Thoracic Surgery News (Archived)

What makes a Cardiothoracic training program great? For many it means that the program “leads” the field in surgical knowledge, blazing a path towards discovery. To oth­ers it means the program trains future surgeons well by teaching them how to operate. Still others feel it is a program with a rich history and an esteemed group of surgeons on its board …the list could go on and on. The Joint Council on Thoracic Surgery Education (JCTSE) recently has begun to focus on identify­ing areas within surgical education that makes a program stand above the rest.

To some, searching for what makes a Cardiothoracic program “great” is pure­ly subjective like a quest for the world’s greatest donut. The goal here is not to form a simple rank list of the most out­standing CT programs; rather, the JCTSE aims to identify traits of pro­grams that support the American Board of Thoracic Surgery’s mission to “pro­tect the public by establishing and main­
taining high standards in thoracic surgery.” The mere ranking of programs in a neat and orderly line likely does not hold much educational purpose. The identification of “great” traits though, does have purpose and will help deliver specific goals from broad educational principals.

The JCTSE and the Thoracic Surgery Residents Association (TSRA) have re­cently taken a first step in collecting these traits of greatness by sending out
a preliminary survey to current cardio­thoracic (CT) residents. The survey con­sisted of 50 questions addressing the relative importance of multiple aspects of CT surgery training programs and ini­tial findings varied from the expected to the surprising. Traditional areas of im­portance such as the reputation of the program, the expectation of trainees functioning as operating surgeon, help in finding employment and a high volume and complexity of cases were at the top
of the list. Surprisingly, other areas queried such as the program’s facilities or if the program is 2 or 3 years were not felt to be important in making a program “outstanding” by current CT residents.

Now that this preliminary data has been collected, a more scientific survey is being developed to administer to fu­ture generations of CT residents. The data from which may ultimately serve as a useful guide to “raise all boats” towards greatness in Cardiothoracic training.

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What makes a Cardiothoracic training program great? For many it means that the program “leads” the field in surgical knowledge, blazing a path towards discovery. To oth­ers it means the program trains future surgeons well by teaching them how to operate. Still others feel it is a program with a rich history and an esteemed group of surgeons on its board …the list could go on and on. The Joint Council on Thoracic Surgery Education (JCTSE) recently has begun to focus on identify­ing areas within surgical education that makes a program stand above the rest.

To some, searching for what makes a Cardiothoracic program “great” is pure­ly subjective like a quest for the world’s greatest donut. The goal here is not to form a simple rank list of the most out­standing CT programs; rather, the JCTSE aims to identify traits of pro­grams that support the American Board of Thoracic Surgery’s mission to “pro­tect the public by establishing and main­
taining high standards in thoracic surgery.” The mere ranking of programs in a neat and orderly line likely does not hold much educational purpose. The identification of “great” traits though, does have purpose and will help deliver specific goals from broad educational principals.

The JCTSE and the Thoracic Surgery Residents Association (TSRA) have re­cently taken a first step in collecting these traits of greatness by sending out
a preliminary survey to current cardio­thoracic (CT) residents. The survey con­sisted of 50 questions addressing the relative importance of multiple aspects of CT surgery training programs and ini­tial findings varied from the expected to the surprising. Traditional areas of im­portance such as the reputation of the program, the expectation of trainees functioning as operating surgeon, help in finding employment and a high volume and complexity of cases were at the top
of the list. Surprisingly, other areas queried such as the program’s facilities or if the program is 2 or 3 years were not felt to be important in making a program “outstanding” by current CT residents.

Now that this preliminary data has been collected, a more scientific survey is being developed to administer to fu­ture generations of CT residents. The data from which may ultimately serve as a useful guide to “raise all boats” towards greatness in Cardiothoracic training.

********* UNDERSET  1  LINES *********

What makes a Cardiothoracic training program great? For many it means that the program “leads” the field in surgical knowledge, blazing a path towards discovery. To oth­ers it means the program trains future surgeons well by teaching them how to operate. Still others feel it is a program with a rich history and an esteemed group of surgeons on its board …the list could go on and on. The Joint Council on Thoracic Surgery Education (JCTSE) recently has begun to focus on identify­ing areas within surgical education that makes a program stand above the rest.

To some, searching for what makes a Cardiothoracic program “great” is pure­ly subjective like a quest for the world’s greatest donut. The goal here is not to form a simple rank list of the most out­standing CT programs; rather, the JCTSE aims to identify traits of pro­grams that support the American Board of Thoracic Surgery’s mission to “pro­tect the public by establishing and main­
taining high standards in thoracic surgery.” The mere ranking of programs in a neat and orderly line likely does not hold much educational purpose. The identification of “great” traits though, does have purpose and will help deliver specific goals from broad educational principals.

The JCTSE and the Thoracic Surgery Residents Association (TSRA) have re­cently taken a first step in collecting these traits of greatness by sending out
a preliminary survey to current cardio­thoracic (CT) residents. The survey con­sisted of 50 questions addressing the relative importance of multiple aspects of CT surgery training programs and ini­tial findings varied from the expected to the surprising. Traditional areas of im­portance such as the reputation of the program, the expectation of trainees functioning as operating surgeon, help in finding employment and a high volume and complexity of cases were at the top
of the list. Surprisingly, other areas queried such as the program’s facilities or if the program is 2 or 3 years were not felt to be important in making a program “outstanding” by current CT residents.

Now that this preliminary data has been collected, a more scientific survey is being developed to administer to fu­ture generations of CT residents. The data from which may ultimately serve as a useful guide to “raise all boats” towards greatness in Cardiothoracic training.

********* UNDERSET  1  LINES *********

TAMPA – Sharing bad news with patients might not be easy, but it’s a skill physicians can learn and is as im­portant as knowing how to ready an EKG or an x-ray, James A. Avery, M.D., said. “What I am proposing is that giving bad news well is a fundamental long-term care physician skill, and competence in this area is critical,” Dr. Avery said at this year’s AMDA – Dedicated to Long Term Care Medicine annual meeting.

“Giving bad news … takes desire, courage, and prac­tice,” said Dr. Avery. “Patients deserve to get bad news delivered with compassion, hope, and integrity.”

Plan ahead for the conversation; start with what the patient knows and wants to know; and develop a com­passionate tone, said Dr. Avery, chief medical officer at Golden Living in Washington, a corporation that fo­cuses on skilled nursing, assisted living, and rehabilita­tion therapy. Also, always provide an appropriate prognosis. “It’s your obligation to bring this up. Patients and families may be afraid to ask.”

What can happen if the conversation is not done cor­rectly? “If bad news is given poorly, it can rob hope and create distress, confusion, and anxiety. It can weaken the patient’s faith and set off a chain of events that adversely affects the survivors for years,” said Dr. Avery.

“I was particularly bad at giving bad news at first,” he said. A pulmonologist by training, he also worked for years in hospice care in both Florida and New York. He spoke with patients who transitioned to hospice from Memorial Sloan-Kettering Cancer Center, New York, for example.

<[stk -1]>“I learned quickly that if I was going to give bad news, not to schedule the patient for midmorning on a Mon­day. It is too chaotic,” Dr. Avery said. Schedule the pa­tient for the first appointment after lunch or at the end of the day. Allow sufficient time and create a comfort­able, private place with tissues available, he added.<[etk]>

Next, determine where each patient is in terms of un­derstanding his or her illness. “Explore and ask,” Dr. Av­ery said. Good questions include:

<[stk -3]>P Is there anyone you want with you in the conversation? <[etk]>

P How do you understand what has happened to you medically?

P What have doctors told you about this illness?

P What do you think caused this illness?

“I cannot tell you how many patients with colon can­cer thought they had it because they took too many antacids,” Dr. Avery said. “Also, I had one woman with breast cancer who responded ‘Burger King.’ She had read an article that fatty foods caused breast cancer and felt guilty that she was leaving her family because she ate burgers instead of salads.”

Also, determine how much the patient wants to know. “About 90% of patients want full information [about their condition], but everyone wants to know everything about treatment.” Physicians also can be in­strumental in allaying end-of-life fears, Dr. Avery said. Regardless of illness, most patients think some symp­tom is going to get worse and worse and crescendo in pain before they die. “How do people with COPD die? Yes, the symptoms get worse, but with COPD, they get COPD narcosis, get sleepy, and drift away.”

Intentionally develop and use a compassionate tone,
Dr. Avery said. This is important because patients sur­veyed after receiving bad news said the attitude of the person who spoke with them was the most important factor. The clarity of the message and privacy were also important, but they ranked far behind clinician attitude.

Allow for silence. Let the message sink in. “Give the patient plenty of time to react, respond, and ask ques­tions.” Also allow tears – “That can be a real problem for a lot of doctors.”

<[stk -1]>A challenge for physicians is to be empathetic with­out breaking down completely, Dr. Avery said. When working in hospice care in New York, he frequently spent the day traveling by subway to clients’ residences. “Am I going to travel around weeping? No. You have to somehow try to meet where they are, but you cannot go there completely. It would be self-destructive.”<[etk]>

“One reason physicians think they do not give bad news well is they fear their own response; that they will break down,” Dr. Avery said. Try to determine the pa­tient’s attitude and reflect it back to them. “This is what you do when things get emotional. And they will cor­rect you if you’re wrong. If you say ‘You sound angry,’ they might say ‘No, I’m upset.’ ”

Another important thing to ask patients is, “Have the doctors told you how long you have?” An accurate prog­nosis will help patients and family prepare, Dr. Avery said. “You have to tell them. If you don’t, they will seek a second opinion and/or leave the long-term care set­ting, because no one has told them.” Less-experienced doctors and doctors who have had a long and strong relationship with a patient can be especially poor at prognostication, he said.

<[stk -1]>Be completely honest and avoid stating a precise amount of time, such as “3 months.” “I say, ‘It could be weeks instead of months,’ or ‘It could be months instead of years.’ If they ask for a more precise prognosis, tell them it’s difficult to say, because it is,” Dr. Avery said. <[etk]>

I have checked the following facts in my story: (Please initial each.)

If you still do not feel comfortable giving the patient bad news, refer the patient to someone who does.

“Call in hospice, call in palliative care. If you cannot give that bad news, you are obligated to do this,” Dr. Avery said.

TAMPA – Sharing bad news with patients might not be easy, but it’s a skill physicians can learn and is as im­portant as knowing how to ready an EKG or an x-ray, James A. Avery, M.D., said. “What I am proposing is that giving bad news well is a fundamental long-term care physician skill, and competence in this area is critical,” Dr. Avery said at this year’s AMDA – Dedicated to Long Term Care Medicine annual meeting.

“Giving bad news … takes desire, courage, and prac­tice,” said Dr. Avery. “Patients deserve to get bad news delivered with compassion, hope, and integrity.”

Plan ahead for the conversation; start with what the patient knows and wants to know; and develop a com­passionate tone, said Dr. Avery, chief medical officer at Golden Living in Washington, a corporation that fo­cuses on skilled nursing, assisted living, and rehabilita­tion therapy. Also, always provide an appropriate prognosis. “It’s your obligation to bring this up. Patients and families may be afraid to ask.”

What can happen if the conversation is not done cor­rectly? “If bad news is given poorly, it can rob hope and create distress, confusion, and anxiety. It can weaken the patient’s faith and set off a chain of events that adversely affects the survivors for years,” said Dr. Avery.

“I was particularly bad at giving bad news at first,” he said. A pulmonologist by training, he also worked for years in hospice care in both Florida and New York. He spoke with patients who transitioned to hospice from Memorial Sloan-Kettering Cancer Center, New York, for example.

<[stk -1]>“I learned quickly that if I was going to give bad news, not to schedule the patient for midmorning on a Mon­day. It is too chaotic,” Dr. Avery said. Schedule the pa­tient for the first appointment after lunch or at the end of the day. Allow sufficient time and create a comfort­able, private place with tissues available, he added.<[etk]>

Next, determine where each patient is in terms of un­derstanding his or her illness. “Explore and ask,” Dr. Av­ery said. Good questions include:

<[stk -3]>P Is there anyone you want with you in the conversation? <[etk]>

P How do you understand what has happened to you medically?

P What have doctors told you about this illness?

P What do you think caused this illness?

“I cannot tell you how many patients with colon can­cer thought they had it because they took too many antacids,” Dr. Avery said. “Also, I had one woman with breast cancer who responded ‘Burger King.’ She had read an article that fatty foods caused breast cancer and felt guilty that she was leaving her family because she ate burgers instead of salads.”

Also, determine how much the patient wants to know. “About 90% of patients want full information [about their condition], but everyone wants to know everything about treatment.” Physicians also can be in­strumental in allaying end-of-life fears, Dr. Avery said. Regardless of illness, most patients think some symp­tom is going to get worse and worse and crescendo in pain before they die. “How do people with COPD die? Yes, the symptoms get worse, but with COPD, they get COPD narcosis, get sleepy, and drift away.”

Intentionally develop and use a compassionate tone,
Dr. Avery said. This is important because patients sur­veyed after receiving bad news said the attitude of the person who spoke with them was the most important factor. The clarity of the message and privacy were also important, but they ranked far behind clinician attitude.

Allow for silence. Let the message sink in. “Give the patient plenty of time to react, respond, and ask ques­tions.” Also allow tears – “That can be a real problem for a lot of doctors.”

<[stk -1]>A challenge for physicians is to be empathetic with­out breaking down completely, Dr. Avery said. When working in hospice care in New York, he frequently spent the day traveling by subway to clients’ residences. “Am I going to travel around weeping? No. You have to somehow try to meet where they are, but you cannot go there completely. It would be self-destructive.”<[etk]>

“One reason physicians think they do not give bad news well is they fear their own response; that they will break down,” Dr. Avery said. Try to determine the pa­tient’s attitude and reflect it back to them. “This is what you do when things get emotional. And they will cor­rect you if you’re wrong. If you say ‘You sound angry,’ they might say ‘No, I’m upset.’ ”

Another important thing to ask patients is, “Have the doctors told you how long you have?” An accurate prog­nosis will help patients and family prepare, Dr. Avery said. “You have to tell them. If you don’t, they will seek a second opinion and/or leave the long-term care set­ting, because no one has told them.” Less-experienced doctors and doctors who have had a long and strong relationship with a patient can be especially poor at prognostication, he said.

<[stk -1]>Be completely honest and avoid stating a precise amount of time, such as “3 months.” “I say, ‘It could be weeks instead of months,’ or ‘It could be months instead of years.’ If they ask for a more precise prognosis, tell them it’s difficult to say, because it is,” Dr. Avery said. <[etk]>

I have checked the following facts in my story: (Please initial each.)

If you still do not feel comfortable giving the patient bad news, refer the patient to someone who does.

“Call in hospice, call in palliative care. If you cannot give that bad news, you are obligated to do this,” Dr. Avery said.

TAMPA – Sharing bad news with patients might not be easy, but it’s a skill physicians can learn and is as im­portant as knowing how to ready an EKG or an x-ray, James A. Avery, M.D., said. “What I am proposing is that giving bad news well is a fundamental long-term care physician skill, and competence in this area is critical,” Dr. Avery said at this year’s AMDA – Dedicated to Long Term Care Medicine annual meeting.

