LOS ANGELES – Treatment with neoadjuvant chemotherapy leads to significant downstaging in a selected group of patients with advanced colon cancer, results from a large registry study showed.

“Neoadjuvant chemotherapy is already established as a treatment strategy in several other types of cancers, such as breast cancer, gastric cancer, and rectal cancer,” lead study author Dr. Moniek Verstegen said at the annual meeting of the American Society of Colon and Rectal Surgeons. “It reduces tumor size and promotes resectability. In colon cancer, however, this treatment strategy is relatively new and not applied very often.”

©BluePlanetEarth/thinkstockphotos.com

Preliminary results from the ongoing FOxTROT trial in the United Kingdom showed that preoperative chemotherapy for radiologically staged, locally advanced, operable primary colon cancer is feasible, with acceptable toxicity and perioperative morbidity, but long-term results are not yet available. The aim of the current study was to see how often neoadjuvant chemotherapy is used in the Netherlands for stage II and III colon cancer and to assess the tumor and nodal downsizing effects. Moreover, perioperative results and long-term outcomes were compared between those treated with neoadjuvant chemotherapy and those who were treated with adjuvant chemotherapy for locally advanced colon cancer.

The researchers searched the Netherlands Cancer Registry from 2008-2012 to identify 24,944 patients diagnosed with stage II and III colon cancer. Dr. Verstegen, a researcher in the department of surgery at Radboud University Medical Center, Nijmegen, Netherlands, reported results from 85 patients who received neoadjuvant chemotherapy and 2,216 who received adjuvant chemotherapy (the control group). Both groups were similar in terms of age (a median of about 65 years), gender, localization of the primary tumor, differentiation grade, morphology, and clinical T and N stage. Multivisceral resections were performed significantly more often in the neoadjuvant group, compared with the control group (21% vs. 5%, respectively; P less than .001). There were no differences between groups in the number of complete resections, nor in the rate of complications. Furthermore, no patient died within 30 days of neoadjuvant chemotherapy after surgery.

Tumor downstaging was observed in 47% of patients treated with neoadjuvant chemotherapy and there were three complete responses. At the same time, nodal downstaging was observed in 50% of patients treated with neoadjuvant chemotherapy. The 3-year overall survival was 73% in both groups.

Dr. Verstegen acknowledged certain limitations of the study, including its retrospective design and the lack of data on recurrences and disease-free survival. “Neoadjuvant chemotherapy seems to be a safe treatment strategy, since we have low postoperative morbidity and mortality rates,” she concluded. “We see comparable outcomes compared to the control group. Prospective trials are needed to confirm the safety and value of neoadjuvant chemotherapy.”

Dr. Verstegen reported having no financial disclosures.

[email protected]

LOS ANGELES – Treatment with neoadjuvant chemotherapy leads to significant downstaging in a selected group of patients with advanced colon cancer, results from a large registry study showed.

“Neoadjuvant chemotherapy is already established as a treatment strategy in several other types of cancers, such as breast cancer, gastric cancer, and rectal cancer,” lead study author Dr. Moniek Verstegen said at the annual meeting of the American Society of Colon and Rectal Surgeons. “It reduces tumor size and promotes resectability. In colon cancer, however, this treatment strategy is relatively new and not applied very often.”

©BluePlanetEarth/thinkstockphotos.com

Preliminary results from the ongoing FOxTROT trial in the United Kingdom showed that preoperative chemotherapy for radiologically staged, locally advanced, operable primary colon cancer is feasible, with acceptable toxicity and perioperative morbidity, but long-term results are not yet available. The aim of the current study was to see how often neoadjuvant chemotherapy is used in the Netherlands for stage II and III colon cancer and to assess the tumor and nodal downsizing effects. Moreover, perioperative results and long-term outcomes were compared between those treated with neoadjuvant chemotherapy and those who were treated with adjuvant chemotherapy for locally advanced colon cancer.

The researchers searched the Netherlands Cancer Registry from 2008-2012 to identify 24,944 patients diagnosed with stage II and III colon cancer. Dr. Verstegen, a researcher in the department of surgery at Radboud University Medical Center, Nijmegen, Netherlands, reported results from 85 patients who received neoadjuvant chemotherapy and 2,216 who received adjuvant chemotherapy (the control group). Both groups were similar in terms of age (a median of about 65 years), gender, localization of the primary tumor, differentiation grade, morphology, and clinical T and N stage. Multivisceral resections were performed significantly more often in the neoadjuvant group, compared with the control group (21% vs. 5%, respectively; P less than .001). There were no differences between groups in the number of complete resections, nor in the rate of complications. Furthermore, no patient died within 30 days of neoadjuvant chemotherapy after surgery.

Tumor downstaging was observed in 47% of patients treated with neoadjuvant chemotherapy and there were three complete responses. At the same time, nodal downstaging was observed in 50% of patients treated with neoadjuvant chemotherapy. The 3-year overall survival was 73% in both groups.

Dr. Verstegen acknowledged certain limitations of the study, including its retrospective design and the lack of data on recurrences and disease-free survival. “Neoadjuvant chemotherapy seems to be a safe treatment strategy, since we have low postoperative morbidity and mortality rates,” she concluded. “We see comparable outcomes compared to the control group. Prospective trials are needed to confirm the safety and value of neoadjuvant chemotherapy.”

Dr. Verstegen reported having no financial disclosures.

[email protected]

LOS ANGELES – Treatment with neoadjuvant chemotherapy leads to significant downstaging in a selected group of patients with advanced colon cancer, results from a large registry study showed.

“Neoadjuvant chemotherapy is already established as a treatment strategy in several other types of cancers, such as breast cancer, gastric cancer, and rectal cancer,” lead study author Dr. Moniek Verstegen said at the annual meeting of the American Society of Colon and Rectal Surgeons. “It reduces tumor size and promotes resectability. In colon cancer, however, this treatment strategy is relatively new and not applied very often.”

©BluePlanetEarth/thinkstockphotos.com

Preliminary results from the ongoing FOxTROT trial in the United Kingdom showed that preoperative chemotherapy for radiologically staged, locally advanced, operable primary colon cancer is feasible, with acceptable toxicity and perioperative morbidity, but long-term results are not yet available. The aim of the current study was to see how often neoadjuvant chemotherapy is used in the Netherlands for stage II and III colon cancer and to assess the tumor and nodal downsizing effects. Moreover, perioperative results and long-term outcomes were compared between those treated with neoadjuvant chemotherapy and those who were treated with adjuvant chemotherapy for locally advanced colon cancer.

The researchers searched the Netherlands Cancer Registry from 2008-2012 to identify 24,944 patients diagnosed with stage II and III colon cancer. Dr. Verstegen, a researcher in the department of surgery at Radboud University Medical Center, Nijmegen, Netherlands, reported results from 85 patients who received neoadjuvant chemotherapy and 2,216 who received adjuvant chemotherapy (the control group). Both groups were similar in terms of age (a median of about 65 years), gender, localization of the primary tumor, differentiation grade, morphology, and clinical T and N stage. Multivisceral resections were performed significantly more often in the neoadjuvant group, compared with the control group (21% vs. 5%, respectively; P less than .001). There were no differences between groups in the number of complete resections, nor in the rate of complications. Furthermore, no patient died within 30 days of neoadjuvant chemotherapy after surgery.

Tumor downstaging was observed in 47% of patients treated with neoadjuvant chemotherapy and there were three complete responses. At the same time, nodal downstaging was observed in 50% of patients treated with neoadjuvant chemotherapy. The 3-year overall survival was 73% in both groups.

Dr. Verstegen acknowledged certain limitations of the study, including its retrospective design and the lack of data on recurrences and disease-free survival. “Neoadjuvant chemotherapy seems to be a safe treatment strategy, since we have low postoperative morbidity and mortality rates,” she concluded. “We see comparable outcomes compared to the control group. Prospective trials are needed to confirm the safety and value of neoadjuvant chemotherapy.”

