SAN ANTONIO – A new pain relief option for multiple rib fractures means that you might not have to wait around anymore for anesthesiology to place thoracic epidurals.

It’s called posterior paramedian subrhomboidal (PoPS) analgesia. A skin incision is made below the lowest fractured rib just paramedian to the spinus processes; a tunneling device is then used to work a catheter upwards under the rhomboids just past the highest fractured rib. The catheter has multiple openings along its length – like a sprinkler hose – so analgesic bathes the intercostal nerves as it runs down from a reservoir into the patient. The reservoir can be set to a desired flow rate or for on-demand use (ON-Q Pain Relief System – Halyard).

A pilot study at the University of Kansas, Kansas City, found that pain control from PoPS was at least equivalent to standard thoracic epidural analgesia (TEA), and that the system can be placed by a variety of hospital staff, not just anesthesiologists.

The 11 PoPS patients also used fewer rescue narcotics than the 19 TEA patients and had less hypotension. Because they weren’t at risk for epidural hematomas, they started venous thromboembolism prophylaxis without delay and at full dose.

“Our results are very promising. PoPS provides pain control similar to that of TEA,” with several “other benefits. You are not relying on one specialty for pain control,” so patients probably get faster relief. “PoPS can also be placed in patients whose injuries prohibit TEA, such as those with spinal cord injuries or increased intracranial pressure,” said investigator Dr. Casey Shelley, a University of Kansas general surgery resident.

PoPS was placed in the study either by anesthesiologists or by a trauma surgeon who practiced placement beforehand in the cadaver lab. The do-it-yourself potential for surgeons “is key. Most of us trauma surgeons are sick of begging anesthesiologists to come place thoracic epidurals,” said an audience member after Dr. Shelley’s presentation at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Courtesy of Dr. Michael Truitt, Methodist Dallas Medical Center

Ropivacaine 0.2% was used in both PoPS and TEA patients, all of whom had at least three broken ribs.

Median pain scores dropped from 8.5 to 2.5 on a 10-point scale an hour after PoPS placement, versus a median drop from 8 to 5 points an hour after TEA (P = .03). Although not statistically significant, median pain scores were about 1.5 points better with PoPS over the next several days, hovering around 3.5 versus around 5 points with TEA. Anesthesiology “usually won’t place high thoracic epidurals. With PoPS, you can tunnel up as far as you need to go to get to higher ribs,” which might explain the better pain control, Dr. Shelley said.

PoPS patients used about 70 mg/day oral morphine equivalents versus about 90 mg/day with TEA through day 6, but again the difference was not statistically significant. Even so, it might explain why six TEA patients (32%) were hypotensive over that time, compared with two PoPS patients (18%).

PoPS patients were a little older on average (mean 63 versus 55 years), with more fractured ribs (mean eight versus seven), and higher Injury Severity Scale scores (mean 20 versus 16). They were also more likely to have bilateral fractures, longer ICU stays (mean 4.9 versus 3.1 days), and longer overall lengths of stay (mean 14.8 versus 9.8 days), but none of those trends were statistically significant.

Both groups had mean chest Abbreviated Injury Scale scores of 3, and there were no statistical differences in daily spirometry readings. The majority of patients in both groups were men.

Favorable results were also reported in 2010 for ON-Q rib pain control, but the investigators did not compare the system to TEA (World J Surg. 2010 Oct;34:2359-62).

Dr. Shelley said Halyard was not involved in the study, and that she has no disclosures.

aotto@frontlinemedcom.com

SAN ANTONIO – A new pain relief option for multiple rib fractures means that you might not have to wait around anymore for anesthesiology to place thoracic epidurals.

It’s called posterior paramedian subrhomboidal (PoPS) analgesia. A skin incision is made below the lowest fractured rib just paramedian to the spinus processes; a tunneling device is then used to work a catheter upwards under the rhomboids just past the highest fractured rib. The catheter has multiple openings along its length – like a sprinkler hose – so analgesic bathes the intercostal nerves as it runs down from a reservoir into the patient. The reservoir can be set to a desired flow rate or for on-demand use (ON-Q Pain Relief System – Halyard).

A pilot study at the University of Kansas, Kansas City, found that pain control from PoPS was at least equivalent to standard thoracic epidural analgesia (TEA), and that the system can be placed by a variety of hospital staff, not just anesthesiologists.

The 11 PoPS patients also used fewer rescue narcotics than the 19 TEA patients and had less hypotension. Because they weren’t at risk for epidural hematomas, they started venous thromboembolism prophylaxis without delay and at full dose.

“Our results are very promising. PoPS provides pain control similar to that of TEA,” with several “other benefits. You are not relying on one specialty for pain control,” so patients probably get faster relief. “PoPS can also be placed in patients whose injuries prohibit TEA, such as those with spinal cord injuries or increased intracranial pressure,” said investigator Dr. Casey Shelley, a University of Kansas general surgery resident.

PoPS was placed in the study either by anesthesiologists or by a trauma surgeon who practiced placement beforehand in the cadaver lab. The do-it-yourself potential for surgeons “is key. Most of us trauma surgeons are sick of begging anesthesiologists to come place thoracic epidurals,” said an audience member after Dr. Shelley’s presentation at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Courtesy of Dr. Michael Truitt, Methodist Dallas Medical Center

Ropivacaine 0.2% was used in both PoPS and TEA patients, all of whom had at least three broken ribs.

Median pain scores dropped from 8.5 to 2.5 on a 10-point scale an hour after PoPS placement, versus a median drop from 8 to 5 points an hour after TEA (P = .03). Although not statistically significant, median pain scores were about 1.5 points better with PoPS over the next several days, hovering around 3.5 versus around 5 points with TEA. Anesthesiology “usually won’t place high thoracic epidurals. With PoPS, you can tunnel up as far as you need to go to get to higher ribs,” which might explain the better pain control, Dr. Shelley said.

PoPS patients used about 70 mg/day oral morphine equivalents versus about 90 mg/day with TEA through day 6, but again the difference was not statistically significant. Even so, it might explain why six TEA patients (32%) were hypotensive over that time, compared with two PoPS patients (18%).

PoPS patients were a little older on average (mean 63 versus 55 years), with more fractured ribs (mean eight versus seven), and higher Injury Severity Scale scores (mean 20 versus 16). They were also more likely to have bilateral fractures, longer ICU stays (mean 4.9 versus 3.1 days), and longer overall lengths of stay (mean 14.8 versus 9.8 days), but none of those trends were statistically significant.

Both groups had mean chest Abbreviated Injury Scale scores of 3, and there were no statistical differences in daily spirometry readings. The majority of patients in both groups were men.

Favorable results were also reported in 2010 for ON-Q rib pain control, but the investigators did not compare the system to TEA (World J Surg. 2010 Oct;34:2359-62).

Dr. Shelley said Halyard was not involved in the study, and that she has no disclosures.

aotto@frontlinemedcom.com

SAN ANTONIO – A new pain relief option for multiple rib fractures means that you might not have to wait around anymore for anesthesiology to place thoracic epidurals.

It’s called posterior paramedian subrhomboidal (PoPS) analgesia. A skin incision is made below the lowest fractured rib just paramedian to the spinus processes; a tunneling device is then used to work a catheter upwards under the rhomboids just past the highest fractured rib. The catheter has multiple openings along its length – like a sprinkler hose – so analgesic bathes the intercostal nerves as it runs down from a reservoir into the patient. The reservoir can be set to a desired flow rate or for on-demand use (ON-Q Pain Relief System – Halyard).

A pilot study at the University of Kansas, Kansas City, found that pain control from PoPS was at least equivalent to standard thoracic epidural analgesia (TEA), and that the system can be placed by a variety of hospital staff, not just anesthesiologists.

The 11 PoPS patients also used fewer rescue narcotics than the 19 TEA patients and had less hypotension. Because they weren’t at risk for epidural hematomas, they started venous thromboembolism prophylaxis without delay and at full dose.

“Our results are very promising. PoPS provides pain control similar to that of TEA,” with several “other benefits. You are not relying on one specialty for pain control,” so patients probably get faster relief. “PoPS can also be placed in patients whose injuries prohibit TEA, such as those with spinal cord injuries or increased intracranial pressure,” said investigator Dr. Casey Shelley, a University of Kansas general surgery resident.

PoPS was placed in the study either by anesthesiologists or by a trauma surgeon who practiced placement beforehand in the cadaver lab. The do-it-yourself potential for surgeons “is key. Most of us trauma surgeons are sick of begging anesthesiologists to come place thoracic epidurals,” said an audience member after Dr. Shelley’s presentation at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Courtesy of Dr. Michael Truitt, Methodist Dallas Medical Center

Ropivacaine 0.2% was used in both PoPS and TEA patients, all of whom had at least three broken ribs.

Median pain scores dropped from 8.5 to 2.5 on a 10-point scale an hour after PoPS placement, versus a median drop from 8 to 5 points an hour after TEA (P = .03). Although not statistically significant, median pain scores were about 1.5 points better with PoPS over the next several days, hovering around 3.5 versus around 5 points with TEA. Anesthesiology “usually won’t place high thoracic epidurals. With PoPS, you can tunnel up as far as you need to go to get to higher ribs,” which might explain the better pain control, Dr. Shelley said.

PoPS patients used about 70 mg/day oral morphine equivalents versus about 90 mg/day with TEA through day 6, but again the difference was not statistically significant. Even so, it might explain why six TEA patients (32%) were hypotensive over that time, compared with two PoPS patients (18%).

PoPS patients were a little older on average (mean 63 versus 55 years), with more fractured ribs (mean eight versus seven), and higher Injury Severity Scale scores (mean 20 versus 16). They were also more likely to have bilateral fractures, longer ICU stays (mean 4.9 versus 3.1 days), and longer overall lengths of stay (mean 14.8 versus 9.8 days), but none of those trends were statistically significant.

Both groups had mean chest Abbreviated Injury Scale scores of 3, and there were no statistical differences in daily spirometry readings. The majority of patients in both groups were men.

Favorable results were also reported in 2010 for ON-Q rib pain control, but the investigators did not compare the system to TEA (World J Surg. 2010 Oct;34:2359-62).

Dr. Shelley said Halyard was not involved in the study, and that she has no disclosures.

aotto@frontlinemedcom.com

EVIDENCE SUMMARY

A Cochrane systematic review of 5 RCTs with a total of 7314 patients evaluated cardiovascular outcomes after 4.7 years follow-up in patients with diabetes who were treated for hypertension to either “lower” or “standard” target blood pressures.¹ One trial in the review (ACCORD, 4734 patients) compared outcomes from significantly lower and standard systolic blood pressures (119/64 mm Hg vs 134/71 mm Hg; P<.0001) in patients with diabetes and either cardiovascular disease or 2 risk factors for cardiovascular disease. The authors evaluated outcomes based on achieved systolic blood pressures rather than intention to treat.

They found a reduced incidence of stroke (risk ratio [RR]=0.58; 95% confidence interval [CI], 0.39-0.88; P=.009; number needed to treat [NNT]=91) but no change in mortality (RR=1.05; 95% CI, 0.84-1.30) at lower blood pressures. Achieving the lower systolic blood pressure increased the number of serious adverse effects, however (RR=2.58; 95% CI, 1.70-3.91; P<.0001; absolute risk increase=2%; number needed to harm=50).

Four RCTs (2580 patients) in the systematic review compared clinical outcomes produced by achieving significantly lower or standard diastolic blood pressure targets (128/76 mm Hg vs 135/83 mm Hg; P<.0001). The trials found no significant difference in total mortality (RR=0.73; 95% CI, 0.53-1.01), stroke (RR=0.67; 95% CI, 0.42-1.05), myocardial infarction (RR=0.95; 95% CI, 0.64-1.40), or congestive heart failure (RR=1.06; 95% CI, 0.58-1.92). Sensitivity analysis of trials comparing diastolic blood pressure targets below 80 mm Hg and below 90 mm Hg showed similar results.

The 4 RCTs didn’t report end-stage renal failure or total serious adverse events. The authors stated that there was a high risk of selection bias in favor of lower blood pressure targets.

Patients with CKD

A systematic review and meta-analysis of 11 RCTs (9287 patients) compared outcomes of achieving lower blood pressure targets or standard targets in patients with CKD. Intensive blood pressure treatment reduced the risk of kidney failure only in patients with proteinuria at baseline (hazard ratio [HR]=0.73; 95% CI, 0.62-0.86; 5 trials, 1703 patients).² Investigators didn’t report the degree of proteinuria for all the trials, but in one trial, patients had proteinuria of 1 to 3 g/d.

Achieved blood pressures in the intensive therapy group averaged 7.7/4.9 mm Hg lower, with pressures typically ranging from 75 to 80 mm Hg diastolic and 125 to 135 mm Hg systolic. Intensive blood pressure lowering didn’t reduce kidney failure in patients without baseline proteinuria (HR=1.12; 95% CI, 0.67-1.87; 3 trials, 1218 patients). Nor did it reduce death (RR=0.94; 95% CI, 0.84-1.05; 10 trials, 6788 patients) or major cardiovascular outcomes (RR=1.09; 95% CI, 0.83-1.42; 5 trials, 5308 patients).