“Giving bad news … takes desire, courage, and prac­tice,” said Dr. Avery. “Patients deserve to get bad news delivered with compassion, hope, and integrity.”

Plan ahead for the conversation; start with what the patient knows and wants to know; and develop a com­passionate tone, said Dr. Avery, chief medical officer at Golden Living in Washington, a corporation that fo­cuses on skilled nursing, assisted living, and rehabilita­tion therapy. Also, always provide an appropriate prognosis. “It’s your obligation to bring this up. Patients and families may be afraid to ask.”

What can happen if the conversation is not done cor­rectly? “If bad news is given poorly, it can rob hope and create distress, confusion, and anxiety. It can weaken the patient’s faith and set off a chain of events that adversely affects the survivors for years,” said Dr. Avery.

“I was particularly bad at giving bad news at first,” he said. A pulmonologist by training, he also worked for years in hospice care in both Florida and New York. He spoke with patients who transitioned to hospice from Memorial Sloan-Kettering Cancer Center, New York, for example.

<[stk -1]>“I learned quickly that if I was going to give bad news, not to schedule the patient for midmorning on a Mon­day. It is too chaotic,” Dr. Avery said. Schedule the pa­tient for the first appointment after lunch or at the end of the day. Allow sufficient time and create a comfort­able, private place with tissues available, he added.<[etk]>

Next, determine where each patient is in terms of un­derstanding his or her illness. “Explore and ask,” Dr. Av­ery said. Good questions include:

<[stk -3]>P Is there anyone you want with you in the conversation? <[etk]>

P How do you understand what has happened to you medically?

P What have doctors told you about this illness?

P What do you think caused this illness?

“I cannot tell you how many patients with colon can­cer thought they had it because they took too many antacids,” Dr. Avery said. “Also, I had one woman with breast cancer who responded ‘Burger King.’ She had read an article that fatty foods caused breast cancer and felt guilty that she was leaving her family because she ate burgers instead of salads.”

Also, determine how much the patient wants to know. “About 90% of patients want full information [about their condition], but everyone wants to know everything about treatment.” Physicians also can be in­strumental in allaying end-of-life fears, Dr. Avery said. Regardless of illness, most patients think some symp­tom is going to get worse and worse and crescendo in pain before they die. “How do people with COPD die? Yes, the symptoms get worse, but with COPD, they get COPD narcosis, get sleepy, and drift away.”

Intentionally develop and use a compassionate tone,
Dr. Avery said. This is important because patients sur­veyed after receiving bad news said the attitude of the person who spoke with them was the most important factor. The clarity of the message and privacy were also important, but they ranked far behind clinician attitude.

Allow for silence. Let the message sink in. “Give the patient plenty of time to react, respond, and ask ques­tions.” Also allow tears – “That can be a real problem for a lot of doctors.”

<[stk -1]>A challenge for physicians is to be empathetic with­out breaking down completely, Dr. Avery said. When working in hospice care in New York, he frequently spent the day traveling by subway to clients’ residences. “Am I going to travel around weeping? No. You have to somehow try to meet where they are, but you cannot go there completely. It would be self-destructive.”<[etk]>

“One reason physicians think they do not give bad news well is they fear their own response; that they will break down,” Dr. Avery said. Try to determine the pa­tient’s attitude and reflect it back to them. “This is what you do when things get emotional. And they will cor­rect you if you’re wrong. If you say ‘You sound angry,’ they might say ‘No, I’m upset.’ ”

Another important thing to ask patients is, “Have the doctors told you how long you have?” An accurate prog­nosis will help patients and family prepare, Dr. Avery said. “You have to tell them. If you don’t, they will seek a second opinion and/or leave the long-term care set­ting, because no one has told them.” Less-experienced doctors and doctors who have had a long and strong relationship with a patient can be especially poor at prognostication, he said.

<[stk -1]>Be completely honest and avoid stating a precise amount of time, such as “3 months.” “I say, ‘It could be weeks instead of months,’ or ‘It could be months instead of years.’ If they ask for a more precise prognosis, tell them it’s difficult to say, because it is,” Dr. Avery said. <[etk]>

I have checked the following facts in my story: (Please initial each.)

If you still do not feel comfortable giving the patient bad news, refer the patient to someone who does.

“Call in hospice, call in palliative care. If you cannot give that bad news, you are obligated to do this,” Dr. Avery said.

Testing for epidermal growth factor receptor mutations is an important step in the evalu­ation process for systemic ther­apy in patients with metastatic or recurrent non–small cell lung cancer according to up­dated recommendations issued by the American Society of Clinical Oncology and the Na­tional Comprehensive Cancer Network.

ASCO issued a provisional clinical opinion (PCO) that pa­tients with advanced non–small cell lung cancer (NSCLC) who are being considered for treat­ment with one of the tyrosine kinase inhibitors (TKIs) that tar­get the epidermal growth factor receptor (EGFR) should under­go EGFR-mutation testing. 

Oncologists have learned that NSCLC is “really a collection of genetically distinct diseases,” ASCO’s PCO panel cochair Dr. Vicki L. Keedy of Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said in a press release. The goal is to “treat pa­tients with drugs that target the molecular drivers of their spe­cific tumors rather than using a one-size-fits-all approach.”

The NCCN earlier updated its clinical management guide­lines to include a category 1 recommendation that EGFR testing should be undertaken after histologic diagnosis of adenocarcinoma, large cell carcinoma, or undifferentiated carcinoma.

The NCCN recommendation does not extend to patients with squamous cell lung cancer, because the incidence of EGFR mutation in this patient subgroup is less than 3.6%, Dr. David S. Ettinger said in March at the organization’s an­nual conference. 

Both groups based their endorse­ments on studies demonstrating that mutations in two regions of EGFR gene appear to predict tumor response to chemotherapy in general, and to TKIs specifically.

Among the research priorities that were identified by ASCO, Dr. Keedy not­ed the trials that are designed to discern whether first-line treatment with a TKI in EGFR mutation–negative patients de­lays chemotherapy or affects outcome; whether chemotherapy prior to TKI treatment in EGFR mutation–positive patients affects outcome; and whether there are clinically significant differences between erlotinib (Tarceva) and gefi­tinib (Iressa) among EGFR mutation–positive patients. 

The last question is of particular in­terest, because gefitinib is not Food and Drug Association approved outside a special program in the United States, whereas erlotinib is currently approved as second-line therapy, she said.

Dr. Ettinger, chair of the NCCN’s NSCLC guideline panel and professor of oncology at Johns Hopkins University in Baltimore, cited findings from the landmark IPASS (Iressa Pan-Asia Study) investigation that compared progres­sion-free and overall survival in 1,217 East Asian patients with advanced NSCLC that was treated with the gefi­tinib or standard carboplatin and paclitaxel chemotherapy. 

IPASS demonstrated that EGFR mu­tation strongly predicted a lower risk of progression on gefitinib vs. chemother­apy (hazard ratio, 0.48), whereas wild-type EGFR predicted a higher risk of progression on gefitinib relative to chemotherapy (HR, 2.85) (N. Engl. J. Med. 2009;361:947-57). 

Similarly, in a pooled analysis of clin­ical outcomes of NSCLC patients who were treated with erlotinib, EGFR mu­tations were associated with a median progression-free survival of 13.2 vs. 5.9 months (J. Cell. Mol. Med. 2010;14:51-69). Neither study demonstrated a dif­ference in overall survival among treated patients with and without EGFR muta­tions, Dr. Ettinger said.

The updated NCCN guidelines also state that the sequencing of KRAS (a G protein involved in the EGFR-related signal transmission) could be useful for the selection of patients as candidates for TKI therapy. The KRAS gene can harbor oncogenic mutations that may render a tumor resistant to EGFR-targeting agents, Dr. Ettinger explained, noting that studies have shown that a KRAS mu­tation in patients with NSCLC “confers a high level of resistance” to TKIs. 

Although the data – which primarily come from retrospective reviews with small sample sizes – are insufficient to make a determination about an associ­ation between KRAS mutation status and survival, he said, they are sufficient to warrant a category 2A recommen­dation for sequencing, as well as a rec­ommendation that patients with a known KRAS mutation should undergo first-line therapy with an agent other than a TKI.

Individuals who test negative for EGFR and KRAS should also be screened for a mutation of the anaplastic lym­phoma kinase (ALK) fusion gene, Dr. Et­tinger said. 

“Patients who screen positive may not benefit from EGFR TKIs, but they may be good candidates for an ALK-targeted therapy,” he said, noting that the inves­tigational ALK-tar­geting drug crizotinib, in par­ticular, has demon­strated positive results in early studies of NSCLC patients with echinoderm mi­crotubule-associat­ed proteinlike 4 (EML4)-ALK translocations (N. Engl. J. Med. 2010;363:1693-703).

With respect to first-line systemic ther­apy, patients with adenocarcinoma, large cell carcinoma, or NSCLC “not other­wise specified” who have an Eastern Co­operative Oncology Group/World Health Organization performance status grade of 0-4 and who test positive for the EGFR mutation prior to first-line thera­py should be treated with erlotinib, ac­cording to the NCCN guidelines. 

Alternatively, the guidelines state that gefitinib can be used in place of erlotinib “in areas of the world where it is avail­able.” 

For patients in whom the EGFR mu­tation is discovered during chemothera­py, the guidelines recommend either adding erlotinib to the current chemotherapy protocol or switching to erlotinib as maintenance treatment.

For patients whose EGFR status is negative or unknown, even in the pres­ence of clinical characteristics that might be suggestive of a mutation (for exam­ple, female, nonsmoker, Asian race), con­ventional chemotherapy is recommended, Dr. Ettinger said. 

In an editorial that accompanied ASCO’s PCO announcement, Dr. Paul A. Bunn Jr. and Dr. Robert C. Doebele of the University of Colorado Cancer Center in Aurora wrote that the grow­ing clinical importance of molecularly defined subgroups of adenocarcinoma signals a “new era of personalized med­icine for patients with advanced lung cancer, in which it will be imperative to match the specific mutations of a patient’s tumor with a specific therapy.” 

The implemen­tation of routine, simultaneous testing of multiple markers will likely be con­ducted on all patients prior to treat­ment initiation, regardless of clinical features, they stated, acknowledging certain procedural challenges, includ­ing obtaining adequate tumor materi­al at the time of diagnostic biopsy and developing testing platforms “that si­multaneously analyze for the presence of somatic mutations, gene fusions, or other genetic challenges.”

The updated NCCN Guidelines for NSCLC are posted at www.nccn.org. The ASCO PCO is posted at www.asco.org/ascov2/Practice+&+Guidelines/Guidelines/Provisional+Clinical+Opinion.

Dr. Ettinger has consultancy agree­ments with the a number of pharma­ceutical companies Dr. Keedy receives commercial research support from Ari­ad Pharmaceuticals, Ziopharm Oncolo­gy, and Amgen Oncology Therapeutics. Dr. Bunn has a consultant or advisory role with a number of pharmaceutical companies. Dr. Doebele disclosed re­search funding from Lilly, ImClone Sys­tems, and Pfizer.

Testing for epidermal growth factor receptor mutations is an important step in the evalu­ation process for systemic ther­apy in patients with metastatic or recurrent non–small cell lung cancer according to up­dated recommendations issued by the American Society of Clinical Oncology and the Na­tional Comprehensive Cancer Network.

ASCO issued a provisional clinical opinion (PCO) that pa­tients with advanced non–small cell lung cancer (NSCLC) who are being considered for treat­ment with one of the tyrosine kinase inhibitors (TKIs) that tar­get the epidermal growth factor receptor (EGFR) should under­go EGFR-mutation testing. 

Oncologists have learned that NSCLC is “really a collection of genetically distinct diseases,” ASCO’s PCO panel cochair Dr. Vicki L. Keedy of Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said in a press release. The goal is to “treat pa­tients with drugs that target the molecular drivers of their spe­cific tumors rather than using a one-size-fits-all approach.”

The NCCN earlier updated its clinical management guide­lines to include a category 1 recommendation that EGFR testing should be undertaken after histologic diagnosis of adenocarcinoma, large cell carcinoma, or undifferentiated carcinoma.

The NCCN recommendation does not extend to patients with squamous cell lung cancer, because the incidence of EGFR mutation in this patient subgroup is less than 3.6%, Dr. David S. Ettinger said in March at the organization’s an­nual conference. 

Both groups based their endorse­ments on studies demonstrating that mutations in two regions of EGFR gene appear to predict tumor response to chemotherapy in general, and to TKIs specifically.

Among the research priorities that were identified by ASCO, Dr. Keedy not­ed the trials that are designed to discern whether first-line treatment with a TKI in EGFR mutation–negative patients de­lays chemotherapy or affects outcome; whether chemotherapy prior to TKI treatment in EGFR mutation–positive patients affects outcome; and whether there are clinically significant differences between erlotinib (Tarceva) and gefi­tinib (Iressa) among EGFR mutation–positive patients. 

The last question is of particular in­terest, because gefitinib is not Food and Drug Association approved outside a special program in the United States, whereas erlotinib is currently approved as second-line therapy, she said.

Dr. Ettinger, chair of the NCCN’s NSCLC guideline panel and professor of oncology at Johns Hopkins University in Baltimore, cited findings from the landmark IPASS (Iressa Pan-Asia Study) investigation that compared progres­sion-free and overall survival in 1,217 East Asian patients with advanced NSCLC that was treated with the gefi­tinib or standard carboplatin and paclitaxel chemotherapy. 

IPASS demonstrated that EGFR mu­tation strongly predicted a lower risk of progression on gefitinib vs. chemother­apy (hazard ratio, 0.48), whereas wild-type EGFR predicted a higher risk of progression on gefitinib relative to chemotherapy (HR, 2.85) (N. Engl. J. Med. 2009;361:947-57). 

Similarly, in a pooled analysis of clin­ical outcomes of NSCLC patients who were treated with erlotinib, EGFR mu­tations were associated with a median progression-free survival of 13.2 vs. 5.9 months (J. Cell. Mol. Med. 2010;14:51-69). Neither study demonstrated a dif­ference in overall survival among treated patients with and without EGFR muta­tions, Dr. Ettinger said.

The updated NCCN guidelines also state that the sequencing of KRAS (a G protein involved in the EGFR-related signal transmission) could be useful for the selection of patients as candidates for TKI therapy. The KRAS gene can harbor oncogenic mutations that may render a tumor resistant to EGFR-targeting agents, Dr. Ettinger explained, noting that studies have shown that a KRAS mu­tation in patients with NSCLC “confers a high level of resistance” to TKIs. 

Although the data – which primarily come from retrospective reviews with small sample sizes – are insufficient to make a determination about an associ­ation between KRAS mutation status and survival, he said, they are sufficient to warrant a category 2A recommen­dation for sequencing, as well as a rec­ommendation that patients with a known KRAS mutation should undergo first-line therapy with an agent other than a TKI.

Individuals who test negative for EGFR and KRAS should also be screened for a mutation of the anaplastic lym­phoma kinase (ALK) fusion gene, Dr. Et­tinger said. 