Dr. Verstegen reported having no financial disclosures.

[email protected]

There was an outdoor equipment designer for a well-known Maine-based outfitter who was fond of saying that there was no such thing as bad weather, just bad or inappropriate clothing. The origin of this pearl is claimed by the Norwegians, the Germans, and the English – all nations that have some experience with inclement weather.

The folks who continue to go about their business regardless of the weather usually place a high value on the benefits of being outdoors. They often claim that they simply feel healthier when they are breathing fresh air. It is likely they have grown up in a place, in a family, and in a culture in which waiting for good weather to get something done means it’s not going to get done.

For example, my daughter-in-law’s visual impairment prevents her from driving a car. As a result, she and my two grandchildren get to almost all of their in-town destinations here in Brunswick, Maine, by bicycle or on foot ... 12 months a year ... rain or shine. They can afford appropriate clothing, but they still get wet and cold from time to time. I have never heard them complain. They accept bad weather as a given just as much as they accept a sunny day as something to enjoy.

While my grandchildren’s attitude toward the weather may not be typical of most 9- and 11-year-olds, they may not be alone in a few decades. Preschools are popping up around the country that not only accept the vagaries in the weather, but embrace the outdoors as an educational tool (“Preschool Without Walls,” by Lillian Mongeau, the New York Times, Dec. 29, 2015). The Natural Start Alliance, founded in 2013, has a membership of 92 preschools whose students spend a significant portion of their school day playing and exploring outdoors rain or shine. While most of these schools emphasize the value of learning from the natural environment, one of my granddaughters attended an outdoors-rain-or-shine preschool in urban San Francisco.

At the other end of the spectrum are the schools that feel obligated to shield their students from the realities of meteorological variability. While excessive sun exposure and tissue-freezing wind chills are to be avoided, a crisp calm sunny day with temperatures in the middle teens can be fun, particularly if there is some dry snow to tromp around in. However, during the months from November 2014 to March 2015, the children who attended Public School 126 in New York City were not given the opportunity to play outside on more than 40 school days. The situation is complicated because their school, which lacks its own playground, must rely on nearby parks (“A Casualty of a Frigid New York Winter: Outdoor School Recess,” by Ginia Bellafante, the New York Times, March 6, 2015). But we aren’t talking Siberia. It was a colder-than-usual winter, but I suspect there must have been more than a few missed opportunities to go outside and enjoy the snow. I wonder how often the decision to stay inside was influenced by teachers and administrators who hadn’t come prepared to spend any more time outside than it took them to walk from the parking lot or bus stop.

The data are accumulating that adding physical activity to the school day improves student behavior and even promotes learning. The evidence that being outside is beneficial is a bit more difficult to find. Early in the last century, when indoor air was saturated with smoke from cooking and open combustion heating sources, many physicians recommended that even for infants, raising a healthy child meant having the child spend a large part of the day outdoors.

It’s time for pediatricians to spread the word to parents that their little darlings won’t catch pneumonia from playing outdoors on a cool damp day. Nor will they shrink if they get a little wet on a rainy day ... but they will run ... and the running will be good for them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

There was an outdoor equipment designer for a well-known Maine-based outfitter who was fond of saying that there was no such thing as bad weather, just bad or inappropriate clothing. The origin of this pearl is claimed by the Norwegians, the Germans, and the English – all nations that have some experience with inclement weather.

The folks who continue to go about their business regardless of the weather usually place a high value on the benefits of being outdoors. They often claim that they simply feel healthier when they are breathing fresh air. It is likely they have grown up in a place, in a family, and in a culture in which waiting for good weather to get something done means it’s not going to get done.

For example, my daughter-in-law’s visual impairment prevents her from driving a car. As a result, she and my two grandchildren get to almost all of their in-town destinations here in Brunswick, Maine, by bicycle or on foot ... 12 months a year ... rain or shine. They can afford appropriate clothing, but they still get wet and cold from time to time. I have never heard them complain. They accept bad weather as a given just as much as they accept a sunny day as something to enjoy.

While my grandchildren’s attitude toward the weather may not be typical of most 9- and 11-year-olds, they may not be alone in a few decades. Preschools are popping up around the country that not only accept the vagaries in the weather, but embrace the outdoors as an educational tool (“Preschool Without Walls,” by Lillian Mongeau, the New York Times, Dec. 29, 2015). The Natural Start Alliance, founded in 2013, has a membership of 92 preschools whose students spend a significant portion of their school day playing and exploring outdoors rain or shine. While most of these schools emphasize the value of learning from the natural environment, one of my granddaughters attended an outdoors-rain-or-shine preschool in urban San Francisco.

At the other end of the spectrum are the schools that feel obligated to shield their students from the realities of meteorological variability. While excessive sun exposure and tissue-freezing wind chills are to be avoided, a crisp calm sunny day with temperatures in the middle teens can be fun, particularly if there is some dry snow to tromp around in. However, during the months from November 2014 to March 2015, the children who attended Public School 126 in New York City were not given the opportunity to play outside on more than 40 school days. The situation is complicated because their school, which lacks its own playground, must rely on nearby parks (“A Casualty of a Frigid New York Winter: Outdoor School Recess,” by Ginia Bellafante, the New York Times, March 6, 2015). But we aren’t talking Siberia. It was a colder-than-usual winter, but I suspect there must have been more than a few missed opportunities to go outside and enjoy the snow. I wonder how often the decision to stay inside was influenced by teachers and administrators who hadn’t come prepared to spend any more time outside than it took them to walk from the parking lot or bus stop.

The data are accumulating that adding physical activity to the school day improves student behavior and even promotes learning. The evidence that being outside is beneficial is a bit more difficult to find. Early in the last century, when indoor air was saturated with smoke from cooking and open combustion heating sources, many physicians recommended that even for infants, raising a healthy child meant having the child spend a large part of the day outdoors.

It’s time for pediatricians to spread the word to parents that their little darlings won’t catch pneumonia from playing outdoors on a cool damp day. Nor will they shrink if they get a little wet on a rainy day ... but they will run ... and the running will be good for them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

There was an outdoor equipment designer for a well-known Maine-based outfitter who was fond of saying that there was no such thing as bad weather, just bad or inappropriate clothing. The origin of this pearl is claimed by the Norwegians, the Germans, and the English – all nations that have some experience with inclement weather.

The folks who continue to go about their business regardless of the weather usually place a high value on the benefits of being outdoors. They often claim that they simply feel healthier when they are breathing fresh air. It is likely they have grown up in a place, in a family, and in a culture in which waiting for good weather to get something done means it’s not going to get done.

For example, my daughter-in-law’s visual impairment prevents her from driving a car. As a result, she and my two grandchildren get to almost all of their in-town destinations here in Brunswick, Maine, by bicycle or on foot ... 12 months a year ... rain or shine. They can afford appropriate clothing, but they still get wet and cold from time to time. I have never heard them complain. They accept bad weather as a given just as much as they accept a sunny day as something to enjoy.

While my grandchildren’s attitude toward the weather may not be typical of most 9- and 11-year-olds, they may not be alone in a few decades. Preschools are popping up around the country that not only accept the vagaries in the weather, but embrace the outdoors as an educational tool (“Preschool Without Walls,” by Lillian Mongeau, the New York Times, Dec. 29, 2015). The Natural Start Alliance, founded in 2013, has a membership of 92 preschools whose students spend a significant portion of their school day playing and exploring outdoors rain or shine. While most of these schools emphasize the value of learning from the natural environment, one of my granddaughters attended an outdoors-rain-or-shine preschool in urban San Francisco.