Patients with coronary artery disease

A meta-analysis of 15 RCTs (66,504 patients) that evaluated tight control of hypertension (≤130/80 mm Hg) compared with standard control (<140/90 mm Hg) in patients with coronary artery disease found reduced rates of heart failure (RR=0.73; 95% CI, 0.64-0.84; 10 trials, 37,990 patients) and stroke (RR=0.82; 95% CI, 0.69-0.98; 9 trials, 8344 patients) but increased rates of hypotension (RR=2.19; 95% CI, 1.80-2.66; 6 trials, 17,836 patients).³

Achieving lower blood pressure targets didn’t reduce all-cause mortality (RR=0.96; 95% CI, 0.89-1.04; 13 trials, 39,262 patients), cardiovascular mortality (RR=0.96; 95% CI, 0.86-1.07; 11 trials, 38,452 patients), myocardial infarction (RR=0.92; 95% CI, 0.85-1.00; 14 trials, 39,696 patients), or angina (RR=0.92; 95% CI, 0.84-1.0; 11 trials, 28,007 patients).  But it slightly increased the need for revascularization (RR=1.06; 95% CI, 1.01-1.12; 11 trials, 38,450 patients).

The SPRINT trial: Promising results for intensive treatment of some patients

The Systolic Blood Pressure Intervention Trial (SPRINT), a large RCT, found that targeting systolic blood pressures below 120 mm Hg (compared with a target below 140 mm Hg) in middle-aged and older patients with increased cardiovascular risk reduced a composite outcome that included cardiovascular death by 25%.⁴

Researchers recruited 9361 patients older than 50 years (mean age 68 years; >28% older than 75 years) with systolic blood pressure between 130 and 180 mm Hg and increased cardiovascular risk defined by one or more of the following: preexisting cardiovascular disease, CKD with estimated glomerular filtration rate between 20 and 60 mL/min/1.73 m², age >75 years, and Framingham 10-year risk of 15% or more. They excluded patients with diabetes or previous stroke.

Patients were randomized to intensive treatment (target systolic BP <120; mean achieved 121.4) or standard treatment (target systolic BP <140; mean achieved 136.2). Treatment typically comprised 3 (intensive) or 2 (standard) agents. The primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or cardiovascular death.

The study, which was originally intended to run for 5 years, was stopped at 3.26 years based on positive results. Intensive treatment improved the primary composite outcome overall (1.65% vs 2.19%; HR=0.75; 95% CI, 0.64-0.89; P<.001; NNT=61 over 3.26 years), all-cause mortality (HR=0.73; 95% CI, 0.60-0.90; P=.003; NNT=90), and cardiovascular death (HR=0.57; 95% CI, 0.38-0.85; P=.005; NNT=172).

However, intensive treatment didn’t significantly improve the primary composite outcome in these subgroups:

• female patients (HR=0.84; 95% CI, 0.62-1.14)
• black patients (HR=0.77; 95% CI, 0.55-1.06)
• patients with preexisting CKD (HR=0.82; 95% CI, 0.63-1.07) or cardiovascular disease (HR=0.83; 95% CI, 0.62-1.09)
• patients younger than 75 years (HR=0.80; 95% CI, 0.64-1.00)
• patients with systolic blood pressures higher than 132 mm Hg (BP >132 to <145 mm Hg, HR=0.77; 95% CI, 0.57-1.03; BP ≥145 mm Hg, HR=0.83; 95% CI, 0.63-1.09).

While the SPRINT study found that targeting systolic BP below 120 mm Hg reduced a composite outcome that included cardiovascular death, it didn’t improve this outcome in certain patient subgroups.

Intensive treatment also produced more net serious adverse events (HR=1.88; 4.7% vs 2.5%; P<.001), including: ≥30% decrease of glomerular filtration rates to values below 60 mL/min/1.73 m² (HR=3.49; 95% CI, 2.44-5.10; P<.001), syncope (HR=1.44; 3.5% vs 2.4%; P=.003), hypotension (HR=1.70; 3.4% vs 2.0%; P<.001), and electrolyte abnormalities (HR=1.38; 3.8% vs 2.8%; P=.006). It didn’t cause injurious falls (HR=1.00; P=.97) or orthostatic hypotension in clinic (HR=0.88; 16.6% vs 18.3%; P=.01).

Guidelines for patients with peripheral artery disease, previous stroke

A national guideline by an expert panel recommended treating patients with hypertension who have peripheral artery disease or previous stroke to standard values for the general population: <140/90 mm Hg if ages 60 years or younger, <150/90 mm Hg if older than 60 years.⁵ 

EVIDENCE SUMMARY

A Cochrane systematic review of 5 RCTs with a total of 7314 patients evaluated cardiovascular outcomes after 4.7 years follow-up in patients with diabetes who were treated for hypertension to either “lower” or “standard” target blood pressures.¹ One trial in the review (ACCORD, 4734 patients) compared outcomes from significantly lower and standard systolic blood pressures (119/64 mm Hg vs 134/71 mm Hg; P<.0001) in patients with diabetes and either cardiovascular disease or 2 risk factors for cardiovascular disease. The authors evaluated outcomes based on achieved systolic blood pressures rather than intention to treat.

They found a reduced incidence of stroke (risk ratio [RR]=0.58; 95% confidence interval [CI], 0.39-0.88; P=.009; number needed to treat [NNT]=91) but no change in mortality (RR=1.05; 95% CI, 0.84-1.30) at lower blood pressures. Achieving the lower systolic blood pressure increased the number of serious adverse effects, however (RR=2.58; 95% CI, 1.70-3.91; P<.0001; absolute risk increase=2%; number needed to harm=50).

Four RCTs (2580 patients) in the systematic review compared clinical outcomes produced by achieving significantly lower or standard diastolic blood pressure targets (128/76 mm Hg vs 135/83 mm Hg; P<.0001). The trials found no significant difference in total mortality (RR=0.73; 95% CI, 0.53-1.01), stroke (RR=0.67; 95% CI, 0.42-1.05), myocardial infarction (RR=0.95; 95% CI, 0.64-1.40), or congestive heart failure (RR=1.06; 95% CI, 0.58-1.92). Sensitivity analysis of trials comparing diastolic blood pressure targets below 80 mm Hg and below 90 mm Hg showed similar results.

The 4 RCTs didn’t report end-stage renal failure or total serious adverse events. The authors stated that there was a high risk of selection bias in favor of lower blood pressure targets.

Patients with CKD

A systematic review and meta-analysis of 11 RCTs (9287 patients) compared outcomes of achieving lower blood pressure targets or standard targets in patients with CKD. Intensive blood pressure treatment reduced the risk of kidney failure only in patients with proteinuria at baseline (hazard ratio [HR]=0.73; 95% CI, 0.62-0.86; 5 trials, 1703 patients).² Investigators didn’t report the degree of proteinuria for all the trials, but in one trial, patients had proteinuria of 1 to 3 g/d.

Achieved blood pressures in the intensive therapy group averaged 7.7/4.9 mm Hg lower, with pressures typically ranging from 75 to 80 mm Hg diastolic and 125 to 135 mm Hg systolic. Intensive blood pressure lowering didn’t reduce kidney failure in patients without baseline proteinuria (HR=1.12; 95% CI, 0.67-1.87; 3 trials, 1218 patients). Nor did it reduce death (RR=0.94; 95% CI, 0.84-1.05; 10 trials, 6788 patients) or major cardiovascular outcomes (RR=1.09; 95% CI, 0.83-1.42; 5 trials, 5308 patients).

Patients with coronary artery disease

A meta-analysis of 15 RCTs (66,504 patients) that evaluated tight control of hypertension (≤130/80 mm Hg) compared with standard control (<140/90 mm Hg) in patients with coronary artery disease found reduced rates of heart failure (RR=0.73; 95% CI, 0.64-0.84; 10 trials, 37,990 patients) and stroke (RR=0.82; 95% CI, 0.69-0.98; 9 trials, 8344 patients) but increased rates of hypotension (RR=2.19; 95% CI, 1.80-2.66; 6 trials, 17,836 patients).³

Achieving lower blood pressure targets didn’t reduce all-cause mortality (RR=0.96; 95% CI, 0.89-1.04; 13 trials, 39,262 patients), cardiovascular mortality (RR=0.96; 95% CI, 0.86-1.07; 11 trials, 38,452 patients), myocardial infarction (RR=0.92; 95% CI, 0.85-1.00; 14 trials, 39,696 patients), or angina (RR=0.92; 95% CI, 0.84-1.0; 11 trials, 28,007 patients).  But it slightly increased the need for revascularization (RR=1.06; 95% CI, 1.01-1.12; 11 trials, 38,450 patients).

The SPRINT trial: Promising results for intensive treatment of some patients

The Systolic Blood Pressure Intervention Trial (SPRINT), a large RCT, found that targeting systolic blood pressures below 120 mm Hg (compared with a target below 140 mm Hg) in middle-aged and older patients with increased cardiovascular risk reduced a composite outcome that included cardiovascular death by 25%.⁴

Researchers recruited 9361 patients older than 50 years (mean age 68 years; >28% older than 75 years) with systolic blood pressure between 130 and 180 mm Hg and increased cardiovascular risk defined by one or more of the following: preexisting cardiovascular disease, CKD with estimated glomerular filtration rate between 20 and 60 mL/min/1.73 m², age >75 years, and Framingham 10-year risk of 15% or more. They excluded patients with diabetes or previous stroke.

Patients were randomized to intensive treatment (target systolic BP <120; mean achieved 121.4) or standard treatment (target systolic BP <140; mean achieved 136.2). Treatment typically comprised 3 (intensive) or 2 (standard) agents. The primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or cardiovascular death.

The study, which was originally intended to run for 5 years, was stopped at 3.26 years based on positive results. Intensive treatment improved the primary composite outcome overall (1.65% vs 2.19%; HR=0.75; 95% CI, 0.64-0.89; P<.001; NNT=61 over 3.26 years), all-cause mortality (HR=0.73; 95% CI, 0.60-0.90; P=.003; NNT=90), and cardiovascular death (HR=0.57; 95% CI, 0.38-0.85; P=.005; NNT=172).

However, intensive treatment didn’t significantly improve the primary composite outcome in these subgroups:

• female patients (HR=0.84; 95% CI, 0.62-1.14)
• black patients (HR=0.77; 95% CI, 0.55-1.06)
• patients with preexisting CKD (HR=0.82; 95% CI, 0.63-1.07) or cardiovascular disease (HR=0.83; 95% CI, 0.62-1.09)
• patients younger than 75 years (HR=0.80; 95% CI, 0.64-1.00)
• patients with systolic blood pressures higher than 132 mm Hg (BP >132 to <145 mm Hg, HR=0.77; 95% CI, 0.57-1.03; BP ≥145 mm Hg, HR=0.83; 95% CI, 0.63-1.09).

While the SPRINT study found that targeting systolic BP below 120 mm Hg reduced a composite outcome that included cardiovascular death, it didn’t improve this outcome in certain patient subgroups.

Intensive treatment also produced more net serious adverse events (HR=1.88; 4.7% vs 2.5%; P<.001), including: ≥30% decrease of glomerular filtration rates to values below 60 mL/min/1.73 m² (HR=3.49; 95% CI, 2.44-5.10; P<.001), syncope (HR=1.44; 3.5% vs 2.4%; P=.003), hypotension (HR=1.70; 3.4% vs 2.0%; P<.001), and electrolyte abnormalities (HR=1.38; 3.8% vs 2.8%; P=.006). It didn’t cause injurious falls (HR=1.00; P=.97) or orthostatic hypotension in clinic (HR=0.88; 16.6% vs 18.3%; P=.01).

Guidelines for patients with peripheral artery disease, previous stroke

A national guideline by an expert panel recommended treating patients with hypertension who have peripheral artery disease or previous stroke to standard values for the general population: <140/90 mm Hg if ages 60 years or younger, <150/90 mm Hg if older than 60 years.⁵ 

EVIDENCE SUMMARY

A Cochrane systematic review of 5 RCTs with a total of 7314 patients evaluated cardiovascular outcomes after 4.7 years follow-up in patients with diabetes who were treated for hypertension to either “lower” or “standard” target blood pressures.¹ One trial in the review (ACCORD, 4734 patients) compared outcomes from significantly lower and standard systolic blood pressures (119/64 mm Hg vs 134/71 mm Hg; P<.0001) in patients with diabetes and either cardiovascular disease or 2 risk factors for cardiovascular disease. The authors evaluated outcomes based on achieved systolic blood pressures rather than intention to treat.