“Patients who screen positive may not benefit from EGFR TKIs, but they may be good candidates for an ALK-targeted therapy,” he said, noting that the inves­tigational ALK-tar­geting drug crizotinib, in par­ticular, has demon­strated positive results in early studies of NSCLC patients with echinoderm mi­crotubule-associat­ed proteinlike 4 (EML4)-ALK translocations (N. Engl. J. Med. 2010;363:1693-703).

With respect to first-line systemic ther­apy, patients with adenocarcinoma, large cell carcinoma, or NSCLC “not other­wise specified” who have an Eastern Co­operative Oncology Group/World Health Organization performance status grade of 0-4 and who test positive for the EGFR mutation prior to first-line thera­py should be treated with erlotinib, ac­cording to the NCCN guidelines. 

Alternatively, the guidelines state that gefitinib can be used in place of erlotinib “in areas of the world where it is avail­able.” 

For patients in whom the EGFR mu­tation is discovered during chemothera­py, the guidelines recommend either adding erlotinib to the current chemotherapy protocol or switching to erlotinib as maintenance treatment.

For patients whose EGFR status is negative or unknown, even in the pres­ence of clinical characteristics that might be suggestive of a mutation (for exam­ple, female, nonsmoker, Asian race), con­ventional chemotherapy is recommended, Dr. Ettinger said. 

In an editorial that accompanied ASCO’s PCO announcement, Dr. Paul A. Bunn Jr. and Dr. Robert C. Doebele of the University of Colorado Cancer Center in Aurora wrote that the grow­ing clinical importance of molecularly defined subgroups of adenocarcinoma signals a “new era of personalized med­icine for patients with advanced lung cancer, in which it will be imperative to match the specific mutations of a patient’s tumor with a specific therapy.” 

The implemen­tation of routine, simultaneous testing of multiple markers will likely be con­ducted on all patients prior to treat­ment initiation, regardless of clinical features, they stated, acknowledging certain procedural challenges, includ­ing obtaining adequate tumor materi­al at the time of diagnostic biopsy and developing testing platforms “that si­multaneously analyze for the presence of somatic mutations, gene fusions, or other genetic challenges.”

The updated NCCN Guidelines for NSCLC are posted at www.nccn.org. The ASCO PCO is posted at www.asco.org/ascov2/Practice+&+Guidelines/Guidelines/Provisional+Clinical+Opinion.

Dr. Ettinger has consultancy agree­ments with the a number of pharma­ceutical companies Dr. Keedy receives commercial research support from Ari­ad Pharmaceuticals, Ziopharm Oncolo­gy, and Amgen Oncology Therapeutics. Dr. Bunn has a consultant or advisory role with a number of pharmaceutical companies. Dr. Doebele disclosed re­search funding from Lilly, ImClone Sys­tems, and Pfizer.

Testing for epidermal growth factor receptor mutations is an important step in the evalu­ation process for systemic ther­apy in patients with metastatic or recurrent non–small cell lung cancer according to up­dated recommendations issued by the American Society of Clinical Oncology and the Na­tional Comprehensive Cancer Network.

ASCO issued a provisional clinical opinion (PCO) that pa­tients with advanced non–small cell lung cancer (NSCLC) who are being considered for treat­ment with one of the tyrosine kinase inhibitors (TKIs) that tar­get the epidermal growth factor receptor (EGFR) should under­go EGFR-mutation testing. 

Oncologists have learned that NSCLC is “really a collection of genetically distinct diseases,” ASCO’s PCO panel cochair Dr. Vicki L. Keedy of Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said in a press release. The goal is to “treat pa­tients with drugs that target the molecular drivers of their spe­cific tumors rather than using a one-size-fits-all approach.”

The NCCN earlier updated its clinical management guide­lines to include a category 1 recommendation that EGFR testing should be undertaken after histologic diagnosis of adenocarcinoma, large cell carcinoma, or undifferentiated carcinoma.

The NCCN recommendation does not extend to patients with squamous cell lung cancer, because the incidence of EGFR mutation in this patient subgroup is less than 3.6%, Dr. David S. Ettinger said in March at the organization’s an­nual conference. 

Both groups based their endorse­ments on studies demonstrating that mutations in two regions of EGFR gene appear to predict tumor response to chemotherapy in general, and to TKIs specifically.

Among the research priorities that were identified by ASCO, Dr. Keedy not­ed the trials that are designed to discern whether first-line treatment with a TKI in EGFR mutation–negative patients de­lays chemotherapy or affects outcome; whether chemotherapy prior to TKI treatment in EGFR mutation–positive patients affects outcome; and whether there are clinically significant differences between erlotinib (Tarceva) and gefi­tinib (Iressa) among EGFR mutation–positive patients. 

The last question is of particular in­terest, because gefitinib is not Food and Drug Association approved outside a special program in the United States, whereas erlotinib is currently approved as second-line therapy, she said.

Dr. Ettinger, chair of the NCCN’s NSCLC guideline panel and professor of oncology at Johns Hopkins University in Baltimore, cited findings from the landmark IPASS (Iressa Pan-Asia Study) investigation that compared progres­sion-free and overall survival in 1,217 East Asian patients with advanced NSCLC that was treated with the gefi­tinib or standard carboplatin and paclitaxel chemotherapy. 

IPASS demonstrated that EGFR mu­tation strongly predicted a lower risk of progression on gefitinib vs. chemother­apy (hazard ratio, 0.48), whereas wild-type EGFR predicted a higher risk of progression on gefitinib relative to chemotherapy (HR, 2.85) (N. Engl. J. Med. 2009;361:947-57). 

Similarly, in a pooled analysis of clin­ical outcomes of NSCLC patients who were treated with erlotinib, EGFR mu­tations were associated with a median progression-free survival of 13.2 vs. 5.9 months (J. Cell. Mol. Med. 2010;14:51-69). Neither study demonstrated a dif­ference in overall survival among treated patients with and without EGFR muta­tions, Dr. Ettinger said.

The updated NCCN guidelines also state that the sequencing of KRAS (a G protein involved in the EGFR-related signal transmission) could be useful for the selection of patients as candidates for TKI therapy. The KRAS gene can harbor oncogenic mutations that may render a tumor resistant to EGFR-targeting agents, Dr. Ettinger explained, noting that studies have shown that a KRAS mu­tation in patients with NSCLC “confers a high level of resistance” to TKIs. 

Although the data – which primarily come from retrospective reviews with small sample sizes – are insufficient to make a determination about an associ­ation between KRAS mutation status and survival, he said, they are sufficient to warrant a category 2A recommen­dation for sequencing, as well as a rec­ommendation that patients with a known KRAS mutation should undergo first-line therapy with an agent other than a TKI.

Individuals who test negative for EGFR and KRAS should also be screened for a mutation of the anaplastic lym­phoma kinase (ALK) fusion gene, Dr. Et­tinger said. 

“Patients who screen positive may not benefit from EGFR TKIs, but they may be good candidates for an ALK-targeted therapy,” he said, noting that the inves­tigational ALK-tar­geting drug crizotinib, in par­ticular, has demon­strated positive results in early studies of NSCLC patients with echinoderm mi­crotubule-associat­ed proteinlike 4 (EML4)-ALK translocations (N. Engl. J. Med. 2010;363:1693-703).

With respect to first-line systemic ther­apy, patients with adenocarcinoma, large cell carcinoma, or NSCLC “not other­wise specified” who have an Eastern Co­operative Oncology Group/World Health Organization performance status grade of 0-4 and who test positive for the EGFR mutation prior to first-line thera­py should be treated with erlotinib, ac­cording to the NCCN guidelines. 

Alternatively, the guidelines state that gefitinib can be used in place of erlotinib “in areas of the world where it is avail­able.” 

For patients in whom the EGFR mu­tation is discovered during chemothera­py, the guidelines recommend either adding erlotinib to the current chemotherapy protocol or switching to erlotinib as maintenance treatment.

For patients whose EGFR status is negative or unknown, even in the pres­ence of clinical characteristics that might be suggestive of a mutation (for exam­ple, female, nonsmoker, Asian race), con­ventional chemotherapy is recommended, Dr. Ettinger said. 

In an editorial that accompanied ASCO’s PCO announcement, Dr. Paul A. Bunn Jr. and Dr. Robert C. Doebele of the University of Colorado Cancer Center in Aurora wrote that the grow­ing clinical importance of molecularly defined subgroups of adenocarcinoma signals a “new era of personalized med­icine for patients with advanced lung cancer, in which it will be imperative to match the specific mutations of a patient’s tumor with a specific therapy.” 

The implemen­tation of routine, simultaneous testing of multiple markers will likely be con­ducted on all patients prior to treat­ment initiation, regardless of clinical features, they stated, acknowledging certain procedural challenges, includ­ing obtaining adequate tumor materi­al at the time of diagnostic biopsy and developing testing platforms “that si­multaneously analyze for the presence of somatic mutations, gene fusions, or other genetic challenges.”

The updated NCCN Guidelines for NSCLC are posted at www.nccn.org. The ASCO PCO is posted at www.asco.org/ascov2/Practice+&+Guidelines/Guidelines/Provisional+Clinical+Opinion.

Dr. Ettinger has consultancy agree­ments with the a number of pharma­ceutical companies Dr. Keedy receives commercial research support from Ari­ad Pharmaceuticals, Ziopharm Oncolo­gy, and Amgen Oncology Therapeutics. Dr. Bunn has a consultant or advisory role with a number of pharmaceutical companies. Dr. Doebele disclosed re­search funding from Lilly, ImClone Sys­tems, and Pfizer.

SAN FRANCISCO – Pretreatment ex­pression of ERCC1 in localized esophageal and gastroesophageal ade­nocarcinomas is a marker for outcomes among patients given trimodality thera­py that includes oxaliplatin-based chemoradiation, investigators reported from a prospective study.

Fully 58% of the 55 patients studied from the Southwest Oncology Group (SWOG) S0356 trial had tumors ex­pressing a high level of mRNA for ERCC1, a key gene in the repair of plat­inum- and radiation-induced DNA dam­age.«http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=103&abstractID=71402»

Compared with their counterparts whose tumors had low expression, these patients were nearly three times more likely to experience progression and more than twice as likely to die, accord­ing to results reported at the meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

“ERCC1 mRNA level is a very promis­ing pretreatment biomarker in patients with localized esophageal and gastroe­sophageal adenocarcinoma treated with trimodality treatment,” asserted lead in­vestigator Dr. Pierre O. Bohanes. “Based on these and published data, the SWOG is planning a prospective biomarker-dri­ven clinical trial.”

“In contrast to the growing number of predictive biomarkers for anticancer agents, there are no established bio­markers to select patients who will ben­efit most from chemoradiation,” he noted. “Utilization of predictive bio­markers to select therapy should lead to higher cure rates.”

The phase II trial, which was largely community based, enrolled patients with clinical stage II or III esophageal or gas­troesophageal junction adenocarcinoma. They underwent tumor biopsy, then chemoradiation (oxaliplatin, 5-fluo­rouracil, and 45-Gy external beam radi­ation), then surgery, and finally more chemotherapy (oxaliplatin and 5-fluo­rouracil).

Response Genetics Inc., manufacturer of several biomarker assays, analyzed tumor ERCC1 mRNA expression for the 55 patients who had sufficient pretreatment tumor tissue. Laser-capture mi­crodissection was used to ensure that only tumor cells were analyzed.

“ERCC1 has been shown to be a crit­ical gene in DNA repair,” Dr. Bohanes explained. “ERCC1 is involved in the nucleotide excision repair pathway, which recognizes and removes platinum-induced DNA adducts.” Higher expres­
sion is associated with resistance to plat­inum compounds, including cisplatin, oxaliplatin, and carboplatin.

“Also more recently, ERCC1 has been shown to be involved in the double-strand break repair pathway, which re­pairs radiation-induced damage,” he further observed.

Tumors were classified as having a high or low level of ERCC1 expression using a cutoff mRNA level of greater than 1.7 for high expression, as estab­lished in previous studies.

The 55 patients studied had a median age of 64 years. Most were men (93%) and white (94%), and had esophageal tu­mors (62%). One-fourth of them were found to have a pathological complete response at the time of surgery.

The median duration of follow-up was 36.8 months, reported Dr. Bohanes, a re­search fellow in medical oncology at the University of Southern California in Los Angeles.

Results showed that patients having high vs. low tumor expression of ERCC1 had a nearly tripled risk of progression (hazard ratio, 2.97; P = .006).«change in ONCR rendition» The medi­an duration of progression-free survival was 14.8 months for the former but was not reached for the latter. Corresponding 2-year rates of progression-free survival were 17% and 67%.

Similarly, patients with tumors having high vs. low expression of ERCC1 had a more than doubling of the risk of death (HR, 2.32; P = .047). «change in ONCR rendition» The median dura­tion of overall survival was 22.4 months for the former but was not reached for the latter. Corresponding 2-year rates of overall survival were 37% and 72%.

Expression of ERCC1 was not associ­ated with pathological complete re­sponse. Also, expression of a host of other genes – XPD and RRM1 (associat­ed with DNA repair), GSTP1 (associated with platinum detoxification), and TS, TP, and DPD (associated with 5-fluo­rouracil metabolism) – was not associat­ed with any of the outcomes studied.

“Biomarker studies are feasible within cooperative groups,” commented Dr. Bohanes, but adequate tissue was avail­able for only 55 of 92 eligible patients. Hence, “future trials need to request ad­ditional endoscopic biopsies to allow for sufficient tumor tissue collection.”

A study shortcoming was an inability to determine whether ERCC1 expression correlates with disease stage, he ac­knowledged.

“The design of this study unfortu­nately did not require preoperative en­doscopic ultrasound because it was thought that it would have hampered the
recruitment of this trial,” he said. “And often, in the community setting, endoscopic ultrasound is not avail­able.”

Also, the study could not deter­mine whether ERCC1 expression is a prognostic marker. “We would need a control arm without platinum agent,” he noted.

<[stk 3]>“I think that the patients with high expression are not benefiting from this treatment” and should be treated with alternative treatments, commented Dr. Heinz-Josef Lenz, senior investigator and chair of the gastrointestinal oncology program at the University of Southern Cali­fornia. <[etk]>

“We have choices, and I think that would certainly be part of the new concept and design going forward, ” he added.

<[stk 3]>Dr. Lenz agreed with an attendee that recruiting patients with esophageal and gastroesophageal cancer to randomized trials has been difficult in the past and it might therefore take many years to obtain important biomarker data. But adaptive trial designs are ad­dressing this issue.<[etk]>

I have checked the following facts in my story: (Please initial each.)

Meeting: 3660-11

Drug names and dosages: SML jsm

Lab test values and their units: n/a na

Citation (e.g., JAMA 2008;299:785-92): n/a na

Investigators’ names and affiliations: SML jsm

All other proper names (e.g., clinical trials; geographic, company, and test names): SML jsm

Investigators’ conflicts of interest and sponsor of study: SML jsm

Please provide your best contact number and email for questions on this story: (206) 393-2459; slondon@speakeasy.net

Notes:

(1) Abstract 2; log in on main ASCO page first -- http://www.asco.org

username: gi_pressaccess

password: pre$$1

Go to Virtual Meeting. Note: search function for this meeting is not working well yet, so better to look by track.

