Thoracic Surgery News (Archived)

In 2013, the AATS Graham Foundation established the “Honoring Our Mentors” Fellowship Program to honor eminent cardiothoracic and thoracic surgeons. The Foundation recently announced the second fellowship in the series, which will honor Marc de Leval.

Honoring Our Mentors recognizes physicians who have demonstrated longstanding leadership and dedication throughout their careers in both their clinical practices and their commitment to training the future generation. The F. Griffith Pearson Fellowship was the first in the program.

Marc R. de Leval Fellowship

About: Currently, there is only limited funding available for North American surgeons to receive specified training at international congenital heart surgery centers. The Fellowship will give young North American trainees and early career congenital heart surgeons the opportunity to spend four (4) to six (6) weeks studying congenital CT surgery techniques at UK/European institutions. Awardees will receive a $5,000 stipend to help cover travel and living costs while abroad.

The Mentor: For over 40 years, Marc de Leval has practiced pediatric cardiothoracic surgery in London. Throughout that time, he has had a close relationship with the American Association for Thoracic Surgery (AATS), starting with his two-year time as a Graham Traveling Fellow (1973-1974). Retired from Britain’s National Health Service (NHS), today de Leval is a Consultant Cardiothoracic Surgeon at the Harley Street Clinic and Professor of Cardiothoracic Surgery at the University of London.

F. Griffith Pearson Fellowship

About: Created in 2013, the Pearson Fellowship supports surgeons who have finished their residencies to advance their clinical thoracic techniques at a North American host institute. Each fellow receives $3,500 to defray living expenses during four (4) to six (6) weeks of training. The first two awardees were named in 2014.

The Mentor: F. Griffith Pearson practiced thoracic surgery at Toronto General Hospital from 1950-1999. Considered one of the fathers of modern tracheal surgery, he was AATS’s 79th President. Under his leadership, University of Toronto established a separate division of thoracic surgery in 1968. Pearson introduced mediastinoscopy to North America in the early 1960s and demonstrated the importance of mediastinal staging for lung cancer, which led to a more rational approach to the diagnosis, staging and treatment of the disease. After retirement, Pearson continued to pioneer as a “surgeon in residence” in Boston and Pittsburgh. Many say that his greatest contribution to thoracic surgery over 50+ years has been his influence on generations of thoracic surgeons.

In 2013, the AATS Graham Foundation established the “Honoring Our Mentors” Fellowship Program to honor eminent cardiothoracic and thoracic surgeons. The Foundation recently announced the second fellowship in the series, which will honor Marc de Leval.

Honoring Our Mentors recognizes physicians who have demonstrated longstanding leadership and dedication throughout their careers in both their clinical practices and their commitment to training the future generation. The F. Griffith Pearson Fellowship was the first in the program.

Marc R. de Leval Fellowship

About: Currently, there is only limited funding available for North American surgeons to receive specified training at international congenital heart surgery centers. The Fellowship will give young North American trainees and early career congenital heart surgeons the opportunity to spend four (4) to six (6) weeks studying congenital CT surgery techniques at UK/European institutions. Awardees will receive a $5,000 stipend to help cover travel and living costs while abroad.

The Mentor: For over 40 years, Marc de Leval has practiced pediatric cardiothoracic surgery in London. Throughout that time, he has had a close relationship with the American Association for Thoracic Surgery (AATS), starting with his two-year time as a Graham Traveling Fellow (1973-1974). Retired from Britain’s National Health Service (NHS), today de Leval is a Consultant Cardiothoracic Surgeon at the Harley Street Clinic and Professor of Cardiothoracic Surgery at the University of London.

F. Griffith Pearson Fellowship

About: Created in 2013, the Pearson Fellowship supports surgeons who have finished their residencies to advance their clinical thoracic techniques at a North American host institute. Each fellow receives $3,500 to defray living expenses during four (4) to six (6) weeks of training. The first two awardees were named in 2014.

The Mentor: F. Griffith Pearson practiced thoracic surgery at Toronto General Hospital from 1950-1999. Considered one of the fathers of modern tracheal surgery, he was AATS’s 79th President. Under his leadership, University of Toronto established a separate division of thoracic surgery in 1968. Pearson introduced mediastinoscopy to North America in the early 1960s and demonstrated the importance of mediastinal staging for lung cancer, which led to a more rational approach to the diagnosis, staging and treatment of the disease. After retirement, Pearson continued to pioneer as a “surgeon in residence” in Boston and Pittsburgh. Many say that his greatest contribution to thoracic surgery over 50+ years has been his influence on generations of thoracic surgeons.

In 2013, the AATS Graham Foundation established the “Honoring Our Mentors” Fellowship Program to honor eminent cardiothoracic and thoracic surgeons. The Foundation recently announced the second fellowship in the series, which will honor Marc de Leval.

Honoring Our Mentors recognizes physicians who have demonstrated longstanding leadership and dedication throughout their careers in both their clinical practices and their commitment to training the future generation. The F. Griffith Pearson Fellowship was the first in the program.

Marc R. de Leval Fellowship

About: Currently, there is only limited funding available for North American surgeons to receive specified training at international congenital heart surgery centers. The Fellowship will give young North American trainees and early career congenital heart surgeons the opportunity to spend four (4) to six (6) weeks studying congenital CT surgery techniques at UK/European institutions. Awardees will receive a $5,000 stipend to help cover travel and living costs while abroad.

The Mentor: For over 40 years, Marc de Leval has practiced pediatric cardiothoracic surgery in London. Throughout that time, he has had a close relationship with the American Association for Thoracic Surgery (AATS), starting with his two-year time as a Graham Traveling Fellow (1973-1974). Retired from Britain’s National Health Service (NHS), today de Leval is a Consultant Cardiothoracic Surgeon at the Harley Street Clinic and Professor of Cardiothoracic Surgery at the University of London.

F. Griffith Pearson Fellowship

About: Created in 2013, the Pearson Fellowship supports surgeons who have finished their residencies to advance their clinical thoracic techniques at a North American host institute. Each fellow receives $3,500 to defray living expenses during four (4) to six (6) weeks of training. The first two awardees were named in 2014.

The Mentor: F. Griffith Pearson practiced thoracic surgery at Toronto General Hospital from 1950-1999. Considered one of the fathers of modern tracheal surgery, he was AATS’s 79th President. Under his leadership, University of Toronto established a separate division of thoracic surgery in 1968. Pearson introduced mediastinoscopy to North America in the early 1960s and demonstrated the importance of mediastinal staging for lung cancer, which led to a more rational approach to the diagnosis, staging and treatment of the disease. After retirement, Pearson continued to pioneer as a “surgeon in residence” in Boston and Pittsburgh. Many say that his greatest contribution to thoracic surgery over 50+ years has been his influence on generations of thoracic surgeons.

SILVER SPRING, MD. – The majority of a Food and Drug Administration Advisory panel agreed that the benefits of adding necitumumab to gemcitabine and cisplatin for patients with squamous non–small cell lung cancer outweighed the risks.

Elizabeth Mechcatie/Frontline Medical News

At the meeting on July 9, the FDA’s Oncologic Drugs Advisory Committee reviewed data from a study that evaluated the anti–epidermal growth factor receptor monoclonal antibody in more than 1,000 patients with stage IV disease. The SQUIRE study was submitted to the FDA by Eli Lilly to support approval of necitumumab for the indication now under review: for use as a first-line treatment, in combination with gemcitabine and cisplatin, for patients with locally advanced or metastatic squamous non–small cell lung cancer (NSCLC). Necitumumab is a recombinant human IgG1 monoclonal antibody that is designed to block the ligand binding site of the human EGFR.

Despite a modest effect on overall survival, a very small but statistically significant effect on progression-free survival, and some safety concerns, 11 of the 12 panelists agreed that the efficacy and safety results of the trial supported a “positive benefit risk assessment” of necitumumab combined with gemcitabine and cisplatin for this group of patients, the main question they were asked by the FDA to discuss. The panel was not asked to specifically vote on whether to recommend approval.

The SQUIRE study, an international phase III study of 1,093 patients with stage IV squamous NSCLC, who had not received chemotherapy for advanced disease, evaluated the safety and efficacy of gemcitabine and cisplatin, with or without necitumumab, administered every 3 weeks, until disease progressed or toxicity became unacceptable, for a maximum of six cycles. The median age of patients was 62 years; they were mostly men and were heavy smokers; 36 patients were enrolled in the United States. (Patients were not selected based on EGFR protein expression but based on tissue pathology.)

Median overall survival (OS), the primary endpoint, was 11.5 months in the necitumumab-treated arm, vs. 9.9 months among controls, a 1.6 month difference that was statistically significant, representing a reduced risk of 16% (hazard ratio, 0.84). Progression-free survival (PFS) was a median of 5.7 months among those in the necitumumab-treated group, vs. 5.5 months, which was also statistically significant and represented a 15% reduced risk (HR, 0.85). There was no significant difference in the objective response rate (ORR), which was 31% among those in the necitumumab arm and 29% among those in the control arm. This is the first study to show an improvement in survival for a first-line treatment for squamous lung cancer, the company officials pointed out.

In the study, there were more venous thromboembolic events (VTEs; 9% vs. 5%) and more cases of sudden death and deaths “not otherwise specified” (2.2% vs. 0.5%) in the necitumumab-treated arm. There were also more cases of hypomagnesemia and skin rashes, and the FDA reviewers pointed out that several cases of sudden death occurred in patients with very low serum magnesium levels. VTEs and sudden or unexplained deaths were also higher among necitumumab-treated patients in another study that evaluated necitumumab in patients with nonsquamous NSCLC, which was stopped early because of the VTE increase; that study found no improvements in OS, PFS or ORR.