At the other end of the spectrum are the schools that feel obligated to shield their students from the realities of meteorological variability. While excessive sun exposure and tissue-freezing wind chills are to be avoided, a crisp calm sunny day with temperatures in the middle teens can be fun, particularly if there is some dry snow to tromp around in. However, during the months from November 2014 to March 2015, the children who attended Public School 126 in New York City were not given the opportunity to play outside on more than 40 school days. The situation is complicated because their school, which lacks its own playground, must rely on nearby parks (“A Casualty of a Frigid New York Winter: Outdoor School Recess,” by Ginia Bellafante, the New York Times, March 6, 2015). But we aren’t talking Siberia. It was a colder-than-usual winter, but I suspect there must have been more than a few missed opportunities to go outside and enjoy the snow. I wonder how often the decision to stay inside was influenced by teachers and administrators who hadn’t come prepared to spend any more time outside than it took them to walk from the parking lot or bus stop.

The data are accumulating that adding physical activity to the school day improves student behavior and even promotes learning. The evidence that being outside is beneficial is a bit more difficult to find. Early in the last century, when indoor air was saturated with smoke from cooking and open combustion heating sources, many physicians recommended that even for infants, raising a healthy child meant having the child spend a large part of the day outdoors.

It’s time for pediatricians to spread the word to parents that their little darlings won’t catch pneumonia from playing outdoors on a cool damp day. Nor will they shrink if they get a little wet on a rainy day ... but they will run ... and the running will be good for them.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

CHICAGO – Adjuvant temozolomide given after radiation therapy improves survival of patients with a form of anaplastic glioma, a rare brain tumor. The patients had anaplastic glioma without 1p/19q co-deletion.

This co-deletion – the short arm of chromosome 1 and the long arm of chromosome 19 – is a favorable marker in the tumor, and patients without the deletion have traditionally done worse than those with the deletion. Until this study, no one knew if temozolomide would improve outcomes of patients without the co-deletion.

The four-arm, Phase III Trial on Concurrent and Adjuvant Temozolomide [TMZ] Chemotherapy in NON-1p/19q Deleted Anaplastic Glioma: The CATNON Intergroup Trial (EORTC 26053-22054), still ongoing, is testing radiotherapy, radiotherapy plus concurrent TMZ, radiotherapy plus 12 months of adjuvant TMZ, or radiotherapy plus concurrent TMZ plus 12 months of adjuvant TMZ. Adjuvant TMZ was given in 12 cycles.

Given the rarity of the tumor, the trial involved 118 institutions on three continents and ran for eight years between 2007 and 2015. From 1407 patients 18 years or older with World Health Organization performance status 0-2 screened, 751 were confirmed to have grade III anaplastic gliomas that were intact for 1p/19q (ie, no deletions). After radiation therapy with 59.4 Gy in 33 fractions, these patients were randomly assigned to one of the four treatment arms.

The trial asked two questions: Does adjuvant chemotherapy after radiotherapy improve outcome, and does chemotherapy concurrent with radiotherapy improve outcomes?

Just after enrollment was completed, a data monitoring committee recommended, based on an interim analysis in October 2015, that the data for the adjuvant arm be released, reported Dr. Martin van den Bent, professor of neuro-oncology at Erasmus MC Cancer Center in Rotterdam, The Netherlands. “It completely came as a surprise,” he said at a press conference at the annual meeting of the American Society of Clinical Oncology.

Comparing radiation with or without concurrent TMZ followed by adjuvant TMZ to treatment without adjuvant therapy, the overall survival at five years increased from 44% without any TMZ or with TMZ concurrent with radiation (n = 372) to 56% with adjuvant temozolomide (n = 373). “This corresponds to a hazard ratio of 0.67, a highly statistically significant increment,” Dr. van den Bent said.

Adjuvant TMZ was also associated with a statistically significant increase in median progression free survival from 19 months without adjuvant therapy to almost 43 months with it.

When patients were stratified by O6-methyl-guanine DNA methyltransferase (MGMT) promoter methylation status, the researchers found that MGMT methylation was prognostic for overall survival but not predictive of improved outcome to adjuvant TMZ.

For the nonadjuvant group, the median overall survival was 41 months (95% CI, 37-61 months), but the groups receiving adjuvant TMZ had not yet reached a median overall survival. “We know now that temozolomide given after radiation therapy improves survival in this disease,” Dr. van den Bent said.

A trial of such a rare disease requires many collaborating centers and oncology groups and a long duration to show improvements in outcome. Collaborating oncology groups across many countries “have shown the capacity to answer important clinical questions in orphan diseases,” he said.

Press conference moderator Dr. Don Dizon of Massachusetts General Hospital, Boston, said, “I think this illustrates… the theme of this year’s meeting, which is Collective Wisdom, and even more than that it illustrates that even with a rare tumor type and using standard chemotherapy it’s very important, and we can select patients who are most likely to benefit from treatment and at the same time potentially spare patients from the toxicities of therapy that they’re unlikely to benefit from.”

Results from the arm of the trial testing temozolomide given only at the time of radiation therapy are not yet available and are expected in 2020. In addition, investigators plan to assess genetic abnormalities that are known to affect prognosis in the disease, specifically MGMT promoter methylation and IDH (isocitrate dehydrogenase) mutation.

Common toxicities with temozolomide were mainly low platelet and white cell counts with severe toxicity in 5-10% of patients.

CHICAGO – Adjuvant temozolomide given after radiation therapy improves survival of patients with a form of anaplastic glioma, a rare brain tumor. The patients had anaplastic glioma without 1p/19q co-deletion.

This co-deletion – the short arm of chromosome 1 and the long arm of chromosome 19 – is a favorable marker in the tumor, and patients without the deletion have traditionally done worse than those with the deletion. Until this study, no one knew if temozolomide would improve outcomes of patients without the co-deletion.

The four-arm, Phase III Trial on Concurrent and Adjuvant Temozolomide [TMZ] Chemotherapy in NON-1p/19q Deleted Anaplastic Glioma: The CATNON Intergroup Trial (EORTC 26053-22054), still ongoing, is testing radiotherapy, radiotherapy plus concurrent TMZ, radiotherapy plus 12 months of adjuvant TMZ, or radiotherapy plus concurrent TMZ plus 12 months of adjuvant TMZ. Adjuvant TMZ was given in 12 cycles.

Given the rarity of the tumor, the trial involved 118 institutions on three continents and ran for eight years between 2007 and 2015. From 1407 patients 18 years or older with World Health Organization performance status 0-2 screened, 751 were confirmed to have grade III anaplastic gliomas that were intact for 1p/19q (ie, no deletions). After radiation therapy with 59.4 Gy in 33 fractions, these patients were randomly assigned to one of the four treatment arms.

The trial asked two questions: Does adjuvant chemotherapy after radiotherapy improve outcome, and does chemotherapy concurrent with radiotherapy improve outcomes?

Just after enrollment was completed, a data monitoring committee recommended, based on an interim analysis in October 2015, that the data for the adjuvant arm be released, reported Dr. Martin van den Bent, professor of neuro-oncology at Erasmus MC Cancer Center in Rotterdam, The Netherlands. “It completely came as a surprise,” he said at a press conference at the annual meeting of the American Society of Clinical Oncology.

Comparing radiation with or without concurrent TMZ followed by adjuvant TMZ to treatment without adjuvant therapy, the overall survival at five years increased from 44% without any TMZ or with TMZ concurrent with radiation (n = 372) to 56% with adjuvant temozolomide (n = 373). “This corresponds to a hazard ratio of 0.67, a highly statistically significant increment,” Dr. van den Bent said.

Adjuvant TMZ was also associated with a statistically significant increase in median progression free survival from 19 months without adjuvant therapy to almost 43 months with it.

When patients were stratified by O6-methyl-guanine DNA methyltransferase (MGMT) promoter methylation status, the researchers found that MGMT methylation was prognostic for overall survival but not predictive of improved outcome to adjuvant TMZ.

For the nonadjuvant group, the median overall survival was 41 months (95% CI, 37-61 months), but the groups receiving adjuvant TMZ had not yet reached a median overall survival. “We know now that temozolomide given after radiation therapy improves survival in this disease,” Dr. van den Bent said.