(2) Either they did not show the conflicts of interest slides at the start of the session or they blew through them at lightspeed. I don’t have any photos of them and they are not up on the Web site. So Dr. Lenz’s conflicts come from a slide in Dr. Bohanes’ talk, where the nature of the conflicts was not given.

“I think we are incorporating now more technologies with the design, which may be more flexible to adapt new findings so that we are not stuck for the next 3 or 5 years to a trial be­cause of low accrual,” he said.

Dr. Bohanes reported that he had no relevant conflicts of interest.

Dr. Lenz reported having relation­ships with Response Genetics Inc. and with Sanofi-Aventis, manufac­turer of oxaliplatin (Eloxatin). 

SAN FRANCISCO – Pretreatment ex­pression of ERCC1 in localized esophageal and gastroesophageal ade­nocarcinomas is a marker for outcomes among patients given trimodality thera­py that includes oxaliplatin-based chemoradiation, investigators reported from a prospective study.

Fully 58% of the 55 patients studied from the Southwest Oncology Group (SWOG) S0356 trial had tumors ex­pressing a high level of mRNA for ERCC1, a key gene in the repair of plat­inum- and radiation-induced DNA dam­age.«http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=103&abstractID=71402»

Compared with their counterparts whose tumors had low expression, these patients were nearly three times more likely to experience progression and more than twice as likely to die, accord­ing to results reported at the meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

“ERCC1 mRNA level is a very promis­ing pretreatment biomarker in patients with localized esophageal and gastroe­sophageal adenocarcinoma treated with trimodality treatment,” asserted lead in­vestigator Dr. Pierre O. Bohanes. “Based on these and published data, the SWOG is planning a prospective biomarker-dri­ven clinical trial.”

“In contrast to the growing number of predictive biomarkers for anticancer agents, there are no established bio­markers to select patients who will ben­efit most from chemoradiation,” he noted. “Utilization of predictive bio­markers to select therapy should lead to higher cure rates.”

The phase II trial, which was largely community based, enrolled patients with clinical stage II or III esophageal or gas­troesophageal junction adenocarcinoma. They underwent tumor biopsy, then chemoradiation (oxaliplatin, 5-fluo­rouracil, and 45-Gy external beam radi­ation), then surgery, and finally more chemotherapy (oxaliplatin and 5-fluo­rouracil).

Response Genetics Inc., manufacturer of several biomarker assays, analyzed tumor ERCC1 mRNA expression for the 55 patients who had sufficient pretreatment tumor tissue. Laser-capture mi­crodissection was used to ensure that only tumor cells were analyzed.

“ERCC1 has been shown to be a crit­ical gene in DNA repair,” Dr. Bohanes explained. “ERCC1 is involved in the nucleotide excision repair pathway, which recognizes and removes platinum-induced DNA adducts.” Higher expres­
sion is associated with resistance to plat­inum compounds, including cisplatin, oxaliplatin, and carboplatin.

“Also more recently, ERCC1 has been shown to be involved in the double-strand break repair pathway, which re­pairs radiation-induced damage,” he further observed.

Tumors were classified as having a high or low level of ERCC1 expression using a cutoff mRNA level of greater than 1.7 for high expression, as estab­lished in previous studies.

The 55 patients studied had a median age of 64 years. Most were men (93%) and white (94%), and had esophageal tu­mors (62%). One-fourth of them were found to have a pathological complete response at the time of surgery.

The median duration of follow-up was 36.8 months, reported Dr. Bohanes, a re­search fellow in medical oncology at the University of Southern California in Los Angeles.

Results showed that patients having high vs. low tumor expression of ERCC1 had a nearly tripled risk of progression (hazard ratio, 2.97; P = .006).«change in ONCR rendition» The medi­an duration of progression-free survival was 14.8 months for the former but was not reached for the latter. Corresponding 2-year rates of progression-free survival were 17% and 67%.

Similarly, patients with tumors having high vs. low expression of ERCC1 had a more than doubling of the risk of death (HR, 2.32; P = .047). «change in ONCR rendition» The median dura­tion of overall survival was 22.4 months for the former but was not reached for the latter. Corresponding 2-year rates of overall survival were 37% and 72%.

Expression of ERCC1 was not associ­ated with pathological complete re­sponse. Also, expression of a host of other genes – XPD and RRM1 (associat­ed with DNA repair), GSTP1 (associated with platinum detoxification), and TS, TP, and DPD (associated with 5-fluo­rouracil metabolism) – was not associat­ed with any of the outcomes studied.

“Biomarker studies are feasible within cooperative groups,” commented Dr. Bohanes, but adequate tissue was avail­able for only 55 of 92 eligible patients. Hence, “future trials need to request ad­ditional endoscopic biopsies to allow for sufficient tumor tissue collection.”

A study shortcoming was an inability to determine whether ERCC1 expression correlates with disease stage, he ac­knowledged.

“The design of this study unfortu­nately did not require preoperative en­doscopic ultrasound because it was thought that it would have hampered the
recruitment of this trial,” he said. “And often, in the community setting, endoscopic ultrasound is not avail­able.”

Also, the study could not deter­mine whether ERCC1 expression is a prognostic marker. “We would need a control arm without platinum agent,” he noted.

<[stk 3]>“I think that the patients with high expression are not benefiting from this treatment” and should be treated with alternative treatments, commented Dr. Heinz-Josef Lenz, senior investigator and chair of the gastrointestinal oncology program at the University of Southern Cali­fornia. <[etk]>

“We have choices, and I think that would certainly be part of the new concept and design going forward, ” he added.

<[stk 3]>Dr. Lenz agreed with an attendee that recruiting patients with esophageal and gastroesophageal cancer to randomized trials has been difficult in the past and it might therefore take many years to obtain important biomarker data. But adaptive trial designs are ad­dressing this issue.<[etk]>

I have checked the following facts in my story: (Please initial each.)

Meeting: 3660-11

Drug names and dosages: SML jsm

Lab test values and their units: n/a na

Citation (e.g., JAMA 2008;299:785-92): n/a na

Investigators’ names and affiliations: SML jsm

All other proper names (e.g., clinical trials; geographic, company, and test names): SML jsm

Investigators’ conflicts of interest and sponsor of study: SML jsm

Please provide your best contact number and email for questions on this story: (206) 393-2459; slondon@speakeasy.net

Notes:

(1) Abstract 2; log in on main ASCO page first -- http://www.asco.org

username: gi_pressaccess

password: pre$$1

Go to Virtual Meeting. Note: search function for this meeting is not working well yet, so better to look by track.

(2) Either they did not show the conflicts of interest slides at the start of the session or they blew through them at lightspeed. I don’t have any photos of them and they are not up on the Web site. So Dr. Lenz’s conflicts come from a slide in Dr. Bohanes’ talk, where the nature of the conflicts was not given.

“I think we are incorporating now more technologies with the design, which may be more flexible to adapt new findings so that we are not stuck for the next 3 or 5 years to a trial be­cause of low accrual,” he said.

Dr. Bohanes reported that he had no relevant conflicts of interest.

Dr. Lenz reported having relation­ships with Response Genetics Inc. and with Sanofi-Aventis, manufac­turer of oxaliplatin (Eloxatin). 

SAN FRANCISCO – Pretreatment ex­pression of ERCC1 in localized esophageal and gastroesophageal ade­nocarcinomas is a marker for outcomes among patients given trimodality thera­py that includes oxaliplatin-based chemoradiation, investigators reported from a prospective study.

Fully 58% of the 55 patients studied from the Southwest Oncology Group (SWOG) S0356 trial had tumors ex­pressing a high level of mRNA for ERCC1, a key gene in the repair of plat­inum- and radiation-induced DNA dam­age.«http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=103&abstractID=71402»

Compared with their counterparts whose tumors had low expression, these patients were nearly three times more likely to experience progression and more than twice as likely to die, accord­ing to results reported at the meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.

“ERCC1 mRNA level is a very promis­ing pretreatment biomarker in patients with localized esophageal and gastroe­sophageal adenocarcinoma treated with trimodality treatment,” asserted lead in­vestigator Dr. Pierre O. Bohanes. “Based on these and published data, the SWOG is planning a prospective biomarker-dri­ven clinical trial.”

“In contrast to the growing number of predictive biomarkers for anticancer agents, there are no established bio­markers to select patients who will ben­efit most from chemoradiation,” he noted. “Utilization of predictive bio­markers to select therapy should lead to higher cure rates.”

The phase II trial, which was largely community based, enrolled patients with clinical stage II or III esophageal or gas­troesophageal junction adenocarcinoma. They underwent tumor biopsy, then chemoradiation (oxaliplatin, 5-fluo­rouracil, and 45-Gy external beam radi­ation), then surgery, and finally more chemotherapy (oxaliplatin and 5-fluo­rouracil).

Response Genetics Inc., manufacturer of several biomarker assays, analyzed tumor ERCC1 mRNA expression for the 55 patients who had sufficient pretreatment tumor tissue. Laser-capture mi­crodissection was used to ensure that only tumor cells were analyzed.

“ERCC1 has been shown to be a crit­ical gene in DNA repair,” Dr. Bohanes explained. “ERCC1 is involved in the nucleotide excision repair pathway, which recognizes and removes platinum-induced DNA adducts.” Higher expres­
sion is associated with resistance to plat­inum compounds, including cisplatin, oxaliplatin, and carboplatin.

“Also more recently, ERCC1 has been shown to be involved in the double-strand break repair pathway, which re­pairs radiation-induced damage,” he further observed.

Tumors were classified as having a high or low level of ERCC1 expression using a cutoff mRNA level of greater than 1.7 for high expression, as estab­lished in previous studies.

The 55 patients studied had a median age of 64 years. Most were men (93%) and white (94%), and had esophageal tu­mors (62%). One-fourth of them were found to have a pathological complete response at the time of surgery.

The median duration of follow-up was 36.8 months, reported Dr. Bohanes, a re­search fellow in medical oncology at the University of Southern California in Los Angeles.

Results showed that patients having high vs. low tumor expression of ERCC1 had a nearly tripled risk of progression (hazard ratio, 2.97; P = .006).«change in ONCR rendition» The medi­an duration of progression-free survival was 14.8 months for the former but was not reached for the latter. Corresponding 2-year rates of progression-free survival were 17% and 67%.

Similarly, patients with tumors having high vs. low expression of ERCC1 had a more than doubling of the risk of death (HR, 2.32; P = .047). «change in ONCR rendition» The median dura­tion of overall survival was 22.4 months for the former but was not reached for the latter. Corresponding 2-year rates of overall survival were 37% and 72%.

Expression of ERCC1 was not associ­ated with pathological complete re­sponse. Also, expression of a host of other genes – XPD and RRM1 (associat­ed with DNA repair), GSTP1 (associated with platinum detoxification), and TS, TP, and DPD (associated with 5-fluo­rouracil metabolism) – was not associat­ed with any of the outcomes studied.

“Biomarker studies are feasible within cooperative groups,” commented Dr. Bohanes, but adequate tissue was avail­able for only 55 of 92 eligible patients. Hence, “future trials need to request ad­ditional endoscopic biopsies to allow for sufficient tumor tissue collection.”

A study shortcoming was an inability to determine whether ERCC1 expression correlates with disease stage, he ac­knowledged.

“The design of this study unfortu­nately did not require preoperative en­doscopic ultrasound because it was thought that it would have hampered the
recruitment of this trial,” he said. “And often, in the community setting, endoscopic ultrasound is not avail­able.”

Also, the study could not deter­mine whether ERCC1 expression is a prognostic marker. “We would need a control arm without platinum agent,” he noted.

<[stk 3]>“I think that the patients with high expression are not benefiting from this treatment” and should be treated with alternative treatments, commented Dr. Heinz-Josef Lenz, senior investigator and chair of the gastrointestinal oncology program at the University of Southern Cali­fornia. <[etk]>

“We have choices, and I think that would certainly be part of the new concept and design going forward, ” he added.

<[stk 3]>Dr. Lenz agreed with an attendee that recruiting patients with esophageal and gastroesophageal cancer to randomized trials has been difficult in the past and it might therefore take many years to obtain important biomarker data. But adaptive trial designs are ad­dressing this issue.<[etk]>

I have checked the following facts in my story: (Please initial each.)

Meeting: 3660-11

Drug names and dosages: SML jsm

Lab test values and their units: n/a na

Citation (e.g., JAMA 2008;299:785-92): n/a na

Investigators’ names and affiliations: SML jsm

All other proper names (e.g., clinical trials; geographic, company, and test names): SML jsm

Investigators’ conflicts of interest and sponsor of study: SML jsm

Please provide your best contact number and email for questions on this story: (206) 393-2459; slondon@speakeasy.net

Notes:

(1) Abstract 2; log in on main ASCO page first -- http://www.asco.org

username: gi_pressaccess

password: pre$$1

Go to Virtual Meeting. Note: search function for this meeting is not working well yet, so better to look by track.

(2) Either they did not show the conflicts of interest slides at the start of the session or they blew through them at lightspeed. I don’t have any photos of them and they are not up on the Web site. So Dr. Lenz’s conflicts come from a slide in Dr. Bohanes’ talk, where the nature of the conflicts was not given.

“I think we are incorporating now more technologies with the design, which may be more flexible to adapt new findings so that we are not stuck for the next 3 or 5 years to a trial be­cause of low accrual,” he said.

Dr. Bohanes reported that he had no relevant conflicts of interest.

Dr. Lenz reported having relation­ships with Response Genetics Inc. and with Sanofi-Aventis, manufac­turer of oxaliplatin (Eloxatin). 

NEW ORLEANS  Select patients with unprotected left main coronary artery stenosis can be effectively treated with percutaneous coronary intervention with sirolimus-eluting stents rather than coronary artery bypass grafting, South Korean investigators reported at a late-breaking clinical trials session of the annual meeting of the American College of Cardiology.

PCI with sirolimus-eluting stents appears to be an alternative to coronary artery bypass grafting based on a noninferior incidence of major cardiac and cerebrovascular events in a median 2-year follow-up of 600 patients with unprotected left main coronary artery stenosis randomized to undergo either CABG or PCI with a sirolimus-eluting stent [Cordis, Johnson & Johnson], said Dr. Seung-Jung Park, the principal investigator of PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease). 

Major adverse cardiac or cerebrovascular events (MACCE) included all-cause death, myocardial infarction, stroke, ischemia-driven target-vessel revascularization, and cerebrovascular events, said Dr. Park of Asan Medical Center, Seoul, South Korea. 

The rate of MACCE at 2 years was comparable at 12.2% for PCI-treated patients and 8.1% for CABG-treated patients. The composite of death, myocardial infarction and stroke  which the investigators considered a marker of safety  was 4.4% in the PCI group and 4.7% in the CABG group. The major difference was the rate of ischemia-driven target-vessel revascularization ? 9% with PCI and 4.2% with CABG. Further, in subgroup analyses, PCI was associated with a higher risk of MACCE in patients with unprotected left main coronary artery stenosis plus three-vessel disease.

Concomitant with the presentation, the results were published online in the New England Journal of Medicine (N. Engl. J. Med. 2011, April 4 [doi: 10.1056/NEJMoa1100452]). 

PRECOMBAT baseline patient characteristics were similar. Mean age was 62 years, 76.5% were men, mean ejection fraction was 60% and high operative risk was noted for 6% of the PCI group and 8% of the CABG group. Median follow-up was 24 months.

The primary end point was a composite comparison of MACCE at 1 year and 2 years. The primary analysis was a noninferiority comparison. 

MACCE occurred in 26 patients assigned to PCI and in 20 patients assigned to CABG, for cumulative event rates of 8.7% and 6.7%, respectively. The 2.0% absolute risk difference supported noninferiority of PCI to CABG (P = .01). When patient analysis was based on the actual treatment received, however, the 1-year cumulative MACCE rates were 9.2% for PCI and 5.9%, for CABG (P = .04 for noninferiority).

The all-cause death rate in year 1 was 2% for PCI and 2.7% for CABG and in year 2 was 2.4% and 3.4%, respectively (P = .45). Cardiac deaths occurred in 1.0% and 2.7%, respectively, at 2 years.

Strokes and myocardial infarction were also infrequent and the rate of these events did not differ between the treatment arms. Symptomatic graft occlusion and stent thrombosis were observed in 0.3% of the PCI group and in 1.4% of the CABG group. There were no differences by subgroup.

Describing the procedural characteristics, Dr. Park noted that in the PCI group the mean number of stents per patient was 2.7 and in the CABG group the mean number of grafts was 2.7. The procedures were completed in 205 PCI patients and in 211 CABG patients, for comparable revascularization rates of 68% and 70%, respectively.

"Our major finding, that event rates after PCI and CABG did not differ signifi?cantly in this clinical setting, are in agreement with the results of the SYN?TAX substudy involving patients with left main coronary artery stenosis," he said.

In SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), CABG showed more benefit than did PCI for the overall study population (N. Engl. J. Med. 2009;360:961-72). 

Among patients with left main coronary artery disease in SYNTAX, however, the 12-month rate of MACCE was similar at 13.7% in the CABG group and 15.8% in the PCI group (P = .44). The rate of repeat revascularization among patients with left main coronary artery disease was 11.8% in the PCI group and 6.5% in the CABG group (P = .02), but the CABG group had 2.7% rate of stroke as compared to a 0.3% rate in the PCI subgroup; (P = .01). 

In SYNTAX, nearly 37% of patients with left main coronary artery disease also had three-vessel disease. The subgroup with concomitant two- or three-vessel disease had higher MACCE rates than did the subgroups of patients with left main coronary artery disease alone or in combination with one-vessel disease.

Event rates at 1 year in SYNTAX were higher than those in PRECOMBAT, and the PRECOMBAT patient population had less complex disease, lower SYNTAX scores, and less comorbidity, Dr. Park said.

Dr. Park reported receiving consulting fees and honoraria from Johnson & Johnson and Cordis. 

NEW ORLEANS  Select patients with unprotected left main coronary artery stenosis can be effectively treated with percutaneous coronary intervention with sirolimus-eluting stents rather than coronary artery bypass grafting, South Korean investigators reported at a late-breaking clinical trials session of the annual meeting of the American College of Cardiology.

PCI with sirolimus-eluting stents appears to be an alternative to coronary artery bypass grafting based on a noninferior incidence of major cardiac and cerebrovascular events in a median 2-year follow-up of 600 patients with unprotected left main coronary artery stenosis randomized to undergo either CABG or PCI with a sirolimus-eluting stent [Cordis, Johnson & Johnson], said Dr. Seung-Jung Park, the principal investigator of PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease). 

Major adverse cardiac or cerebrovascular events (MACCE) included all-cause death, myocardial infarction, stroke, ischemia-driven target-vessel revascularization, and cerebrovascular events, said Dr. Park of Asan Medical Center, Seoul, South Korea. 

The rate of MACCE at 2 years was comparable at 12.2% for PCI-treated patients and 8.1% for CABG-treated patients. The composite of death, myocardial infarction and stroke  which the investigators considered a marker of safety  was 4.4% in the PCI group and 4.7% in the CABG group. The major difference was the rate of ischemia-driven target-vessel revascularization ? 9% with PCI and 4.2% with CABG. Further, in subgroup analyses, PCI was associated with a higher risk of MACCE in patients with unprotected left main coronary artery stenosis plus three-vessel disease.

Concomitant with the presentation, the results were published online in the New England Journal of Medicine (N. Engl. J. Med. 2011, April 4 [doi: 10.1056/NEJMoa1100452]). 

PRECOMBAT baseline patient characteristics were similar. Mean age was 62 years, 76.5% were men, mean ejection fraction was 60% and high operative risk was noted for 6% of the PCI group and 8% of the CABG group. Median follow-up was 24 months.

The primary end point was a composite comparison of MACCE at 1 year and 2 years. The primary analysis was a noninferiority comparison. 

MACCE occurred in 26 patients assigned to PCI and in 20 patients assigned to CABG, for cumulative event rates of 8.7% and 6.7%, respectively. The 2.0% absolute risk difference supported noninferiority of PCI to CABG (P = .01). When patient analysis was based on the actual treatment received, however, the 1-year cumulative MACCE rates were 9.2% for PCI and 5.9%, for CABG (P = .04 for noninferiority).

The all-cause death rate in year 1 was 2% for PCI and 2.7% for CABG and in year 2 was 2.4% and 3.4%, respectively (P = .45). Cardiac deaths occurred in 1.0% and 2.7%, respectively, at 2 years.

Strokes and myocardial infarction were also infrequent and the rate of these events did not differ between the treatment arms. Symptomatic graft occlusion and stent thrombosis were observed in 0.3% of the PCI group and in 1.4% of the CABG group. There were no differences by subgroup.

Describing the procedural characteristics, Dr. Park noted that in the PCI group the mean number of stents per patient was 2.7 and in the CABG group the mean number of grafts was 2.7. The procedures were completed in 205 PCI patients and in 211 CABG patients, for comparable revascularization rates of 68% and 70%, respectively.

"Our major finding, that event rates after PCI and CABG did not differ signifi?cantly in this clinical setting, are in agreement with the results of the SYN?TAX substudy involving patients with left main coronary artery stenosis," he said.

In SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), CABG showed more benefit than did PCI for the overall study population (N. Engl. J. Med. 2009;360:961-72). 

Among patients with left main coronary artery disease in SYNTAX, however, the 12-month rate of MACCE was similar at 13.7% in the CABG group and 15.8% in the PCI group (P = .44). The rate of repeat revascularization among patients with left main coronary artery disease was 11.8% in the PCI group and 6.5% in the CABG group (P = .02), but the CABG group had 2.7% rate of stroke as compared to a 0.3% rate in the PCI subgroup; (P = .01). 

In SYNTAX, nearly 37% of patients with left main coronary artery disease also had three-vessel disease. The subgroup with concomitant two- or three-vessel disease had higher MACCE rates than did the subgroups of patients with left main coronary artery disease alone or in combination with one-vessel disease.

Event rates at 1 year in SYNTAX were higher than those in PRECOMBAT, and the PRECOMBAT patient population had less complex disease, lower SYNTAX scores, and less comorbidity, Dr. Park said.

Dr. Park reported receiving consulting fees and honoraria from Johnson & Johnson and Cordis. 

NEW ORLEANS  Select patients with unprotected left main coronary artery stenosis can be effectively treated with percutaneous coronary intervention with sirolimus-eluting stents rather than coronary artery bypass grafting, South Korean investigators reported at a late-breaking clinical trials session of the annual meeting of the American College of Cardiology.

PCI with sirolimus-eluting stents appears to be an alternative to coronary artery bypass grafting based on a noninferior incidence of major cardiac and cerebrovascular events in a median 2-year follow-up of 600 patients with unprotected left main coronary artery stenosis randomized to undergo either CABG or PCI with a sirolimus-eluting stent [Cordis, Johnson & Johnson], said Dr. Seung-Jung Park, the principal investigator of PRECOMBAT (Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease). 

Major adverse cardiac or cerebrovascular events (MACCE) included all-cause death, myocardial infarction, stroke, ischemia-driven target-vessel revascularization, and cerebrovascular events, said Dr. Park of Asan Medical Center, Seoul, South Korea. 

The rate of MACCE at 2 years was comparable at 12.2% for PCI-treated patients and 8.1% for CABG-treated patients. The composite of death, myocardial infarction and stroke  which the investigators considered a marker of safety  was 4.4% in the PCI group and 4.7% in the CABG group. The major difference was the rate of ischemia-driven target-vessel revascularization ? 9% with PCI and 4.2% with CABG. Further, in subgroup analyses, PCI was associated with a higher risk of MACCE in patients with unprotected left main coronary artery stenosis plus three-vessel disease.

Concomitant with the presentation, the results were published online in the New England Journal of Medicine (N. Engl. J. Med. 2011, April 4 [doi: 10.1056/NEJMoa1100452]). 

PRECOMBAT baseline patient characteristics were similar. Mean age was 62 years, 76.5% were men, mean ejection fraction was 60% and high operative risk was noted for 6% of the PCI group and 8% of the CABG group. Median follow-up was 24 months.

The primary end point was a composite comparison of MACCE at 1 year and 2 years. The primary analysis was a noninferiority comparison. 

MACCE occurred in 26 patients assigned to PCI and in 20 patients assigned to CABG, for cumulative event rates of 8.7% and 6.7%, respectively. The 2.0% absolute risk difference supported noninferiority of PCI to CABG (P = .01). When patient analysis was based on the actual treatment received, however, the 1-year cumulative MACCE rates were 9.2% for PCI and 5.9%, for CABG (P = .04 for noninferiority).

The all-cause death rate in year 1 was 2% for PCI and 2.7% for CABG and in year 2 was 2.4% and 3.4%, respectively (P = .45). Cardiac deaths occurred in 1.0% and 2.7%, respectively, at 2 years.

Strokes and myocardial infarction were also infrequent and the rate of these events did not differ between the treatment arms. Symptomatic graft occlusion and stent thrombosis were observed in 0.3% of the PCI group and in 1.4% of the CABG group. There were no differences by subgroup.

Describing the procedural characteristics, Dr. Park noted that in the PCI group the mean number of stents per patient was 2.7 and in the CABG group the mean number of grafts was 2.7. The procedures were completed in 205 PCI patients and in 211 CABG patients, for comparable revascularization rates of 68% and 70%, respectively.

"Our major finding, that event rates after PCI and CABG did not differ signifi?cantly in this clinical setting, are in agreement with the results of the SYN?TAX substudy involving patients with left main coronary artery stenosis," he said.

In SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), CABG showed more benefit than did PCI for the overall study population (N. Engl. J. Med. 2009;360:961-72). 

Among patients with left main coronary artery disease in SYNTAX, however, the 12-month rate of MACCE was similar at 13.7% in the CABG group and 15.8% in the PCI group (P = .44). The rate of repeat revascularization among patients with left main coronary artery disease was 11.8% in the PCI group and 6.5% in the CABG group (P = .02), but the CABG group had 2.7% rate of stroke as compared to a 0.3% rate in the PCI subgroup; (P = .01). 

In SYNTAX, nearly 37% of patients with left main coronary artery disease also had three-vessel disease. The subgroup with concomitant two- or three-vessel disease had higher MACCE rates than did the subgroups of patients with left main coronary artery disease alone or in combination with one-vessel disease.

Event rates at 1 year in SYNTAX were higher than those in PRECOMBAT, and the PRECOMBAT patient population had less complex disease, lower SYNTAX scores, and less comorbidity, Dr. Park said.

Dr. Park reported receiving consulting fees and honoraria from Johnson & Johnson and Cordis. 

In patients with three-vessel or left main coronary artery disease, coronary artery bypass graft surgery provides greater relief from angina at 6 months and at 12 months after revascularization than does per?cutaneous coronary intervention with paclitaxel-eluting stents, according to a report in the New England Journal of Medicine.

EMBARGOED UNTIL 5 PM WED. 3/16

This benefit with CABG was consistent across a broad range of patient characteristics, said Dr. David J. Cohen of Saint Lukes Mid America Heart Institute, University of Missouri Kansas City, and his associates in the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial. SYNTAX was funded by Boston Scientific, maker of the paclitaxel-eluting stent.

SYNTAX was an international randomized trial in which 1,800 patients with three-vessel or left main coronary artery disease underwent either CABG or percutaneous coronary intervention (PCI) with placement of paclitaxel-eluting stents in 2005-2007.

The rate of the composite primary efficacy end point of death, myocardial infarction, stroke, or repeat revascularization was found to be lower with CABG at 1 year.

The current analysis was a quality-of-life substudy of SYNTAX aimed at determining whether the two approaches differed with regard to relief from angina and quality of life. It included 903 patients who had been randomly assigned to PCI with stents and 897 who had been assigned to CABG.

At baseline, approximately 12% of the subjects reported having daily angina and 20% reported no angina; the remaining subjects reported occasional angina.

Both PCI and CABG led to significant improvements in disease-specific and general health status over the course of 12 months, according to the investigators.

The primary quality-of-life end point was the score on the Seattle Angina Questionnaire angina frequency subscale. The improvement in this score was slightly but significantly greater with CABG than with PCI at 6 and 12 months.

?There were marked benefits with PCI as compared with CABG in general health-related quality of life as assessed by the SF-36 [Medical Outcomes Study 36-Item Short Form Health Survey] as well as EQ-SD [European Quality of Life

********* TEXT BREAK *********5-Dimensions instrument] at 1 month, but these differences had largely disappeared by 6 months, Dr. Cohen and his col?leagues reported (N. Engl. J. Med. 2011;364:1016-26).

<[stk 2]>Subgroup analysis showed that CABGs superiority in reducing the frequency of angina persisted across a broad range of patients. <[etk]>

<[stk 2]>Subjects who had reported daily or weekly angina at baseline showed significantly better relief after CABG than after PCI, although they reported that the extent of the benefit was small (76.3% vs. 71.6%, respectively, P = .05). <[etk]>

<[stk 3]>However, the majority of the study subjects had reported less frequent or no angina at baseline, and there was no significant difference in relief from angina between the two approaches in this large subgroup. <[etk]>

The researchers noted that these findings ?reflect only the first year of follow-up after revascularization; whether similar effects are observed over the long term is currently un?known.?

I have checked the following facts in my story:

MM     Drug names and dosages MSL

NA     Lab test values and their units NA

MM     Nos. are correct and add up, and percentages based on those nos. are correct MSL

MM    Citation MSL

MM     Investigators? names and affiliations MSL

MM     All other proper names (e.g., clinical trials; geographic, company, and test names) MSL

MM     Investigators? conflicts of interest and sponsor of study MSL

Best contact number = 301-325-5890; email = moon2dc@yahoo.com

Dr. Cohen and his associates reported that they had ties to numerous industry sources, including Boston Scientific. 

********* UNDERSET  1  LINES *********

In patients with three-vessel or left main coronary artery disease, coronary artery bypass graft surgery provides greater relief from angina at 6 months and at 12 months after revascularization than does per?cutaneous coronary intervention with paclitaxel-eluting stents, according to a report in the New England Journal of Medicine.

EMBARGOED UNTIL 5 PM WED. 3/16

This benefit with CABG was consistent across a broad range of patient characteristics, said Dr. David J. Cohen of Saint Lukes Mid America Heart Institute, University of Missouri Kansas City, and his associates in the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial. SYNTAX was funded by Boston Scientific, maker of the paclitaxel-eluting stent.

SYNTAX was an international randomized trial in which 1,800 patients with three-vessel or left main coronary artery disease underwent either CABG or percutaneous coronary intervention (PCI) with placement of paclitaxel-eluting stents in 2005-2007.

The rate of the composite primary efficacy end point of death, myocardial infarction, stroke, or repeat revascularization was found to be lower with CABG at 1 year.

The current analysis was a quality-of-life substudy of SYNTAX aimed at determining whether the two approaches differed with regard to relief from angina and quality of life. It included 903 patients who had been randomly assigned to PCI with stents and 897 who had been assigned to CABG.

At baseline, approximately 12% of the subjects reported having daily angina and 20% reported no angina; the remaining subjects reported occasional angina.

Both PCI and CABG led to significant improvements in disease-specific and general health status over the course of 12 months, according to the investigators.

The primary quality-of-life end point was the score on the Seattle Angina Questionnaire angina frequency subscale. The improvement in this score was slightly but significantly greater with CABG than with PCI at 6 and 12 months.

?There were marked benefits with PCI as compared with CABG in general health-related quality of life as assessed by the SF-36 [Medical Outcomes Study 36-Item Short Form Health Survey] as well as EQ-SD [European Quality of Life

********* TEXT BREAK *********5-Dimensions instrument] at 1 month, but these differences had largely disappeared by 6 months, Dr. Cohen and his col?leagues reported (N. Engl. J. Med. 2011;364:1016-26).

<[stk 2]>Subgroup analysis showed that CABGs superiority in reducing the frequency of angina persisted across a broad range of patients. <[etk]>

<[stk 2]>Subjects who had reported daily or weekly angina at baseline showed significantly better relief after CABG than after PCI, although they reported that the extent of the benefit was small (76.3% vs. 71.6%, respectively, P = .05). <[etk]>

<[stk 3]>However, the majority of the study subjects had reported less frequent or no angina at baseline, and there was no significant difference in relief from angina between the two approaches in this large subgroup. <[etk]>

The researchers noted that these findings ?reflect only the first year of follow-up after revascularization; whether similar effects are observed over the long term is currently un?known.?

I have checked the following facts in my story:

MM     Drug names and dosages MSL

NA     Lab test values and their units NA

MM     Nos. are correct and add up, and percentages based on those nos. are correct MSL

MM    Citation MSL

MM     Investigators? names and affiliations MSL

MM     All other proper names (e.g., clinical trials; geographic, company, and test names) MSL

MM     Investigators? conflicts of interest and sponsor of study MSL

Best contact number = 301-325-5890; email = moon2dc@yahoo.com

Dr. Cohen and his associates reported that they had ties to numerous industry sources, including Boston Scientific. 

********* UNDERSET  1  LINES *********

In patients with three-vessel or left main coronary artery disease, coronary artery bypass graft surgery provides greater relief from angina at 6 months and at 12 months after revascularization than does per?cutaneous coronary intervention with paclitaxel-eluting stents, according to a report in the New England Journal of Medicine.

EMBARGOED UNTIL 5 PM WED. 3/16

This benefit with CABG was consistent across a broad range of patient characteristics, said Dr. David J. Cohen of Saint Lukes Mid America Heart Institute, University of Missouri Kansas City, and his associates in the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) trial. SYNTAX was funded by Boston Scientific, maker of the paclitaxel-eluting stent.

SYNTAX was an international randomized trial in which 1,800 patients with three-vessel or left main coronary artery disease underwent either CABG or percutaneous coronary intervention (PCI) with placement of paclitaxel-eluting stents in 2005-2007.

The rate of the composite primary efficacy end point of death, myocardial infarction, stroke, or repeat revascularization was found to be lower with CABG at 1 year.

The current analysis was a quality-of-life substudy of SYNTAX aimed at determining whether the two approaches differed with regard to relief from angina and quality of life. It included 903 patients who had been randomly assigned to PCI with stents and 897 who had been assigned to CABG.

At baseline, approximately 12% of the subjects reported having daily angina and 20% reported no angina; the remaining subjects reported occasional angina.

Both PCI and CABG led to significant improvements in disease-specific and general health status over the course of 12 months, according to the investigators.

The primary quality-of-life end point was the score on the Seattle Angina Questionnaire angina frequency subscale. The improvement in this score was slightly but significantly greater with CABG than with PCI at 6 and 12 months.

?There were marked benefits with PCI as compared with CABG in general health-related quality of life as assessed by the SF-36 [Medical Outcomes Study 36-Item Short Form Health Survey] as well as EQ-SD [European Quality of Life

********* TEXT BREAK *********5-Dimensions instrument] at 1 month, but these differences had largely disappeared by 6 months, Dr. Cohen and his col?leagues reported (N. Engl. J. Med. 2011;364:1016-26).

<[stk 2]>Subgroup analysis showed that CABGs superiority in reducing the frequency of angina persisted across a broad range of patients. <[etk]>

<[stk 2]>Subjects who had reported daily or weekly angina at baseline showed significantly better relief after CABG than after PCI, although they reported that the extent of the benefit was small (76.3% vs. 71.6%, respectively, P = .05). <[etk]>

<[stk 3]>However, the majority of the study subjects had reported less frequent or no angina at baseline, and there was no significant difference in relief from angina between the two approaches in this large subgroup. <[etk]>

The researchers noted that these findings ?reflect only the first year of follow-up after revascularization; whether similar effects are observed over the long term is currently un?known.?

I have checked the following facts in my story:

MM     Drug names and dosages MSL

NA     Lab test values and their units NA

MM     Nos. are correct and add up, and percentages based on those nos. are correct MSL

MM    Citation MSL

MM     Investigators? names and affiliations MSL

MM     All other proper names (e.g., clinical trials; geographic, company, and test names) MSL

MM     Investigators? conflicts of interest and sponsor of study MSL

Best contact number = 301-325-5890; email = moon2dc@yahoo.com

Dr. Cohen and his associates reported that they had ties to numerous industry sources, including Boston Scientific. 

********* UNDERSET  1  LINES *********

A scientific statement from the American Heart As­sociation provides guidance for the management of the more severe forms of venous thromboembolism.

The statement focuses on three areas: massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pul­monary hypertension. “The goal is to provide practi­cal advice to enable the busy clinician to optimize the management of patients with these severe manifesta­tions of [venous thromboembolism],” said the writing committee, cochaired by Dr. Michael R. Jaff and Dr. M. Sean McMurtry (Circulation 2011 Mar. 21 [doi:10.1161/CIR.0b013e318214914f]).« http://www.theheart.org/article/1200965.do»

<[stk -1]>In an interview, Dr. McMurtry noted that because these disease areas have less data to support manage­ment strategies than do other areas of cardiovascular medicine, most of the recommendations in the docu­ment are class II (“it is reasonable” or “may be consid­ered”) with level of evidence B or C (limited populations evaluated). “The authors hope that this document will inspire more research into these conditions,” said Dr. McMurtry of the University of Alberta, Edmonton.<[etk]>

<[stk -3]>The document begins by defining “massive,” “sub­massive,” and “low-risk” pulmonary embolism (PE), and provides data for the various techniques used to identify patients at increased risk for adverse short-term outcomes in acute PE. <[etk]>

Beyond initial heparin anticoagulation therapy, the use of fibrinolytic drugs is reasonable for patients with massive acute PE and an acceptable risk of bleeding complications, the statement said. It may also be con­sidered for patients with submassive acute PE judged to have clinical evidence of an adverse prognosis (new hemodynamic instability, worsening respiratory insuf­ficiency, severe right ventricle [RV] dysfunction, or major myocardial necrosis) and a low risk of bleeding.

Fibrinolysis is not recommended for patients with low-risk PE, or submassive PE with minor RV dys­function, minor myocardial necrosis, and no clinical worsening. Fibrinolysis is also not recommended for undifferentiated cardiac arrest, wrote Dr. McMurtry and Dr. Jaff of Harvard Medical School, and coauthors.

In addition, recommendations are provided for oth­er areas in which data are sparse and optimal manage­ment is unclear, including catheter-based therapies. Transcatheter procedures can be performed as an al­ternative to thrombolysis when there are contraindi­cations or when emergency surgical thrombectomy is unavailable or contraindicated. Catheter interventions can also be performed when thrombolysis has failed to improve hemodynamics in the acute setting.

Hybrid therapy that includes both catheter-based clot fragmentation and local thrombolysis is an emerging strategy, the committee noted.

Adult patients with any confirmed acute PE who have contraindications to anticoagulation or have active bleeding should receive an inferior vena cava (IVC) fil­ter. Further specific guidance is given for the type of fil­ter and for monitoring.

<[stk -1]>Iliofemoral Deep Vein Thrombosis (IVDVT) refers to complete or partial thrombosis of any part of the iliac vein or the common femoral vein, with or without in­volvement of other lower-extremity veins or the IVC. Under this heading, the document addresses the use of initial coagulant therapy, long-term anticoagulant ther­apy, compression therapy, IVC filters, and thrombore­ductive strategies, including systemic, catheter-directed, percutaneous mechanical, and pharmacomechanical thrombolysis. Surgical venous thrombectomy is also dis­cussed as an alternative method of thrombus removal. <[etk]>

«qc'er: pls fact check these next 2 grafs»<[stk -2]>“Reasonable” angiopathy and stenting options for older adolescents and adults include the use of percuta­neous transluminal venous angioplasty and stent place­ment in the iliac vein to treat obstructive lesions after catheter-directed thrombolysis (CDT), pharmacome­chanical CDT (PCDT), or surgical venous thrombecto­my, and placement of iliac vein stents to reduce postthrombotic symptoms and heal venous ulcers in pa­tients with advanced postthrombotic symptoms and il­iac vein obstruction. “For obstructive iliac vein lesions that extend into the common femoral vein, caudal ex­tension of stents into the common femoral vein is rea­sonable if unavoidable.” Guidelines regarding subsequent therapeutic anticoagulation are also provided. <[etk]>

The authors noted that “the use of percutaneous transluminal venous angioplasty in children may be rea­sonable, but this practice has not been well studied and may be associated with a greater risk of vasospasm.”

The section on chronic thromboembolic pulmonary hypertension (CTEPH) outlines the classification, risk factors, clinical presentation, diagnosis, and treatment with pulmonary endarterectomy and medical therapies. The condition is a syndrome of dyspnea, fatigue, and exercise intolerance caused by proximal thromboem­bolic obstruction and distal remodeling of the pul­monary circulation that leads to elevated pulmonary artery pressure and progressive RV failure.

Patients with unexplained dyspnea, exercise intoler­ance, or clinical evidence of right-sided heart failure, with or without a prior history of symptomatic venous thromboembolism, should be evaluated for CTEPH, and it is reasonable to evaluate patients with an echocar­diogram 6 weeks after an acute pulmonary embolism to screen for persistent pulmonary hypertension that may predict the development of CTEPH.

Patients with objectively proven CTEPH should be promptly evaluated for pulmonary endarterectomy, even if symptoms are mild, and receive indefinite ther­apeutic anticoagulation in the absence of contraindi­cations, they advised.

I have checked the following facts in my story: (Please initial each.)

 lf MET    drug names and dosages -

 lf MET    lab test values and their units -

lf MET     whether nos. are correct and add up, and whether percentages based on those nos. are correct -

lf MET     citation (e.g., JAMA 2008;299:785-92) -

 lf MET    investigators’ names and affiliations -

 lf MET     all other proper names (e.g., clinical trials; geographic, company, and test names) –..

 lf MET    investigators' conflicts of interest and sponsor of study – 

Dr. McMurtry reported no relavant disclosures.

********* UNDERSET  1  LINES *********

A scientific statement from the American Heart As­sociation provides guidance for the management of the more severe forms of venous thromboembolism.

The statement focuses on three areas: massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pul­monary hypertension. “The goal is to provide practi­cal advice to enable the busy clinician to optimize the management of patients with these severe manifesta­tions of [venous thromboembolism],” said the writing committee, cochaired by Dr. Michael R. Jaff and Dr. M. Sean McMurtry (Circulation 2011 Mar. 21 [doi:10.1161/CIR.0b013e318214914f]).« http://www.theheart.org/article/1200965.do»

<[stk -1]>In an interview, Dr. McMurtry noted that because these disease areas have less data to support manage­ment strategies than do other areas of cardiovascular medicine, most of the recommendations in the docu­ment are class II (“it is reasonable” or “may be consid­ered”) with level of evidence B or C (limited populations evaluated). “The authors hope that this document will inspire more research into these conditions,” said Dr. McMurtry of the University of Alberta, Edmonton.<[etk]>

<[stk -3]>The document begins by defining “massive,” “sub­massive,” and “low-risk” pulmonary embolism (PE), and provides data for the various techniques used to identify patients at increased risk for adverse short-term outcomes in acute PE. <[etk]>

Beyond initial heparin anticoagulation therapy, the use of fibrinolytic drugs is reasonable for patients with massive acute PE and an acceptable risk of bleeding complications, the statement said. It may also be con­sidered for patients with submassive acute PE judged to have clinical evidence of an adverse prognosis (new hemodynamic instability, worsening respiratory insuf­ficiency, severe right ventricle [RV] dysfunction, or major myocardial necrosis) and a low risk of bleeding.

Fibrinolysis is not recommended for patients with low-risk PE, or submassive PE with minor RV dys­function, minor myocardial necrosis, and no clinical worsening. Fibrinolysis is also not recommended for undifferentiated cardiac arrest, wrote Dr. McMurtry and Dr. Jaff of Harvard Medical School, and coauthors.

In addition, recommendations are provided for oth­er areas in which data are sparse and optimal manage­ment is unclear, including catheter-based therapies. Transcatheter procedures can be performed as an al­ternative to thrombolysis when there are contraindi­cations or when emergency surgical thrombectomy is unavailable or contraindicated. Catheter interventions can also be performed when thrombolysis has failed to improve hemodynamics in the acute setting.

Hybrid therapy that includes both catheter-based clot fragmentation and local thrombolysis is an emerging strategy, the committee noted.

Adult patients with any confirmed acute PE who have contraindications to anticoagulation or have active bleeding should receive an inferior vena cava (IVC) fil­ter. Further specific guidance is given for the type of fil­ter and for monitoring.

<[stk -1]>Iliofemoral Deep Vein Thrombosis (IVDVT) refers to complete or partial thrombosis of any part of the iliac vein or the common femoral vein, with or without in­volvement of other lower-extremity veins or the IVC. Under this heading, the document addresses the use of initial coagulant therapy, long-term anticoagulant ther­apy, compression therapy, IVC filters, and thrombore­ductive strategies, including systemic, catheter-directed, percutaneous mechanical, and pharmacomechanical thrombolysis. Surgical venous thrombectomy is also dis­cussed as an alternative method of thrombus removal. <[etk]>

«qc'er: pls fact check these next 2 grafs»<[stk -2]>“Reasonable” angiopathy and stenting options for older adolescents and adults include the use of percuta­neous transluminal venous angioplasty and stent place­ment in the iliac vein to treat obstructive lesions after catheter-directed thrombolysis (CDT), pharmacome­chanical CDT (PCDT), or surgical venous thrombecto­my, and placement of iliac vein stents to reduce postthrombotic symptoms and heal venous ulcers in pa­tients with advanced postthrombotic symptoms and il­iac vein obstruction. “For obstructive iliac vein lesions that extend into the common femoral vein, caudal ex­tension of stents into the common femoral vein is rea­sonable if unavoidable.” Guidelines regarding subsequent therapeutic anticoagulation are also provided. <[etk]>

The authors noted that “the use of percutaneous transluminal venous angioplasty in children may be rea­sonable, but this practice has not been well studied and may be associated with a greater risk of vasospasm.”

The section on chronic thromboembolic pulmonary hypertension (CTEPH) outlines the classification, risk factors, clinical presentation, diagnosis, and treatment with pulmonary endarterectomy and medical therapies. The condition is a syndrome of dyspnea, fatigue, and exercise intolerance caused by proximal thromboem­bolic obstruction and distal remodeling of the pul­monary circulation that leads to elevated pulmonary artery pressure and progressive RV failure.

Patients with unexplained dyspnea, exercise intoler­ance, or clinical evidence of right-sided heart failure, with or without a prior history of symptomatic venous thromboembolism, should be evaluated for CTEPH, and it is reasonable to evaluate patients with an echocar­diogram 6 weeks after an acute pulmonary embolism to screen for persistent pulmonary hypertension that may predict the development of CTEPH.

Patients with objectively proven CTEPH should be promptly evaluated for pulmonary endarterectomy, even if symptoms are mild, and receive indefinite ther­apeutic anticoagulation in the absence of contraindi­cations, they advised.

I have checked the following facts in my story: (Please initial each.)

 lf MET    drug names and dosages -

 lf MET    lab test values and their units -

lf MET     whether nos. are correct and add up, and whether percentages based on those nos. are correct -

lf MET     citation (e.g., JAMA 2008;299:785-92) -

 lf MET    investigators’ names and affiliations -

 lf MET     all other proper names (e.g., clinical trials; geographic, company, and test names) –..

 lf MET    investigators' conflicts of interest and sponsor of study – 

Dr. McMurtry reported no relavant disclosures.

********* UNDERSET  1  LINES *********

A scientific statement from the American Heart As­sociation provides guidance for the management of the more severe forms of venous thromboembolism.

The statement focuses on three areas: massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pul­monary hypertension. “The goal is to provide practi­cal advice to enable the busy clinician to optimize the management of patients with these severe manifesta­tions of [venous thromboembolism],” said the writing committee, cochaired by Dr. Michael R. Jaff and Dr. M. Sean McMurtry (Circulation 2011 Mar. 21 [doi:10.1161/CIR.0b013e318214914f]).« http://www.theheart.org/article/1200965.do»

<[stk -1]>In an interview, Dr. McMurtry noted that because these disease areas have less data to support manage­ment strategies than do other areas of cardiovascular medicine, most of the recommendations in the docu­ment are class II (“it is reasonable” or “may be consid­ered”) with level of evidence B or C (limited populations evaluated). “The authors hope that this document will inspire more research into these conditions,” said Dr. McMurtry of the University of Alberta, Edmonton.<[etk]>

<[stk -3]>The document begins by defining “massive,” “sub­massive,” and “low-risk” pulmonary embolism (PE), and provides data for the various techniques used to identify patients at increased risk for adverse short-term outcomes in acute PE. <[etk]>

Beyond initial heparin anticoagulation therapy, the use of fibrinolytic drugs is reasonable for patients with massive acute PE and an acceptable risk of bleeding complications, the statement said. It may also be con­sidered for patients with submassive acute PE judged to have clinical evidence of an adverse prognosis (new hemodynamic instability, worsening respiratory insuf­ficiency, severe right ventricle [RV] dysfunction, or major myocardial necrosis) and a low risk of bleeding.

Fibrinolysis is not recommended for patients with low-risk PE, or submassive PE with minor RV dys­function, minor myocardial necrosis, and no clinical worsening. Fibrinolysis is also not recommended for undifferentiated cardiac arrest, wrote Dr. McMurtry and Dr. Jaff of Harvard Medical School, and coauthors.

In addition, recommendations are provided for oth­er areas in which data are sparse and optimal manage­ment is unclear, including catheter-based therapies. Transcatheter procedures can be performed as an al­ternative to thrombolysis when there are contraindi­cations or when emergency surgical thrombectomy is unavailable or contraindicated. Catheter interventions can also be performed when thrombolysis has failed to improve hemodynamics in the acute setting.

Hybrid therapy that includes both catheter-based clot fragmentation and local thrombolysis is an emerging strategy, the committee noted.

Adult patients with any confirmed acute PE who have contraindications to anticoagulation or have active bleeding should receive an inferior vena cava (IVC) fil­ter. Further specific guidance is given for the type of fil­ter and for monitoring.

<[stk -1]>Iliofemoral Deep Vein Thrombosis (IVDVT) refers to complete or partial thrombosis of any part of the iliac vein or the common femoral vein, with or without in­volvement of other lower-extremity veins or the IVC. Under this heading, the document addresses the use of initial coagulant therapy, long-term anticoagulant ther­apy, compression therapy, IVC filters, and thrombore­ductive strategies, including systemic, catheter-directed, percutaneous mechanical, and pharmacomechanical thrombolysis. Surgical venous thrombectomy is also dis­cussed as an alternative method of thrombus removal. <[etk]>

«qc'er: pls fact check these next 2 grafs»<[stk -2]>“Reasonable” angiopathy and stenting options for older adolescents and adults include the use of percuta­neous transluminal venous angioplasty and stent place­ment in the iliac vein to treat obstructive lesions after catheter-directed thrombolysis (CDT), pharmacome­chanical CDT (PCDT), or surgical venous thrombecto­my, and placement of iliac vein stents to reduce postthrombotic symptoms and heal venous ulcers in pa­tients with advanced postthrombotic symptoms and il­iac vein obstruction. “For obstructive iliac vein lesions that extend into the common femoral vein, caudal ex­tension of stents into the common femoral vein is rea­sonable if unavoidable.” Guidelines regarding subsequent therapeutic anticoagulation are also provided. <[etk]>

The authors noted that “the use of percutaneous transluminal venous angioplasty in children may be rea­sonable, but this practice has not been well studied and may be associated with a greater risk of vasospasm.”

The section on chronic thromboembolic pulmonary hypertension (CTEPH) outlines the classification, risk factors, clinical presentation, diagnosis, and treatment with pulmonary endarterectomy and medical therapies. The condition is a syndrome of dyspnea, fatigue, and exercise intolerance caused by proximal thromboem­bolic obstruction and distal remodeling of the pul­monary circulation that leads to elevated pulmonary artery pressure and progressive RV failure.

Patients with unexplained dyspnea, exercise intoler­ance, or clinical evidence of right-sided heart failure, with or without a prior history of symptomatic venous thromboembolism, should be evaluated for CTEPH, and it is reasonable to evaluate patients with an echocar­diogram 6 weeks after an acute pulmonary embolism to screen for persistent pulmonary hypertension that may predict the development of CTEPH.

Patients with objectively proven CTEPH should be promptly evaluated for pulmonary endarterectomy, even if symptoms are mild, and receive indefinite ther­apeutic anticoagulation in the absence of contraindi­cations, they advised.

I have checked the following facts in my story: (Please initial each.)

 lf MET    drug names and dosages -

 lf MET    lab test values and their units -

lf MET     whether nos. are correct and add up, and whether percentages based on those nos. are correct -

lf MET     citation (e.g., JAMA 2008;299:785-92) -

 lf MET    investigators’ names and affiliations -

 lf MET     all other proper names (e.g., clinical trials; geographic, company, and test names) –..

 lf MET    investigators' conflicts of interest and sponsor of study – 

Dr. McMurtry reported no relavant disclosures.

********* UNDERSET  1  LINES *********

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

The American College of Cardiolo­gy Foundation and the American Heart Association have published updated guidelines for managing pa­tients with unstable angina/non–ST el­evation myocardial infarction, taking into consideration the use of a newer agent, prasugrel, as an alternative to clopidogrel, and recommending diag­nostic angiography sooner for patients at high risk, among other changes.

The guidelines, published March 28in the Journal of the American College of Cardiology  (Am. J. Cardiol. 2011 March 28 [doi:10.1016/j.jacc.2011.02.009]) and based on the most recent clinical trial ev­idence available, update recommenda­tions from 2007, and include several changes clinicians should be aware of, the guidelines’ lead author, Dr. R. Scott Wright of the Mayo Clinic in Rochester, Minn., said in an e-mail interview. These are, in order of importance:

• The timing of invasive therapy in medium- and high-risk patients.
• The role of triple- vs. dual-antiplatelet therapy in patients at medium and high risk.
• The role of invasive therapy in pa­tients with chronic kidney disease.
• The importance of participating in quality improvement processes.
• The role of prasugrel in non–ST ele­vation acute coronary syndrome.

Clinicians face tough decisions about when to perform an invasive strategy such as diagnostic coronary angiography – whether within hours of presentation or days, Dr. Wright and his colleagues wrote in their analysis.

Immediate catheterization with revas­cularization of unstable coronary lesions may prevent ischemic events that would otherwise occur during medical therapy – but pretreatment with antithrombotics “may diminish thrombus burden and ‘passivate’ unstable plaques,” improving the safety of the procedure and reducing the risk of ischemic complications.

<[stk 2]>The new guidelines, based on findings from three randomized controlled trials evaluating the timing of angiography, recommend an early invasive strategy (12-24 hours after presentation) over a delayed invasive strategy (more than 24 hours after presentation) for initially stabilized high-risk patients with UA/NSTEMI. <[etk]>

“For patients not at high risk, a delayed invasive approach is also reasonable,” Dr. Wright and his colleagues wrote.

Several changes to earlier recommen­dations for antiplatelet therapy are con­tained in the new guidelines, including altered loading doses for clopidogrel to counter the potential for the drug to be less effective in some patient groups, and the addition of prasugrel, which was approved by the Food and Drug Ad­ministration after the last guidelines were published.

Prasugrel, in a randomized controlled trial comparing it with clopidogrel, was shown to be superior in reducing clinical events but at the expense of an increased risk of bleeding, the guideline writers noted.

In March 2010 the FDA issued a warn­ing that in some patient groups clopido­grel is less effective than it should be because of a genetic variant that inhibits the body’s conversion of the prodrug to the drug.

However, Dr. Wright and his col­leagues stopped short of endorsing pra­sugrel as a first choice over clopidogrel because of the higher bleeding risk and other considerations. People aged 75 years or older, those with a history of transient ischemic attack or stroke or with active pathological bleeding, and people weighing less than 60 kg saw no benefit and/or net harm from prasugrel, they noted.

Dr. Wright and his colleagues also changed recommendations involving glycoprotein IIB/IIIa inhibitors, noting that recent studies “more strongly sup­port a strategy of selective rather than provisional use of GP IIb/IIIa inhibitor
therapy as part of triple-antiplatelet ther­apy,” due to concerns about the poten­tial bleeding risks. Therefore, according to the new guidelines, for UA/NSTEMI patients who are at low risk of ischemic events or at high risk of bleeding and who are already receiving aspirin and clopidogrel, upstream GP IIb/IIIa in­hibitors are not recommended.

People with kidney disease should re­ceive adequate preparatory hydration before catheterization, say the new guidelines, which also tweak earlier recommendations about the contrast agents used in angiography.

Finally, the guidelines recommend that clinicians and hospitals “participate in a standardized quality-of-care data registry designed to track and measure outcomes, complications, and adherence to evidence-based processes of care and quality improvement for UA/NSTEMI.” No such recommendation had been included in the 2007 guidelines.

I have checked the following facts in my story: (Please initial each.)

<[stk 1]>Dr. Wright declared no conflicts of in­terest. Several of Dr. Wright’s coau­thors, including Dr. Jeffrey L. Anderson, the writing committee’s vice chair, dis­closed consultant relationships with pharmaceutical firms Sanofi-Aventis, Bristol Myers-Squibb, Lilly, and Daiichi. Members with conflicts were not per­mitted to vote on recommended drug therapies.

Patients who quit smoking shortly before undergo­ing surgery are not at increased risk of postopera­tive complications, compared with those who continue to smoke, according to a report published online in the Archives of Internal Medicine.

“Until some new evidence of harm emerges, firm ad­vice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time,” said Katie Myers, M.Sc., of Queen Mary, University of London and her associates.

<[stk -3]>Publication of a study in 1989 with 39 subjects sug­gested that “stopping smoking leads to a decrease in coughing and an increase in sputum production.” Al­though that article did not show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery “to minimize the increase in pulmonary complications in recent quitters.” <[etk]>

<[stk -2]>Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as “high quality” the three studies that also used biochem­ical testing to validate subjects’ self-report of their smok­ing status. These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.<[etk]>

<[stk -3]>Only one of the studies showed a significant effect of smoking cessation, and that was in favor of recent quit­ting. When the results were pooled, there was “no ben­eficial or detrimental effect of quitting within 8 weeks before surgery compared with continued smoking.” <[etk]><[stk -2]>The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications. <[etk]>

“In conclusion, there is currently no suggestion, ei­ther from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications,” the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archintern­med.2011.97]).

The reluctance to allow or encourage smoking ces­sation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has di­rectly examined mucociliary clearance in surgical pa­tients shortly after smoking cessation, and that study found no significant difference between surgical pa­tients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

im, ob               embargoed until 4 pm 3/14

{Copy eds. -- I had to get some of my figures from charts and tables because they weren't in the text of the article. -- mam}

I have checked the following facts in my story:

NA     Drug names and dosages

NA     Lab test values and their units

MM     Nos. are correct and add up, and percentages based on those nos. are correct

MM/ew   Citation

MM/ew     Investigators’ names and affiliations

MM /ew    All other proper names (e.g., clinical trials; geographic, company, and test names)

MM     Investigators’ conflicts of interest and sponsor of study

Best contact number = 301-325-5890; email = The study is limited by its observational nature and by the small number of studies available for review.

Ms. Myers reported no conflicts.

********* UNDERSET  1  LINES *********

Patients who quit smoking shortly before undergo­ing surgery are not at increased risk of postopera­tive complications, compared with those who continue to smoke, according to a report published online in the Archives of Internal Medicine.