Among those agreeing that the risk-benefit assessment was positive, Dr. Michael Menefee of the Mayo Clinic, Jacksonville, Fla., said “Yes was the simple answer, but there are still caveats” regarding toxicity and the magnitude of the overall benefit.

“The survival benefit is modest but it’s real,” said Dr. Deborah Armstrong, the panel chair and professor of oncology, Johns Hopkins University, Baltimore, who also voted positively. She strongly encouraged continuing efforts to manage the toxicities of necitumumab, which she said might improve the risk-benefit balance further.

The panelist who did not agree was Dr. Tito Fojo, a senior investigator and director of the medical oncology fellowship program at the National Cancer Institute. He said that the study did not provide him with enough confidence. Noting it is a very difficult disease to treat, he said, “I just wish the data were much better.” His concerns included the possibility that those in the control arm, who received a median of five treatment cycles may have received less chemotherapy than those in the necitumumab arm, who received a median of six cycles.

Speaking on behalf of Eli Lilly at the meeting, Dr. David Gandara, director of the thoracic oncology program at the University of California Davis Comprehensive Cancer Center, said that although EGFR mutations are rare in squamous NSCLC, “the EGFR pathway itself is biologically relevant.” Necitumumab “attacks that pathway in ways independent of those associated with EGFR tyrosine-kinase inhibitors and independent of EGFR mutation status,” he added.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. The FDA decision is expected by the end of 2015, an Eli Lilly spokesperson said.

emechcatie@frontlinemedcom.com

SILVER SPRING, MD. – The majority of a Food and Drug Administration Advisory panel agreed that the benefits of adding necitumumab to gemcitabine and cisplatin for patients with squamous non–small cell lung cancer outweighed the risks.

Elizabeth Mechcatie/Frontline Medical News

At the meeting on July 9, the FDA’s Oncologic Drugs Advisory Committee reviewed data from a study that evaluated the anti–epidermal growth factor receptor monoclonal antibody in more than 1,000 patients with stage IV disease. The SQUIRE study was submitted to the FDA by Eli Lilly to support approval of necitumumab for the indication now under review: for use as a first-line treatment, in combination with gemcitabine and cisplatin, for patients with locally advanced or metastatic squamous non–small cell lung cancer (NSCLC). Necitumumab is a recombinant human IgG1 monoclonal antibody that is designed to block the ligand binding site of the human EGFR.

Despite a modest effect on overall survival, a very small but statistically significant effect on progression-free survival, and some safety concerns, 11 of the 12 panelists agreed that the efficacy and safety results of the trial supported a “positive benefit risk assessment” of necitumumab combined with gemcitabine and cisplatin for this group of patients, the main question they were asked by the FDA to discuss. The panel was not asked to specifically vote on whether to recommend approval.

The SQUIRE study, an international phase III study of 1,093 patients with stage IV squamous NSCLC, who had not received chemotherapy for advanced disease, evaluated the safety and efficacy of gemcitabine and cisplatin, with or without necitumumab, administered every 3 weeks, until disease progressed or toxicity became unacceptable, for a maximum of six cycles. The median age of patients was 62 years; they were mostly men and were heavy smokers; 36 patients were enrolled in the United States. (Patients were not selected based on EGFR protein expression but based on tissue pathology.)

Median overall survival (OS), the primary endpoint, was 11.5 months in the necitumumab-treated arm, vs. 9.9 months among controls, a 1.6 month difference that was statistically significant, representing a reduced risk of 16% (hazard ratio, 0.84). Progression-free survival (PFS) was a median of 5.7 months among those in the necitumumab-treated group, vs. 5.5 months, which was also statistically significant and represented a 15% reduced risk (HR, 0.85). There was no significant difference in the objective response rate (ORR), which was 31% among those in the necitumumab arm and 29% among those in the control arm. This is the first study to show an improvement in survival for a first-line treatment for squamous lung cancer, the company officials pointed out.

In the study, there were more venous thromboembolic events (VTEs; 9% vs. 5%) and more cases of sudden death and deaths “not otherwise specified” (2.2% vs. 0.5%) in the necitumumab-treated arm. There were also more cases of hypomagnesemia and skin rashes, and the FDA reviewers pointed out that several cases of sudden death occurred in patients with very low serum magnesium levels. VTEs and sudden or unexplained deaths were also higher among necitumumab-treated patients in another study that evaluated necitumumab in patients with nonsquamous NSCLC, which was stopped early because of the VTE increase; that study found no improvements in OS, PFS or ORR.

Among those agreeing that the risk-benefit assessment was positive, Dr. Michael Menefee of the Mayo Clinic, Jacksonville, Fla., said “Yes was the simple answer, but there are still caveats” regarding toxicity and the magnitude of the overall benefit.

“The survival benefit is modest but it’s real,” said Dr. Deborah Armstrong, the panel chair and professor of oncology, Johns Hopkins University, Baltimore, who also voted positively. She strongly encouraged continuing efforts to manage the toxicities of necitumumab, which she said might improve the risk-benefit balance further.

The panelist who did not agree was Dr. Tito Fojo, a senior investigator and director of the medical oncology fellowship program at the National Cancer Institute. He said that the study did not provide him with enough confidence. Noting it is a very difficult disease to treat, he said, “I just wish the data were much better.” His concerns included the possibility that those in the control arm, who received a median of five treatment cycles may have received less chemotherapy than those in the necitumumab arm, who received a median of six cycles.

Speaking on behalf of Eli Lilly at the meeting, Dr. David Gandara, director of the thoracic oncology program at the University of California Davis Comprehensive Cancer Center, said that although EGFR mutations are rare in squamous NSCLC, “the EGFR pathway itself is biologically relevant.” Necitumumab “attacks that pathway in ways independent of those associated with EGFR tyrosine-kinase inhibitors and independent of EGFR mutation status,” he added.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. The FDA decision is expected by the end of 2015, an Eli Lilly spokesperson said.

emechcatie@frontlinemedcom.com

SILVER SPRING, MD. – The majority of a Food and Drug Administration Advisory panel agreed that the benefits of adding necitumumab to gemcitabine and cisplatin for patients with squamous non–small cell lung cancer outweighed the risks.

Elizabeth Mechcatie/Frontline Medical News

At the meeting on July 9, the FDA’s Oncologic Drugs Advisory Committee reviewed data from a study that evaluated the anti–epidermal growth factor receptor monoclonal antibody in more than 1,000 patients with stage IV disease. The SQUIRE study was submitted to the FDA by Eli Lilly to support approval of necitumumab for the indication now under review: for use as a first-line treatment, in combination with gemcitabine and cisplatin, for patients with locally advanced or metastatic squamous non–small cell lung cancer (NSCLC). Necitumumab is a recombinant human IgG1 monoclonal antibody that is designed to block the ligand binding site of the human EGFR.

Despite a modest effect on overall survival, a very small but statistically significant effect on progression-free survival, and some safety concerns, 11 of the 12 panelists agreed that the efficacy and safety results of the trial supported a “positive benefit risk assessment” of necitumumab combined with gemcitabine and cisplatin for this group of patients, the main question they were asked by the FDA to discuss. The panel was not asked to specifically vote on whether to recommend approval.

The SQUIRE study, an international phase III study of 1,093 patients with stage IV squamous NSCLC, who had not received chemotherapy for advanced disease, evaluated the safety and efficacy of gemcitabine and cisplatin, with or without necitumumab, administered every 3 weeks, until disease progressed or toxicity became unacceptable, for a maximum of six cycles. The median age of patients was 62 years; they were mostly men and were heavy smokers; 36 patients were enrolled in the United States. (Patients were not selected based on EGFR protein expression but based on tissue pathology.)

Median overall survival (OS), the primary endpoint, was 11.5 months in the necitumumab-treated arm, vs. 9.9 months among controls, a 1.6 month difference that was statistically significant, representing a reduced risk of 16% (hazard ratio, 0.84). Progression-free survival (PFS) was a median of 5.7 months among those in the necitumumab-treated group, vs. 5.5 months, which was also statistically significant and represented a 15% reduced risk (HR, 0.85). There was no significant difference in the objective response rate (ORR), which was 31% among those in the necitumumab arm and 29% among those in the control arm. This is the first study to show an improvement in survival for a first-line treatment for squamous lung cancer, the company officials pointed out.

In the study, there were more venous thromboembolic events (VTEs; 9% vs. 5%) and more cases of sudden death and deaths “not otherwise specified” (2.2% vs. 0.5%) in the necitumumab-treated arm. There were also more cases of hypomagnesemia and skin rashes, and the FDA reviewers pointed out that several cases of sudden death occurred in patients with very low serum magnesium levels. VTEs and sudden or unexplained deaths were also higher among necitumumab-treated patients in another study that evaluated necitumumab in patients with nonsquamous NSCLC, which was stopped early because of the VTE increase; that study found no improvements in OS, PFS or ORR.

Among those agreeing that the risk-benefit assessment was positive, Dr. Michael Menefee of the Mayo Clinic, Jacksonville, Fla., said “Yes was the simple answer, but there are still caveats” regarding toxicity and the magnitude of the overall benefit.

“The survival benefit is modest but it’s real,” said Dr. Deborah Armstrong, the panel chair and professor of oncology, Johns Hopkins University, Baltimore, who also voted positively. She strongly encouraged continuing efforts to manage the toxicities of necitumumab, which she said might improve the risk-benefit balance further.

The panelist who did not agree was Dr. Tito Fojo, a senior investigator and director of the medical oncology fellowship program at the National Cancer Institute. He said that the study did not provide him with enough confidence. Noting it is a very difficult disease to treat, he said, “I just wish the data were much better.” His concerns included the possibility that those in the control arm, who received a median of five treatment cycles may have received less chemotherapy than those in the necitumumab arm, who received a median of six cycles.

Speaking on behalf of Eli Lilly at the meeting, Dr. David Gandara, director of the thoracic oncology program at the University of California Davis Comprehensive Cancer Center, said that although EGFR mutations are rare in squamous NSCLC, “the EGFR pathway itself is biologically relevant.” Necitumumab “attacks that pathway in ways independent of those associated with EGFR tyrosine-kinase inhibitors and independent of EGFR mutation status,” he added.

The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting. The FDA decision is expected by the end of 2015, an Eli Lilly spokesperson said.

emechcatie@frontlinemedcom.com

Results from a large, multinational phase III trial showed that consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiation with the same agents failed to improve progression-free survival in patients with locally advanced non–small cell lung cancer (NSCLC), according to a report published online in the Journal of Clinical Oncology.

After a median follow up of 50.7 months, progression-free survival (PFS) for the arm that received consolidation chemotherapy (CC) was 8.1 months, compared with 9.1 months for the arm that did not receive CC (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .36). Median overall survival (OS) was also similar between groups: 20.6 vs. 21.8 months, respectively (P = .44).

Among patients assigned to the CC arm, only 42.1% received all three planned cycles, 54.1% completed at least two cycles, and 31.6% did not receive any CC.

“The major obstacle in this trial was that many patients could not complete the three planned cycles of CC,” wrote Dr. Jin Seok Ahn of the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and colleagues. A large proportion of patients failed to start CC because of disease progression or death, and many patients had incomplete recovery from the adverse effects of concurrent chemoradiation. “A full-dose doublet regimen of CC in our trial might have further reduced the rate of completing the three planned cycles of CC,” the investigators noted (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.60.0130]).

The randomized phase III trial included 420 patients with inoperable stage IIIA or IIIB non–small cell lung cancer, enrolled from 31 centers in Korea, China, and Taiwan from 2005 to 2011.

Patients older than 60 years, who had similar baseline characteristics to younger patients, experienced significant benefit from CC (HR 0.72), for reasons that remain unexplained.

An exploratory biomarker study indicated the expression of ERCC1 and class III beta-tubulin was not correlated with PFS or OS.

The study was supported in part by Sanofi-Aventis Korea. Dr. Jin Seok Ahn reported financial ties to Eli Lilly, Pfizer, and Roche. Several of his coauthors reported ties to industry sources.

Results from a large, multinational phase III trial showed that consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiation with the same agents failed to improve progression-free survival in patients with locally advanced non–small cell lung cancer (NSCLC), according to a report published online in the Journal of Clinical Oncology.

After a median follow up of 50.7 months, progression-free survival (PFS) for the arm that received consolidation chemotherapy (CC) was 8.1 months, compared with 9.1 months for the arm that did not receive CC (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .36). Median overall survival (OS) was also similar between groups: 20.6 vs. 21.8 months, respectively (P = .44).

Among patients assigned to the CC arm, only 42.1% received all three planned cycles, 54.1% completed at least two cycles, and 31.6% did not receive any CC.

“The major obstacle in this trial was that many patients could not complete the three planned cycles of CC,” wrote Dr. Jin Seok Ahn of the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and colleagues. A large proportion of patients failed to start CC because of disease progression or death, and many patients had incomplete recovery from the adverse effects of concurrent chemoradiation. “A full-dose doublet regimen of CC in our trial might have further reduced the rate of completing the three planned cycles of CC,” the investigators noted (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.60.0130]).

The randomized phase III trial included 420 patients with inoperable stage IIIA or IIIB non–small cell lung cancer, enrolled from 31 centers in Korea, China, and Taiwan from 2005 to 2011.

Patients older than 60 years, who had similar baseline characteristics to younger patients, experienced significant benefit from CC (HR 0.72), for reasons that remain unexplained.

An exploratory biomarker study indicated the expression of ERCC1 and class III beta-tubulin was not correlated with PFS or OS.

The study was supported in part by Sanofi-Aventis Korea. Dr. Jin Seok Ahn reported financial ties to Eli Lilly, Pfizer, and Roche. Several of his coauthors reported ties to industry sources.

Results from a large, multinational phase III trial showed that consolidation chemotherapy with docetaxel and cisplatin after concurrent chemoradiation with the same agents failed to improve progression-free survival in patients with locally advanced non–small cell lung cancer (NSCLC), according to a report published online in the Journal of Clinical Oncology.

After a median follow up of 50.7 months, progression-free survival (PFS) for the arm that received consolidation chemotherapy (CC) was 8.1 months, compared with 9.1 months for the arm that did not receive CC (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .36). Median overall survival (OS) was also similar between groups: 20.6 vs. 21.8 months, respectively (P = .44).

Among patients assigned to the CC arm, only 42.1% received all three planned cycles, 54.1% completed at least two cycles, and 31.6% did not receive any CC.

“The major obstacle in this trial was that many patients could not complete the three planned cycles of CC,” wrote Dr. Jin Seok Ahn of the Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and colleagues. A large proportion of patients failed to start CC because of disease progression or death, and many patients had incomplete recovery from the adverse effects of concurrent chemoradiation. “A full-dose doublet regimen of CC in our trial might have further reduced the rate of completing the three planned cycles of CC,” the investigators noted (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.60.0130]).

The randomized phase III trial included 420 patients with inoperable stage IIIA or IIIB non–small cell lung cancer, enrolled from 31 centers in Korea, China, and Taiwan from 2005 to 2011.

Patients older than 60 years, who had similar baseline characteristics to younger patients, experienced significant benefit from CC (HR 0.72), for reasons that remain unexplained.

An exploratory biomarker study indicated the expression of ERCC1 and class III beta-tubulin was not correlated with PFS or OS.

The study was supported in part by Sanofi-Aventis Korea. Dr. Jin Seok Ahn reported financial ties to Eli Lilly, Pfizer, and Roche. Several of his coauthors reported ties to industry sources.

PARIS – Thought leaders in interventional cardiology have been quick to throw cold water on recent reports of valve leaflet thickening and abnormal leaflet motion being detected in roughly 10% of patients after transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement.

“The take home message for the interventional community is there is no need for clinicians to modify their practice in relation to patient selection, TAVI implantation, or follow-up protocols. Specifically, there is no role for systematic CT or transesophageal echocardiographic follow-up of asymptomatic TAVI patients because they’re not at clinical risk, and these additional procedures carry risk in themselves,” Dr. Bernard Prendergast said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/Frontline Medical News

“Whilst there is room here for speculation and conjecture, I think most of us are confident that some of these findings may represent imaging artifact or reflect the natural history of biological valve leaflets, which has never been examined in such detail in the past,” added Dr. Prendergast, director of the cardiac structural intervention program at Guys and St. Thomas’ Hospital in London and cochair of the special EuroPCR session devoted to the emerging data on valve leaflet abnormalities.

The session featured three separate studies totaling 345 patients who underwent sophisticated, high-resolution 4D CT imaging or transesophageal echocardiography 5 days or more following TAVI or, less frequently, after surgical aortic valve replacement. Roughly 10% of patients showed a spectrum of leaflet abnormalities: thickening, mildly impaired motion, and/or thin films believed to be thrombi.

The leaflet abnormalities weren’t associated with any particular valve. And, as was emphasized by Dr. Prendergast and other speakers, to date these abnormalities haven’t been associated with a single case of stroke, systemic embolism, or valve failure.

Indeed, more than 100,000 TAVI procedures have been performed worldwide, and stroke rates in contemporary randomized trials and large registries are in the 1%-2% range. That’s better than with surgical valve replacement, Dr. Prendergast observed.

“Nowadays we can see much more than we could in the past, when we worked with 2D echocardiography,” observed discussant Dr. Jeroen J. Bax, professor of cardiology and director of noninvasive cardiology imaging at Leiden (the Netherlands) University Medical Center. “We see things that we do not completely understand. We could say that technology has outpaced our clinical understanding. But although we see things, at the moment there is no consequence in terms of hemodynamic performance or clinical outcomes. And this phenomenon of leaflet thickening has been occurring with surgical aortic valve replacement for many, many years and we simply didn’t realize it.”

Dr. Franz-Josef Neumann, who led one of the three studies, reported that 4D CT on day 5 post TAVI revealed leaflet abnormalities, all completely asymptomatic, in 16 of 154 patients. Two-thirds of the study population were on dual antiplatelet therapy at the time, the rest on a single antiplatelet agent. Dual antiplatelet therapy didn’t protect against leaflet thickening or other abnormalities.

All 16 affected patients were placed on an oral vitamin K antagonist with a target international normalized ratio (INR) of 2.5-3.5. To date, 11 of the 16 have undergone follow-up high-resolution CT after a median of 77 days. The leaflet thickening was resolved in all instances, according to Dr. Neumann, medical director of the department of cardiology and angiology at the University of Freiburg (Germany).

Bruce Jancin/Frontline Medical News

Dr. Raj R. Makkar presented a study of 125 patients who underwent high-resolution imaging after TAVI. Importantly, none of those who were on warfarin as part of their post-TAVI regimen developed leaflet abnormalities.

But he cautioned his colleagues against overreacting to the studies he and Dr. Neumann presented by placing all of their TAVI patients on an oral anticoagulant. He noted that the current TAVI population is elderly and laden with many comorbid conditions, placing them at high risk for bleeding complications.

There is at present no standard, guideline-recommended antiplatelet/antithrombotic regimen for before, during, or after TAVI. Working out the optimal protective drug regimen in this population is now a priority in light of the leaflet abnormality findings, but it will take time and require careful study, said Dr. Makkar, associate director of the Cedars Sinai Heart Institute in Los Angeles.

“Everyone is talking about anticoagulation as the imminent solution. But I want to emphasize that it comes with a price in terms of bleeding. These images are beautiful in terms of spatial resolution, but we must resist our temptation while the industry works on designing less thrombogenic valves,” the cardiologist added.

Discussant Dr. Christoph K. Naber confessed he was “stunned” by the images of leaflet abnormalities.

“Although we haven’t seen any clinical consequences, we have to keep in mind that the group of patients is still small. We have very good experience with TAVI; it has saved the lives of many patients. We know it’s a very good therapy. But if we believe we can go further and offer it to younger, lower-risk patients who will have their device for a longer time, then we should take the time and money to understand what is going on here and what consequences it could have. It’s something we should closely watch, especially if we want to extend the indication,” said Dr. Naber, director of the department of cardiology and angiology at the Contilia Cardiovascular Center in Essen, Germany.

He disclosed that he serves as a consultant to Abbott Vascular, Biotronik, Medtronic, and The Medicines Company. Dr. Makkar has received research grants from Edwards Lifesciences, St. Jude Medical, and Boston Scientific. Dr. Prendergast is on the speakers’ bureau for Edwards Lifesciences.

bjancin@frontlinemedcom

PARIS – Thought leaders in interventional cardiology have been quick to throw cold water on recent reports of valve leaflet thickening and abnormal leaflet motion being detected in roughly 10% of patients after transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement.

“The take home message for the interventional community is there is no need for clinicians to modify their practice in relation to patient selection, TAVI implantation, or follow-up protocols. Specifically, there is no role for systematic CT or transesophageal echocardiographic follow-up of asymptomatic TAVI patients because they’re not at clinical risk, and these additional procedures carry risk in themselves,” Dr. Bernard Prendergast said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/Frontline Medical News

“Whilst there is room here for speculation and conjecture, I think most of us are confident that some of these findings may represent imaging artifact or reflect the natural history of biological valve leaflets, which has never been examined in such detail in the past,” added Dr. Prendergast, director of the cardiac structural intervention program at Guys and St. Thomas’ Hospital in London and cochair of the special EuroPCR session devoted to the emerging data on valve leaflet abnormalities.

The session featured three separate studies totaling 345 patients who underwent sophisticated, high-resolution 4D CT imaging or transesophageal echocardiography 5 days or more following TAVI or, less frequently, after surgical aortic valve replacement. Roughly 10% of patients showed a spectrum of leaflet abnormalities: thickening, mildly impaired motion, and/or thin films believed to be thrombi.

The leaflet abnormalities weren’t associated with any particular valve. And, as was emphasized by Dr. Prendergast and other speakers, to date these abnormalities haven’t been associated with a single case of stroke, systemic embolism, or valve failure.

Indeed, more than 100,000 TAVI procedures have been performed worldwide, and stroke rates in contemporary randomized trials and large registries are in the 1%-2% range. That’s better than with surgical valve replacement, Dr. Prendergast observed.

“Nowadays we can see much more than we could in the past, when we worked with 2D echocardiography,” observed discussant Dr. Jeroen J. Bax, professor of cardiology and director of noninvasive cardiology imaging at Leiden (the Netherlands) University Medical Center. “We see things that we do not completely understand. We could say that technology has outpaced our clinical understanding. But although we see things, at the moment there is no consequence in terms of hemodynamic performance or clinical outcomes. And this phenomenon of leaflet thickening has been occurring with surgical aortic valve replacement for many, many years and we simply didn’t realize it.”

Dr. Franz-Josef Neumann, who led one of the three studies, reported that 4D CT on day 5 post TAVI revealed leaflet abnormalities, all completely asymptomatic, in 16 of 154 patients. Two-thirds of the study population were on dual antiplatelet therapy at the time, the rest on a single antiplatelet agent. Dual antiplatelet therapy didn’t protect against leaflet thickening or other abnormalities.

All 16 affected patients were placed on an oral vitamin K antagonist with a target international normalized ratio (INR) of 2.5-3.5. To date, 11 of the 16 have undergone follow-up high-resolution CT after a median of 77 days. The leaflet thickening was resolved in all instances, according to Dr. Neumann, medical director of the department of cardiology and angiology at the University of Freiburg (Germany).

Bruce Jancin/Frontline Medical News

Dr. Raj R. Makkar presented a study of 125 patients who underwent high-resolution imaging after TAVI. Importantly, none of those who were on warfarin as part of their post-TAVI regimen developed leaflet abnormalities.

But he cautioned his colleagues against overreacting to the studies he and Dr. Neumann presented by placing all of their TAVI patients on an oral anticoagulant. He noted that the current TAVI population is elderly and laden with many comorbid conditions, placing them at high risk for bleeding complications.

There is at present no standard, guideline-recommended antiplatelet/antithrombotic regimen for before, during, or after TAVI. Working out the optimal protective drug regimen in this population is now a priority in light of the leaflet abnormality findings, but it will take time and require careful study, said Dr. Makkar, associate director of the Cedars Sinai Heart Institute in Los Angeles.

“Everyone is talking about anticoagulation as the imminent solution. But I want to emphasize that it comes with a price in terms of bleeding. These images are beautiful in terms of spatial resolution, but we must resist our temptation while the industry works on designing less thrombogenic valves,” the cardiologist added.

Discussant Dr. Christoph K. Naber confessed he was “stunned” by the images of leaflet abnormalities.

“Although we haven’t seen any clinical consequences, we have to keep in mind that the group of patients is still small. We have very good experience with TAVI; it has saved the lives of many patients. We know it’s a very good therapy. But if we believe we can go further and offer it to younger, lower-risk patients who will have their device for a longer time, then we should take the time and money to understand what is going on here and what consequences it could have. It’s something we should closely watch, especially if we want to extend the indication,” said Dr. Naber, director of the department of cardiology and angiology at the Contilia Cardiovascular Center in Essen, Germany.

He disclosed that he serves as a consultant to Abbott Vascular, Biotronik, Medtronic, and The Medicines Company. Dr. Makkar has received research grants from Edwards Lifesciences, St. Jude Medical, and Boston Scientific. Dr. Prendergast is on the speakers’ bureau for Edwards Lifesciences.

bjancin@frontlinemedcom

PARIS – Thought leaders in interventional cardiology have been quick to throw cold water on recent reports of valve leaflet thickening and abnormal leaflet motion being detected in roughly 10% of patients after transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement.

“The take home message for the interventional community is there is no need for clinicians to modify their practice in relation to patient selection, TAVI implantation, or follow-up protocols. Specifically, there is no role for systematic CT or transesophageal echocardiographic follow-up of asymptomatic TAVI patients because they’re not at clinical risk, and these additional procedures carry risk in themselves,” Dr. Bernard Prendergast said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/Frontline Medical News

“Whilst there is room here for speculation and conjecture, I think most of us are confident that some of these findings may represent imaging artifact or reflect the natural history of biological valve leaflets, which has never been examined in such detail in the past,” added Dr. Prendergast, director of the cardiac structural intervention program at Guys and St. Thomas’ Hospital in London and cochair of the special EuroPCR session devoted to the emerging data on valve leaflet abnormalities.

The session featured three separate studies totaling 345 patients who underwent sophisticated, high-resolution 4D CT imaging or transesophageal echocardiography 5 days or more following TAVI or, less frequently, after surgical aortic valve replacement. Roughly 10% of patients showed a spectrum of leaflet abnormalities: thickening, mildly impaired motion, and/or thin films believed to be thrombi.

The leaflet abnormalities weren’t associated with any particular valve. And, as was emphasized by Dr. Prendergast and other speakers, to date these abnormalities haven’t been associated with a single case of stroke, systemic embolism, or valve failure.

Indeed, more than 100,000 TAVI procedures have been performed worldwide, and stroke rates in contemporary randomized trials and large registries are in the 1%-2% range. That’s better than with surgical valve replacement, Dr. Prendergast observed.

“Nowadays we can see much more than we could in the past, when we worked with 2D echocardiography,” observed discussant Dr. Jeroen J. Bax, professor of cardiology and director of noninvasive cardiology imaging at Leiden (the Netherlands) University Medical Center. “We see things that we do not completely understand. We could say that technology has outpaced our clinical understanding. But although we see things, at the moment there is no consequence in terms of hemodynamic performance or clinical outcomes. And this phenomenon of leaflet thickening has been occurring with surgical aortic valve replacement for many, many years and we simply didn’t realize it.”

Dr. Franz-Josef Neumann, who led one of the three studies, reported that 4D CT on day 5 post TAVI revealed leaflet abnormalities, all completely asymptomatic, in 16 of 154 patients. Two-thirds of the study population were on dual antiplatelet therapy at the time, the rest on a single antiplatelet agent. Dual antiplatelet therapy didn’t protect against leaflet thickening or other abnormalities.

All 16 affected patients were placed on an oral vitamin K antagonist with a target international normalized ratio (INR) of 2.5-3.5. To date, 11 of the 16 have undergone follow-up high-resolution CT after a median of 77 days. The leaflet thickening was resolved in all instances, according to Dr. Neumann, medical director of the department of cardiology and angiology at the University of Freiburg (Germany).

Bruce Jancin/Frontline Medical News

Dr. Raj R. Makkar presented a study of 125 patients who underwent high-resolution imaging after TAVI. Importantly, none of those who were on warfarin as part of their post-TAVI regimen developed leaflet abnormalities.

But he cautioned his colleagues against overreacting to the studies he and Dr. Neumann presented by placing all of their TAVI patients on an oral anticoagulant. He noted that the current TAVI population is elderly and laden with many comorbid conditions, placing them at high risk for bleeding complications.

There is at present no standard, guideline-recommended antiplatelet/antithrombotic regimen for before, during, or after TAVI. Working out the optimal protective drug regimen in this population is now a priority in light of the leaflet abnormality findings, but it will take time and require careful study, said Dr. Makkar, associate director of the Cedars Sinai Heart Institute in Los Angeles.

“Everyone is talking about anticoagulation as the imminent solution. But I want to emphasize that it comes with a price in terms of bleeding. These images are beautiful in terms of spatial resolution, but we must resist our temptation while the industry works on designing less thrombogenic valves,” the cardiologist added.

Discussant Dr. Christoph K. Naber confessed he was “stunned” by the images of leaflet abnormalities.

“Although we haven’t seen any clinical consequences, we have to keep in mind that the group of patients is still small. We have very good experience with TAVI; it has saved the lives of many patients. We know it’s a very good therapy. But if we believe we can go further and offer it to younger, lower-risk patients who will have their device for a longer time, then we should take the time and money to understand what is going on here and what consequences it could have. It’s something we should closely watch, especially if we want to extend the indication,” said Dr. Naber, director of the department of cardiology and angiology at the Contilia Cardiovascular Center in Essen, Germany.

He disclosed that he serves as a consultant to Abbott Vascular, Biotronik, Medtronic, and The Medicines Company. Dr. Makkar has received research grants from Edwards Lifesciences, St. Jude Medical, and Boston Scientific. Dr. Prendergast is on the speakers’ bureau for Edwards Lifesciences.

bjancin@frontlinemedcom

Injecting patients with a molecular contrast agent before lung cancer surgery and then using fluorescent imaging during the operation proved safe and somewhat effective at finding lung adenocarcinomas and discovering tumor metastases in a pilot clinical trial of 50 patients.

Investigators from the University of Pennsylvania, Philadelphia, and Emory (Atlanta) and Purdue (West Lafayette, Ind.) universities reported their findings online in the Journal of Thoracic and Cardiovascular Surgery (2015 [doi:10.1016/j.jtcvs.2015.05.014]).

“We believe the most important finding in this study was the ability to systemically inject our contrast agent into patients prior to surgery and have 92% of the lung adenocarcinomas fluoresce in the operating room,” Dr. Olugbenga Okusanya of the University of Pennsylvania, Philadelphia, and his colleagues said. Their approach overcomes some of the limitations of other contrast agents for imaging of lung cancer.

The approach involves intravenous administration of 0.1 mg/kg of a fluorescent folate receptor-alpha (FR-alpha)–targeted molecule contrast agent 4 hours before surgery. The specific agent they used is a synthetic conjugate between folate and fluorescein isothiocyanate that binds to serum proteins.

They set out to determine if an optical-targeted molecular contrast agent to FR-alpha could bind lung adenocarcinoma and then if real-time optical imaging, either in situ or ex vivo during surgery, would show the lesions. The 50 study subjects all had biopsy-confirmed lung adenocarcinoma. In the OR, the researchers used a gantry-mounted fluorescent imaging system to capture images of the tumors.

With the operating room lights switched off, imaging of the cancer was captured by fluorescence and white light in situ. The lung was deflated during imaging to expose as much of the lung surface to the imaging as possible. The in situ optical imaging required on average eight minutes to perform. Only seven tumors (14%) appeared fluorescent in situ before they were excised. Computed tomography (CT) before surgery showed that all seven of these tumors were below the pleural surface and within 1.2 cm of the lung surface.

Among the other 43 tumors, 39 exhibited uniform fluorescence once the surgical team exposed their surfaces while 4 – all invasive adenocarcinomas – did not. Final pathology confirmed that all 50 tumors were cancerous.

“With further refinements, this tool may prove useful in locating adenocarcinomas deeper in the lung parenchyma, lymph nodes and at pleural and resection margins,” Dr. Okusanya and his coauthors said.

The investigators noted that one advantage of this imaging strategy is that it can locate tumors of varying sizes, subtypes and metabolic activity with tumor-to-background ratios “not markedly different” among them. “This finding demonstrates that intraoperative molecular imaging may be potentially broadly applicable to all FR-alpha lung tumors,” they said.

Other advantages is that wavelength fluorophore poses no radiation exposure and that surgeons readily understand optical imaging “with no need for special training to interpret or process the data.” They did acknowledge that a significant drawback of the molecular contrast agent was its lack of penetration into the lung parenchyma.

“New molecular tools are emerging to identify lung adenocarcinomas during pulmonary resection,” Dr. Okusanya and colleagues said. “This technology will permit precise visualization of tumor margins, localization of small malignant ground-glass opacities, and accurate selection of lymph nodes with metastatic cancer cells. With miniaturization of imaging devices, this method will be particularly useful in minimally invasive surgery.”

The pilot clinical trial was partially supported by grant from the Biomedical Laboratory Research & Development Service of the Veterans Affairs Office of Research and Development and by the CHEST Foundation One Breath Clinical Research Award (SS).

Dr. Shuming Nie is a coauthor and a consultant for Spectropath, a start-up company that is developing advanced instrumentation and nanoparticle contrast agents. Dr. Philip S. Low is a coauthor and a consultant and stakeholder in OnTarget Laboratories. None of the other coauthors had any relationships to disclose.

Injecting patients with a molecular contrast agent before lung cancer surgery and then using fluorescent imaging during the operation proved safe and somewhat effective at finding lung adenocarcinomas and discovering tumor metastases in a pilot clinical trial of 50 patients.

Investigators from the University of Pennsylvania, Philadelphia, and Emory (Atlanta) and Purdue (West Lafayette, Ind.) universities reported their findings online in the Journal of Thoracic and Cardiovascular Surgery (2015 [doi:10.1016/j.jtcvs.2015.05.014]).

“We believe the most important finding in this study was the ability to systemically inject our contrast agent into patients prior to surgery and have 92% of the lung adenocarcinomas fluoresce in the operating room,” Dr. Olugbenga Okusanya of the University of Pennsylvania, Philadelphia, and his colleagues said. Their approach overcomes some of the limitations of other contrast agents for imaging of lung cancer.

The approach involves intravenous administration of 0.1 mg/kg of a fluorescent folate receptor-alpha (FR-alpha)–targeted molecule contrast agent 4 hours before surgery. The specific agent they used is a synthetic conjugate between folate and fluorescein isothiocyanate that binds to serum proteins.

They set out to determine if an optical-targeted molecular contrast agent to FR-alpha could bind lung adenocarcinoma and then if real-time optical imaging, either in situ or ex vivo during surgery, would show the lesions. The 50 study subjects all had biopsy-confirmed lung adenocarcinoma. In the OR, the researchers used a gantry-mounted fluorescent imaging system to capture images of the tumors.

With the operating room lights switched off, imaging of the cancer was captured by fluorescence and white light in situ. The lung was deflated during imaging to expose as much of the lung surface to the imaging as possible. The in situ optical imaging required on average eight minutes to perform. Only seven tumors (14%) appeared fluorescent in situ before they were excised. Computed tomography (CT) before surgery showed that all seven of these tumors were below the pleural surface and within 1.2 cm of the lung surface.

Among the other 43 tumors, 39 exhibited uniform fluorescence once the surgical team exposed their surfaces while 4 – all invasive adenocarcinomas – did not. Final pathology confirmed that all 50 tumors were cancerous.

“With further refinements, this tool may prove useful in locating adenocarcinomas deeper in the lung parenchyma, lymph nodes and at pleural and resection margins,” Dr. Okusanya and his coauthors said.

The investigators noted that one advantage of this imaging strategy is that it can locate tumors of varying sizes, subtypes and metabolic activity with tumor-to-background ratios “not markedly different” among them. “This finding demonstrates that intraoperative molecular imaging may be potentially broadly applicable to all FR-alpha lung tumors,” they said.

Other advantages is that wavelength fluorophore poses no radiation exposure and that surgeons readily understand optical imaging “with no need for special training to interpret or process the data.” They did acknowledge that a significant drawback of the molecular contrast agent was its lack of penetration into the lung parenchyma.

“New molecular tools are emerging to identify lung adenocarcinomas during pulmonary resection,” Dr. Okusanya and colleagues said. “This technology will permit precise visualization of tumor margins, localization of small malignant ground-glass opacities, and accurate selection of lymph nodes with metastatic cancer cells. With miniaturization of imaging devices, this method will be particularly useful in minimally invasive surgery.”

The pilot clinical trial was partially supported by grant from the Biomedical Laboratory Research & Development Service of the Veterans Affairs Office of Research and Development and by the CHEST Foundation One Breath Clinical Research Award (SS).

Dr. Shuming Nie is a coauthor and a consultant for Spectropath, a start-up company that is developing advanced instrumentation and nanoparticle contrast agents. Dr. Philip S. Low is a coauthor and a consultant and stakeholder in OnTarget Laboratories. None of the other coauthors had any relationships to disclose.

Injecting patients with a molecular contrast agent before lung cancer surgery and then using fluorescent imaging during the operation proved safe and somewhat effective at finding lung adenocarcinomas and discovering tumor metastases in a pilot clinical trial of 50 patients.

Investigators from the University of Pennsylvania, Philadelphia, and Emory (Atlanta) and Purdue (West Lafayette, Ind.) universities reported their findings online in the Journal of Thoracic and Cardiovascular Surgery (2015 [doi:10.1016/j.jtcvs.2015.05.014]).

“We believe the most important finding in this study was the ability to systemically inject our contrast agent into patients prior to surgery and have 92% of the lung adenocarcinomas fluoresce in the operating room,” Dr. Olugbenga Okusanya of the University of Pennsylvania, Philadelphia, and his colleagues said. Their approach overcomes some of the limitations of other contrast agents for imaging of lung cancer.

The approach involves intravenous administration of 0.1 mg/kg of a fluorescent folate receptor-alpha (FR-alpha)–targeted molecule contrast agent 4 hours before surgery. The specific agent they used is a synthetic conjugate between folate and fluorescein isothiocyanate that binds to serum proteins.

They set out to determine if an optical-targeted molecular contrast agent to FR-alpha could bind lung adenocarcinoma and then if real-time optical imaging, either in situ or ex vivo during surgery, would show the lesions. The 50 study subjects all had biopsy-confirmed lung adenocarcinoma. In the OR, the researchers used a gantry-mounted fluorescent imaging system to capture images of the tumors.

With the operating room lights switched off, imaging of the cancer was captured by fluorescence and white light in situ. The lung was deflated during imaging to expose as much of the lung surface to the imaging as possible. The in situ optical imaging required on average eight minutes to perform. Only seven tumors (14%) appeared fluorescent in situ before they were excised. Computed tomography (CT) before surgery showed that all seven of these tumors were below the pleural surface and within 1.2 cm of the lung surface.

Among the other 43 tumors, 39 exhibited uniform fluorescence once the surgical team exposed their surfaces while 4 – all invasive adenocarcinomas – did not. Final pathology confirmed that all 50 tumors were cancerous.

“With further refinements, this tool may prove useful in locating adenocarcinomas deeper in the lung parenchyma, lymph nodes and at pleural and resection margins,” Dr. Okusanya and his coauthors said.

The investigators noted that one advantage of this imaging strategy is that it can locate tumors of varying sizes, subtypes and metabolic activity with tumor-to-background ratios “not markedly different” among them. “This finding demonstrates that intraoperative molecular imaging may be potentially broadly applicable to all FR-alpha lung tumors,” they said.

Other advantages is that wavelength fluorophore poses no radiation exposure and that surgeons readily understand optical imaging “with no need for special training to interpret or process the data.” They did acknowledge that a significant drawback of the molecular contrast agent was its lack of penetration into the lung parenchyma.

“New molecular tools are emerging to identify lung adenocarcinomas during pulmonary resection,” Dr. Okusanya and colleagues said. “This technology will permit precise visualization of tumor margins, localization of small malignant ground-glass opacities, and accurate selection of lymph nodes with metastatic cancer cells. With miniaturization of imaging devices, this method will be particularly useful in minimally invasive surgery.”

The pilot clinical trial was partially supported by grant from the Biomedical Laboratory Research & Development Service of the Veterans Affairs Office of Research and Development and by the CHEST Foundation One Breath Clinical Research Award (SS).

Dr. Shuming Nie is a coauthor and a consultant for Spectropath, a start-up company that is developing advanced instrumentation and nanoparticle contrast agents. Dr. Philip S. Low is a coauthor and a consultant and stakeholder in OnTarget Laboratories. None of the other coauthors had any relationships to disclose.

An acute aortic tear can be lethal, and more cardiac surgeons are favoring extended aortic arch replacement in these cases. Cardiac surgeons have tried many different arch replacement techniques, but en bloc repair and double- or triple-branch stent grafting carry significant risks, so a team of cardiac surgeons in Beijing has reported good 2-year results with a novel technique that combines stented elephant-trunk implantation with preservation of key vessels.

The technique accomplishes total arch replacement with the stent while preserving the autologous brachiocephalic vessels.

“This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic patch wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results,” wrote Dr. Li-Zhong Sun and colleagues at Beijing’s Capital Medical University (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.002]).

There are four keys to the procedure:

• The use of forceps to grasp the stent-free sewing edge of the stented elephant trunk and straightening of the spiral shaped Dacron graft to approximately 3 cm.

• Preservation of the native brachiocephalic vessels.

• Creating a residual aortic wall containing the innominate artery and LCCA that’s as small as possible.

• An end-to-side anastomosis between the left subclavian artery (LSCA) and the left common carotid artery (LCCA), a key junction in their technique.

The 20 study subjects had surgery within 2 weeks of the onset of pain. All 20 were discharged after the procedure, and in a mean follow-up period of 26 months, 18 had good outcomes while 1 patient had thoracoabdominal aortic replacement 9 months after the initial surgery (1 patient was lost to follow-up).

The researchers used computed tomography to confirm patency of the anastomosis between the LSCA and LCCA.

In 2 of the 20 patients, the aorta was normal with aortic dissection limited to the descending aorta. In the remaining patients, the investigators observed thrombus obliteration of the false lumen around the surgical graft in 16, partial thrombosis in 1 and patency in 1.

The surgical technique exposes the right axillary artery through a right subclavicular incision and a median sternotomy, then dissects and exposes the brachiocephalic vessels and the transverse arch. Dissection of the LSCA and LCCA is the key step in making the end-to-end anastomosis between the two vessels. The researchers accomplished this by partially transecting the sternocleidomastoid muscle and other cervical muscles.

Dr. Sun and coauthors said that a separated graft technique offers a number of advantages over other techniques for aortic arch reconstruction. While en bloc repair preserves the native brachiocephalic vessels and, thus, results in long-term patency, the technique carries risk for postoperative rupture of the aortic patch containing the brachiocephalic vessels. Double- or triple-branched stent grafting has resulted in shifting or kinking of the graft and eventually graft occlusion or aortic disruption.

The authors acknowledged the study’s small sample size, and that the outcomes are “preliminary.” They said long-term follow-up would be required to confirm the outcomes.

They had no disclosures to report.

An acute aortic tear can be lethal, and more cardiac surgeons are favoring extended aortic arch replacement in these cases. Cardiac surgeons have tried many different arch replacement techniques, but en bloc repair and double- or triple-branch stent grafting carry significant risks, so a team of cardiac surgeons in Beijing has reported good 2-year results with a novel technique that combines stented elephant-trunk implantation with preservation of key vessels.

The technique accomplishes total arch replacement with the stent while preserving the autologous brachiocephalic vessels.

“This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic patch wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results,” wrote Dr. Li-Zhong Sun and colleagues at Beijing’s Capital Medical University (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.002]).

There are four keys to the procedure:

• The use of forceps to grasp the stent-free sewing edge of the stented elephant trunk and straightening of the spiral shaped Dacron graft to approximately 3 cm.

• Preservation of the native brachiocephalic vessels.

• Creating a residual aortic wall containing the innominate artery and LCCA that’s as small as possible.

• An end-to-side anastomosis between the left subclavian artery (LSCA) and the left common carotid artery (LCCA), a key junction in their technique.

The 20 study subjects had surgery within 2 weeks of the onset of pain. All 20 were discharged after the procedure, and in a mean follow-up period of 26 months, 18 had good outcomes while 1 patient had thoracoabdominal aortic replacement 9 months after the initial surgery (1 patient was lost to follow-up).

The researchers used computed tomography to confirm patency of the anastomosis between the LSCA and LCCA.

In 2 of the 20 patients, the aorta was normal with aortic dissection limited to the descending aorta. In the remaining patients, the investigators observed thrombus obliteration of the false lumen around the surgical graft in 16, partial thrombosis in 1 and patency in 1.

The surgical technique exposes the right axillary artery through a right subclavicular incision and a median sternotomy, then dissects and exposes the brachiocephalic vessels and the transverse arch. Dissection of the LSCA and LCCA is the key step in making the end-to-end anastomosis between the two vessels. The researchers accomplished this by partially transecting the sternocleidomastoid muscle and other cervical muscles.

Dr. Sun and coauthors said that a separated graft technique offers a number of advantages over other techniques for aortic arch reconstruction. While en bloc repair preserves the native brachiocephalic vessels and, thus, results in long-term patency, the technique carries risk for postoperative rupture of the aortic patch containing the brachiocephalic vessels. Double- or triple-branched stent grafting has resulted in shifting or kinking of the graft and eventually graft occlusion or aortic disruption.

The authors acknowledged the study’s small sample size, and that the outcomes are “preliminary.” They said long-term follow-up would be required to confirm the outcomes.

They had no disclosures to report.

An acute aortic tear can be lethal, and more cardiac surgeons are favoring extended aortic arch replacement in these cases. Cardiac surgeons have tried many different arch replacement techniques, but en bloc repair and double- or triple-branch stent grafting carry significant risks, so a team of cardiac surgeons in Beijing has reported good 2-year results with a novel technique that combines stented elephant-trunk implantation with preservation of key vessels.

The technique accomplishes total arch replacement with the stent while preserving the autologous brachiocephalic vessels.

“This technique simplified hemostasis and anastomosis, reduced the size of the residual aortic patch wall, and preserved the autologous brachiocephalic vessels, yielding satisfactory surgical results,” wrote Dr. Li-Zhong Sun and colleagues at Beijing’s Capital Medical University (J. Thorac. Cardiovasc. Surg. 2015 [doi:10.1016/j.jtcvs.2015.03.002]).

There are four keys to the procedure:

• The use of forceps to grasp the stent-free sewing edge of the stented elephant trunk and straightening of the spiral shaped Dacron graft to approximately 3 cm.

• Preservation of the native brachiocephalic vessels.

• Creating a residual aortic wall containing the innominate artery and LCCA that’s as small as possible.

• An end-to-side anastomosis between the left subclavian artery (LSCA) and the left common carotid artery (LCCA), a key junction in their technique.

The 20 study subjects had surgery within 2 weeks of the onset of pain. All 20 were discharged after the procedure, and in a mean follow-up period of 26 months, 18 had good outcomes while 1 patient had thoracoabdominal aortic replacement 9 months after the initial surgery (1 patient was lost to follow-up).

The researchers used computed tomography to confirm patency of the anastomosis between the LSCA and LCCA.

In 2 of the 20 patients, the aorta was normal with aortic dissection limited to the descending aorta. In the remaining patients, the investigators observed thrombus obliteration of the false lumen around the surgical graft in 16, partial thrombosis in 1 and patency in 1.

The surgical technique exposes the right axillary artery through a right subclavicular incision and a median sternotomy, then dissects and exposes the brachiocephalic vessels and the transverse arch. Dissection of the LSCA and LCCA is the key step in making the end-to-end anastomosis between the two vessels. The researchers accomplished this by partially transecting the sternocleidomastoid muscle and other cervical muscles.

Dr. Sun and coauthors said that a separated graft technique offers a number of advantages over other techniques for aortic arch reconstruction. While en bloc repair preserves the native brachiocephalic vessels and, thus, results in long-term patency, the technique carries risk for postoperative rupture of the aortic patch containing the brachiocephalic vessels. Double- or triple-branched stent grafting has resulted in shifting or kinking of the graft and eventually graft occlusion or aortic disruption.

The authors acknowledged the study’s small sample size, and that the outcomes are “preliminary.” They said long-term follow-up would be required to confirm the outcomes.

They had no disclosures to report.

The nature of U.S. transcatheter aortic valve replacement (TAVR) shifted dramatically in mid-June when the Food and Drug Administration, in two separate actions timed just days apart, approved marketing of next-generation models for the only two transcatheter aortic valve replacement systems on the U.S. market.

For inoperable or high-risk patients in came the Edwards Sapien 3 and the CoreValve Evolut R systems, and out went the Sapien XT and the original CoreValve. In the process the transcatheter aortic valve replacement (TAVR) procedures available to American patients on a routine basis became smaller – meaning more likely to use transfemoral approaches, less likely to cause substantial paravalvular leak, less likely to cause stroke, and in the case of the Evolut system also became repositionable and less likely to result in the need for a pacemaker.

With approvals of these two latest-generation devices, in both cases based on follow-up data of only 30 days, “we have really expanded the types of patients who can be treated with TAVR in the U.S., and we can do it with better products and get better outcomes. I am thrilled this technology will be available to patients,” said Dr. Jeffrey J. Popma, a lead investigator for the Evolut U.S. pivotal trial and professor of medicine at Harvard University in Boston.

Mitchel L. Zoler/Frontline Medical News

The pair of approvals were also notable as clear demonstration that the FDA was willing to base its decisions on 30-day follow-up data, a step closer to the approval model it applies to heart valves placed using open surgery. Perhaps most attention-grabbing of all, the FDA based its approval of the Evolut system on data from a total of 151 patients, with 60 coming from the ex-U.S. trial designed to secure a CE mark in Europe, and the other 91 patients the first ones enrolled in what was designed to be the U.S. pivotal trial for Evolut, with a planned enrollment of 250 patients that had almost fully filled by mid-June.

“This was a really good week for the FDA,” said Dr. Popma. “The FDA approved devices with reasonable assurance of safety and efficacy but without the burden of requiring 1 or more years follow-up. We are seeing a changed FDA,” he declared in an interview.

Although the full dataset for all 151 patients that the FDA used to approve the self-expanding Evolut system has not yet been released, investigators from the U.S. trial say data from their first 91 patients looked similar to the 60 patients in the CE trial, the results of which appeared in a poster in March at the annual scientific sessions of the American College of Cardiology.

The CE trial enrolled 60 symptomatic extreme- or high-risk patients at six centers in Australia, New Zealand, and the United Kingdom, who averaged 83 years old and had an average Society of Thoracic Surgeons predicted mortality estimate of 7%. Fifty-nine of the 60 patients (98%) had their TAVR done via the transfemoral route, and during 30-day follow-up no patients died and none had a stroke. The researchers identified a moderate or severe paravalvular leak in 3% of patients after 30 days, and 12% of patients had a new need for a pacemaker. By comparison, in the CoreValve pivotal trial for the first-generation version of this self-expanding valve, death occurred in 3% of patients after 30 days, major strokes in 4%, moderate or severe paravalvular leaks occurred in 9%, and 20% of patients by that point had required placement of a new pacemaker (N. Engl. J. Med. 2014;370:1790-8).

The striking reductions in more severe paravalvular leaks and in the need for a pacemaker likely related at least in part to the ability to reposition the Evolut valve during placement as long as the valve was not more than 80% deployed and as long as retrieval was not attempted more than three times.

Repositioning is “huge” said Dr. Mathew R. Williams, chief of adult cardiac surgery and director of interventional cardiology at New York University, and one of two lead investigators on the U.S. CoreValve Evolut R pivotal trial. “We don’t need to use it most of the time, but having that ability reduces stress and helps make the operator more comfortable,” he said in an interview. The more optimized positioning allowed by the recapture feature likely helped minimize both paravalvular leaks and the valve’s ability to trigger an arrhythmia and need for pacing. In the CE trial the operator used the repositioning function in 15 patients (25%) for a total of 22 repositioning events.

Like Dr. Popma, Dr. Williams welcomed the June 17 approval of the Sapien 3 TAVR system, based on 30-day outcomes from all 583 patients enrolled in the U.S. pivotal trial. Results from that study became public last March in a late-breaker report at the American College of Cardiology meeting.

Mitchel L. Zoler/Frontline Medical News

Sapien 3 treatment of high-risk, symptomatic patients, who averaged 83 years old and had a STS predicted mortality rate of 8.6%, resulted in a 2% mortality rate, a 1.5% stroke rate, a 3% rate of moderate or severe paravalvular leaks, and 13% of patients had a new need for a pacemaker, Dr. Susheel Kodali reported when he presented these data in March. Trial investigators were able to place the Sapien 3 aortic valve via a transfemoral approach in 491 of the 583 patients (84%) enrolled in the study. The adverse outcomes with Sapien 3 contrasted with rates for the prior Sapien XT TAVR system of 3.5% for 30-day mortality, 4.3% for strokes, and a 24% rate of moderate or severe paravalvular leak, said Dr. Kodali, director of the heart valve program at Columbia University in New York.

While the Sapien 3 and Evolut systems appeared to produce roughly similar outcomes for parameters like 30-day mortality, stroke, and paravalvular leak rates, with both systems outperforming what they displaced, the Evolut has two important differences, compared with Sapien 3. First, the Evolut is slightly smaller, with the ability to traverse arteries as narrow as 5 mm, whereas the minimum vessel size for Sapien 3 passage is 5.5 mm; second, Evolute is repositionable, while Sapien 3 is not.

The CoreValve Evolut R trials were sponsored by Medtronic. Dr. Popma has received research grants from and served as a speaker on behalf of Medtronic. He has also been a speaker for Abbott Vascular, Boston Scientific, Covidien, Cook Medical, and Direct Flow Medical and has received research support from five other companies. Dr. Williams has been a consultant to and received research support from Medtronic and has also been a consultant to Edwards and Direct Flow Medical. The Sapien 3 trial was sponsored by Edwards. Dr. Kodali has received research support from Edwards, has an equity interest in Thubrikar Aortic Valve, has received honoraria from St. Jude, and has served on the steering committee for trials sponsored by Claret Medical and Meril.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The nature of U.S. transcatheter aortic valve replacement (TAVR) shifted dramatically in mid-June when the Food and Drug Administration, in two separate actions timed just days apart, approved marketing of next-generation models for the only two transcatheter aortic valve replacement systems on the U.S. market.

For inoperable or high-risk patients in came the Edwards Sapien 3 and the CoreValve Evolut R systems, and out went the Sapien XT and the original CoreValve. In the process the transcatheter aortic valve replacement (TAVR) procedures available to American patients on a routine basis became smaller – meaning more likely to use transfemoral approaches, less likely to cause substantial paravalvular leak, less likely to cause stroke, and in the case of the Evolut system also became repositionable and less likely to result in the need for a pacemaker.

With approvals of these two latest-generation devices, in both cases based on follow-up data of only 30 days, “we have really expanded the types of patients who can be treated with TAVR in the U.S., and we can do it with better products and get better outcomes. I am thrilled this technology will be available to patients,” said Dr. Jeffrey J. Popma, a lead investigator for the Evolut U.S. pivotal trial and professor of medicine at Harvard University in Boston.

Mitchel L. Zoler/Frontline Medical News

The pair of approvals were also notable as clear demonstration that the FDA was willing to base its decisions on 30-day follow-up data, a step closer to the approval model it applies to heart valves placed using open surgery. Perhaps most attention-grabbing of all, the FDA based its approval of the Evolut system on data from a total of 151 patients, with 60 coming from the ex-U.S. trial designed to secure a CE mark in Europe, and the other 91 patients the first ones enrolled in what was designed to be the U.S. pivotal trial for Evolut, with a planned enrollment of 250 patients that had almost fully filled by mid-June.

“This was a really good week for the FDA,” said Dr. Popma. “The FDA approved devices with reasonable assurance of safety and efficacy but without the burden of requiring 1 or more years follow-up. We are seeing a changed FDA,” he declared in an interview.

Although the full dataset for all 151 patients that the FDA used to approve the self-expanding Evolut system has not yet been released, investigators from the U.S. trial say data from their first 91 patients looked similar to the 60 patients in the CE trial, the results of which appeared in a poster in March at the annual scientific sessions of the American College of Cardiology.

The CE trial enrolled 60 symptomatic extreme- or high-risk patients at six centers in Australia, New Zealand, and the United Kingdom, who averaged 83 years old and had an average Society of Thoracic Surgeons predicted mortality estimate of 7%. Fifty-nine of the 60 patients (98%) had their TAVR done via the transfemoral route, and during 30-day follow-up no patients died and none had a stroke. The researchers identified a moderate or severe paravalvular leak in 3% of patients after 30 days, and 12% of patients had a new need for a pacemaker. By comparison, in the CoreValve pivotal trial for the first-generation version of this self-expanding valve, death occurred in 3% of patients after 30 days, major strokes in 4%, moderate or severe paravalvular leaks occurred in 9%, and 20% of patients by that point had required placement of a new pacemaker (N. Engl. J. Med. 2014;370:1790-8).

The striking reductions in more severe paravalvular leaks and in the need for a pacemaker likely related at least in part to the ability to reposition the Evolut valve during placement as long as the valve was not more than 80% deployed and as long as retrieval was not attempted more than three times.

Repositioning is “huge” said Dr. Mathew R. Williams, chief of adult cardiac surgery and director of interventional cardiology at New York University, and one of two lead investigators on the U.S. CoreValve Evolut R pivotal trial. “We don’t need to use it most of the time, but having that ability reduces stress and helps make the operator more comfortable,” he said in an interview. The more optimized positioning allowed by the recapture feature likely helped minimize both paravalvular leaks and the valve’s ability to trigger an arrhythmia and need for pacing. In the CE trial the operator used the repositioning function in 15 patients (25%) for a total of 22 repositioning events.

Like Dr. Popma, Dr. Williams welcomed the June 17 approval of the Sapien 3 TAVR system, based on 30-day outcomes from all 583 patients enrolled in the U.S. pivotal trial. Results from that study became public last March in a late-breaker report at the American College of Cardiology meeting.

Mitchel L. Zoler/Frontline Medical News

Sapien 3 treatment of high-risk, symptomatic patients, who averaged 83 years old and had a STS predicted mortality rate of 8.6%, resulted in a 2% mortality rate, a 1.5% stroke rate, a 3% rate of moderate or severe paravalvular leaks, and 13% of patients had a new need for a pacemaker, Dr. Susheel Kodali reported when he presented these data in March. Trial investigators were able to place the Sapien 3 aortic valve via a transfemoral approach in 491 of the 583 patients (84%) enrolled in the study. The adverse outcomes with Sapien 3 contrasted with rates for the prior Sapien XT TAVR system of 3.5% for 30-day mortality, 4.3% for strokes, and a 24% rate of moderate or severe paravalvular leak, said Dr. Kodali, director of the heart valve program at Columbia University in New York.

While the Sapien 3 and Evolut systems appeared to produce roughly similar outcomes for parameters like 30-day mortality, stroke, and paravalvular leak rates, with both systems outperforming what they displaced, the Evolut has two important differences, compared with Sapien 3. First, the Evolut is slightly smaller, with the ability to traverse arteries as narrow as 5 mm, whereas the minimum vessel size for Sapien 3 passage is 5.5 mm; second, Evolute is repositionable, while Sapien 3 is not.

The CoreValve Evolut R trials were sponsored by Medtronic. Dr. Popma has received research grants from and served as a speaker on behalf of Medtronic. He has also been a speaker for Abbott Vascular, Boston Scientific, Covidien, Cook Medical, and Direct Flow Medical and has received research support from five other companies. Dr. Williams has been a consultant to and received research support from Medtronic and has also been a consultant to Edwards and Direct Flow Medical. The Sapien 3 trial was sponsored by Edwards. Dr. Kodali has received research support from Edwards, has an equity interest in Thubrikar Aortic Valve, has received honoraria from St. Jude, and has served on the steering committee for trials sponsored by Claret Medical and Meril.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

The nature of U.S. transcatheter aortic valve replacement (TAVR) shifted dramatically in mid-June when the Food and Drug Administration, in two separate actions timed just days apart, approved marketing of next-generation models for the only two transcatheter aortic valve replacement systems on the U.S. market.

For inoperable or high-risk patients in came the Edwards Sapien 3 and the CoreValve Evolut R systems, and out went the Sapien XT and the original CoreValve. In the process the transcatheter aortic valve replacement (TAVR) procedures available to American patients on a routine basis became smaller – meaning more likely to use transfemoral approaches, less likely to cause substantial paravalvular leak, less likely to cause stroke, and in the case of the Evolut system also became repositionable and less likely to result in the need for a pacemaker.

With approvals of these two latest-generation devices, in both cases based on follow-up data of only 30 days, “we have really expanded the types of patients who can be treated with TAVR in the U.S., and we can do it with better products and get better outcomes. I am thrilled this technology will be available to patients,” said Dr. Jeffrey J. Popma, a lead investigator for the Evolut U.S. pivotal trial and professor of medicine at Harvard University in Boston.

Mitchel L. Zoler/Frontline Medical News

The pair of approvals were also notable as clear demonstration that the FDA was willing to base its decisions on 30-day follow-up data, a step closer to the approval model it applies to heart valves placed using open surgery. Perhaps most attention-grabbing of all, the FDA based its approval of the Evolut system on data from a total of 151 patients, with 60 coming from the ex-U.S. trial designed to secure a CE mark in Europe, and the other 91 patients the first ones enrolled in what was designed to be the U.S. pivotal trial for Evolut, with a planned enrollment of 250 patients that had almost fully filled by mid-June.

“This was a really good week for the FDA,” said Dr. Popma. “The FDA approved devices with reasonable assurance of safety and efficacy but without the burden of requiring 1 or more years follow-up. We are seeing a changed FDA,” he declared in an interview.

Although the full dataset for all 151 patients that the FDA used to approve the self-expanding Evolut system has not yet been released, investigators from the U.S. trial say data from their first 91 patients looked similar to the 60 patients in the CE trial, the results of which appeared in a poster in March at the annual scientific sessions of the American College of Cardiology.

The CE trial enrolled 60 symptomatic extreme- or high-risk patients at six centers in Australia, New Zealand, and the United Kingdom, who averaged 83 years old and had an average Society of Thoracic Surgeons predicted mortality estimate of 7%. Fifty-nine of the 60 patients (98%) had their TAVR done via the transfemoral route, and during 30-day follow-up no patients died and none had a stroke. The researchers identified a moderate or severe paravalvular leak in 3% of patients after 30 days, and 12% of patients had a new need for a pacemaker. By comparison, in the CoreValve pivotal trial for the first-generation version of this self-expanding valve, death occurred in 3% of patients after 30 days, major strokes in 4%, moderate or severe paravalvular leaks occurred in 9%, and 20% of patients by that point had required placement of a new pacemaker (N. Engl. J. Med. 2014;370:1790-8).

The striking reductions in more severe paravalvular leaks and in the need for a pacemaker likely related at least in part to the ability to reposition the Evolut valve during placement as long as the valve was not more than 80% deployed and as long as retrieval was not attempted more than three times.

Repositioning is “huge” said Dr. Mathew R. Williams, chief of adult cardiac surgery and director of interventional cardiology at New York University, and one of two lead investigators on the U.S. CoreValve Evolut R pivotal trial. “We don’t need to use it most of the time, but having that ability reduces stress and helps make the operator more comfortable,” he said in an interview. The more optimized positioning allowed by the recapture feature likely helped minimize both paravalvular leaks and the valve’s ability to trigger an arrhythmia and need for pacing. In the CE trial the operator used the repositioning function in 15 patients (25%) for a total of 22 repositioning events.

Like Dr. Popma, Dr. Williams welcomed the June 17 approval of the Sapien 3 TAVR system, based on 30-day outcomes from all 583 patients enrolled in the U.S. pivotal trial. Results from that study became public last March in a late-breaker report at the American College of Cardiology meeting.

Mitchel L. Zoler/Frontline Medical News

Sapien 3 treatment of high-risk, symptomatic patients, who averaged 83 years old and had a STS predicted mortality rate of 8.6%, resulted in a 2% mortality rate, a 1.5% stroke rate, a 3% rate of moderate or severe paravalvular leaks, and 13% of patients had a new need for a pacemaker, Dr. Susheel Kodali reported when he presented these data in March. Trial investigators were able to place the Sapien 3 aortic valve via a transfemoral approach in 491 of the 583 patients (84%) enrolled in the study. The adverse outcomes with Sapien 3 contrasted with rates for the prior Sapien XT TAVR system of 3.5% for 30-day mortality, 4.3% for strokes, and a 24% rate of moderate or severe paravalvular leak, said Dr. Kodali, director of the heart valve program at Columbia University in New York.

While the Sapien 3 and Evolut systems appeared to produce roughly similar outcomes for parameters like 30-day mortality, stroke, and paravalvular leak rates, with both systems outperforming what they displaced, the Evolut has two important differences, compared with Sapien 3. First, the Evolut is slightly smaller, with the ability to traverse arteries as narrow as 5 mm, whereas the minimum vessel size for Sapien 3 passage is 5.5 mm; second, Evolute is repositionable, while Sapien 3 is not.

The CoreValve Evolut R trials were sponsored by Medtronic. Dr. Popma has received research grants from and served as a speaker on behalf of Medtronic. He has also been a speaker for Abbott Vascular, Boston Scientific, Covidien, Cook Medical, and Direct Flow Medical and has received research support from five other companies. Dr. Williams has been a consultant to and received research support from Medtronic and has also been a consultant to Edwards and Direct Flow Medical. The Sapien 3 trial was sponsored by Edwards. Dr. Kodali has received research support from Edwards, has an equity interest in Thubrikar Aortic Valve, has received honoraria from St. Jude, and has served on the steering committee for trials sponsored by Claret Medical and Meril.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler