,” commented Dr. David R. Holmes Jr., an interventional cardiologist and professor at the Mayo Clinic in Rochester, Minn. “We base many of our guidelines on the results from randomized, controlled trials. It’s true that there are reports of lower-risk patients undergoing TAVR, but we now have results from a well-designed trial with well-controlled and adjudicated endpoints that documents the safety and efficacy of TAVR in intermediate-risk patients,” Dr. Holmes said in an interview.

“The results will have a very important influence on the choice between TAVR and surgery,” commented Dr. Duane S. Pinto, an interventional cardiologist at Beth Israel Deaconess Medical Center in Boston. “It validates the strategy” of using TAVR in patients with a risk score of 4%-8%. “TAVR has already been used in these patients, but these results validate this, especially when used in a transfemoral approach,” Dr. Pinto said in an interview.

One aspect of PARTNER 2A that received a lot of discussion at the meeting was whether enrolled patients could appropriately be characterized as “intermediate” in their risk level. Although their average STS risk score of 5.8% fell squarely within the target range specified for the study, they averaged 82 years old, and other clinical features at baseline suggested a higher risk population. The published report of the PARTNER 2A results that appeared online concurrent with Dr. Smith’s report at the meeting (New Engl J Med 2016;doi:10.1056/NEJMoa1514616) acknowledged that STS risk scores of 4%-8% place the enrolled patients into the upper 20% for risk of all U.S. patients who undergo surgical aortic-valve replacement

“I would characterize the enrolled patients as ‘less high risk’ rather than intermediate risk,” said Dr. Pinto.

But as Dr. Smith explained “even if the enrolled patients are not ‘intermediate’ risk they are at a different risk level” than were the patients enrolled in the prior TAVR randomized trials.

In the PARTNER 1 high-risk trial, the overall 1-year rate of all-cause mortality was 24% and 27% in the TAVR and surgical arms of the study, respectively. In the CoreValve trial these rates were 14% with TAVR and 19% with surgery. In PARTNER 2A 1-year all-cause mortality was 12% with TAVR and 13% with surgery.

Two other notable findings of PARTNER 2A were the superior outcomes of patients who underwent TAVR using a transfemoral approach, and the improved outcomes that all TAVR patients had compared with surgical valve replacement for several secondary outcomes.

The rate of the study’s primary outcome, all-cause death or disabling stroke after 2 years, was cut by a relative 21% in the 77% of TAVR patients who underwent a transfemoral procedure, compared with the surgery patients, a difference that was of borderline statistical significance. In contrast, the entire group of TAVR patients, including those treated via nontransfemoral routes, had an 11% relative reduction of the primary endpoint, compared with surgery, a difference that was not statistically significant but did easily meet the study’s prespecified definition of noninferority. Dr. Smith and others were especially encouraged by these findings as PARTNER 2A used the older Sapien XT TAVR system that is not often used today in U.S. practice. When U.S. patients undergo TAVR with a balloon-expandable valve they most often receive treatment with the S3 system, much smaller than XT and hence much more likely to be used with a transfemoral approach.

Other secondary outcomes included life-threatening or disabling bleeding events, which after 2 years had occurred in 17% of the TAVR patients and 47% of those who underwent surgery; atrial fibrillation, which occurred in 11% of the TAVR patients and 27% of those undergoing surgery; and acute kidney injury which occurred in 4% of TAVR patients and 6% of the surgery patients. With 2-year follow-up, the rate of disabling strokes was 6% in both arms of the study.

PARTNER 2A was sponsored by Edwards Lifesciences, the company that markets the Sapien TAVR systems. Dr. Smith has received travel grants from Edwards. Dr. Holmes had no disclosures, Dr. Pinto has been a consultant to Medtronic.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Transcatheter aortic-valve replacement performed as well as surgical-valve replacement in patients with an intermediate mortality risk in a prospective, randomized trial with more than 2,000 patients followed for 2 years, the first randomized trial to compare the efficacy and safety of transcatheter aortic-valve replacement against surgical replacement in patients who did not have a high mortality risk.

The results “support TAVR [transcatheter aortic-valve replacement] as an alternative to surgery in intermediate-risk patients similar to those included in this trial,” said Dr. Craig R. Smith at the annual meeting of the American College of Cardiology. The findings from the Placement of Aortic Transcatheter Valves (PARTNER) 2 cohort A trial “will increase use of TAVR,” predicted Dr. Smith, professor and chairman of surgery at New York–Presbyterian Hospital/Columbia University in New York.

Mitchel L. Zoler/Frontline Medical News

Until now, TAVR had been compared with surgical aortic-valve replacement in two prospective, randomized trials that both enrolled either high-risk or inoperable patients with severe aortic stenosis, the PARTNER 1 trial that tested the original Sapien TAVR system, and the U.S. CoreValve High-Risk Study that tested the original CoreValve system (often now called CoreValve classic). The average Society of Thoracic Surgeons (STS) operative risk score of high-risk patients enrolled in PARTNER 1 was 11.8%, and the average risk score in patients enrolled in the CoreValve study was 7.3%. In contrast, the design of PARTNER 2A specified that enrolled patients have a STS risk score of 4%-8%, a criterion actually met by 81% of the enrolled patients, and the average STS risk score of all patients enrolled in PARTNER 2A was 5.8%.

Although U.S. labeling for both the Sapien valve and its later iterations, Sapien XT and S3, and for CoreValve and its later iteration, Evolut R, specify that treated patients should have a STS risk score of at least 8%, the labeling also gives the heart teams that perform TAVR the latitude to treat patients with risk scores below 8% when the heart teams identify other patient factors that confer high risk such as frailty or comorbidities. U.S. and European TAVR registries have documented that many patients with STS risk scores below 8% have undergone TAVR since these systems received regulatory approval. The new results from PARTNER 2A may change that by leading to revised labeling that cuts the STS risk-score threshold.

“These findings might lead to a labeling change that would avoid a lot of the patient-evaluation gymnastics that have been used to justify” TAVR treatment, noted Dr. Smith. New labeling like this “would sanction what is already going on” in terms of which patients undergo TAVR.

Others who heard these results at the meeting agreed they were an important milestone in TAVR development and its expanding use.

Mitchel L. Zoler/Frontline Medical News

The new results “make a huge difference,” commented Dr. David R. Holmes Jr., an interventional cardiologist and professor at the Mayo Clinic in Rochester, Minn. “We base many of our guidelines on the results from randomized, controlled trials. It’s true that there are reports of lower-risk patients undergoing TAVR, but we now have results from a well-designed trial with well-controlled and adjudicated endpoints that documents the safety and efficacy of TAVR in intermediate-risk patients,” Dr. Holmes said in an interview.

“The results will have a very important influence on the choice between TAVR and surgery,” commented Dr. Duane S. Pinto, an interventional cardiologist at Beth Israel Deaconess Medical Center in Boston. “It validates the strategy” of using TAVR in patients with a risk score of 4%-8%. “TAVR has already been used in these patients, but these results validate this, especially when used in a transfemoral approach,” Dr. Pinto said in an interview.

One aspect of PARTNER 2A that received a lot of discussion at the meeting was whether enrolled patients could appropriately be characterized as “intermediate” in their risk level. Although their average STS risk score of 5.8% fell squarely within the target range specified for the study, they averaged 82 years old, and other clinical features at baseline suggested a higher risk population. The published report of the PARTNER 2A results that appeared online concurrent with Dr. Smith’s report at the meeting (New Engl J Med 2016;doi:10.1056/NEJMoa1514616) acknowledged that STS risk scores of 4%-8% place the enrolled patients into the upper 20% for risk of all U.S. patients who undergo surgical aortic-valve replacement

“I would characterize the enrolled patients as ‘less high risk’ rather than intermediate risk,” said Dr. Pinto.

But as Dr. Smith explained “even if the enrolled patients are not ‘intermediate’ risk they are at a different risk level” than were the patients enrolled in the prior TAVR randomized trials.

In the PARTNER 1 high-risk trial, the overall 1-year rate of all-cause mortality was 24% and 27% in the TAVR and surgical arms of the study, respectively. In the CoreValve trial these rates were 14% with TAVR and 19% with surgery. In PARTNER 2A 1-year all-cause mortality was 12% with TAVR and 13% with surgery.

Two other notable findings of PARTNER 2A were the superior outcomes of patients who underwent TAVR using a transfemoral approach, and the improved outcomes that all TAVR patients had compared with surgical valve replacement for several secondary outcomes.

The rate of the study’s primary outcome, all-cause death or disabling stroke after 2 years, was cut by a relative 21% in the 77% of TAVR patients who underwent a transfemoral procedure, compared with the surgery patients, a difference that was of borderline statistical significance. In contrast, the entire group of TAVR patients, including those treated via nontransfemoral routes, had an 11% relative reduction of the primary endpoint, compared with surgery, a difference that was not statistically significant but did easily meet the study’s prespecified definition of noninferority. Dr. Smith and others were especially encouraged by these findings as PARTNER 2A used the older Sapien XT TAVR system that is not often used today in U.S. practice. When U.S. patients undergo TAVR with a balloon-expandable valve they most often receive treatment with the S3 system, much smaller than XT and hence much more likely to be used with a transfemoral approach.

Other secondary outcomes included life-threatening or disabling bleeding events, which after 2 years had occurred in 17% of the TAVR patients and 47% of those who underwent surgery; atrial fibrillation, which occurred in 11% of the TAVR patients and 27% of those undergoing surgery; and acute kidney injury which occurred in 4% of TAVR patients and 6% of the surgery patients. With 2-year follow-up, the rate of disabling strokes was 6% in both arms of the study.