“Until some new evidence of harm emerges, firm ad­vice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time,” said Katie Myers, M.Sc., of Queen Mary, University of London and her associates.

<[stk -3]>Publication of a study in 1989 with 39 subjects sug­gested that “stopping smoking leads to a decrease in coughing and an increase in sputum production.” Al­though that article did not show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery “to minimize the increase in pulmonary complications in recent quitters.” <[etk]>

<[stk -2]>Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as “high quality” the three studies that also used biochem­ical testing to validate subjects’ self-report of their smok­ing status. These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.<[etk]>

<[stk -3]>Only one of the studies showed a significant effect of smoking cessation, and that was in favor of recent quit­ting. When the results were pooled, there was “no ben­eficial or detrimental effect of quitting within 8 weeks before surgery compared with continued smoking.” <[etk]><[stk -2]>The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications. <[etk]>

“In conclusion, there is currently no suggestion, ei­ther from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications,” the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archintern­med.2011.97]).

The reluctance to allow or encourage smoking ces­sation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has di­rectly examined mucociliary clearance in surgical pa­tients shortly after smoking cessation, and that study found no significant difference between surgical pa­tients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

im, ob               embargoed until 4 pm 3/14

{Copy eds. -- I had to get some of my figures from charts and tables because they weren't in the text of the article. -- mam}

I have checked the following facts in my story:

NA     Drug names and dosages

NA     Lab test values and their units

MM     Nos. are correct and add up, and percentages based on those nos. are correct

MM/ew   Citation

MM/ew     Investigators’ names and affiliations

MM /ew    All other proper names (e.g., clinical trials; geographic, company, and test names)

MM     Investigators’ conflicts of interest and sponsor of study

Best contact number = 301-325-5890; email = The study is limited by its observational nature and by the small number of studies available for review.

Ms. Myers reported no conflicts.

********* UNDERSET  1  LINES *********

Patients who quit smoking shortly before undergo­ing surgery are not at increased risk of postopera­tive complications, compared with those who continue to smoke, according to a report published online in the Archives of Internal Medicine.

“Until some new evidence of harm emerges, firm ad­vice to stop smoking and an offer of smoking cessation treatment to those who need it can be provided to presurgical patients at any time,” said Katie Myers, M.Sc., of Queen Mary, University of London and her associates.

<[stk -3]>Publication of a study in 1989 with 39 subjects sug­gested that “stopping smoking leads to a decrease in coughing and an increase in sputum production.” Al­though that article did not show a significant effect of smoking cessation on postoperative complications, it has continued to influence routine practice; in fact, some treatment guidelines recommend against smoking cessation in the 2 months prior to surgery “to minimize the increase in pulmonary complications in recent quitters.” <[etk]>

<[stk -2]>Ms. Myers and her colleagues reviewed the literature for all studies that allowed comparisons of postoperative complications in patients who stopped smoking 8 weeks or less before undergoing surgery (recent quitters) and patients who continued to smoke. They then performed a meta-analysis of the nine studies that did so, rating as “high quality” the three studies that also used biochem­ical testing to validate subjects’ self-report of their smok­ing status. These studies involved 889 subjects, including 448 recent quitters and 441 continuing smokers.<[etk]>

<[stk -3]>Only one of the studies showed a significant effect of smoking cessation, and that was in favor of recent quit­ting. When the results were pooled, there was “no ben­eficial or detrimental effect of quitting within 8 weeks before surgery compared with continued smoking.” <[etk]><[stk -2]>The results were the same in an analysis of the three high-quality studies, and likewise when the analysis was restricted to only pulmonary postoperative complications. <[etk]>

“In conclusion, there is currently no suggestion, ei­ther from any single study or from combinations of studies, that quitting smoking shortly before surgery increases postoperative complications,” the investigators said (Arch. Intern. Med. 2011 [doi:10.1001/archintern­med.2011.97]).

The reluctance to allow or encourage smoking ces­sation shortly before surgery is based on unconfirmed assumptions. Only one study in the literature has di­rectly examined mucociliary clearance in surgical pa­tients shortly after smoking cessation, and that study found no significant difference between surgical pa­tients who had recently quit and those who continued to smoke, Ms. Myers and her associates noted.

im, ob               embargoed until 4 pm 3/14

{Copy eds. -- I had to get some of my figures from charts and tables because they weren't in the text of the article. -- mam}

I have checked the following facts in my story:

NA     Drug names and dosages

NA     Lab test values and their units

MM     Nos. are correct and add up, and percentages based on those nos. are correct

MM/ew   Citation

MM/ew     Investigators’ names and affiliations

MM /ew    All other proper names (e.g., clinical trials; geographic, company, and test names)

MM     Investigators’ conflicts of interest and sponsor of study

Best contact number = 301-325-5890; email = The study is limited by its observational nature and by the small number of studies available for review.

Ms. Myers reported no conflicts.

********* UNDERSET  1  LINES *********

After months of deliberation, offi­cials at the Centers for Medicare and Medicaid Services released a proposed rule outlining how physicians, hospitals, and long-term care facilities can work together to form accountable care organizations and share in the sav­ings they achieve for Medicare.

The voluntary program was created under the Affordable Care Act and will begin in Jan. 2012. Under the proposal, accountable care organizations (ACOs) could include physicians in group prac­tice, networks of individual practices, hospitals that employ physicians, and partnerships among these entities, as well as other providers. The idea is for ACOs to be a partnership among a range of physicians, including specialists and primary care providers. However, only primary care providers will be able to form an ACO, according to CMS.

<[stk -1]>According to the proposed rule, providers in the ACO would continue to receive their regular fee-for-service pay­ments under Medicare, but they could also qualify for additional payment if their care resulted in savings to the pro­gram. The proposed framework requires that ACOs meet certain quality standards and demonstrate that they have reduced costs in order to be eligible to share in any savings. The proposal outlines 65 quality measures in five quality domains: patient experience, care coordination, patient safety, preventive health, and care of at-risk and frail elderly populations.For qc, not for linking. <http://www.healthcare.gov/news/factsheets/accountablecare03312011a.html > <[etk]>

“ACOs aren’t just a new way to pay for care; they’re a new model for the organization and delivery of the care under Medicare,” Dr. Donald Berwick, CMS administrator, said during a press con­ference to announce the proposed rule.

Dr. Berwick said he doesn’t know how many ACOs will form under the pro­gram, but that the level of interest is “enormous.”

Since the Affordable Care Act was passed last year, the health care com­
munity has been buzzing about how ACOs might be structured and if they could succeed in reducing health care costs. Integrated care organizations like Geisinger Health System in Danville, Pa., are considered to have a leg up because their hospital and outpatient care is already coordinated.

But Dr. Berwick said that the propos­al allows for ACOs at various levels of development to participate. For example, less developed ACOs can choose to re­ceive only shared savings for 2 years be­fore assuming risk. More mature organizations can assume risk immedi­ately but be eligible for greater levels of shared savings. “Our aim is to create on-ramps that will allow many to participate, depending on the different levels of maturity they are starting with,” Dr. Berwick said.

CMS officials estimate that the pro­gram could result in as much as $960 mil­lion in Medicare savings over 3 years.

<[stk -3]>Although federal officials said that they expect the coordinated care to pay divi­dends in savings to Medicare, ACOs will not be set up like HMOs. Medicare bene­ficiaries will still be able to see their choice of providers under fee-for-service Medicare. Providers will be the ones that enroll in ACOs and must notify patients they are receiving care within an ACO. <[etk]>

In addition to the ACO proposed rule, the Department of Justice and the Federal Trade Commission have also issued guidance on how physicians and hospi­tals that form an ACO can steer clear of antitrust laws. «http://www.ftc.gov/opp/aco» Officials at the CMS and the Office of the Inspector General have also issued a notice on potential waivers that could be granted in connection with the shared savings program, «http://www.ofr.gov/OFRUpload/OFRData/2011-07884_PI.pdf» and the In­ternal Revenue Service has issued new guidance for tax-exempt hospitals seek­ing to participate in the program.«http://www.irs.gov/pub/irs-drop/n-11-20.pdf»

I have checked the following facts in my story: (Please initial each.)

The CMS will be accepting comments on the proposed rule for 60 days<official publication date in the FR is April 7>. The agency also plans a series of open-door forums and listening sessions to explain the proposal and to get feedback from the public.

After months of deliberation, offi­cials at the Centers for Medicare and Medicaid Services released a proposed rule outlining how physicians, hospitals, and long-term care facilities can work together to form accountable care organizations and share in the sav­ings they achieve for Medicare.

The voluntary program was created under the Affordable Care Act and will begin in Jan. 2012. Under the proposal, accountable care organizations (ACOs) could include physicians in group prac­tice, networks of individual practices, hospitals that employ physicians, and partnerships among these entities, as well as other providers. The idea is for ACOs to be a partnership among a range of physicians, including specialists and primary care providers. However, only primary care providers will be able to form an ACO, according to CMS.

<[stk -1]>According to the proposed rule, providers in the ACO would continue to receive their regular fee-for-service pay­ments under Medicare, but they could also qualify for additional payment if their care resulted in savings to the pro­gram. The proposed framework requires that ACOs meet certain quality standards and demonstrate that they have reduced costs in order to be eligible to share in any savings. The proposal outlines 65 quality measures in five quality domains: patient experience, care coordination, patient safety, preventive health, and care of at-risk and frail elderly populations.For qc, not for linking. <http://www.healthcare.gov/news/factsheets/accountablecare03312011a.html > <[etk]>

“ACOs aren’t just a new way to pay for care; they’re a new model for the organization and delivery of the care under Medicare,” Dr. Donald Berwick, CMS administrator, said during a press con­ference to announce the proposed rule.

Dr. Berwick said he doesn’t know how many ACOs will form under the pro­gram, but that the level of interest is “enormous.”

Since the Affordable Care Act was passed last year, the health care com­
munity has been buzzing about how ACOs might be structured and if they could succeed in reducing health care costs. Integrated care organizations like Geisinger Health System in Danville, Pa., are considered to have a leg up because their hospital and outpatient care is already coordinated.

But Dr. Berwick said that the propos­al allows for ACOs at various levels of development to participate. For example, less developed ACOs can choose to re­ceive only shared savings for 2 years be­fore assuming risk. More mature organizations can assume risk immedi­ately but be eligible for greater levels of shared savings. “Our aim is to create on-ramps that will allow many to participate, depending on the different levels of maturity they are starting with,” Dr. Berwick said.

CMS officials estimate that the pro­gram could result in as much as $960 mil­lion in Medicare savings over 3 years.

<[stk -3]>Although federal officials said that they expect the coordinated care to pay divi­dends in savings to Medicare, ACOs will not be set up like HMOs. Medicare bene­ficiaries will still be able to see their choice of providers under fee-for-service Medicare. Providers will be the ones that enroll in ACOs and must notify patients they are receiving care within an ACO. <[etk]>

In addition to the ACO proposed rule, the Department of Justice and the Federal Trade Commission have also issued guidance on how physicians and hospi­tals that form an ACO can steer clear of antitrust laws. «http://www.ftc.gov/opp/aco» Officials at the CMS and the Office of the Inspector General have also issued a notice on potential waivers that could be granted in connection with the shared savings program, «http://www.ofr.gov/OFRUpload/OFRData/2011-07884_PI.pdf» and the In­ternal Revenue Service has issued new guidance for tax-exempt hospitals seek­ing to participate in the program.«http://www.irs.gov/pub/irs-drop/n-11-20.pdf»

I have checked the following facts in my story: (Please initial each.)

The CMS will be accepting comments on the proposed rule for 60 days<official publication date in the FR is April 7>. The agency also plans a series of open-door forums and listening sessions to explain the proposal and to get feedback from the public.

After months of deliberation, offi­cials at the Centers for Medicare and Medicaid Services released a proposed rule outlining how physicians, hospitals, and long-term care facilities can work together to form accountable care organizations and share in the sav­ings they achieve for Medicare.

The voluntary program was created under the Affordable Care Act and will begin in Jan. 2012. Under the proposal, accountable care organizations (ACOs) could include physicians in group prac­tice, networks of individual practices, hospitals that employ physicians, and partnerships among these entities, as well as other providers. The idea is for ACOs to be a partnership among a range of physicians, including specialists and primary care providers. However, only primary care providers will be able to form an ACO, according to CMS.

<[stk -1]>According to the proposed rule, providers in the ACO would continue to receive their regular fee-for-service pay­ments under Medicare, but they could also qualify for additional payment if their care resulted in savings to the pro­gram. The proposed framework requires that ACOs meet certain quality standards and demonstrate that they have reduced costs in order to be eligible to share in any savings. The proposal outlines 65 quality measures in five quality domains: patient experience, care coordination, patient safety, preventive health, and care of at-risk and frail elderly populations.For qc, not for linking. <http://www.healthcare.gov/news/factsheets/accountablecare03312011a.html > <[etk]>

“ACOs aren’t just a new way to pay for care; they’re a new model for the organization and delivery of the care under Medicare,” Dr. Donald Berwick, CMS administrator, said during a press con­ference to announce the proposed rule.

Dr. Berwick said he doesn’t know how many ACOs will form under the pro­gram, but that the level of interest is “enormous.”

Since the Affordable Care Act was passed last year, the health care com­
munity has been buzzing about how ACOs might be structured and if they could succeed in reducing health care costs. Integrated care organizations like Geisinger Health System in Danville, Pa., are considered to have a leg up because their hospital and outpatient care is already coordinated.

But Dr. Berwick said that the propos­al allows for ACOs at various levels of development to participate. For example, less developed ACOs can choose to re­ceive only shared savings for 2 years be­fore assuming risk. More mature organizations can assume risk immedi­ately but be eligible for greater levels of shared savings. “Our aim is to create on-ramps that will allow many to participate, depending on the different levels of maturity they are starting with,” Dr. Berwick said.

CMS officials estimate that the pro­gram could result in as much as $960 mil­lion in Medicare savings over 3 years.

<[stk -3]>Although federal officials said that they expect the coordinated care to pay divi­dends in savings to Medicare, ACOs will not be set up like HMOs. Medicare bene­ficiaries will still be able to see their choice of providers under fee-for-service Medicare. Providers will be the ones that enroll in ACOs and must notify patients they are receiving care within an ACO. <[etk]>

In addition to the ACO proposed rule, the Department of Justice and the Federal Trade Commission have also issued guidance on how physicians and hospi­tals that form an ACO can steer clear of antitrust laws. «http://www.ftc.gov/opp/aco» Officials at the CMS and the Office of the Inspector General have also issued a notice on potential waivers that could be granted in connection with the shared savings program, «http://www.ofr.gov/OFRUpload/OFRData/2011-07884_PI.pdf» and the In­ternal Revenue Service has issued new guidance for tax-exempt hospitals seek­ing to participate in the program.«http://www.irs.gov/pub/irs-drop/n-11-20.pdf»

I have checked the following facts in my story: (Please initial each.)

The CMS will be accepting comments on the proposed rule for 60 days<official publication date in the FR is April 7>. The agency also plans a series of open-door forums and listening sessions to explain the proposal and to get feedback from the public.