A trial of such a rare disease requires many collaborating centers and oncology groups and a long duration to show improvements in outcome. Collaborating oncology groups across many countries “have shown the capacity to answer important clinical questions in orphan diseases,” he said.

Press conference moderator Dr. Don Dizon of Massachusetts General Hospital, Boston, said, “I think this illustrates… the theme of this year’s meeting, which is Collective Wisdom, and even more than that it illustrates that even with a rare tumor type and using standard chemotherapy it’s very important, and we can select patients who are most likely to benefit from treatment and at the same time potentially spare patients from the toxicities of therapy that they’re unlikely to benefit from.”

Results from the arm of the trial testing temozolomide given only at the time of radiation therapy are not yet available and are expected in 2020. In addition, investigators plan to assess genetic abnormalities that are known to affect prognosis in the disease, specifically MGMT promoter methylation and IDH (isocitrate dehydrogenase) mutation.

Common toxicities with temozolomide were mainly low platelet and white cell counts with severe toxicity in 5-10% of patients.

CHICAGO – Adjuvant temozolomide given after radiation therapy improves survival of patients with a form of anaplastic glioma, a rare brain tumor. The patients had anaplastic glioma without 1p/19q co-deletion.

This co-deletion – the short arm of chromosome 1 and the long arm of chromosome 19 – is a favorable marker in the tumor, and patients without the deletion have traditionally done worse than those with the deletion. Until this study, no one knew if temozolomide would improve outcomes of patients without the co-deletion.

The four-arm, Phase III Trial on Concurrent and Adjuvant Temozolomide [TMZ] Chemotherapy in NON-1p/19q Deleted Anaplastic Glioma: The CATNON Intergroup Trial (EORTC 26053-22054), still ongoing, is testing radiotherapy, radiotherapy plus concurrent TMZ, radiotherapy plus 12 months of adjuvant TMZ, or radiotherapy plus concurrent TMZ plus 12 months of adjuvant TMZ. Adjuvant TMZ was given in 12 cycles.

Given the rarity of the tumor, the trial involved 118 institutions on three continents and ran for eight years between 2007 and 2015. From 1407 patients 18 years or older with World Health Organization performance status 0-2 screened, 751 were confirmed to have grade III anaplastic gliomas that were intact for 1p/19q (ie, no deletions). After radiation therapy with 59.4 Gy in 33 fractions, these patients were randomly assigned to one of the four treatment arms.

The trial asked two questions: Does adjuvant chemotherapy after radiotherapy improve outcome, and does chemotherapy concurrent with radiotherapy improve outcomes?

Just after enrollment was completed, a data monitoring committee recommended, based on an interim analysis in October 2015, that the data for the adjuvant arm be released, reported Dr. Martin van den Bent, professor of neuro-oncology at Erasmus MC Cancer Center in Rotterdam, The Netherlands. “It completely came as a surprise,” he said at a press conference at the annual meeting of the American Society of Clinical Oncology.

Comparing radiation with or without concurrent TMZ followed by adjuvant TMZ to treatment without adjuvant therapy, the overall survival at five years increased from 44% without any TMZ or with TMZ concurrent with radiation (n = 372) to 56% with adjuvant temozolomide (n = 373). “This corresponds to a hazard ratio of 0.67, a highly statistically significant increment,” Dr. van den Bent said.

Adjuvant TMZ was also associated with a statistically significant increase in median progression free survival from 19 months without adjuvant therapy to almost 43 months with it.

When patients were stratified by O6-methyl-guanine DNA methyltransferase (MGMT) promoter methylation status, the researchers found that MGMT methylation was prognostic for overall survival but not predictive of improved outcome to adjuvant TMZ.

For the nonadjuvant group, the median overall survival was 41 months (95% CI, 37-61 months), but the groups receiving adjuvant TMZ had not yet reached a median overall survival. “We know now that temozolomide given after radiation therapy improves survival in this disease,” Dr. van den Bent said.

A trial of such a rare disease requires many collaborating centers and oncology groups and a long duration to show improvements in outcome. Collaborating oncology groups across many countries “have shown the capacity to answer important clinical questions in orphan diseases,” he said.

Press conference moderator Dr. Don Dizon of Massachusetts General Hospital, Boston, said, “I think this illustrates… the theme of this year’s meeting, which is Collective Wisdom, and even more than that it illustrates that even with a rare tumor type and using standard chemotherapy it’s very important, and we can select patients who are most likely to benefit from treatment and at the same time potentially spare patients from the toxicities of therapy that they’re unlikely to benefit from.”

Results from the arm of the trial testing temozolomide given only at the time of radiation therapy are not yet available and are expected in 2020. In addition, investigators plan to assess genetic abnormalities that are known to affect prognosis in the disease, specifically MGMT promoter methylation and IDH (isocitrate dehydrogenase) mutation.

Common toxicities with temozolomide were mainly low platelet and white cell counts with severe toxicity in 5-10% of patients.

CHICAGO – Up-front high-dose melphalan and autologous stem cell transplantation (ASCT) was superior to bortezomib-melphalan-prednisone (VMP) for fit patients younger than age 65 years with newly diagnosed multiple myeloma, based on the interim results from a randomized study of the European Myeloma Network.

With more than 1,200 patients, the study is the largest trial yet to show superior progression-free survival for ASCT. Follow-up has been too short to show significance for overall survival.

“Up-front ASCT was associated with a significant improvement in progression-free survival as compared to bortezomib-melphalan-prednisone in the overall patient population, (and the advantage) was retained across prespecified subgroups of patients at low and high risk … (as well as) in a multivariate analysis” of the overall population, Dr. Michele Cavo of the University of Bologna, Italy, reported at the annual meeting of the American Society of Clinical Oncology. “Up-front high-dose melphalan and ASCT continue to be the reference treatment choice for fit patients with newly diagnosed multiple myeloma, even in the novel agent era.”

ASCT was associated with higher rates of grade 3 or more adverse events in nearly every category, however, with the exception of peripheral nephropathy.

For the study, 1,266 patients, stratified by International Staging System stage and FISH (fluorescence in situ hybridization) analysis, were randomized to either VMP (512 pts) or to high-dose melphalan and ASCT (754 pts). At the meeting, Dr. Cavo reported on the study’s interim outcome results in 695 patients who had ASCT and 497 newly diagnosed patients who received VMP.

At 3 years, progression-free survival rates were 66.1% in the ASCT patients and 57.5% in the VMP patients. The median progression-free survival had not yet been reached in the ASCT patients and was 44 months in the bortezomib-melphalan-prednisone patients. (hazard ratio, 95% confidence interval, 0.73 [0.59-0.90]; P = .003).

Stringent complete responses were seen in 18.2% of patients in the VMP group and 17% of the ASCT group; Complete responses occurred in 25.3% of both groups. The main difference observed was in the number of very good partial responses, seen in 30.4% of the VMP group and in 43.2% of the ASCT group. Also, 11.2% of those in the VMP group had less than a partial response while that was the case for only 3.3% of the ASCT group.

Alternatively, the rate of grade 3 or more adverse events was higher in the ASCT group, with 17.5% experiencing febrile neutropenia, 15.6% mucositis, 3.2% sepsis, and 2.6% respiratory infections. The rates of these side effects in the VMP group were 0.2%, 0%, 0%, and 1.7%, respectively. The only grade 3 or more adverse event seen with greater frequency in the VMP group was peripheral neuropathy, seen in 13.8% as compared with 1.6% in the ASCT group.

Dr. Cavo receives honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. He serves as a consultant or advisor to and is on the speakers bureau for Amgen. Celgene, Janssen.

Abstract 8000

[email protected]

On Twitter @maryjodales

This story was updated on June 10, 2016.

CHICAGO – Up-front high-dose melphalan and autologous stem cell transplantation (ASCT) was superior to bortezomib-melphalan-prednisone (VMP) for fit patients younger than age 65 years with newly diagnosed multiple myeloma, based on the interim results from a randomized study of the European Myeloma Network.

With more than 1,200 patients, the study is the largest trial yet to show superior progression-free survival for ASCT. Follow-up has been too short to show significance for overall survival.

“Up-front ASCT was associated with a significant improvement in progression-free survival as compared to bortezomib-melphalan-prednisone in the overall patient population, (and the advantage) was retained across prespecified subgroups of patients at low and high risk … (as well as) in a multivariate analysis” of the overall population, Dr. Michele Cavo of the University of Bologna, Italy, reported at the annual meeting of the American Society of Clinical Oncology. “Up-front high-dose melphalan and ASCT continue to be the reference treatment choice for fit patients with newly diagnosed multiple myeloma, even in the novel agent era.”

ASCT was associated with higher rates of grade 3 or more adverse events in nearly every category, however, with the exception of peripheral nephropathy.

For the study, 1,266 patients, stratified by International Staging System stage and FISH (fluorescence in situ hybridization) analysis, were randomized to either VMP (512 pts) or to high-dose melphalan and ASCT (754 pts). At the meeting, Dr. Cavo reported on the study’s interim outcome results in 695 patients who had ASCT and 497 newly diagnosed patients who received VMP.

At 3 years, progression-free survival rates were 66.1% in the ASCT patients and 57.5% in the VMP patients. The median progression-free survival had not yet been reached in the ASCT patients and was 44 months in the bortezomib-melphalan-prednisone patients. (hazard ratio, 95% confidence interval, 0.73 [0.59-0.90]; P = .003).

Stringent complete responses were seen in 18.2% of patients in the VMP group and 17% of the ASCT group; Complete responses occurred in 25.3% of both groups. The main difference observed was in the number of very good partial responses, seen in 30.4% of the VMP group and in 43.2% of the ASCT group. Also, 11.2% of those in the VMP group had less than a partial response while that was the case for only 3.3% of the ASCT group.

Alternatively, the rate of grade 3 or more adverse events was higher in the ASCT group, with 17.5% experiencing febrile neutropenia, 15.6% mucositis, 3.2% sepsis, and 2.6% respiratory infections. The rates of these side effects in the VMP group were 0.2%, 0%, 0%, and 1.7%, respectively. The only grade 3 or more adverse event seen with greater frequency in the VMP group was peripheral neuropathy, seen in 13.8% as compared with 1.6% in the ASCT group.

Dr. Cavo receives honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. He serves as a consultant or advisor to and is on the speakers bureau for Amgen. Celgene, Janssen.

Abstract 8000

[email protected]

On Twitter @maryjodales

This story was updated on June 10, 2016.

CHICAGO – Up-front high-dose melphalan and autologous stem cell transplantation (ASCT) was superior to bortezomib-melphalan-prednisone (VMP) for fit patients younger than age 65 years with newly diagnosed multiple myeloma, based on the interim results from a randomized study of the European Myeloma Network.

With more than 1,200 patients, the study is the largest trial yet to show superior progression-free survival for ASCT. Follow-up has been too short to show significance for overall survival.

“Up-front ASCT was associated with a significant improvement in progression-free survival as compared to bortezomib-melphalan-prednisone in the overall patient population, (and the advantage) was retained across prespecified subgroups of patients at low and high risk … (as well as) in a multivariate analysis” of the overall population, Dr. Michele Cavo of the University of Bologna, Italy, reported at the annual meeting of the American Society of Clinical Oncology. “Up-front high-dose melphalan and ASCT continue to be the reference treatment choice for fit patients with newly diagnosed multiple myeloma, even in the novel agent era.”

ASCT was associated with higher rates of grade 3 or more adverse events in nearly every category, however, with the exception of peripheral nephropathy.

For the study, 1,266 patients, stratified by International Staging System stage and FISH (fluorescence in situ hybridization) analysis, were randomized to either VMP (512 pts) or to high-dose melphalan and ASCT (754 pts). At the meeting, Dr. Cavo reported on the study’s interim outcome results in 695 patients who had ASCT and 497 newly diagnosed patients who received VMP.

At 3 years, progression-free survival rates were 66.1% in the ASCT patients and 57.5% in the VMP patients. The median progression-free survival had not yet been reached in the ASCT patients and was 44 months in the bortezomib-melphalan-prednisone patients. (hazard ratio, 95% confidence interval, 0.73 [0.59-0.90]; P = .003).

Stringent complete responses were seen in 18.2% of patients in the VMP group and 17% of the ASCT group; Complete responses occurred in 25.3% of both groups. The main difference observed was in the number of very good partial responses, seen in 30.4% of the VMP group and in 43.2% of the ASCT group. Also, 11.2% of those in the VMP group had less than a partial response while that was the case for only 3.3% of the ASCT group.

Alternatively, the rate of grade 3 or more adverse events was higher in the ASCT group, with 17.5% experiencing febrile neutropenia, 15.6% mucositis, 3.2% sepsis, and 2.6% respiratory infections. The rates of these side effects in the VMP group were 0.2%, 0%, 0%, and 1.7%, respectively. The only grade 3 or more adverse event seen with greater frequency in the VMP group was peripheral neuropathy, seen in 13.8% as compared with 1.6% in the ASCT group.

Dr. Cavo receives honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda. He serves as a consultant or advisor to and is on the speakers bureau for Amgen. Celgene, Janssen.

Abstract 8000

[email protected]

On Twitter @maryjodales

This story was updated on June 10, 2016.

SHM’s implementation toolkits provide hospitalists with the resources they need to lead quality improvement projects on a variety of clinical topics, including a new toolkit on venous thromboembolism (VTE) released in May. The new toolkit features a literature review, an implementation guide, and additional reference materials, such as discharge instructions and checklists. Be on the lookout for information about an upcoming webinar series on the treatment of patients with VTE with free CME.

Don’t miss other online toolkits and implementation guides from SHM, covering:

• COPD
• Acute coronary syndrome
• Pain management
• Glycemic control

Check out all available toolkits at www.hospitalmedicine.org/qi.

Brett Radler is SHM’s communications coordinator.

SHM’s implementation toolkits provide hospitalists with the resources they need to lead quality improvement projects on a variety of clinical topics, including a new toolkit on venous thromboembolism (VTE) released in May. The new toolkit features a literature review, an implementation guide, and additional reference materials, such as discharge instructions and checklists. Be on the lookout for information about an upcoming webinar series on the treatment of patients with VTE with free CME.

Don’t miss other online toolkits and implementation guides from SHM, covering:

• COPD
• Acute coronary syndrome
• Pain management
• Glycemic control

Check out all available toolkits at www.hospitalmedicine.org/qi.

Brett Radler is SHM’s communications coordinator.

SHM’s implementation toolkits provide hospitalists with the resources they need to lead quality improvement projects on a variety of clinical topics, including a new toolkit on venous thromboembolism (VTE) released in May. The new toolkit features a literature review, an implementation guide, and additional reference materials, such as discharge instructions and checklists. Be on the lookout for information about an upcoming webinar series on the treatment of patients with VTE with free CME.

Don’t miss other online toolkits and implementation guides from SHM, covering:

• COPD
• Acute coronary syndrome
• Pain management
• Glycemic control

Check out all available toolkits at www.hospitalmedicine.org/qi.

Brett Radler is SHM’s communications coordinator.

During the chat, we invite you to join the conversation with Robert Mahoney, MD, associate professor of medicine at the Washington University School of Medicine, and Vinny Arora, MD, #JHMChat moderator and JHM deputy editor, to discuss the recent JHM publication “As-Needed Intravenous Antihypertensive Therapy and Blood Pressure Control.”

Participating in a #JHMChat allows you to have a dialogue with experts in the field conducting research with implications for your daily practice, network with fellow hospital medicine professionals, and lend your expertise to help others improve patient care. As you get ready for the chat, follow us and our Twitter partners:

• @JHospMedicine (Journal of Hospital Medicine)
• @SHMLive (Society of Hospital Medicine)
• @mahoneyr (Dr. Mahoney)
• @FutureDocs (Dr. Arora)
• @CostsofCare and @ABIMFoundation (#JHMChat partners)

On chat day, don’t forget to include #JHMChat in each of your tweets related to the chat to make sure all participants see them and are able to respond. To learn more, read the featured paper, and check out transcripts from our first three chats, visit www.hospitalmedicine.org/jhmchat.

See you on Twitter!

Brett Radler is SHM’s communications coordinator.

During the chat, we invite you to join the conversation with Robert Mahoney, MD, associate professor of medicine at the Washington University School of Medicine, and Vinny Arora, MD, #JHMChat moderator and JHM deputy editor, to discuss the recent JHM publication “As-Needed Intravenous Antihypertensive Therapy and Blood Pressure Control.”

Participating in a #JHMChat allows you to have a dialogue with experts in the field conducting research with implications for your daily practice, network with fellow hospital medicine professionals, and lend your expertise to help others improve patient care. As you get ready for the chat, follow us and our Twitter partners:

• @JHospMedicine (Journal of Hospital Medicine)
• @SHMLive (Society of Hospital Medicine)
• @mahoneyr (Dr. Mahoney)
• @FutureDocs (Dr. Arora)
• @CostsofCare and @ABIMFoundation (#JHMChat partners)

On chat day, don’t forget to include #JHMChat in each of your tweets related to the chat to make sure all participants see them and are able to respond. To learn more, read the featured paper, and check out transcripts from our first three chats, visit www.hospitalmedicine.org/jhmchat.

See you on Twitter!

Brett Radler is SHM’s communications coordinator.

During the chat, we invite you to join the conversation with Robert Mahoney, MD, associate professor of medicine at the Washington University School of Medicine, and Vinny Arora, MD, #JHMChat moderator and JHM deputy editor, to discuss the recent JHM publication “As-Needed Intravenous Antihypertensive Therapy and Blood Pressure Control.”

Participating in a #JHMChat allows you to have a dialogue with experts in the field conducting research with implications for your daily practice, network with fellow hospital medicine professionals, and lend your expertise to help others improve patient care. As you get ready for the chat, follow us and our Twitter partners:

• @JHospMedicine (Journal of Hospital Medicine)
• @SHMLive (Society of Hospital Medicine)
• @mahoneyr (Dr. Mahoney)
• @FutureDocs (Dr. Arora)
• @CostsofCare and @ABIMFoundation (#JHMChat partners)

On chat day, don’t forget to include #JHMChat in each of your tweets related to the chat to make sure all participants see them and are able to respond. To learn more, read the featured paper, and check out transcripts from our first three chats, visit www.hospitalmedicine.org/jhmchat.

See you on Twitter!

Brett Radler is SHM’s communications coordinator.

Aspirin tablets

Photo credit: Jill Watson

Researchers say they may have found a new use for an ancient anti-inflammatory drug, salicylate, which was first described by the Greek physician Hippocrates.

“Salicylic acid is one of the oldest drugs on the planet,” said senior author Eric Verdin, MD, of the Gladstone Institutes/UCSF, “dating back to the Egyptians and the Greeks, but we're still discovering new things about it.”

Its derivatives, acetylsalicylic acid, or aspirin, and diflunisal suppress 2 key proteins, CREB-binding protein (CBP) and p300, which control levels of proteins that cause inflammation or are involved in cell growth.

By inhibiting p300 and CBP, salicylic acid and diflunisal block the activation of these proteins and prevent cellular damage caused by inflammation. The research team believes that both p300 and CBP can be targeted by drugs, which would have important clinical implications.

Earlier research conducted by coauthor Stephen D. Nimer, MD, of the University of Miami Miller School of Medicine in Florida, and colleagues found a link between p300 and the leukemia-promoting protein AML1-ETO.

In the current study, published in eLife, researchers tested whether suppressing p300 with diflunisal would suppress leukemia growth in mice.

The research team inoculated SCID mice with Kasumi-1 cells, an AML cell line with the t(8;21) translocation, which represents one of the subtypes of CBF leukemia.

Three weeks later, they started treating the mice with diflunisal. Diflunisal reduced tumor size in a dose-dependent manner, and after 3 weeks of treatment, the tumors were significantly smaller than in the vehicle-treated control mice.

In fact, the researchers noted most tumors disappeared in mice treated with higher doses of diflunisal. The researchers also pointed out that diflunisal, an FDA-approved drug containing a salicylic acid substructure, inhibited CBP/p300 more potently than salicylate.

The researchers concluded that diflunisal and salicylate have promise as an oral therapy for AML patients with a t(8;21) translocation, and called it “an exciting potential application” for this new characterization of older drugs.

“Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs,” Dr Verdin added.

The scientists are now pursuing a clinical trial to test whether salicylic acid can treat patients with leukemia as part of novel combination therapies.

Aspirin tablets

Photo credit: Jill Watson

Researchers say they may have found a new use for an ancient anti-inflammatory drug, salicylate, which was first described by the Greek physician Hippocrates.

“Salicylic acid is one of the oldest drugs on the planet,” said senior author Eric Verdin, MD, of the Gladstone Institutes/UCSF, “dating back to the Egyptians and the Greeks, but we're still discovering new things about it.”

Its derivatives, acetylsalicylic acid, or aspirin, and diflunisal suppress 2 key proteins, CREB-binding protein (CBP) and p300, which control levels of proteins that cause inflammation or are involved in cell growth.

By inhibiting p300 and CBP, salicylic acid and diflunisal block the activation of these proteins and prevent cellular damage caused by inflammation. The research team believes that both p300 and CBP can be targeted by drugs, which would have important clinical implications.

Earlier research conducted by coauthor Stephen D. Nimer, MD, of the University of Miami Miller School of Medicine in Florida, and colleagues found a link between p300 and the leukemia-promoting protein AML1-ETO.

In the current study, published in eLife, researchers tested whether suppressing p300 with diflunisal would suppress leukemia growth in mice.

The research team inoculated SCID mice with Kasumi-1 cells, an AML cell line with the t(8;21) translocation, which represents one of the subtypes of CBF leukemia.

Three weeks later, they started treating the mice with diflunisal. Diflunisal reduced tumor size in a dose-dependent manner, and after 3 weeks of treatment, the tumors were significantly smaller than in the vehicle-treated control mice.

In fact, the researchers noted most tumors disappeared in mice treated with higher doses of diflunisal. The researchers also pointed out that diflunisal, an FDA-approved drug containing a salicylic acid substructure, inhibited CBP/p300 more potently than salicylate.

The researchers concluded that diflunisal and salicylate have promise as an oral therapy for AML patients with a t(8;21) translocation, and called it “an exciting potential application” for this new characterization of older drugs.

“Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs,” Dr Verdin added.

The scientists are now pursuing a clinical trial to test whether salicylic acid can treat patients with leukemia as part of novel combination therapies.

Aspirin tablets

Photo credit: Jill Watson

Researchers say they may have found a new use for an ancient anti-inflammatory drug, salicylate, which was first described by the Greek physician Hippocrates.

“Salicylic acid is one of the oldest drugs on the planet,” said senior author Eric Verdin, MD, of the Gladstone Institutes/UCSF, “dating back to the Egyptians and the Greeks, but we're still discovering new things about it.”

Its derivatives, acetylsalicylic acid, or aspirin, and diflunisal suppress 2 key proteins, CREB-binding protein (CBP) and p300, which control levels of proteins that cause inflammation or are involved in cell growth.

By inhibiting p300 and CBP, salicylic acid and diflunisal block the activation of these proteins and prevent cellular damage caused by inflammation. The research team believes that both p300 and CBP can be targeted by drugs, which would have important clinical implications.

Earlier research conducted by coauthor Stephen D. Nimer, MD, of the University of Miami Miller School of Medicine in Florida, and colleagues found a link between p300 and the leukemia-promoting protein AML1-ETO.

In the current study, published in eLife, researchers tested whether suppressing p300 with diflunisal would suppress leukemia growth in mice.

The research team inoculated SCID mice with Kasumi-1 cells, an AML cell line with the t(8;21) translocation, which represents one of the subtypes of CBF leukemia.

Three weeks later, they started treating the mice with diflunisal. Diflunisal reduced tumor size in a dose-dependent manner, and after 3 weeks of treatment, the tumors were significantly smaller than in the vehicle-treated control mice.

In fact, the researchers noted most tumors disappeared in mice treated with higher doses of diflunisal. The researchers also pointed out that diflunisal, an FDA-approved drug containing a salicylic acid substructure, inhibited CBP/p300 more potently than salicylate.

The researchers concluded that diflunisal and salicylate have promise as an oral therapy for AML patients with a t(8;21) translocation, and called it “an exciting potential application” for this new characterization of older drugs.

“Uncovering this pathway of inflammation that salicylic acid acts upon opens up a host of new clinical possibilities for these drugs,” Dr Verdin added.

The scientists are now pursuing a clinical trial to test whether salicylic acid can treat patients with leukemia as part of novel combination therapies.

Clinical question: Does coronary artery bypass grafting added to medical therapy decrease mortality in patients with coronary artery disease and systolic heart failure?

Bottom line: Coronary artery bypass grafting (CABG) plus medical therapy decreases mortality as compared with medical therapy alone in patients with ischemic cardiomyopathy. You would need to treat 14 patients with CABG to prevent one death. (LOE = 1b)

Reference: Velazquez EJ, Lee KL, Jones RH, et al, for the STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374(16):1511-1520.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using concealed allocation, these investigators randomized patients with heart failure with ejection fraction of 35% or less and coronary artery disease amenable to CABG to receive either guideline-directed medical therapy plus CABG (n = 610) or guideline-directed medical therapy alone (n = 602). The 2 groups were similar at baseline and the majority was categorized as New York Heart Failure Association class II. Overall, 91% of the CABG group underwent the procedure within the first year following randomization. Notably, 20% of the medical therapy group also underwent CABG during the long-term follow-up period (11% crossed over to CABG within the first year). The medial duration for follow-up was 9.8 years and analysis was by intention to treat. CABG plus medical therapy resulted in fewer deaths over 10 years as compared with medical therapy alone (59% vs 66%; hazard ratio [HR] = 0.84; 95% CI 0.73 - 0.97; P = .02). The CABG group also had fewer deaths specifically from cardiovascular causes (40% vs 49%; P = .006). A per-protocol analysis showed an even greater benefit with CABG (HR = 0.77; 0.67 - 0.90; P = .001) suggesting that the crossovers in this trial may have diluted the observed effect of CABG.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does coronary artery bypass grafting added to medical therapy decrease mortality in patients with coronary artery disease and systolic heart failure?

Bottom line: Coronary artery bypass grafting (CABG) plus medical therapy decreases mortality as compared with medical therapy alone in patients with ischemic cardiomyopathy. You would need to treat 14 patients with CABG to prevent one death. (LOE = 1b)

Reference: Velazquez EJ, Lee KL, Jones RH, et al, for the STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374(16):1511-1520.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using concealed allocation, these investigators randomized patients with heart failure with ejection fraction of 35% or less and coronary artery disease amenable to CABG to receive either guideline-directed medical therapy plus CABG (n = 610) or guideline-directed medical therapy alone (n = 602). The 2 groups were similar at baseline and the majority was categorized as New York Heart Failure Association class II. Overall, 91% of the CABG group underwent the procedure within the first year following randomization. Notably, 20% of the medical therapy group also underwent CABG during the long-term follow-up period (11% crossed over to CABG within the first year). The medial duration for follow-up was 9.8 years and analysis was by intention to treat. CABG plus medical therapy resulted in fewer deaths over 10 years as compared with medical therapy alone (59% vs 66%; hazard ratio [HR] = 0.84; 95% CI 0.73 - 0.97; P = .02). The CABG group also had fewer deaths specifically from cardiovascular causes (40% vs 49%; P = .006). A per-protocol analysis showed an even greater benefit with CABG (HR = 0.77; 0.67 - 0.90; P = .001) suggesting that the crossovers in this trial may have diluted the observed effect of CABG.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does coronary artery bypass grafting added to medical therapy decrease mortality in patients with coronary artery disease and systolic heart failure?

Bottom line: Coronary artery bypass grafting (CABG) plus medical therapy decreases mortality as compared with medical therapy alone in patients with ischemic cardiomyopathy. You would need to treat 14 patients with CABG to prevent one death. (LOE = 1b)

Reference: Velazquez EJ, Lee KL, Jones RH, et al, for the STICHES Investigators. Coronary-artery bypass surgery in patients with ischemic cardiomyopathy. N Engl J Med 2016;374(16):1511-1520.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using concealed allocation, these investigators randomized patients with heart failure with ejection fraction of 35% or less and coronary artery disease amenable to CABG to receive either guideline-directed medical therapy plus CABG (n = 610) or guideline-directed medical therapy alone (n = 602). The 2 groups were similar at baseline and the majority was categorized as New York Heart Failure Association class II. Overall, 91% of the CABG group underwent the procedure within the first year following randomization. Notably, 20% of the medical therapy group also underwent CABG during the long-term follow-up period (11% crossed over to CABG within the first year). The medial duration for follow-up was 9.8 years and analysis was by intention to treat. CABG plus medical therapy resulted in fewer deaths over 10 years as compared with medical therapy alone (59% vs 66%; hazard ratio [HR] = 0.84; 95% CI 0.73 - 0.97; P = .02). The CABG group also had fewer deaths specifically from cardiovascular causes (40% vs 49%; P = .006). A per-protocol analysis showed an even greater benefit with CABG (HR = 0.77; 0.67 - 0.90; P = .001) suggesting that the crossovers in this trial may have diluted the observed effect of CABG.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of stent retrievers in conjunction with tissue plasminogen activator improve outcomes in patients with acute ischemic stroke?

Bottom line: The use of stent retriever devices in addition to tissue plasminogen activator (tPA) in patients with anterior circulation acute ischemic stroke results in more patients with functional independence at 90 days. Based on data from the studies included in this review, the American Heart Association/American Stroke Association guidelines now strongly recommend the use of stent retrievers with class 1a level of evidence. (LOE = 1a)

Reference: Touma L, Filion KB, Sterling LH, Atallah R, Windle SB, Eisenberg MJ. Stent retrievers for the treatment of acute ischemic stroke. JAMA Neurol 2016;73(3):275-281.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Intra-arterial therapy using stent retriever devices for thrombectomy added to standard therapy with tPA is a promising treatment for acute ischemic stroke. Four recent randomized controlled trials examining the effectiveness of stent retrievers have been terminated early because of the strong benefit seen with this therapy.

In this study, investigators searched MEDLINE, EMBASE, and the Cochrane Library, as well as trial registries and references of included studies, to find randomized controlled trials that compared stent retrievers plus tPA with tPA alone. Two authors independently extracted data from the 5 included studies (N = 1287) and assessed study quality using the Cochrane Collaboration Risk of Bias Tool.

All studies included patients with imaging-confirmed anterior circulation strokes and used the modified Rankin Scale (mRS) to assess for improvement in functional status at 90 days. Four of the 5 studies only included patients with excellent pre-stroke functional independence. Additionally, 4 of the 5 studies restricted stent retriever therapy to patients who presented within 6 hours of onset of stroke symptoms. The studies had a low risk of bias overall.

The pooled 90-day outcomes showed that patients who received stent retriever therapy plus tPA were more likely to achieve greater functional independence, defined as an mRS score of 0 to 2, than patients who received tPA alone (relative risk 1.72; 95% CI 1.38 - 1.99). You would need to treat 6 patients with stent retriever therapy to have one patient achieve functional independence. There were no significant differences detected in mortality or in the rates of intracranial bleeds or parenchymal hematomas.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of stent retrievers in conjunction with tissue plasminogen activator improve outcomes in patients with acute ischemic stroke?

Bottom line: The use of stent retriever devices in addition to tissue plasminogen activator (tPA) in patients with anterior circulation acute ischemic stroke results in more patients with functional independence at 90 days. Based on data from the studies included in this review, the American Heart Association/American Stroke Association guidelines now strongly recommend the use of stent retrievers with class 1a level of evidence. (LOE = 1a)

Reference: Touma L, Filion KB, Sterling LH, Atallah R, Windle SB, Eisenberg MJ. Stent retrievers for the treatment of acute ischemic stroke. JAMA Neurol 2016;73(3):275-281.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Intra-arterial therapy using stent retriever devices for thrombectomy added to standard therapy with tPA is a promising treatment for acute ischemic stroke. Four recent randomized controlled trials examining the effectiveness of stent retrievers have been terminated early because of the strong benefit seen with this therapy.

In this study, investigators searched MEDLINE, EMBASE, and the Cochrane Library, as well as trial registries and references of included studies, to find randomized controlled trials that compared stent retrievers plus tPA with tPA alone. Two authors independently extracted data from the 5 included studies (N = 1287) and assessed study quality using the Cochrane Collaboration Risk of Bias Tool.

All studies included patients with imaging-confirmed anterior circulation strokes and used the modified Rankin Scale (mRS) to assess for improvement in functional status at 90 days. Four of the 5 studies only included patients with excellent pre-stroke functional independence. Additionally, 4 of the 5 studies restricted stent retriever therapy to patients who presented within 6 hours of onset of stroke symptoms. The studies had a low risk of bias overall.

The pooled 90-day outcomes showed that patients who received stent retriever therapy plus tPA were more likely to achieve greater functional independence, defined as an mRS score of 0 to 2, than patients who received tPA alone (relative risk 1.72; 95% CI 1.38 - 1.99). You would need to treat 6 patients with stent retriever therapy to have one patient achieve functional independence. There were no significant differences detected in mortality or in the rates of intracranial bleeds or parenchymal hematomas.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of stent retrievers in conjunction with tissue plasminogen activator improve outcomes in patients with acute ischemic stroke?

Bottom line: The use of stent retriever devices in addition to tissue plasminogen activator (tPA) in patients with anterior circulation acute ischemic stroke results in more patients with functional independence at 90 days. Based on data from the studies included in this review, the American Heart Association/American Stroke Association guidelines now strongly recommend the use of stent retrievers with class 1a level of evidence. (LOE = 1a)

Reference: Touma L, Filion KB, Sterling LH, Atallah R, Windle SB, Eisenberg MJ. Stent retrievers for the treatment of acute ischemic stroke. JAMA Neurol 2016;73(3):275-281.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Intra-arterial therapy using stent retriever devices for thrombectomy added to standard therapy with tPA is a promising treatment for acute ischemic stroke. Four recent randomized controlled trials examining the effectiveness of stent retrievers have been terminated early because of the strong benefit seen with this therapy.

In this study, investigators searched MEDLINE, EMBASE, and the Cochrane Library, as well as trial registries and references of included studies, to find randomized controlled trials that compared stent retrievers plus tPA with tPA alone. Two authors independently extracted data from the 5 included studies (N = 1287) and assessed study quality using the Cochrane Collaboration Risk of Bias Tool.

All studies included patients with imaging-confirmed anterior circulation strokes and used the modified Rankin Scale (mRS) to assess for improvement in functional status at 90 days. Four of the 5 studies only included patients with excellent pre-stroke functional independence. Additionally, 4 of the 5 studies restricted stent retriever therapy to patients who presented within 6 hours of onset of stroke symptoms. The studies had a low risk of bias overall.

The pooled 90-day outcomes showed that patients who received stent retriever therapy plus tPA were more likely to achieve greater functional independence, defined as an mRS score of 0 to 2, than patients who received tPA alone (relative risk 1.72; 95% CI 1.38 - 1.99). You would need to treat 6 patients with stent retriever therapy to have one patient achieve functional independence. There were no significant differences detected in mortality or in the rates of intracranial bleeds or parenchymal hematomas.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

SAN DIEGO – Inpatient infliximab rescue for severe, steroid-refractory ulcerative colitis is more likely to work if patients receive a second infusion 3 days after the first, according to a review of 55 University of Michigan, Ann Arbor, patients.

The traditional approach is one inpatient 5-mg/kg infusion, followed by either colectomy or subsequent outpatient infusions, depending on response. In 2013, physicians at the university began offering a second infusion at 72 hours to patients whose C-reactive protein (CRP) levels did not drop below 0.7 mg/dL after their first infusion, and they also began opting more often for 10-mg/kg dosing.

The review found that 90-day colectomy-free survival was 50% in the 16 accelerated-dosing patients, up from 10.2% in the 36 patients treated with the traditional approach (P less than .001). The finding has led to a new, more aggressive infliximab protocol for inpatient ulcerative colitis.

Among patients who did undergo colectomies, postoperative complications were similar between the two groups. But for reasons that are not clear, 30-day postoperative readmission rates were higher in accelerated patients (58% vs. 25%).

In an interview at the annual Digestive Disease Week, lead investigator Dr. Shail Govani of the University of Michigan explained the thinking behind the new approach, how CRP/albumin ratios come into play, and how to counsel patients in light of the findings.

 [email protected]

SAN DIEGO – Inpatient infliximab rescue for severe, steroid-refractory ulcerative colitis is more likely to work if patients receive a second infusion 3 days after the first, according to a review of 55 University of Michigan, Ann Arbor, patients.

The traditional approach is one inpatient 5-mg/kg infusion, followed by either colectomy or subsequent outpatient infusions, depending on response. In 2013, physicians at the university began offering a second infusion at 72 hours to patients whose C-reactive protein (CRP) levels did not drop below 0.7 mg/dL after their first infusion, and they also began opting more often for 10-mg/kg dosing.

The review found that 90-day colectomy-free survival was 50% in the 16 accelerated-dosing patients, up from 10.2% in the 36 patients treated with the traditional approach (P less than .001). The finding has led to a new, more aggressive infliximab protocol for inpatient ulcerative colitis.

Among patients who did undergo colectomies, postoperative complications were similar between the two groups. But for reasons that are not clear, 30-day postoperative readmission rates were higher in accelerated patients (58% vs. 25%).

In an interview at the annual Digestive Disease Week, lead investigator Dr. Shail Govani of the University of Michigan explained the thinking behind the new approach, how CRP/albumin ratios come into play, and how to counsel patients in light of the findings.

 [email protected]

SAN DIEGO – Inpatient infliximab rescue for severe, steroid-refractory ulcerative colitis is more likely to work if patients receive a second infusion 3 days after the first, according to a review of 55 University of Michigan, Ann Arbor, patients.

The traditional approach is one inpatient 5-mg/kg infusion, followed by either colectomy or subsequent outpatient infusions, depending on response. In 2013, physicians at the university began offering a second infusion at 72 hours to patients whose C-reactive protein (CRP) levels did not drop below 0.7 mg/dL after their first infusion, and they also began opting more often for 10-mg/kg dosing.

The review found that 90-day colectomy-free survival was 50% in the 16 accelerated-dosing patients, up from 10.2% in the 36 patients treated with the traditional approach (P less than .001). The finding has led to a new, more aggressive infliximab protocol for inpatient ulcerative colitis.

Among patients who did undergo colectomies, postoperative complications were similar between the two groups. But for reasons that are not clear, 30-day postoperative readmission rates were higher in accelerated patients (58% vs. 25%).

In an interview at the annual Digestive Disease Week, lead investigator Dr. Shail Govani of the University of Michigan explained the thinking behind the new approach, how CRP/albumin ratios come into play, and how to counsel patients in light of the findings.

 [email protected]