PARTNER 2A was sponsored by Edwards Lifesciences, the company that markets the Sapien TAVR systems. Dr. Smith has received travel grants from Edwards. Dr. Holmes had no disclosures, Dr. Pinto has been a consultant to Medtronic.

[email protected]

On Twitter @mitchelzoler

CHICAGO – Transcatheter aortic-valve replacement performed as well as surgical-valve replacement in patients with an intermediate mortality risk in a prospective, randomized trial with more than 2,000 patients followed for 2 years, the first randomized trial to compare the efficacy and safety of transcatheter aortic-valve replacement against surgical replacement in patients who did not have a high mortality risk.

The results “support TAVR [transcatheter aortic-valve replacement] as an alternative to surgery in intermediate-risk patients similar to those included in this trial,” said Dr. Craig R. Smith at the annual meeting of the American College of Cardiology. The findings from the Placement of Aortic Transcatheter Valves (PARTNER) 2 cohort A trial “will increase use of TAVR,” predicted Dr. Smith, professor and chairman of surgery at New York–Presbyterian Hospital/Columbia University in New York.

Mitchel L. Zoler/Frontline Medical News

Until now, TAVR had been compared with surgical aortic-valve replacement in two prospective, randomized trials that both enrolled either high-risk or inoperable patients with severe aortic stenosis, the PARTNER 1 trial that tested the original Sapien TAVR system, and the U.S. CoreValve High-Risk Study that tested the original CoreValve system (often now called CoreValve classic). The average Society of Thoracic Surgeons (STS) operative risk score of high-risk patients enrolled in PARTNER 1 was 11.8%, and the average risk score in patients enrolled in the CoreValve study was 7.3%. In contrast, the design of PARTNER 2A specified that enrolled patients have a STS risk score of 4%-8%, a criterion actually met by 81% of the enrolled patients, and the average STS risk score of all patients enrolled in PARTNER 2A was 5.8%.

Although U.S. labeling for both the Sapien valve and its later iterations, Sapien XT and S3, and for CoreValve and its later iteration, Evolut R, specify that treated patients should have a STS risk score of at least 8%, the labeling also gives the heart teams that perform TAVR the latitude to treat patients with risk scores below 8% when the heart teams identify other patient factors that confer high risk such as frailty or comorbidities. U.S. and European TAVR registries have documented that many patients with STS risk scores below 8% have undergone TAVR since these systems received regulatory approval. The new results from PARTNER 2A may change that by leading to revised labeling that cuts the STS risk-score threshold.

“These findings might lead to a labeling change that would avoid a lot of the patient-evaluation gymnastics that have been used to justify” TAVR treatment, noted Dr. Smith. New labeling like this “would sanction what is already going on” in terms of which patients undergo TAVR.

Others who heard these results at the meeting agreed they were an important milestone in TAVR development and its expanding use.

Mitchel L. Zoler/Frontline Medical News

The new results “make a huge difference,” commented Dr. David R. Holmes Jr., an interventional cardiologist and professor at the Mayo Clinic in Rochester, Minn. “We base many of our guidelines on the results from randomized, controlled trials. It’s true that there are reports of lower-risk patients undergoing TAVR, but we now have results from a well-designed trial with well-controlled and adjudicated endpoints that documents the safety and efficacy of TAVR in intermediate-risk patients,” Dr. Holmes said in an interview.

“The results will have a very important influence on the choice between TAVR and surgery,” commented Dr. Duane S. Pinto, an interventional cardiologist at Beth Israel Deaconess Medical Center in Boston. “It validates the strategy” of using TAVR in patients with a risk score of 4%-8%. “TAVR has already been used in these patients, but these results validate this, especially when used in a transfemoral approach,” Dr. Pinto said in an interview.

One aspect of PARTNER 2A that received a lot of discussion at the meeting was whether enrolled patients could appropriately be characterized as “intermediate” in their risk level. Although their average STS risk score of 5.8% fell squarely within the target range specified for the study, they averaged 82 years old, and other clinical features at baseline suggested a higher risk population. The published report of the PARTNER 2A results that appeared online concurrent with Dr. Smith’s report at the meeting (New Engl J Med 2016;doi:10.1056/NEJMoa1514616) acknowledged that STS risk scores of 4%-8% place the enrolled patients into the upper 20% for risk of all U.S. patients who undergo surgical aortic-valve replacement

“I would characterize the enrolled patients as ‘less high risk’ rather than intermediate risk,” said Dr. Pinto.

But as Dr. Smith explained “even if the enrolled patients are not ‘intermediate’ risk they are at a different risk level” than were the patients enrolled in the prior TAVR randomized trials.

In the PARTNER 1 high-risk trial, the overall 1-year rate of all-cause mortality was 24% and 27% in the TAVR and surgical arms of the study, respectively. In the CoreValve trial these rates were 14% with TAVR and 19% with surgery. In PARTNER 2A 1-year all-cause mortality was 12% with TAVR and 13% with surgery.

Two other notable findings of PARTNER 2A were the superior outcomes of patients who underwent TAVR using a transfemoral approach, and the improved outcomes that all TAVR patients had compared with surgical valve replacement for several secondary outcomes.

The rate of the study’s primary outcome, all-cause death or disabling stroke after 2 years, was cut by a relative 21% in the 77% of TAVR patients who underwent a transfemoral procedure, compared with the surgery patients, a difference that was of borderline statistical significance. In contrast, the entire group of TAVR patients, including those treated via nontransfemoral routes, had an 11% relative reduction of the primary endpoint, compared with surgery, a difference that was not statistically significant but did easily meet the study’s prespecified definition of noninferority. Dr. Smith and others were especially encouraged by these findings as PARTNER 2A used the older Sapien XT TAVR system that is not often used today in U.S. practice. When U.S. patients undergo TAVR with a balloon-expandable valve they most often receive treatment with the S3 system, much smaller than XT and hence much more likely to be used with a transfemoral approach.

Other secondary outcomes included life-threatening or disabling bleeding events, which after 2 years had occurred in 17% of the TAVR patients and 47% of those who underwent surgery; atrial fibrillation, which occurred in 11% of the TAVR patients and 27% of those undergoing surgery; and acute kidney injury which occurred in 4% of TAVR patients and 6% of the surgery patients. With 2-year follow-up, the rate of disabling strokes was 6% in both arms of the study.

PARTNER 2A was sponsored by Edwards Lifesciences, the company that markets the Sapien TAVR systems. Dr. Smith has received travel grants from Edwards. Dr. Holmes had no disclosures, Dr. Pinto has been a consultant to Medtronic.

[email protected]

On Twitter @mitchelzoler

CHICAGO – The “groundbreaking” results from the PARTNER 2 trial of transcatheter aortic valve replacement in patients at intermediate risk for death or complications from surgical replacement of a stenotic aortic valve provide substantially increased certainty that the transcatheter approach is at least as good as surgical valve replacement, commented Dr. Roxana Mehran in a video interview at the annual meeting of the American College of Cardiology.

In addition to providing important new data on the equivalence of surgical and transcatheter aortic valve replacement (TAVR) in a new target population--intermediate-risk patients, the findings from the randomized, multicenter PARTNER trial, which enrolled 2,032 patients, may also lead to expansion of the Food and Drug Administration labeling of the balloon-expandable TAVR device used in the study, the Sapien XT, to intermediate-risk patients. This expanded indication may also apply to the newer, smaller and more advanced iteration of this device, the Sapien 3, which has largely replaced the XT in U.S. practice, Dr. Mehran suggested.

Although the results came from the XT TAVR system, “these results have big relevance” to current U.S. practice said Dr. Mehran, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York.

The primary outcome of the Placement of Aortic Transcatheter Valves (PARTNER) 2 trial showed that all-cause mortality or disabling stroke after 2 years follow-up occurred in 21.2% (695) of the surgery patients and 19.3% (775) of the TAVR patients, meeting the prespecified noninferiority endpoint, with a P value of .001. Full results from the study were published online concurrent with their presentation at the meeting (New Engl J Med 2016;doi:10.1056/NEJMoa1514616).

Dr. Mehran has received consultant fees and honoraria from Abbott Vascular, AstraZeneca, and Bayer.

[email protected]

On Twitter @mitchelzoler

CHICAGO – The “groundbreaking” results from the PARTNER 2 trial of transcatheter aortic valve replacement in patients at intermediate risk for death or complications from surgical replacement of a stenotic aortic valve provide substantially increased certainty that the transcatheter approach is at least as good as surgical valve replacement, commented Dr. Roxana Mehran in a video interview at the annual meeting of the American College of Cardiology.

In addition to providing important new data on the equivalence of surgical and transcatheter aortic valve replacement (TAVR) in a new target population--intermediate-risk patients, the findings from the randomized, multicenter PARTNER trial, which enrolled 2,032 patients, may also lead to expansion of the Food and Drug Administration labeling of the balloon-expandable TAVR device used in the study, the Sapien XT, to intermediate-risk patients. This expanded indication may also apply to the newer, smaller and more advanced iteration of this device, the Sapien 3, which has largely replaced the XT in U.S. practice, Dr. Mehran suggested.

Although the results came from the XT TAVR system, “these results have big relevance” to current U.S. practice said Dr. Mehran, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York.

The primary outcome of the Placement of Aortic Transcatheter Valves (PARTNER) 2 trial showed that all-cause mortality or disabling stroke after 2 years follow-up occurred in 21.2% (695) of the surgery patients and 19.3% (775) of the TAVR patients, meeting the prespecified noninferiority endpoint, with a P value of .001. Full results from the study were published online concurrent with their presentation at the meeting (New Engl J Med 2016;doi:10.1056/NEJMoa1514616).

Dr. Mehran has received consultant fees and honoraria from Abbott Vascular, AstraZeneca, and Bayer.

[email protected]

On Twitter @mitchelzoler

CHICAGO – The “groundbreaking” results from the PARTNER 2 trial of transcatheter aortic valve replacement in patients at intermediate risk for death or complications from surgical replacement of a stenotic aortic valve provide substantially increased certainty that the transcatheter approach is at least as good as surgical valve replacement, commented Dr. Roxana Mehran in a video interview at the annual meeting of the American College of Cardiology.

In addition to providing important new data on the equivalence of surgical and transcatheter aortic valve replacement (TAVR) in a new target population--intermediate-risk patients, the findings from the randomized, multicenter PARTNER trial, which enrolled 2,032 patients, may also lead to expansion of the Food and Drug Administration labeling of the balloon-expandable TAVR device used in the study, the Sapien XT, to intermediate-risk patients. This expanded indication may also apply to the newer, smaller and more advanced iteration of this device, the Sapien 3, which has largely replaced the XT in U.S. practice, Dr. Mehran suggested.

Although the results came from the XT TAVR system, “these results have big relevance” to current U.S. practice said Dr. Mehran, professor and director of interventional cardiovascular research at Mount Sinai Hospital in New York.

The primary outcome of the Placement of Aortic Transcatheter Valves (PARTNER) 2 trial showed that all-cause mortality or disabling stroke after 2 years follow-up occurred in 21.2% (695) of the surgery patients and 19.3% (775) of the TAVR patients, meeting the prespecified noninferiority endpoint, with a P value of .001. Full results from the study were published online concurrent with their presentation at the meeting (New Engl J Med 2016;doi:10.1056/NEJMoa1514616).

Dr. Mehran has received consultant fees and honoraria from Abbott Vascular, AstraZeneca, and Bayer.

[email protected]

On Twitter @mitchelzoler

SAN DIEGO – Young women and girls with gynecologic malignancies more often present with pain and masses greater than 5 cm in size, compared with their counterparts who have benign disease. Additionally, gynecologic oncologists are inconsistently involved in the management of this patient population.

Those are key findings from a study that set out to compare the clinical presentation and surgical outcomes of women and girls younger than 21 years old who had a pelvic mass.

Doug Brunk/Frontline Medical News

“If something is suspicious, it’s not a bad idea to get your colleagues who specialize in gynecologic cancer involved sooner rather than later,” Dr. Teuta Shemshedini, the lead study author, said in an interview at the annual meeting of the Society of Gynecologic Oncology. Clinicians who specialize in gynecologic oncology “were often talked to either intraoperatively or postoperatively, so we were kind of working backwards when we could have sat with patients and the families before the surgery and worked forward.”

Dr. Shemshedini, who is a fourth-year resident in the department of obstetrics and gynecology at Westchester Medical Center, Valhalla, N.Y., and her associates reviewed medical records of all women and girls younger than 21 years old who underwent primary surgery for a pelvic mass at the medical center from 2010 to 2015.

Of the 138 patients evaluated, 77 were included in the final analysis: 57 who had benign disease and 20 who had malignant disease. The mean age of the patients was 13.5 years and the mean adnexal mass size was 9.8 cm in the benign group, compared with 15.5 cm in the malignant group (P = .005). The most common presentation was pain, which occurred in 75% of all cases.

Gynecologic oncologists were consulted on 10 cases (13%), with six of the 10 consults (60%) requested by pediatric gynecologists. However, only two of eight (25%) were preoperative consults in malignant cases.

The researchers also observed that tumors greater than 10 cm in size were found in 75% of malignancies, and all tumors 5 cm or smaller were benign (14%). Clinicians did not use tumor markers in 29% of the entire study group, even though tumor markers were elevated in 70% of the malignant cases.

Laparoscopic surgery was performed in 35 patients (45%), with a majority of cases being benign. The most common benign tumors were mature teratomas (70%). The most common malignant tumors were borderline ovarian tumors (35%), followed by immature teratomas (20%), and mixed germ cell tumors (20%). More than half of malignant tumors (55%) were stage I.

“The most surprising part was that we weren’t getting gynecologic oncology involved soon enough,” Dr. Shemshedini said. “I think most people are very surprised when a mass comes back as cancer in kids, especially ovarian cancer. In adults we see epithelial cancer most commonly, while in kids it’s more of the germ cell tumors. Those are rare.”

Dr. Shemshedini reported having no financial disclosures.

[email protected]

SAN DIEGO – Young women and girls with gynecologic malignancies more often present with pain and masses greater than 5 cm in size, compared with their counterparts who have benign disease. Additionally, gynecologic oncologists are inconsistently involved in the management of this patient population.

Those are key findings from a study that set out to compare the clinical presentation and surgical outcomes of women and girls younger than 21 years old who had a pelvic mass.

Doug Brunk/Frontline Medical News

“If something is suspicious, it’s not a bad idea to get your colleagues who specialize in gynecologic cancer involved sooner rather than later,” Dr. Teuta Shemshedini, the lead study author, said in an interview at the annual meeting of the Society of Gynecologic Oncology. Clinicians who specialize in gynecologic oncology “were often talked to either intraoperatively or postoperatively, so we were kind of working backwards when we could have sat with patients and the families before the surgery and worked forward.”

Dr. Shemshedini, who is a fourth-year resident in the department of obstetrics and gynecology at Westchester Medical Center, Valhalla, N.Y., and her associates reviewed medical records of all women and girls younger than 21 years old who underwent primary surgery for a pelvic mass at the medical center from 2010 to 2015.

Of the 138 patients evaluated, 77 were included in the final analysis: 57 who had benign disease and 20 who had malignant disease. The mean age of the patients was 13.5 years and the mean adnexal mass size was 9.8 cm in the benign group, compared with 15.5 cm in the malignant group (P = .005). The most common presentation was pain, which occurred in 75% of all cases.

Gynecologic oncologists were consulted on 10 cases (13%), with six of the 10 consults (60%) requested by pediatric gynecologists. However, only two of eight (25%) were preoperative consults in malignant cases.

The researchers also observed that tumors greater than 10 cm in size were found in 75% of malignancies, and all tumors 5 cm or smaller were benign (14%). Clinicians did not use tumor markers in 29% of the entire study group, even though tumor markers were elevated in 70% of the malignant cases.

Laparoscopic surgery was performed in 35 patients (45%), with a majority of cases being benign. The most common benign tumors were mature teratomas (70%). The most common malignant tumors were borderline ovarian tumors (35%), followed by immature teratomas (20%), and mixed germ cell tumors (20%). More than half of malignant tumors (55%) were stage I.

“The most surprising part was that we weren’t getting gynecologic oncology involved soon enough,” Dr. Shemshedini said. “I think most people are very surprised when a mass comes back as cancer in kids, especially ovarian cancer. In adults we see epithelial cancer most commonly, while in kids it’s more of the germ cell tumors. Those are rare.”

Dr. Shemshedini reported having no financial disclosures.

[email protected]

SAN DIEGO – Young women and girls with gynecologic malignancies more often present with pain and masses greater than 5 cm in size, compared with their counterparts who have benign disease. Additionally, gynecologic oncologists are inconsistently involved in the management of this patient population.

Those are key findings from a study that set out to compare the clinical presentation and surgical outcomes of women and girls younger than 21 years old who had a pelvic mass.

Doug Brunk/Frontline Medical News

“If something is suspicious, it’s not a bad idea to get your colleagues who specialize in gynecologic cancer involved sooner rather than later,” Dr. Teuta Shemshedini, the lead study author, said in an interview at the annual meeting of the Society of Gynecologic Oncology. Clinicians who specialize in gynecologic oncology “were often talked to either intraoperatively or postoperatively, so we were kind of working backwards when we could have sat with patients and the families before the surgery and worked forward.”

Dr. Shemshedini, who is a fourth-year resident in the department of obstetrics and gynecology at Westchester Medical Center, Valhalla, N.Y., and her associates reviewed medical records of all women and girls younger than 21 years old who underwent primary surgery for a pelvic mass at the medical center from 2010 to 2015.

Of the 138 patients evaluated, 77 were included in the final analysis: 57 who had benign disease and 20 who had malignant disease. The mean age of the patients was 13.5 years and the mean adnexal mass size was 9.8 cm in the benign group, compared with 15.5 cm in the malignant group (P = .005). The most common presentation was pain, which occurred in 75% of all cases.

Gynecologic oncologists were consulted on 10 cases (13%), with six of the 10 consults (60%) requested by pediatric gynecologists. However, only two of eight (25%) were preoperative consults in malignant cases.

The researchers also observed that tumors greater than 10 cm in size were found in 75% of malignancies, and all tumors 5 cm or smaller were benign (14%). Clinicians did not use tumor markers in 29% of the entire study group, even though tumor markers were elevated in 70% of the malignant cases.

Laparoscopic surgery was performed in 35 patients (45%), with a majority of cases being benign. The most common benign tumors were mature teratomas (70%). The most common malignant tumors were borderline ovarian tumors (35%), followed by immature teratomas (20%), and mixed germ cell tumors (20%). More than half of malignant tumors (55%) were stage I.

“The most surprising part was that we weren’t getting gynecologic oncology involved soon enough,” Dr. Shemshedini said. “I think most people are very surprised when a mass comes back as cancer in kids, especially ovarian cancer. In adults we see epithelial cancer most commonly, while in kids it’s more of the germ cell tumors. Those are rare.”

Dr. Shemshedini reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with stage IB cervical cancer, deep stromal invasion and large tumor size are the two biggest factors associated with increased risk of recurrence. Higher risk-weighted surgical-pathological scores were also associated with decreased benefit of concurrent chemoradiotherapy after surgery.

Those are key findings from a Gynecologic Oncology Group (GOG) ancillary data analysis reported by Dr. Koji Matsuo at the annual meeting of the Society of Gynecologic Oncology.

“Surgery remains the mainstay of treatment for early-stage cervical cancer,” Dr. Matsuo, assistant director of the gynecologic oncology clinic at the University of Southern California, Los Angeles, said in an interview prior to the meeting. “Surgical specimen is useful to identify certain types of factors that can benefit from postoperative adjuvant therapy with concurrent chemoradiotherapy. Traditionally, tumor factors are grouped into high, intermediate, and low risk. Tumors often exhibit multiple risk factors and magnitude of significance for survival may differ across the tumor factors. In this study, we examined the effects of combination of multiple risk factors by weighing magnitude of significance for recurrence.”

The researchers analyzed data from 1,538 stage IB cervical cancer patients who underwent primary radical hysterectomy and pelvic lymphadenectomy. They used a multivariate model to examine hazard ratios associated with disease-free survival (DFS) for seven surgical-pathological risk factors: nodal metastasis, parametrial involvement, surgical margin, lymphovascular space invasion (LVSI), deep stromal invasion, large tumor, and histology. Next, they used a risk-weighted surgical-pathological score (a sum of HR scores) to determine DFS and compared it to a traditional risk factor model.

The median age of patients in the study was 41 years, the median follow-up time was 84 months, the recurrence rate was 26%, and the mortality rate was 27%.

Dr. Matsuo reported that based on the risk-weighted surgical-pathological score model, factors associated with the highest risk of recurrence were deep stromal invasion (HR 1.85), large tumor size (HR 1.81), parametrial involvement (HR 1.73), LVSI (HR 1.37), histology (HR 1.30), and nodal metastasis (HR 1.29; P less than .05 for all).

The 5-year DFS rates based on risk-weighted scores were 85.6% for score 0, 89.1% for the first quartile, 79.6% for the second quartile, 69.3% for the third quartile, and 50.2% for fourth quartile (P less than .001). A fourth-quartile score in the risk-weighted model had a significantly lower 5-year DFS rate, compared with the traditional risk factor model high-risk group (50.2% vs. 60.9%; P less than .001).

Dr. Matsuo and his associates also found that higher risk-weighted surgical-pathological scores were associated with decreased benefit of concurrent chemoradiotherapy after surgery.

“That has been the mainstay of postoperative treatment in adjuvant therapy for a group of cervical cancer with high risk of recurrence,” he said. “It is beneficial to be aware that each tumor factor has a different risk for recurrence and tumors may exhibit multiple risk factors that can be associated with decreased benefit of concurrent chemoradiotherapy after surgical treatment.”

He acknowledged certain limitations of the study, including the lack of information regarding the site of recurrence.

Dr. Matsuo reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with stage IB cervical cancer, deep stromal invasion and large tumor size are the two biggest factors associated with increased risk of recurrence. Higher risk-weighted surgical-pathological scores were also associated with decreased benefit of concurrent chemoradiotherapy after surgery.

Those are key findings from a Gynecologic Oncology Group (GOG) ancillary data analysis reported by Dr. Koji Matsuo at the annual meeting of the Society of Gynecologic Oncology.

“Surgery remains the mainstay of treatment for early-stage cervical cancer,” Dr. Matsuo, assistant director of the gynecologic oncology clinic at the University of Southern California, Los Angeles, said in an interview prior to the meeting. “Surgical specimen is useful to identify certain types of factors that can benefit from postoperative adjuvant therapy with concurrent chemoradiotherapy. Traditionally, tumor factors are grouped into high, intermediate, and low risk. Tumors often exhibit multiple risk factors and magnitude of significance for survival may differ across the tumor factors. In this study, we examined the effects of combination of multiple risk factors by weighing magnitude of significance for recurrence.”

The researchers analyzed data from 1,538 stage IB cervical cancer patients who underwent primary radical hysterectomy and pelvic lymphadenectomy. They used a multivariate model to examine hazard ratios associated with disease-free survival (DFS) for seven surgical-pathological risk factors: nodal metastasis, parametrial involvement, surgical margin, lymphovascular space invasion (LVSI), deep stromal invasion, large tumor, and histology. Next, they used a risk-weighted surgical-pathological score (a sum of HR scores) to determine DFS and compared it to a traditional risk factor model.

The median age of patients in the study was 41 years, the median follow-up time was 84 months, the recurrence rate was 26%, and the mortality rate was 27%.

Dr. Matsuo reported that based on the risk-weighted surgical-pathological score model, factors associated with the highest risk of recurrence were deep stromal invasion (HR 1.85), large tumor size (HR 1.81), parametrial involvement (HR 1.73), LVSI (HR 1.37), histology (HR 1.30), and nodal metastasis (HR 1.29; P less than .05 for all).

The 5-year DFS rates based on risk-weighted scores were 85.6% for score 0, 89.1% for the first quartile, 79.6% for the second quartile, 69.3% for the third quartile, and 50.2% for fourth quartile (P less than .001). A fourth-quartile score in the risk-weighted model had a significantly lower 5-year DFS rate, compared with the traditional risk factor model high-risk group (50.2% vs. 60.9%; P less than .001).

Dr. Matsuo and his associates also found that higher risk-weighted surgical-pathological scores were associated with decreased benefit of concurrent chemoradiotherapy after surgery.

“That has been the mainstay of postoperative treatment in adjuvant therapy for a group of cervical cancer with high risk of recurrence,” he said. “It is beneficial to be aware that each tumor factor has a different risk for recurrence and tumors may exhibit multiple risk factors that can be associated with decreased benefit of concurrent chemoradiotherapy after surgical treatment.”

He acknowledged certain limitations of the study, including the lack of information regarding the site of recurrence.

Dr. Matsuo reported having no financial disclosures.

[email protected]

SAN DIEGO – Among patients with stage IB cervical cancer, deep stromal invasion and large tumor size are the two biggest factors associated with increased risk of recurrence. Higher risk-weighted surgical-pathological scores were also associated with decreased benefit of concurrent chemoradiotherapy after surgery.

Those are key findings from a Gynecologic Oncology Group (GOG) ancillary data analysis reported by Dr. Koji Matsuo at the annual meeting of the Society of Gynecologic Oncology.

“Surgery remains the mainstay of treatment for early-stage cervical cancer,” Dr. Matsuo, assistant director of the gynecologic oncology clinic at the University of Southern California, Los Angeles, said in an interview prior to the meeting. “Surgical specimen is useful to identify certain types of factors that can benefit from postoperative adjuvant therapy with concurrent chemoradiotherapy. Traditionally, tumor factors are grouped into high, intermediate, and low risk. Tumors often exhibit multiple risk factors and magnitude of significance for survival may differ across the tumor factors. In this study, we examined the effects of combination of multiple risk factors by weighing magnitude of significance for recurrence.”

The researchers analyzed data from 1,538 stage IB cervical cancer patients who underwent primary radical hysterectomy and pelvic lymphadenectomy. They used a multivariate model to examine hazard ratios associated with disease-free survival (DFS) for seven surgical-pathological risk factors: nodal metastasis, parametrial involvement, surgical margin, lymphovascular space invasion (LVSI), deep stromal invasion, large tumor, and histology. Next, they used a risk-weighted surgical-pathological score (a sum of HR scores) to determine DFS and compared it to a traditional risk factor model.

The median age of patients in the study was 41 years, the median follow-up time was 84 months, the recurrence rate was 26%, and the mortality rate was 27%.

Dr. Matsuo reported that based on the risk-weighted surgical-pathological score model, factors associated with the highest risk of recurrence were deep stromal invasion (HR 1.85), large tumor size (HR 1.81), parametrial involvement (HR 1.73), LVSI (HR 1.37), histology (HR 1.30), and nodal metastasis (HR 1.29; P less than .05 for all).

The 5-year DFS rates based on risk-weighted scores were 85.6% for score 0, 89.1% for the first quartile, 79.6% for the second quartile, 69.3% for the third quartile, and 50.2% for fourth quartile (P less than .001). A fourth-quartile score in the risk-weighted model had a significantly lower 5-year DFS rate, compared with the traditional risk factor model high-risk group (50.2% vs. 60.9%; P less than .001).

Dr. Matsuo and his associates also found that higher risk-weighted surgical-pathological scores were associated with decreased benefit of concurrent chemoradiotherapy after surgery.

“That has been the mainstay of postoperative treatment in adjuvant therapy for a group of cervical cancer with high risk of recurrence,” he said. “It is beneficial to be aware that each tumor factor has a different risk for recurrence and tumors may exhibit multiple risk factors that can be associated with decreased benefit of concurrent chemoradiotherapy after surgical treatment.”

He acknowledged certain limitations of the study, including the lack of information regarding the site of recurrence.

Dr. Matsuo reported having no financial disclosures.

[email protected]