They found a reduced incidence of stroke (risk ratio [RR]=0.58; 95% confidence interval [CI], 0.39-0.88; P=.009; number needed to treat [NNT]=91) but no change in mortality (RR=1.05; 95% CI, 0.84-1.30) at lower blood pressures. Achieving the lower systolic blood pressure increased the number of serious adverse effects, however (RR=2.58; 95% CI, 1.70-3.91; P<.0001; absolute risk increase=2%; number needed to harm=50).

Four RCTs (2580 patients) in the systematic review compared clinical outcomes produced by achieving significantly lower or standard diastolic blood pressure targets (128/76 mm Hg vs 135/83 mm Hg; P<.0001). The trials found no significant difference in total mortality (RR=0.73; 95% CI, 0.53-1.01), stroke (RR=0.67; 95% CI, 0.42-1.05), myocardial infarction (RR=0.95; 95% CI, 0.64-1.40), or congestive heart failure (RR=1.06; 95% CI, 0.58-1.92). Sensitivity analysis of trials comparing diastolic blood pressure targets below 80 mm Hg and below 90 mm Hg showed similar results.

The 4 RCTs didn’t report end-stage renal failure or total serious adverse events. The authors stated that there was a high risk of selection bias in favor of lower blood pressure targets.

Patients with CKD

A systematic review and meta-analysis of 11 RCTs (9287 patients) compared outcomes of achieving lower blood pressure targets or standard targets in patients with CKD. Intensive blood pressure treatment reduced the risk of kidney failure only in patients with proteinuria at baseline (hazard ratio [HR]=0.73; 95% CI, 0.62-0.86; 5 trials, 1703 patients).² Investigators didn’t report the degree of proteinuria for all the trials, but in one trial, patients had proteinuria of 1 to 3 g/d.

Achieved blood pressures in the intensive therapy group averaged 7.7/4.9 mm Hg lower, with pressures typically ranging from 75 to 80 mm Hg diastolic and 125 to 135 mm Hg systolic. Intensive blood pressure lowering didn’t reduce kidney failure in patients without baseline proteinuria (HR=1.12; 95% CI, 0.67-1.87; 3 trials, 1218 patients). Nor did it reduce death (RR=0.94; 95% CI, 0.84-1.05; 10 trials, 6788 patients) or major cardiovascular outcomes (RR=1.09; 95% CI, 0.83-1.42; 5 trials, 5308 patients).

Patients with coronary artery disease

A meta-analysis of 15 RCTs (66,504 patients) that evaluated tight control of hypertension (≤130/80 mm Hg) compared with standard control (<140/90 mm Hg) in patients with coronary artery disease found reduced rates of heart failure (RR=0.73; 95% CI, 0.64-0.84; 10 trials, 37,990 patients) and stroke (RR=0.82; 95% CI, 0.69-0.98; 9 trials, 8344 patients) but increased rates of hypotension (RR=2.19; 95% CI, 1.80-2.66; 6 trials, 17,836 patients).³

Achieving lower blood pressure targets didn’t reduce all-cause mortality (RR=0.96; 95% CI, 0.89-1.04; 13 trials, 39,262 patients), cardiovascular mortality (RR=0.96; 95% CI, 0.86-1.07; 11 trials, 38,452 patients), myocardial infarction (RR=0.92; 95% CI, 0.85-1.00; 14 trials, 39,696 patients), or angina (RR=0.92; 95% CI, 0.84-1.0; 11 trials, 28,007 patients).  But it slightly increased the need for revascularization (RR=1.06; 95% CI, 1.01-1.12; 11 trials, 38,450 patients).

The SPRINT trial: Promising results for intensive treatment of some patients

The Systolic Blood Pressure Intervention Trial (SPRINT), a large RCT, found that targeting systolic blood pressures below 120 mm Hg (compared with a target below 140 mm Hg) in middle-aged and older patients with increased cardiovascular risk reduced a composite outcome that included cardiovascular death by 25%.⁴

Researchers recruited 9361 patients older than 50 years (mean age 68 years; >28% older than 75 years) with systolic blood pressure between 130 and 180 mm Hg and increased cardiovascular risk defined by one or more of the following: preexisting cardiovascular disease, CKD with estimated glomerular filtration rate between 20 and 60 mL/min/1.73 m², age >75 years, and Framingham 10-year risk of 15% or more. They excluded patients with diabetes or previous stroke.

Patients were randomized to intensive treatment (target systolic BP <120; mean achieved 121.4) or standard treatment (target systolic BP <140; mean achieved 136.2). Treatment typically comprised 3 (intensive) or 2 (standard) agents. The primary outcome was a composite of myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or cardiovascular death.

The study, which was originally intended to run for 5 years, was stopped at 3.26 years based on positive results. Intensive treatment improved the primary composite outcome overall (1.65% vs 2.19%; HR=0.75; 95% CI, 0.64-0.89; P<.001; NNT=61 over 3.26 years), all-cause mortality (HR=0.73; 95% CI, 0.60-0.90; P=.003; NNT=90), and cardiovascular death (HR=0.57; 95% CI, 0.38-0.85; P=.005; NNT=172).

However, intensive treatment didn’t significantly improve the primary composite outcome in these subgroups:

• female patients (HR=0.84; 95% CI, 0.62-1.14)
• black patients (HR=0.77; 95% CI, 0.55-1.06)
• patients with preexisting CKD (HR=0.82; 95% CI, 0.63-1.07) or cardiovascular disease (HR=0.83; 95% CI, 0.62-1.09)
• patients younger than 75 years (HR=0.80; 95% CI, 0.64-1.00)
• patients with systolic blood pressures higher than 132 mm Hg (BP >132 to <145 mm Hg, HR=0.77; 95% CI, 0.57-1.03; BP ≥145 mm Hg, HR=0.83; 95% CI, 0.63-1.09).

While the SPRINT study found that targeting systolic BP below 120 mm Hg reduced a composite outcome that included cardiovascular death, it didn’t improve this outcome in certain patient subgroups.

Intensive treatment also produced more net serious adverse events (HR=1.88; 4.7% vs 2.5%; P<.001), including: ≥30% decrease of glomerular filtration rates to values below 60 mL/min/1.73 m² (HR=3.49; 95% CI, 2.44-5.10; P<.001), syncope (HR=1.44; 3.5% vs 2.4%; P=.003), hypotension (HR=1.70; 3.4% vs 2.0%; P<.001), and electrolyte abnormalities (HR=1.38; 3.8% vs 2.8%; P=.006). It didn’t cause injurious falls (HR=1.00; P=.97) or orthostatic hypotension in clinic (HR=0.88; 16.6% vs 18.3%; P=.01).

Guidelines for patients with peripheral artery disease, previous stroke

A national guideline by an expert panel recommended treating patients with hypertension who have peripheral artery disease or previous stroke to standard values for the general population: <140/90 mm Hg if ages 60 years or younger, <150/90 mm Hg if older than 60 years.⁵ 

EVIDENCE SUMMARY

A 2007 Cochrane review of 12 RCTs with 671 patients compared the efficacy of corticosteroid injections for CTS with placebo injections or other nonsurgical interventions.¹ Patients who received corticosteroid injections showed clinical improvement at one month or less compared with placebo (2 trials, 141 patients; 73% corticosteroids vs 28% placebo; relative risk [RR]=2.58; 95% confidence interval [CI], 1.72-3.87; number needed to treat [NNT]=2).

Compared with systemic corticosteroids, corticosteroid injections didn’t improve symptoms on a Global Symptom Score (scale of 0-50, with 50 indicating the most severe symptoms) at 2 weeks (one trial, 60 patients; mean difference [MD]= −4.2; 95% CI, −8.7 to 0.26), but did improve symptoms at 8 weeks (MD= −7.16; 95% CI, −11.5 to −2.86) and 12 weeks (MD= −7.1; 95% CI, −11.7 to −2.52).

Patients showed no difference in scores between corticosteroid injection and oral anti-inflammatory medication with neutral angle wrist splints on the Symptom Severity Scale (1 to 5, with 5 indicating the most severe symptoms) at 2 weeks (1 trial, 23 patients [37 wrists]; MD=0.0; 95% CI, −0.64 to 0.64) or 8 weeks (MD=0.1; 95% CI, −0.33 to 0.53).

Higher corticosteroid dose reduces surgery at one year

A 2013 high-quality RCT with 111 patients assessed pain relief and rates of surgery at one year with local corticosteroid injections for CTS.² This trial had 3 arms with 37 patients in each: 80-mg methylprednisolone injection, 40-mg methylprednisolone injection, or placebo injection.

Both corticosteroid groups showed greater improvement on the Symptom Severity Scale at 10 weeks compared with placebo (40-mg methylprednisolone group: MD= −0.88; 95% CI, −1.3 to −0.46; 80-mg methylprednisolone group: MD= −0.64; 95% CI, −1.06 to −0.21). There was no difference between the methylprednisolone groups.

The incidence of surgery at one year was lower in the 80-mg methylprednisolone group compared with placebo (73% vs 92%; RR=0.79; 95% CI, 0.64-0.99; NNT=5) but not in the 40-mg methylprednisolone group compared with placebo (81% vs 92%; RR=0.88; 95% CI, 0.73-1.06).

Corticosteroids improve symptoms and disability, but effects wear off

A randomized double-blind, placebo-controlled trial conducted in 2010 examined the effectiveness of corticosteroid injections given by general practitioners to 69 patients with CTS.³ Patients were randomized to receive 10 mg of either triamcinolone or saline. They were reassessed after one week, and patients in the saline injection group who had inadequate symptom relief received a triamcinolone injection as bail-out treatment. Follow-up by patient questionnaire was done at 1, 3, 6, and 12 months.

Investigators assessed symptoms and disability using the Symptom Severity Scale and Functional Disability Scale, which are part of the Boston Carpal Tunnel Questionnaire. Like the Symptom Severity Scale, the Functional Disability Scale is scored from 1 to 5, with higher scores indicating more severe disability.

One week after treatment, the corticosteroid group showed greater improvement in symptom severity and functional disability than the saline group (symptom severity decreased from 2.9 to 1.9 with triamcinolone vs 2.8 to 2.5 with saline; MD=0.64; 95% CI, 0.32-0.96; functional disability decreased from 2.5 to 1.9 with triamcinolone but remained at 2.4 with saline; MD=0.59; 95% CI, 0.23-0.94).

Long-term follow-up of 35 patients who responded to corticosteroid injections found that the effects wore off over 12 months when assessed using the Symptom Severity Scale (mean score 1.5 at 1 month, 2.0 at 12 months; P=.08).

Surgery rates at one and 5 years

A 2012 prospective cohort study examined the 5-year rate of surgical intervention after a 20-mg methylprednisolone injection in 824 patients diagnosed with CTS who had failed conservative treatment.⁴ A total of 500 patients had a relapse of symptoms, and 372 of them elected to have a second injection. A Kaplan-Meier survivorship analysis determined rates of surgical intervention to be 14.5% (95% CI, 11.9-17) at one year and 33.2% (95% CI, 28.7-37.8) at 5 years.

RECOMMENDATION

A 2010 American Academy of Orthopaedic Surgeons evidence-based practice guideline on the treatment of CTS  recommends corticosteroid injection before considering surgery (Grade B, Level 1 suggested recommendation with good evidence).⁵

EVIDENCE SUMMARY

A 2007 Cochrane review of 12 RCTs with 671 patients compared the efficacy of corticosteroid injections for CTS with placebo injections or other nonsurgical interventions.¹ Patients who received corticosteroid injections showed clinical improvement at one month or less compared with placebo (2 trials, 141 patients; 73% corticosteroids vs 28% placebo; relative risk [RR]=2.58; 95% confidence interval [CI], 1.72-3.87; number needed to treat [NNT]=2).

Compared with systemic corticosteroids, corticosteroid injections didn’t improve symptoms on a Global Symptom Score (scale of 0-50, with 50 indicating the most severe symptoms) at 2 weeks (one trial, 60 patients; mean difference [MD]= −4.2; 95% CI, −8.7 to 0.26), but did improve symptoms at 8 weeks (MD= −7.16; 95% CI, −11.5 to −2.86) and 12 weeks (MD= −7.1; 95% CI, −11.7 to −2.52).

Patients showed no difference in scores between corticosteroid injection and oral anti-inflammatory medication with neutral angle wrist splints on the Symptom Severity Scale (1 to 5, with 5 indicating the most severe symptoms) at 2 weeks (1 trial, 23 patients [37 wrists]; MD=0.0; 95% CI, −0.64 to 0.64) or 8 weeks (MD=0.1; 95% CI, −0.33 to 0.53).

Higher corticosteroid dose reduces surgery at one year

A 2013 high-quality RCT with 111 patients assessed pain relief and rates of surgery at one year with local corticosteroid injections for CTS.² This trial had 3 arms with 37 patients in each: 80-mg methylprednisolone injection, 40-mg methylprednisolone injection, or placebo injection.

Both corticosteroid groups showed greater improvement on the Symptom Severity Scale at 10 weeks compared with placebo (40-mg methylprednisolone group: MD= −0.88; 95% CI, −1.3 to −0.46; 80-mg methylprednisolone group: MD= −0.64; 95% CI, −1.06 to −0.21). There was no difference between the methylprednisolone groups.

The incidence of surgery at one year was lower in the 80-mg methylprednisolone group compared with placebo (73% vs 92%; RR=0.79; 95% CI, 0.64-0.99; NNT=5) but not in the 40-mg methylprednisolone group compared with placebo (81% vs 92%; RR=0.88; 95% CI, 0.73-1.06).

Corticosteroids improve symptoms and disability, but effects wear off

A randomized double-blind, placebo-controlled trial conducted in 2010 examined the effectiveness of corticosteroid injections given by general practitioners to 69 patients with CTS.³ Patients were randomized to receive 10 mg of either triamcinolone or saline. They were reassessed after one week, and patients in the saline injection group who had inadequate symptom relief received a triamcinolone injection as bail-out treatment. Follow-up by patient questionnaire was done at 1, 3, 6, and 12 months.

Investigators assessed symptoms and disability using the Symptom Severity Scale and Functional Disability Scale, which are part of the Boston Carpal Tunnel Questionnaire. Like the Symptom Severity Scale, the Functional Disability Scale is scored from 1 to 5, with higher scores indicating more severe disability.

One week after treatment, the corticosteroid group showed greater improvement in symptom severity and functional disability than the saline group (symptom severity decreased from 2.9 to 1.9 with triamcinolone vs 2.8 to 2.5 with saline; MD=0.64; 95% CI, 0.32-0.96; functional disability decreased from 2.5 to 1.9 with triamcinolone but remained at 2.4 with saline; MD=0.59; 95% CI, 0.23-0.94).

Long-term follow-up of 35 patients who responded to corticosteroid injections found that the effects wore off over 12 months when assessed using the Symptom Severity Scale (mean score 1.5 at 1 month, 2.0 at 12 months; P=.08).

Surgery rates at one and 5 years

A 2012 prospective cohort study examined the 5-year rate of surgical intervention after a 20-mg methylprednisolone injection in 824 patients diagnosed with CTS who had failed conservative treatment.⁴ A total of 500 patients had a relapse of symptoms, and 372 of them elected to have a second injection. A Kaplan-Meier survivorship analysis determined rates of surgical intervention to be 14.5% (95% CI, 11.9-17) at one year and 33.2% (95% CI, 28.7-37.8) at 5 years.

RECOMMENDATION

A 2010 American Academy of Orthopaedic Surgeons evidence-based practice guideline on the treatment of CTS  recommends corticosteroid injection before considering surgery (Grade B, Level 1 suggested recommendation with good evidence).⁵

EVIDENCE SUMMARY

A 2007 Cochrane review of 12 RCTs with 671 patients compared the efficacy of corticosteroid injections for CTS with placebo injections or other nonsurgical interventions.¹ Patients who received corticosteroid injections showed clinical improvement at one month or less compared with placebo (2 trials, 141 patients; 73% corticosteroids vs 28% placebo; relative risk [RR]=2.58; 95% confidence interval [CI], 1.72-3.87; number needed to treat [NNT]=2).

Compared with systemic corticosteroids, corticosteroid injections didn’t improve symptoms on a Global Symptom Score (scale of 0-50, with 50 indicating the most severe symptoms) at 2 weeks (one trial, 60 patients; mean difference [MD]= −4.2; 95% CI, −8.7 to 0.26), but did improve symptoms at 8 weeks (MD= −7.16; 95% CI, −11.5 to −2.86) and 12 weeks (MD= −7.1; 95% CI, −11.7 to −2.52).

Patients showed no difference in scores between corticosteroid injection and oral anti-inflammatory medication with neutral angle wrist splints on the Symptom Severity Scale (1 to 5, with 5 indicating the most severe symptoms) at 2 weeks (1 trial, 23 patients [37 wrists]; MD=0.0; 95% CI, −0.64 to 0.64) or 8 weeks (MD=0.1; 95% CI, −0.33 to 0.53).

Higher corticosteroid dose reduces surgery at one year

A 2013 high-quality RCT with 111 patients assessed pain relief and rates of surgery at one year with local corticosteroid injections for CTS.² This trial had 3 arms with 37 patients in each: 80-mg methylprednisolone injection, 40-mg methylprednisolone injection, or placebo injection.

Both corticosteroid groups showed greater improvement on the Symptom Severity Scale at 10 weeks compared with placebo (40-mg methylprednisolone group: MD= −0.88; 95% CI, −1.3 to −0.46; 80-mg methylprednisolone group: MD= −0.64; 95% CI, −1.06 to −0.21). There was no difference between the methylprednisolone groups.

The incidence of surgery at one year was lower in the 80-mg methylprednisolone group compared with placebo (73% vs 92%; RR=0.79; 95% CI, 0.64-0.99; NNT=5) but not in the 40-mg methylprednisolone group compared with placebo (81% vs 92%; RR=0.88; 95% CI, 0.73-1.06).

Corticosteroids improve symptoms and disability, but effects wear off

A randomized double-blind, placebo-controlled trial conducted in 2010 examined the effectiveness of corticosteroid injections given by general practitioners to 69 patients with CTS.³ Patients were randomized to receive 10 mg of either triamcinolone or saline. They were reassessed after one week, and patients in the saline injection group who had inadequate symptom relief received a triamcinolone injection as bail-out treatment. Follow-up by patient questionnaire was done at 1, 3, 6, and 12 months.

Investigators assessed symptoms and disability using the Symptom Severity Scale and Functional Disability Scale, which are part of the Boston Carpal Tunnel Questionnaire. Like the Symptom Severity Scale, the Functional Disability Scale is scored from 1 to 5, with higher scores indicating more severe disability.

One week after treatment, the corticosteroid group showed greater improvement in symptom severity and functional disability than the saline group (symptom severity decreased from 2.9 to 1.9 with triamcinolone vs 2.8 to 2.5 with saline; MD=0.64; 95% CI, 0.32-0.96; functional disability decreased from 2.5 to 1.9 with triamcinolone but remained at 2.4 with saline; MD=0.59; 95% CI, 0.23-0.94).

Long-term follow-up of 35 patients who responded to corticosteroid injections found that the effects wore off over 12 months when assessed using the Symptom Severity Scale (mean score 1.5 at 1 month, 2.0 at 12 months; P=.08).

Surgery rates at one and 5 years

A 2012 prospective cohort study examined the 5-year rate of surgical intervention after a 20-mg methylprednisolone injection in 824 patients diagnosed with CTS who had failed conservative treatment.⁴ A total of 500 patients had a relapse of symptoms, and 372 of them elected to have a second injection. A Kaplan-Meier survivorship analysis determined rates of surgical intervention to be 14.5% (95% CI, 11.9-17) at one year and 33.2% (95% CI, 28.7-37.8) at 5 years.

RECOMMENDATION

A 2010 American Academy of Orthopaedic Surgeons evidence-based practice guideline on the treatment of CTS  recommends corticosteroid injection before considering surgery (Grade B, Level 1 suggested recommendation with good evidence).⁵

SAN FRANCISCO – Receiving adjuvant therapy for pancreatic cancer at a center that treats a high volume of patients with the disease confers a survival advantage, according to results of a retrospective cohort study reported at the symposium sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.

The analysis of 245 patients found that those given adjuvant therapy at Virginia Mason Medical Center – a high-volume center seeing up to 300 patients with newly diagnosed pancreatic cancer each year and putting about a third of them in trials – had a 37% reduction in the adjusted risk of death when compared with peers referred to community clinics for this therapy, reported first author Margaret T. Mandelson, Ph.D., director of research and quality at the center’s cancer institute in Seattle.

Susan London/Frontline Medical News

“Our study does lend some support to the concept of using high-volume centers for all therapy components for pancreatic cancer that is treated with curative intent,” she commented. “Ongoing investigation of patterns of care and volume impact in medical oncology is certainly warranted.”

A variety of factors may be driving the observed survival difference, such as the regimens used, with some evidence suggesting, for example, that patients treated in the community are more likely to receive single-agent therapy, she noted.

“We know that we have a strong setting for supportive care [at the center] and that we try to maximize our patients’ tolerance to treatment,” she added. “We have a high rate of completion of treatment in this setting. And of course the impact of optimism and hope cannot be underestimated in this patient population.”

Giving the academic medical center perspective, Dr. James L. Abbruzzese of the Duke Cancer Institute, Duke University, Durham, N.C., speculated that volume is a proxy for processes of care: staffing, use of guidelines or treatment algorithms, staging practices, and especially a multidisciplinary approach with components such as tumor boards and use of clinical trials. And larger centers are in a better position to offer these processes.

Susan London/Frontline Medical Media

“While the primary determinant of the long-term outcome of patients requires adequate volumes, I don’t think this is the whole answer,” he summarized. “I think it relies on and relates much more to the processes and the extent to which we can bring the multidisciplinary team to the patients.”

Giving the community oncology perspective, Dr. Michael V. Seiden, chief medical officer of the US Oncology Network, contended that instead of focusing solely on outcomes, the field should be focusing on the value of care, broadly defined as outcome divided by cost.

“I don’t really think this is a discussion about should your pancreatic cancer be treated in the community or in an academic center or a large regional health center. What we have to realize is that tens of thousands of patients with pancreatic cancer who will be diagnosed in the years ahead are going to receive care across the country in a lot of different venues,” he commented. “The questions we need to answer are how do we maximize value? What should be done in the ‘mouse’ hospitals? What should be done in the gigantic centers of excellence? What should be done in the well-organized health care systems? And what should be done in the community? Because delivering maximal value requires keeping an eye not only on best outcomes, but also on patient convenience and cost.”

Giving some background to the study, Dr. Mandelson noted that a volume-outcome relationship has been established when it comes to surgery for pancreatic cancer, but not when it comes to adjuvant therapy for the disease.

She and her colleagues used registry data to identify patients who received a pancreatic cancer diagnosis during 2003-2014 and underwent primary resection at Virginia Mason Medical Center. They compared outcomes between those who stayed at the center to receive their adjuvant therapy and those who were referred to a community oncology practice to receive this therapy.

Patients were excluded if they had received neoadjuvant therapy, had synchronous cancers, died or were lost to follow-up within 3 months of surgery, or had contraindications to receiving adjuvant therapy. Also excluded were any who declined this therapy and for whom a medical oncologist could not be identified.

Results showed that the patients treated in the high-volume center and in community clinics were similar with respect to sex, insurance status, travel distance to a high-volume center, performance status, and tumor size, nodal status, and margin status, Dr. Mandelson reported. Those treated in the community were, on average, 5 years older.

At the high-volume center, 96% of patients started chemotherapy, 81% received a multiagent regimen, and 53% underwent chemoradiation. Detailed data on therapies received were not available for the community group.

The patients treated in the high-volume center had a more than one-third reduction in the adjusted risk of death relative to peers treated in the community (hazard ratio, 0.63; P less than .01). Median overall survival was 43.6 months for the former, compared with 27.9 months for the latter (P less than .01). The corresponding 5-year rates of overall survival were 38.6% and 24.8% (P less than .01).

“We know from the literature that pancreas cancer is undertreated in the community as a whole, both from the surgical perspective and the medical perspective. So it wouldn’t be surprising if some of the patients with a referral to an outside oncologist in fact never received treatment,” Dr. Mandelson commented.

“The patient population that received surgery in the community setting and then came to Virginia Mason for adjuvant therapy has not yet been analyzed, which is essentially the inverse of this study,” she noted. “That will be very powerful evidence.”

Dr. Mandelson disclosed that she had no relevant conflicts of interest. Dr. Abbruzzese disclosed that he receives honoraria from Celgene and Halozyme, and that he has a consulting or advisory role with Acerta Pharma, Bessor, Celgene, Cornerstone Pharma, Daiichi Sankyo, EMD Serono, Halozyme, Progen, Merck Sharpe & Dohme, Sun BioPharma, and Viba Therapeutics. Dr. Seiden disclosed that he is an employee of McKesson Specialty Health and Texas Oncology; that he is chief medical officer of US Oncology; and that he owns stock in and receives travel expenses from McKesson Specialty Health.

tor@frontlinemedcom.com

SAN FRANCISCO – Receiving adjuvant therapy for pancreatic cancer at a center that treats a high volume of patients with the disease confers a survival advantage, according to results of a retrospective cohort study reported at the symposium sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.

The analysis of 245 patients found that those given adjuvant therapy at Virginia Mason Medical Center – a high-volume center seeing up to 300 patients with newly diagnosed pancreatic cancer each year and putting about a third of them in trials – had a 37% reduction in the adjusted risk of death when compared with peers referred to community clinics for this therapy, reported first author Margaret T. Mandelson, Ph.D., director of research and quality at the center’s cancer institute in Seattle.

Susan London/Frontline Medical News

“Our study does lend some support to the concept of using high-volume centers for all therapy components for pancreatic cancer that is treated with curative intent,” she commented. “Ongoing investigation of patterns of care and volume impact in medical oncology is certainly warranted.”

A variety of factors may be driving the observed survival difference, such as the regimens used, with some evidence suggesting, for example, that patients treated in the community are more likely to receive single-agent therapy, she noted.

“We know that we have a strong setting for supportive care [at the center] and that we try to maximize our patients’ tolerance to treatment,” she added. “We have a high rate of completion of treatment in this setting. And of course the impact of optimism and hope cannot be underestimated in this patient population.”

Giving the academic medical center perspective, Dr. James L. Abbruzzese of the Duke Cancer Institute, Duke University, Durham, N.C., speculated that volume is a proxy for processes of care: staffing, use of guidelines or treatment algorithms, staging practices, and especially a multidisciplinary approach with components such as tumor boards and use of clinical trials. And larger centers are in a better position to offer these processes.

Susan London/Frontline Medical Media

“While the primary determinant of the long-term outcome of patients requires adequate volumes, I don’t think this is the whole answer,” he summarized. “I think it relies on and relates much more to the processes and the extent to which we can bring the multidisciplinary team to the patients.”

Giving the community oncology perspective, Dr. Michael V. Seiden, chief medical officer of the US Oncology Network, contended that instead of focusing solely on outcomes, the field should be focusing on the value of care, broadly defined as outcome divided by cost.

“I don’t really think this is a discussion about should your pancreatic cancer be treated in the community or in an academic center or a large regional health center. What we have to realize is that tens of thousands of patients with pancreatic cancer who will be diagnosed in the years ahead are going to receive care across the country in a lot of different venues,” he commented. “The questions we need to answer are how do we maximize value? What should be done in the ‘mouse’ hospitals? What should be done in the gigantic centers of excellence? What should be done in the well-organized health care systems? And what should be done in the community? Because delivering maximal value requires keeping an eye not only on best outcomes, but also on patient convenience and cost.”

Giving some background to the study, Dr. Mandelson noted that a volume-outcome relationship has been established when it comes to surgery for pancreatic cancer, but not when it comes to adjuvant therapy for the disease.

She and her colleagues used registry data to identify patients who received a pancreatic cancer diagnosis during 2003-2014 and underwent primary resection at Virginia Mason Medical Center. They compared outcomes between those who stayed at the center to receive their adjuvant therapy and those who were referred to a community oncology practice to receive this therapy.

Patients were excluded if they had received neoadjuvant therapy, had synchronous cancers, died or were lost to follow-up within 3 months of surgery, or had contraindications to receiving adjuvant therapy. Also excluded were any who declined this therapy and for whom a medical oncologist could not be identified.

Results showed that the patients treated in the high-volume center and in community clinics were similar with respect to sex, insurance status, travel distance to a high-volume center, performance status, and tumor size, nodal status, and margin status, Dr. Mandelson reported. Those treated in the community were, on average, 5 years older.

At the high-volume center, 96% of patients started chemotherapy, 81% received a multiagent regimen, and 53% underwent chemoradiation. Detailed data on therapies received were not available for the community group.

The patients treated in the high-volume center had a more than one-third reduction in the adjusted risk of death relative to peers treated in the community (hazard ratio, 0.63; P less than .01). Median overall survival was 43.6 months for the former, compared with 27.9 months for the latter (P less than .01). The corresponding 5-year rates of overall survival were 38.6% and 24.8% (P less than .01).

“We know from the literature that pancreas cancer is undertreated in the community as a whole, both from the surgical perspective and the medical perspective. So it wouldn’t be surprising if some of the patients with a referral to an outside oncologist in fact never received treatment,” Dr. Mandelson commented.

“The patient population that received surgery in the community setting and then came to Virginia Mason for adjuvant therapy has not yet been analyzed, which is essentially the inverse of this study,” she noted. “That will be very powerful evidence.”

Dr. Mandelson disclosed that she had no relevant conflicts of interest. Dr. Abbruzzese disclosed that he receives honoraria from Celgene and Halozyme, and that he has a consulting or advisory role with Acerta Pharma, Bessor, Celgene, Cornerstone Pharma, Daiichi Sankyo, EMD Serono, Halozyme, Progen, Merck Sharpe & Dohme, Sun BioPharma, and Viba Therapeutics. Dr. Seiden disclosed that he is an employee of McKesson Specialty Health and Texas Oncology; that he is chief medical officer of US Oncology; and that he owns stock in and receives travel expenses from McKesson Specialty Health.

tor@frontlinemedcom.com

SAN FRANCISCO – Receiving adjuvant therapy for pancreatic cancer at a center that treats a high volume of patients with the disease confers a survival advantage, according to results of a retrospective cohort study reported at the symposium sponsored by ASCO, ASTRO, the American Gastroenterological Association, and the Society of Surgical Oncology.

The analysis of 245 patients found that those given adjuvant therapy at Virginia Mason Medical Center – a high-volume center seeing up to 300 patients with newly diagnosed pancreatic cancer each year and putting about a third of them in trials – had a 37% reduction in the adjusted risk of death when compared with peers referred to community clinics for this therapy, reported first author Margaret T. Mandelson, Ph.D., director of research and quality at the center’s cancer institute in Seattle.

Susan London/Frontline Medical News

“Our study does lend some support to the concept of using high-volume centers for all therapy components for pancreatic cancer that is treated with curative intent,” she commented. “Ongoing investigation of patterns of care and volume impact in medical oncology is certainly warranted.”

A variety of factors may be driving the observed survival difference, such as the regimens used, with some evidence suggesting, for example, that patients treated in the community are more likely to receive single-agent therapy, she noted.

“We know that we have a strong setting for supportive care [at the center] and that we try to maximize our patients’ tolerance to treatment,” she added. “We have a high rate of completion of treatment in this setting. And of course the impact of optimism and hope cannot be underestimated in this patient population.”

Giving the academic medical center perspective, Dr. James L. Abbruzzese of the Duke Cancer Institute, Duke University, Durham, N.C., speculated that volume is a proxy for processes of care: staffing, use of guidelines or treatment algorithms, staging practices, and especially a multidisciplinary approach with components such as tumor boards and use of clinical trials. And larger centers are in a better position to offer these processes.

Susan London/Frontline Medical Media

“While the primary determinant of the long-term outcome of patients requires adequate volumes, I don’t think this is the whole answer,” he summarized. “I think it relies on and relates much more to the processes and the extent to which we can bring the multidisciplinary team to the patients.”

Giving the community oncology perspective, Dr. Michael V. Seiden, chief medical officer of the US Oncology Network, contended that instead of focusing solely on outcomes, the field should be focusing on the value of care, broadly defined as outcome divided by cost.

“I don’t really think this is a discussion about should your pancreatic cancer be treated in the community or in an academic center or a large regional health center. What we have to realize is that tens of thousands of patients with pancreatic cancer who will be diagnosed in the years ahead are going to receive care across the country in a lot of different venues,” he commented. “The questions we need to answer are how do we maximize value? What should be done in the ‘mouse’ hospitals? What should be done in the gigantic centers of excellence? What should be done in the well-organized health care systems? And what should be done in the community? Because delivering maximal value requires keeping an eye not only on best outcomes, but also on patient convenience and cost.”

Giving some background to the study, Dr. Mandelson noted that a volume-outcome relationship has been established when it comes to surgery for pancreatic cancer, but not when it comes to adjuvant therapy for the disease.

She and her colleagues used registry data to identify patients who received a pancreatic cancer diagnosis during 2003-2014 and underwent primary resection at Virginia Mason Medical Center. They compared outcomes between those who stayed at the center to receive their adjuvant therapy and those who were referred to a community oncology practice to receive this therapy.

Patients were excluded if they had received neoadjuvant therapy, had synchronous cancers, died or were lost to follow-up within 3 months of surgery, or had contraindications to receiving adjuvant therapy. Also excluded were any who declined this therapy and for whom a medical oncologist could not be identified.

Results showed that the patients treated in the high-volume center and in community clinics were similar with respect to sex, insurance status, travel distance to a high-volume center, performance status, and tumor size, nodal status, and margin status, Dr. Mandelson reported. Those treated in the community were, on average, 5 years older.

At the high-volume center, 96% of patients started chemotherapy, 81% received a multiagent regimen, and 53% underwent chemoradiation. Detailed data on therapies received were not available for the community group.

The patients treated in the high-volume center had a more than one-third reduction in the adjusted risk of death relative to peers treated in the community (hazard ratio, 0.63; P less than .01). Median overall survival was 43.6 months for the former, compared with 27.9 months for the latter (P less than .01). The corresponding 5-year rates of overall survival were 38.6% and 24.8% (P less than .01).

“We know from the literature that pancreas cancer is undertreated in the community as a whole, both from the surgical perspective and the medical perspective. So it wouldn’t be surprising if some of the patients with a referral to an outside oncologist in fact never received treatment,” Dr. Mandelson commented.

“The patient population that received surgery in the community setting and then came to Virginia Mason for adjuvant therapy has not yet been analyzed, which is essentially the inverse of this study,” she noted. “That will be very powerful evidence.”

Dr. Mandelson disclosed that she had no relevant conflicts of interest. Dr. Abbruzzese disclosed that he receives honoraria from Celgene and Halozyme, and that he has a consulting or advisory role with Acerta Pharma, Bessor, Celgene, Cornerstone Pharma, Daiichi Sankyo, EMD Serono, Halozyme, Progen, Merck Sharpe & Dohme, Sun BioPharma, and Viba Therapeutics. Dr. Seiden disclosed that he is an employee of McKesson Specialty Health and Texas Oncology; that he is chief medical officer of US Oncology; and that he owns stock in and receives travel expenses from McKesson Specialty Health.

tor@frontlinemedcom.com

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of the immunostimulatory antibody elotuzumab (Empliciti).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice and is expected to deliver its final decision on elotuzumab within 3 months.

The CHMP’s positive opinion of elotuzumab is based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab as Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of the immunostimulatory antibody elotuzumab (Empliciti).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice and is expected to deliver its final decision on elotuzumab within 3 months.

The CHMP’s positive opinion of elotuzumab is based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab as Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

Elotuzumab (Empliciti)

Photo courtesy of

Bristol-Myers Squibb

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of the immunostimulatory antibody elotuzumab (Empliciti).

The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma (MM) who have received at least 1 prior therapy.

The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice and is expected to deliver its final decision on elotuzumab within 3 months.

The CHMP’s positive opinion of elotuzumab is based on data from the phase 3 ELOQUENT-2 trial, which were presented at ASCO 2015 and published in NEJM.

The trial included 646 MM patients who had received 1 to 3 prior therapies. Baseline patient demographics and disease characteristics were well balanced between treatment arms.

Patients were randomized 1:1 to receive either elotuzumab at 10 mg/kg in combination with lenalidomide and dexamethasone (len-dex) or len-dex alone in 4-week cycles until disease progression or unacceptable toxicity.

The minimum follow-up for all study subjects was 24 months. The co-primary endpoints were progression-free survival (PFS) and overall response rate.

The overall response rate was 78.5% in the elotuzumab arm and 65.5% in the len-dex arm (P=0.0002).

The median PFS was 19.4 months in the elotuzumab arm and 14.9 months in the len-dex arm (P=0.0004). At 1 year, the PFS was 68% in the elotuzumab arm and 57% in the len-dex arm. At 2 years, the PFS was 41% and 27%, respectively.

The most common adverse events in the elotuzumab arm and len-dex arm, respectively, were fatigue (61.6% vs 51.7%), diarrhea (46.9% vs 36.0%), pyrexia (37.4% vs 24.6%), constipation (35.5% vs 27.1%), cough (34.3% vs 18.9%), peripheral neuropathy (26.7% vs 20.8%), nasopharyngitis (24.5% vs 19.2%), upper respiratory tract infection (22.6% vs 17.4%), decreased appetite (20.8% vs 12.6%), and pneumonia (20.1% vs 14.2%).

Serious adverse events occurred in 65.4% of patients in the elotuzumab arm and 56.5% in the len-dex arm. The most frequent events were pneumonia, pyrexia, respiratory tract infection, anemia, pulmonary embolism, and acute renal failure.

Bristol-Myers Squibb and AbbVie are co-developing elotuzumab as Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.

Patients undergoing endoscopic total extraperitoneal repair (TEP) of hernias had less persistent pain and greater mobility than those whose hernias were repaired using the Lichtenstein technique.

For their research, conducted in Sweden, researchers led by Dr. Linn Westin of the Karolinska Institutet in Stockholm and colleagues randomized 384 adult men with primary unilateral inguinal hernia to surgery with Lichtenstein using local anesthesia (n = 191) or TEP with general anesthesia (n = 193). Patients underwent operations in two hospitals between 2006 and 2011, with four surgeons participating, and the same heavyweight mesh was used in both groups.

All patients were followed for 1 year for postoperative pain, recurrence of hernias, difficulty in performing daily activities, complications, and use of analgesics. Pain was measured using the Inguinal Pain Questionnaire (IPQ).

In a paper published in the February issue of Annals of Surgery (2016;263:240-3), Dr. Westin and colleagues reported that the group randomized to TEP saw significantly less persistent mild pain at 1 year, compared with the Lichtenstein group. In the TEP group 39 patients reported such pain, compared with 62 in the Lichtenstein group (20.7% vs. 33.2,% P = .007).

Five TEP patients reported pain in the groin that limited their ability to perform physical exercise, while 14 in the Lichtenstein group reported similar pain, a difference that reached statistical significance (2.7% vs. 7.5%, P = .034). Severe pain, defined as pain affecting most activities, was comparable in both groups, with four patients in the TEP group and six in the Lichtenstein group reporting severe pain (2.1% and 3.2%, P = .543).

No significant between-group differences were seen in recurrences, use of pain medications, or specific measures of mobility, such as being able to sit or stand for more than 30 minutes at a stretch.

“Our results show a clinically significant advantage in favor of TEP regarding long-term postoperative pain, and justify the use of TEP for routine inguinal hernia surgery,” Dr. Westin and colleagues noted in their analysis. Their findings, they said, should prompt more extensive training of surgeons in the TEP technique.

The investigators noted as a limitation of their study that it was not powered to detect differences in severe pain, which could be considered more clinically relevant than mild persistent pain.

Patients’ pain outcomes may have been related to surgeons’ handling of the nerves in the inguinal tract, they wrote.

Also, they noted, the same heavyweight mesh was used in all operations in the study, for consistency, despite the fact that, after the initiation of the trial, lightweight mesh was shown in studies to be associated with less pain. Dr. Westin and colleagues wrote that their findings would be applicable to surgeries using lightweight mesh, which might further limit pain.

Their results, they wrote, suggested that TEP should be considered a valid first choice not only for the study population, which included only men with primary unilateral hernias, but for those with bilateral or recurrent hernias and also for women.

The study was funded by the Uppsala-Orebro Regional Research Council, Stockholm County Council, Swedish Society of Medicine, and Olle Engqvist Research Foundation. None of the investigators declared conflicts of interest.

acssurgerynews@frontlinemedcom.com

Patients undergoing endoscopic total extraperitoneal repair (TEP) of hernias had less persistent pain and greater mobility than those whose hernias were repaired using the Lichtenstein technique.

For their research, conducted in Sweden, researchers led by Dr. Linn Westin of the Karolinska Institutet in Stockholm and colleagues randomized 384 adult men with primary unilateral inguinal hernia to surgery with Lichtenstein using local anesthesia (n = 191) or TEP with general anesthesia (n = 193). Patients underwent operations in two hospitals between 2006 and 2011, with four surgeons participating, and the same heavyweight mesh was used in both groups.

All patients were followed for 1 year for postoperative pain, recurrence of hernias, difficulty in performing daily activities, complications, and use of analgesics. Pain was measured using the Inguinal Pain Questionnaire (IPQ).

In a paper published in the February issue of Annals of Surgery (2016;263:240-3), Dr. Westin and colleagues reported that the group randomized to TEP saw significantly less persistent mild pain at 1 year, compared with the Lichtenstein group. In the TEP group 39 patients reported such pain, compared with 62 in the Lichtenstein group (20.7% vs. 33.2,% P = .007).

Five TEP patients reported pain in the groin that limited their ability to perform physical exercise, while 14 in the Lichtenstein group reported similar pain, a difference that reached statistical significance (2.7% vs. 7.5%, P = .034). Severe pain, defined as pain affecting most activities, was comparable in both groups, with four patients in the TEP group and six in the Lichtenstein group reporting severe pain (2.1% and 3.2%, P = .543).

No significant between-group differences were seen in recurrences, use of pain medications, or specific measures of mobility, such as being able to sit or stand for more than 30 minutes at a stretch.

“Our results show a clinically significant advantage in favor of TEP regarding long-term postoperative pain, and justify the use of TEP for routine inguinal hernia surgery,” Dr. Westin and colleagues noted in their analysis. Their findings, they said, should prompt more extensive training of surgeons in the TEP technique.

The investigators noted as a limitation of their study that it was not powered to detect differences in severe pain, which could be considered more clinically relevant than mild persistent pain.

Patients’ pain outcomes may have been related to surgeons’ handling of the nerves in the inguinal tract, they wrote.

Also, they noted, the same heavyweight mesh was used in all operations in the study, for consistency, despite the fact that, after the initiation of the trial, lightweight mesh was shown in studies to be associated with less pain. Dr. Westin and colleagues wrote that their findings would be applicable to surgeries using lightweight mesh, which might further limit pain.

Their results, they wrote, suggested that TEP should be considered a valid first choice not only for the study population, which included only men with primary unilateral hernias, but for those with bilateral or recurrent hernias and also for women.

The study was funded by the Uppsala-Orebro Regional Research Council, Stockholm County Council, Swedish Society of Medicine, and Olle Engqvist Research Foundation. None of the investigators declared conflicts of interest.

acssurgerynews@frontlinemedcom.com

Patients undergoing endoscopic total extraperitoneal repair (TEP) of hernias had less persistent pain and greater mobility than those whose hernias were repaired using the Lichtenstein technique.

For their research, conducted in Sweden, researchers led by Dr. Linn Westin of the Karolinska Institutet in Stockholm and colleagues randomized 384 adult men with primary unilateral inguinal hernia to surgery with Lichtenstein using local anesthesia (n = 191) or TEP with general anesthesia (n = 193). Patients underwent operations in two hospitals between 2006 and 2011, with four surgeons participating, and the same heavyweight mesh was used in both groups.

All patients were followed for 1 year for postoperative pain, recurrence of hernias, difficulty in performing daily activities, complications, and use of analgesics. Pain was measured using the Inguinal Pain Questionnaire (IPQ).

In a paper published in the February issue of Annals of Surgery (2016;263:240-3), Dr. Westin and colleagues reported that the group randomized to TEP saw significantly less persistent mild pain at 1 year, compared with the Lichtenstein group. In the TEP group 39 patients reported such pain, compared with 62 in the Lichtenstein group (20.7% vs. 33.2,% P = .007).

Five TEP patients reported pain in the groin that limited their ability to perform physical exercise, while 14 in the Lichtenstein group reported similar pain, a difference that reached statistical significance (2.7% vs. 7.5%, P = .034). Severe pain, defined as pain affecting most activities, was comparable in both groups, with four patients in the TEP group and six in the Lichtenstein group reporting severe pain (2.1% and 3.2%, P = .543).

No significant between-group differences were seen in recurrences, use of pain medications, or specific measures of mobility, such as being able to sit or stand for more than 30 minutes at a stretch.

“Our results show a clinically significant advantage in favor of TEP regarding long-term postoperative pain, and justify the use of TEP for routine inguinal hernia surgery,” Dr. Westin and colleagues noted in their analysis. Their findings, they said, should prompt more extensive training of surgeons in the TEP technique.

The investigators noted as a limitation of their study that it was not powered to detect differences in severe pain, which could be considered more clinically relevant than mild persistent pain.

Patients’ pain outcomes may have been related to surgeons’ handling of the nerves in the inguinal tract, they wrote.

Also, they noted, the same heavyweight mesh was used in all operations in the study, for consistency, despite the fact that, after the initiation of the trial, lightweight mesh was shown in studies to be associated with less pain. Dr. Westin and colleagues wrote that their findings would be applicable to surgeries using lightweight mesh, which might further limit pain.

Their results, they wrote, suggested that TEP should be considered a valid first choice not only for the study population, which included only men with primary unilateral hernias, but for those with bilateral or recurrent hernias and also for women.

The study was funded by the Uppsala-Orebro Regional Research Council, Stockholm County Council, Swedish Society of Medicine, and Olle Engqvist Research Foundation. None of the investigators declared conflicts of interest.

acssurgerynews@frontlinemedcom.com

SNOWMASS, COLO. – A clear message from the first-ever randomized trial of surgical mitral valve repair versus replacement for patients with severe ischemic mitral regurgitation is that replacement should be utilized more liberally, Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

The results of prosthetic valve implantation proved far more durable than repair. At 2 years of follow-up in this 251-patient multicenter trial conducted by the Cardiothoracic Surgical Trials Network (CSTN), the incidence of recurrent moderate or severe mitral regurgitation was just 3.8% in the valve replacement group, compared with 58.8% with repair via restrictive annuloplasty. As a result, the repair group had significantly more heart failure–related adverse events and cardiovascular hospitalizations and a lower rate of clinically meaningful improvement in quality of life scores, noted Dr. Mack, an investigator in the trial and medical director of the Baylor Health Care System in Plano, Tex.

“I think surgical mitral valve replacement has had a bad name over the years, and one of the reasons is because of the worse left ventricular function afterwards. However, that was a casualty of excising the mitral valve and the subvalvular apparatus, causing atrial-ventricular disconnection. We’ve gotten smarter about this. The techniques we now use are valve sparing,” the cardiothoracic surgeon said.

He was quick to add, however, that the CSTN study results are by no means the death knell for restrictive mitral annuloplasty. Indeed, participants in the mitral valve repair group who didn’t develop recurrent regurgitation actually experienced significant positive reverse remodeling as reflected by improvement in their left ventricular end-systolic volume index, the primary endpoint of the study (N Engl J Med. 2016;374:344-35).

The key to successful outcomes in mitral valve repair is to save the procedure for patients who are unlikely to develop recurrent regurgitation. And a substudy of the CTSN trial led by Dr. Irving L. Kron, professor of surgery at the University of Virginia, Charlottesville, provides practical guidance on that score. The investigators conducted a logistic regression analysis of the mitral valve repair group’s baseline echocardiographic and clinical characteristics and identified a collection of strong predictors of recurrent regurgitation within 2 years (J Thorac Cardiovasc Surg. 2015 Mar;149[3]:752-61).

“The bottom line is, the more tethering you have of the mitral valve leaflets, the more likely you are to have recurrent mitral regurgitation after mitral valve annuloplasty,” Dr. Mack said.

The predictors of recurrent regurgitation included a coaptation depth greater than 10 mm, a posterior leaflet angle in excess of 45 degrees, a distal anterior leaflet angle greater than 25 degrees, inferior basal aneurysm, mitral annular calcification, and a left ventricular end diastolic diameter greater than 65 mm, as well as other indices of advanced left ventricular remodeling.

No or only mild annular dilation, as occurs, for example, in patients whose mitral regurgitation is caused by atrial fibrillation, is another independent predictor of recurrent regurgitation post repair.

“Shrinking the annulus isn’t going to make a difference if the annulus wasn’t dilated to begin with,” the surgeon observed. “If surgery is performed, we now know those patients who are most likely to recur – and they should have mitral valve replacement. If those factors are not present, then repair is still a viable option,” according to Dr. Mack.

That being said, it’s still not known whether correcting severe ischemic mitral regurgitation prolongs life or improves quality of life long term, compared with guideline-directed medical therapy, he stressed.

“Secondary mitral regurgitation is a disease of the left ventricle, not the mitral valve. So it’s possible that mitral regurgitation reduction has no benefit because the regurgitation is a surrogate marker not causally related to outcome. I don’t think so, but it is a possibility,” Dr. Mack conceded.

This is a clinically important unresolved question because secondary mitral regurgitation is extremely common. In a retrospective echocardiographic study of 558 heart failure patients with a left ventricular ejection fraction of 35% or less and class III-IV symptoms, 90% of them had some degree of mitral regurgitation (J Card Fail. 2004 Aug;10[4]:285-91).

Together with Columbia University cardiologist Dr. Gregg W. Stone, Dr. Mack is coprincipal investigator of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, which is expected to provide an answer to this key question. The multicenter U.S. study involves a planned 420 patients with severely symptomatic secondary mitral regurgitation who are deemed at prohibitive risk for surgery. They are to be randomized to guideline-directed medical therapy with or without transcatheter mitral valve repair using the MitraClip device. Enrollment should be completed by May, with initial results available in late 2017.

Dr. Mack reported receiving research grants from Abbott Vascular, which is sponsoring the COAPT trial, as well as from Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – A clear message from the first-ever randomized trial of surgical mitral valve repair versus replacement for patients with severe ischemic mitral regurgitation is that replacement should be utilized more liberally, Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

The results of prosthetic valve implantation proved far more durable than repair. At 2 years of follow-up in this 251-patient multicenter trial conducted by the Cardiothoracic Surgical Trials Network (CSTN), the incidence of recurrent moderate or severe mitral regurgitation was just 3.8% in the valve replacement group, compared with 58.8% with repair via restrictive annuloplasty. As a result, the repair group had significantly more heart failure–related adverse events and cardiovascular hospitalizations and a lower rate of clinically meaningful improvement in quality of life scores, noted Dr. Mack, an investigator in the trial and medical director of the Baylor Health Care System in Plano, Tex.

“I think surgical mitral valve replacement has had a bad name over the years, and one of the reasons is because of the worse left ventricular function afterwards. However, that was a casualty of excising the mitral valve and the subvalvular apparatus, causing atrial-ventricular disconnection. We’ve gotten smarter about this. The techniques we now use are valve sparing,” the cardiothoracic surgeon said.

He was quick to add, however, that the CSTN study results are by no means the death knell for restrictive mitral annuloplasty. Indeed, participants in the mitral valve repair group who didn’t develop recurrent regurgitation actually experienced significant positive reverse remodeling as reflected by improvement in their left ventricular end-systolic volume index, the primary endpoint of the study (N Engl J Med. 2016;374:344-35).

The key to successful outcomes in mitral valve repair is to save the procedure for patients who are unlikely to develop recurrent regurgitation. And a substudy of the CTSN trial led by Dr. Irving L. Kron, professor of surgery at the University of Virginia, Charlottesville, provides practical guidance on that score. The investigators conducted a logistic regression analysis of the mitral valve repair group’s baseline echocardiographic and clinical characteristics and identified a collection of strong predictors of recurrent regurgitation within 2 years (J Thorac Cardiovasc Surg. 2015 Mar;149[3]:752-61).

“The bottom line is, the more tethering you have of the mitral valve leaflets, the more likely you are to have recurrent mitral regurgitation after mitral valve annuloplasty,” Dr. Mack said.

The predictors of recurrent regurgitation included a coaptation depth greater than 10 mm, a posterior leaflet angle in excess of 45 degrees, a distal anterior leaflet angle greater than 25 degrees, inferior basal aneurysm, mitral annular calcification, and a left ventricular end diastolic diameter greater than 65 mm, as well as other indices of advanced left ventricular remodeling.

No or only mild annular dilation, as occurs, for example, in patients whose mitral regurgitation is caused by atrial fibrillation, is another independent predictor of recurrent regurgitation post repair.

“Shrinking the annulus isn’t going to make a difference if the annulus wasn’t dilated to begin with,” the surgeon observed. “If surgery is performed, we now know those patients who are most likely to recur – and they should have mitral valve replacement. If those factors are not present, then repair is still a viable option,” according to Dr. Mack.

That being said, it’s still not known whether correcting severe ischemic mitral regurgitation prolongs life or improves quality of life long term, compared with guideline-directed medical therapy, he stressed.

“Secondary mitral regurgitation is a disease of the left ventricle, not the mitral valve. So it’s possible that mitral regurgitation reduction has no benefit because the regurgitation is a surrogate marker not causally related to outcome. I don’t think so, but it is a possibility,” Dr. Mack conceded.

This is a clinically important unresolved question because secondary mitral regurgitation is extremely common. In a retrospective echocardiographic study of 558 heart failure patients with a left ventricular ejection fraction of 35% or less and class III-IV symptoms, 90% of them had some degree of mitral regurgitation (J Card Fail. 2004 Aug;10[4]:285-91).

Together with Columbia University cardiologist Dr. Gregg W. Stone, Dr. Mack is coprincipal investigator of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, which is expected to provide an answer to this key question. The multicenter U.S. study involves a planned 420 patients with severely symptomatic secondary mitral regurgitation who are deemed at prohibitive risk for surgery. They are to be randomized to guideline-directed medical therapy with or without transcatheter mitral valve repair using the MitraClip device. Enrollment should be completed by May, with initial results available in late 2017.

Dr. Mack reported receiving research grants from Abbott Vascular, which is sponsoring the COAPT trial, as well as from Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – A clear message from the first-ever randomized trial of surgical mitral valve repair versus replacement for patients with severe ischemic mitral regurgitation is that replacement should be utilized more liberally, Dr. Michael J. Mack said at the Annual Cardiovascular Conference at Snowmass.

The results of prosthetic valve implantation proved far more durable than repair. At 2 years of follow-up in this 251-patient multicenter trial conducted by the Cardiothoracic Surgical Trials Network (CSTN), the incidence of recurrent moderate or severe mitral regurgitation was just 3.8% in the valve replacement group, compared with 58.8% with repair via restrictive annuloplasty. As a result, the repair group had significantly more heart failure–related adverse events and cardiovascular hospitalizations and a lower rate of clinically meaningful improvement in quality of life scores, noted Dr. Mack, an investigator in the trial and medical director of the Baylor Health Care System in Plano, Tex.

“I think surgical mitral valve replacement has had a bad name over the years, and one of the reasons is because of the worse left ventricular function afterwards. However, that was a casualty of excising the mitral valve and the subvalvular apparatus, causing atrial-ventricular disconnection. We’ve gotten smarter about this. The techniques we now use are valve sparing,” the cardiothoracic surgeon said.

He was quick to add, however, that the CSTN study results are by no means the death knell for restrictive mitral annuloplasty. Indeed, participants in the mitral valve repair group who didn’t develop recurrent regurgitation actually experienced significant positive reverse remodeling as reflected by improvement in their left ventricular end-systolic volume index, the primary endpoint of the study (N Engl J Med. 2016;374:344-35).

The key to successful outcomes in mitral valve repair is to save the procedure for patients who are unlikely to develop recurrent regurgitation. And a substudy of the CTSN trial led by Dr. Irving L. Kron, professor of surgery at the University of Virginia, Charlottesville, provides practical guidance on that score. The investigators conducted a logistic regression analysis of the mitral valve repair group’s baseline echocardiographic and clinical characteristics and identified a collection of strong predictors of recurrent regurgitation within 2 years (J Thorac Cardiovasc Surg. 2015 Mar;149[3]:752-61).

“The bottom line is, the more tethering you have of the mitral valve leaflets, the more likely you are to have recurrent mitral regurgitation after mitral valve annuloplasty,” Dr. Mack said.

The predictors of recurrent regurgitation included a coaptation depth greater than 10 mm, a posterior leaflet angle in excess of 45 degrees, a distal anterior leaflet angle greater than 25 degrees, inferior basal aneurysm, mitral annular calcification, and a left ventricular end diastolic diameter greater than 65 mm, as well as other indices of advanced left ventricular remodeling.

No or only mild annular dilation, as occurs, for example, in patients whose mitral regurgitation is caused by atrial fibrillation, is another independent predictor of recurrent regurgitation post repair.

“Shrinking the annulus isn’t going to make a difference if the annulus wasn’t dilated to begin with,” the surgeon observed. “If surgery is performed, we now know those patients who are most likely to recur – and they should have mitral valve replacement. If those factors are not present, then repair is still a viable option,” according to Dr. Mack.

That being said, it’s still not known whether correcting severe ischemic mitral regurgitation prolongs life or improves quality of life long term, compared with guideline-directed medical therapy, he stressed.

“Secondary mitral regurgitation is a disease of the left ventricle, not the mitral valve. So it’s possible that mitral regurgitation reduction has no benefit because the regurgitation is a surrogate marker not causally related to outcome. I don’t think so, but it is a possibility,” Dr. Mack conceded.

This is a clinically important unresolved question because secondary mitral regurgitation is extremely common. In a retrospective echocardiographic study of 558 heart failure patients with a left ventricular ejection fraction of 35% or less and class III-IV symptoms, 90% of them had some degree of mitral regurgitation (J Card Fail. 2004 Aug;10[4]:285-91).

Together with Columbia University cardiologist Dr. Gregg W. Stone, Dr. Mack is coprincipal investigator of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, which is expected to provide an answer to this key question. The multicenter U.S. study involves a planned 420 patients with severely symptomatic secondary mitral regurgitation who are deemed at prohibitive risk for surgery. They are to be randomized to guideline-directed medical therapy with or without transcatheter mitral valve repair using the MitraClip device. Enrollment should be completed by May, with initial results available in late 2017.

Dr. Mack reported receiving research grants from Abbott Vascular, which is sponsoring the COAPT trial, as well as from Edwards Lifesciences.

bjancin@frontlinemedcom.com

The blood-draw device

Photo courtesy of

Velano Vascular

The US Food and Drug Administration (FDA) has granted 510(k) clearance for a new iteration of a needle-free blood-draw device produced by Velano Vascular.

The device was originally cleared by the FDA last year.

It resembles a common syringe and allows peripheral intravenous catheters to be repurposed to draw blood from patients.

The goal of this is to reduce the need for additional needle sticks among patients receiving medications and hydration via intravenous delivery.

The new clearance for the blood-draw device covers a pair of modifications aimed at inpatient blood draws.

The first modification is a clamp for use with syringe draws. And the second is a revised indication for use that removes a limitation on when the device can be used with in-dwelling peripheral intravenous catheters.

“We rapidly implemented and pursued FDA clearance for these modifications based on input from patients and medical professionals who are using and systematically assessing our blood-draw technology,” said Eric Stone, co-founder & CEO of Velano Vascular.

Velano Vascular said it is working closely with clinical and non-profit partners, including Brigham and Women’s Hospital, Intermountain Healthcare, Griffin Health, The University of Pennsylvania Health System, The Children’s Hospital of Philadelphia, Children’s National Hospital, and Planetree, to capture patient and practitioner input regarding today’s approaches to inpatient blood draws and how the Velano technology could eventually become a standard of care.

The blood-draw device

Photo courtesy of

Velano Vascular

The US Food and Drug Administration (FDA) has granted 510(k) clearance for a new iteration of a needle-free blood-draw device produced by Velano Vascular.

The device was originally cleared by the FDA last year.

It resembles a common syringe and allows peripheral intravenous catheters to be repurposed to draw blood from patients.

The goal of this is to reduce the need for additional needle sticks among patients receiving medications and hydration via intravenous delivery.

The new clearance for the blood-draw device covers a pair of modifications aimed at inpatient blood draws.

The first modification is a clamp for use with syringe draws. And the second is a revised indication for use that removes a limitation on when the device can be used with in-dwelling peripheral intravenous catheters.

“We rapidly implemented and pursued FDA clearance for these modifications based on input from patients and medical professionals who are using and systematically assessing our blood-draw technology,” said Eric Stone, co-founder & CEO of Velano Vascular.

Velano Vascular said it is working closely with clinical and non-profit partners, including Brigham and Women’s Hospital, Intermountain Healthcare, Griffin Health, The University of Pennsylvania Health System, The Children’s Hospital of Philadelphia, Children’s National Hospital, and Planetree, to capture patient and practitioner input regarding today’s approaches to inpatient blood draws and how the Velano technology could eventually become a standard of care.

The blood-draw device

Photo courtesy of

Velano Vascular

The US Food and Drug Administration (FDA) has granted 510(k) clearance for a new iteration of a needle-free blood-draw device produced by Velano Vascular.

The device was originally cleared by the FDA last year.

It resembles a common syringe and allows peripheral intravenous catheters to be repurposed to draw blood from patients.

The goal of this is to reduce the need for additional needle sticks among patients receiving medications and hydration via intravenous delivery.

The new clearance for the blood-draw device covers a pair of modifications aimed at inpatient blood draws.

The first modification is a clamp for use with syringe draws. And the second is a revised indication for use that removes a limitation on when the device can be used with in-dwelling peripheral intravenous catheters.

“We rapidly implemented and pursued FDA clearance for these modifications based on input from patients and medical professionals who are using and systematically assessing our blood-draw technology,” said Eric Stone, co-founder & CEO of Velano Vascular.

Velano Vascular said it is working closely with clinical and non-profit partners, including Brigham and Women’s Hospital, Intermountain Healthcare, Griffin Health, The University of Pennsylvania Health System, The Children’s Hospital of Philadelphia, Children’s National Hospital, and Planetree, to capture patient and practitioner input regarding today’s approaches to inpatient blood draws and how the Velano technology could eventually become a standard of care.

Treatment of childhood medulloblastoma with proton radiotherapy resulted in acceptable toxicity, with no observed cardiac, pulmonary, or gastrointestinal late effects, and achieved outcomes that were similar to those of photon (x-ray)-based therapy.

At a median follow up of 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16% (95% confidence interval, 6-29). The Full Scale Intelligence Quotient decreased significantly, particularly in children younger than 8 years, driven mostly by drops in processing speed and verbal comprehension. The cumulative incidence of any hormone deficit at 7 years was 63% (95% CI, 48-75).

For all patients, progression-free survival (PFS) at 5 years was 80% (95% CI, 67-88) and overall survival (OS) was 83% (95% CI, 70-90). For patients with standard-risk disease, PFS was 85% (95% CI, 69-93) and OS was 86% (95% CI, 70-94); for intermediate-risk disease, PFS was 67% (95% CI, 19-90) and OS was 67% (95% CI, 19-90); for high-risk disease, PFS was 71% (95% CI, 41-88) and OS was 79% (95% CI, 47-93). These rates are similar to previously published outcomes of 81%-83% for PFS and 85%-86% for OS (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00167-9).

“Therefore, the similar disease control coupled with similar patterns of failure should quell concerns raised about the differences in relative biologic effectiveness of passively scattered proton radiotherapy,” wrote Dr. Torunn Yock, chief of pediatric radiation oncology at Massachusetts General Hospital, Boston, and colleagues.

“Although there remain some effects of treatment on hearing, endocrine, and neurocognitive outcomes – particularly in younger patients – other late effects common in photon-treated patients, such as cardiac, pulmonary, and gastrointestinal toxic effects, were absent,” they said.

Medulloblastoma survivors often have treatment-related adverse late effects, and proton radiotherapy is used to mitigate late effects by decreasing the volume of normal tissue irradiated.

The estimated mean loss per year of IQ points, at –1.5, was less than IQ differences reported in previous studies, which ranged from –1.9 to –5.8 depending on age, craniospinal irradiation dosing, boost volumes, and length of follow-up.

There were no observed cardiac effects, and no patients had restrictive lung disease, which can occur in 24%-50% of long-term survivors treated with craniospinal photon irradiation. In addition, there were no new cases of gastrointestinal toxic effects that have occurred in up to 44% of photon-treated patients.

The prospective, nonrandomized phase II study carried out at Massachusetts General Hospital, Boston, evaluated 59 patients aged 3-21 years (median age 6.6 years) who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk). All patients received chemotherapy and 55 had a near or gross total resection.

Treatment of childhood medulloblastoma with proton radiotherapy resulted in acceptable toxicity, with no observed cardiac, pulmonary, or gastrointestinal late effects, and achieved outcomes that were similar to those of photon (x-ray)-based therapy.

At a median follow up of 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16% (95% confidence interval, 6-29). The Full Scale Intelligence Quotient decreased significantly, particularly in children younger than 8 years, driven mostly by drops in processing speed and verbal comprehension. The cumulative incidence of any hormone deficit at 7 years was 63% (95% CI, 48-75).

For all patients, progression-free survival (PFS) at 5 years was 80% (95% CI, 67-88) and overall survival (OS) was 83% (95% CI, 70-90). For patients with standard-risk disease, PFS was 85% (95% CI, 69-93) and OS was 86% (95% CI, 70-94); for intermediate-risk disease, PFS was 67% (95% CI, 19-90) and OS was 67% (95% CI, 19-90); for high-risk disease, PFS was 71% (95% CI, 41-88) and OS was 79% (95% CI, 47-93). These rates are similar to previously published outcomes of 81%-83% for PFS and 85%-86% for OS (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00167-9).

“Therefore, the similar disease control coupled with similar patterns of failure should quell concerns raised about the differences in relative biologic effectiveness of passively scattered proton radiotherapy,” wrote Dr. Torunn Yock, chief of pediatric radiation oncology at Massachusetts General Hospital, Boston, and colleagues.

“Although there remain some effects of treatment on hearing, endocrine, and neurocognitive outcomes – particularly in younger patients – other late effects common in photon-treated patients, such as cardiac, pulmonary, and gastrointestinal toxic effects, were absent,” they said.

Medulloblastoma survivors often have treatment-related adverse late effects, and proton radiotherapy is used to mitigate late effects by decreasing the volume of normal tissue irradiated.

The estimated mean loss per year of IQ points, at –1.5, was less than IQ differences reported in previous studies, which ranged from –1.9 to –5.8 depending on age, craniospinal irradiation dosing, boost volumes, and length of follow-up.

There were no observed cardiac effects, and no patients had restrictive lung disease, which can occur in 24%-50% of long-term survivors treated with craniospinal photon irradiation. In addition, there were no new cases of gastrointestinal toxic effects that have occurred in up to 44% of photon-treated patients.

The prospective, nonrandomized phase II study carried out at Massachusetts General Hospital, Boston, evaluated 59 patients aged 3-21 years (median age 6.6 years) who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk). All patients received chemotherapy and 55 had a near or gross total resection.

Treatment of childhood medulloblastoma with proton radiotherapy resulted in acceptable toxicity, with no observed cardiac, pulmonary, or gastrointestinal late effects, and achieved outcomes that were similar to those of photon (x-ray)-based therapy.

At a median follow up of 5 years, the cumulative incidence of grade 3 to 4 hearing loss was 16% (95% confidence interval, 6-29). The Full Scale Intelligence Quotient decreased significantly, particularly in children younger than 8 years, driven mostly by drops in processing speed and verbal comprehension. The cumulative incidence of any hormone deficit at 7 years was 63% (95% CI, 48-75).

For all patients, progression-free survival (PFS) at 5 years was 80% (95% CI, 67-88) and overall survival (OS) was 83% (95% CI, 70-90). For patients with standard-risk disease, PFS was 85% (95% CI, 69-93) and OS was 86% (95% CI, 70-94); for intermediate-risk disease, PFS was 67% (95% CI, 19-90) and OS was 67% (95% CI, 19-90); for high-risk disease, PFS was 71% (95% CI, 41-88) and OS was 79% (95% CI, 47-93). These rates are similar to previously published outcomes of 81%-83% for PFS and 85%-86% for OS (Lancet Onc. 2016 Jan 29. doi: 10.1016/S1470-2045(15)00167-9).

“Therefore, the similar disease control coupled with similar patterns of failure should quell concerns raised about the differences in relative biologic effectiveness of passively scattered proton radiotherapy,” wrote Dr. Torunn Yock, chief of pediatric radiation oncology at Massachusetts General Hospital, Boston, and colleagues.

“Although there remain some effects of treatment on hearing, endocrine, and neurocognitive outcomes – particularly in younger patients – other late effects common in photon-treated patients, such as cardiac, pulmonary, and gastrointestinal toxic effects, were absent,” they said.

Medulloblastoma survivors often have treatment-related adverse late effects, and proton radiotherapy is used to mitigate late effects by decreasing the volume of normal tissue irradiated.

The estimated mean loss per year of IQ points, at –1.5, was less than IQ differences reported in previous studies, which ranged from –1.9 to –5.8 depending on age, craniospinal irradiation dosing, boost volumes, and length of follow-up.

There were no observed cardiac effects, and no patients had restrictive lung disease, which can occur in 24%-50% of long-term survivors treated with craniospinal photon irradiation. In addition, there were no new cases of gastrointestinal toxic effects that have occurred in up to 44% of photon-treated patients.

The prospective, nonrandomized phase II study carried out at Massachusetts General Hospital, Boston, evaluated 59 patients aged 3-21 years (median age 6.6 years) who had medulloblastoma (39 standard risk, 6 intermediate risk, and 14 high risk). All patients received chemotherapy and 55 had a near or gross total resection.

PHOENIX – Use of transcatheter aortic valve replacement continued to expand through the first half of 2015, but the procedure remained primarily targeted to patients at least 80 years old, according to data collected in a U.S. postmarketing registry.

When the Food and Drug Administration first approved a transcatheter aortic valve replacement (TAVR) system for routine U.S. use in late 2011, the patients who underwent TAVR “were either at very high risk or inoperable, and we’ve seen that move into high-risk patients – and I’m sure we’ll see more introduction of this into patients who are at medium risk,” said Dr. Frederick L. Grover in a video interview at the annual meeting of the Society of Thoracic Surgeons.

Despite this downward trend in risk level, the median and average ages of TAVR patients remain above 80 years.

In 2015, U.S. TAVR recipients had a median age of 83 years and a mean age of 81 years, virtually unchanged from the 84-year median and 82-year mean during routine U.S. practice in 2012, the first year for data collection by the STS and American College of Cardiology Transcatheter Valve Therapy (TVT) Registry. Dr. Grover reported the latest data from the registry at the meeting, through roughly the first half of 2015.

“There has been some movement downward” from 2012 to 2014 in the predicted 30-day mortality rate of patients as measured by their preprocedural STS risk score. The rate declined from an average predicted mortality rate of 7.05% in 2012 to an average of 6.69% among patients treated during 2014.

Despite this shift, TAVR patients remain highly vulnerable to surgical complications because of their advanced age and frailty, said Dr. Grover, a professor of cardiothoracic surgery at the University of Colorado in Aurora and vice chairman of the registry steering committee.

STS encourages surgeons and cardiologists who collaborate on the heart teams that judge patient suitability for TAVR to measure frailty with the 5-meter walk test, run sequentially three times. Patients who take an average of 6 seconds or more to complete the test are deemed frail and eligible for TAVR. Registry data show that during 2012-2014, 81% of TAVR patients met this frailty criterion.

Perhaps the most notable statistics in the registry are the snowballing numbers of procedures performed, which have come close to doubling each year.

In the first full year of commercial use, 2012, 4,601 patients underwent TAVR, which jumped to 9,128 patients in 2013, 16,314 patients in 2014, and 23,002 patients during just the first part of 2015, Dr. Grover reported.

Dr. Grover had no relevant disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PHOENIX – Use of transcatheter aortic valve replacement continued to expand through the first half of 2015, but the procedure remained primarily targeted to patients at least 80 years old, according to data collected in a U.S. postmarketing registry.

When the Food and Drug Administration first approved a transcatheter aortic valve replacement (TAVR) system for routine U.S. use in late 2011, the patients who underwent TAVR “were either at very high risk or inoperable, and we’ve seen that move into high-risk patients – and I’m sure we’ll see more introduction of this into patients who are at medium risk,” said Dr. Frederick L. Grover in a video interview at the annual meeting of the Society of Thoracic Surgeons.

Despite this downward trend in risk level, the median and average ages of TAVR patients remain above 80 years.

In 2015, U.S. TAVR recipients had a median age of 83 years and a mean age of 81 years, virtually unchanged from the 84-year median and 82-year mean during routine U.S. practice in 2012, the first year for data collection by the STS and American College of Cardiology Transcatheter Valve Therapy (TVT) Registry. Dr. Grover reported the latest data from the registry at the meeting, through roughly the first half of 2015.

“There has been some movement downward” from 2012 to 2014 in the predicted 30-day mortality rate of patients as measured by their preprocedural STS risk score. The rate declined from an average predicted mortality rate of 7.05% in 2012 to an average of 6.69% among patients treated during 2014.

Despite this shift, TAVR patients remain highly vulnerable to surgical complications because of their advanced age and frailty, said Dr. Grover, a professor of cardiothoracic surgery at the University of Colorado in Aurora and vice chairman of the registry steering committee.

STS encourages surgeons and cardiologists who collaborate on the heart teams that judge patient suitability for TAVR to measure frailty with the 5-meter walk test, run sequentially three times. Patients who take an average of 6 seconds or more to complete the test are deemed frail and eligible for TAVR. Registry data show that during 2012-2014, 81% of TAVR patients met this frailty criterion.

Perhaps the most notable statistics in the registry are the snowballing numbers of procedures performed, which have come close to doubling each year.

In the first full year of commercial use, 2012, 4,601 patients underwent TAVR, which jumped to 9,128 patients in 2013, 16,314 patients in 2014, and 23,002 patients during just the first part of 2015, Dr. Grover reported.

Dr. Grover had no relevant disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

PHOENIX – Use of transcatheter aortic valve replacement continued to expand through the first half of 2015, but the procedure remained primarily targeted to patients at least 80 years old, according to data collected in a U.S. postmarketing registry.

When the Food and Drug Administration first approved a transcatheter aortic valve replacement (TAVR) system for routine U.S. use in late 2011, the patients who underwent TAVR “were either at very high risk or inoperable, and we’ve seen that move into high-risk patients – and I’m sure we’ll see more introduction of this into patients who are at medium risk,” said Dr. Frederick L. Grover in a video interview at the annual meeting of the Society of Thoracic Surgeons.

Despite this downward trend in risk level, the median and average ages of TAVR patients remain above 80 years.

In 2015, U.S. TAVR recipients had a median age of 83 years and a mean age of 81 years, virtually unchanged from the 84-year median and 82-year mean during routine U.S. practice in 2012, the first year for data collection by the STS and American College of Cardiology Transcatheter Valve Therapy (TVT) Registry. Dr. Grover reported the latest data from the registry at the meeting, through roughly the first half of 2015.

“There has been some movement downward” from 2012 to 2014 in the predicted 30-day mortality rate of patients as measured by their preprocedural STS risk score. The rate declined from an average predicted mortality rate of 7.05% in 2012 to an average of 6.69% among patients treated during 2014.

Despite this shift, TAVR patients remain highly vulnerable to surgical complications because of their advanced age and frailty, said Dr. Grover, a professor of cardiothoracic surgery at the University of Colorado in Aurora and vice chairman of the registry steering committee.

STS encourages surgeons and cardiologists who collaborate on the heart teams that judge patient suitability for TAVR to measure frailty with the 5-meter walk test, run sequentially three times. Patients who take an average of 6 seconds or more to complete the test are deemed frail and eligible for TAVR. Registry data show that during 2012-2014, 81% of TAVR patients met this frailty criterion.

Perhaps the most notable statistics in the registry are the snowballing numbers of procedures performed, which have come close to doubling each year.

In the first full year of commercial use, 2012, 4,601 patients underwent TAVR, which jumped to 9,128 patients in 2013, 16,314 patients in 2014, and 23,002 patients during just the first part of 2015, Dr. Grover reported.

Dr. Grover had no relevant disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler