Neil Osterweil

BOSTON – In addition to causing cavities, oral microbes may be linked to the risk for health care–associated pneumonia, a small study has shown.

In the study, intubated patients in an ICU were found to have oral microbial profiles that were significantly different from those of similar patients who did not develop pneumonia, reported Dr. Samit Joshi of the section of infectious diseases at Yale University in New Haven, Conn.

The study investigators also found that mouth-dwelling microbe profiles of community-dwelling healthy adults differed markedly from those of adults at higher risk for pneumonia, including nursing home residents and patients on mechanical ventilation.

"We showed that as the risk for pneumonia increased among these three groups of adults, that certain types of bacteria living in their mouths decreased. Interestingly, in the adults who actually developed pneumonia, other disease-causing bacteria in their mouths actually increased days before those adults developed pneumonia," Dr. Joshi said in a briefing.

The findings suggest that genetic sequencing of oral microbial communities in patients’ mouths may provide novel methods for targeted prevention of pneumonia, he added.

The investigators took swab samples from the mouths of 19 healthy, community-dwelling adults (mean age, 60.1 years); 10 nursing home residents (86.2 years); and 8 patients in an ICU (51.6 years). The nursing home residents had been living in the facility for a mean of 33.2 months; the ICU patients had been in the unit for a mean of 3.6 days.

Samples of bacteria collected from the palate, buccal mucosa, tongue, and gingival crevice were then analyzed with165 ribosomal RNA pyrosequencing, a sophisticated technology suitable for complex microbiome analyses, but not available for bedside or point of care assays.

"We showed that as the risk for pneumonia increased among these three groups of adults, that certain types of bacteria living in their mouths decreased."

The authors found that bugs in the family Streptococcaceae were the dominant oral residents, but in proportions that differed significantly among the three patient groups: 65% among community dwellers, 43% among nursing home residents, and 33% among the ICU patients, all of whom were on mechanical ventilation.

Three of the patients went on to develop pneumonia at around 1 week of their ICU stay, and these patients had significantly smaller average proportions of oral Steptococcaceae species than did ICU patients who did not develop pneumonia (0.07% vs. 49%).

The authors then looked at the mean weighted UniFrac distance, which allows for phylogenetic comparisons of microbial communities, and found a significant difference between ICU residents who developed pneumonia and those who were spared from it.

"This discovery has implications for how we prevent pneumonia in the future," Dr. Joshi said at the annual meeting of the Infectious Diseases Society of America. "It may lead to new and improved ways that we can prevent pneumonia by maintaining the composition of bacteria which live inside our mouths, or by maintaining our local immune defense mechanisms."

The idea that microbial communities may be markers of disease is "exciting," said Dr. David Relman, professor of medicine at Stanford (Calif.) University. "What we don’t know right now is whether the two are linked causally – these changes in the microbial composition and the onset of disease – but regardless, I think there is value in understanding these novel kinds of markers of pneumococcal disease," he commented. Dr. Relman was not involved in the study, but moderated a briefing where the data were presented.

The study was funded by the National Institute on Aging and the Howard Hughes Medical Institute. Dr. Joshi and Dr. Relman each reported that they had no relevant financial disclosures.

BOSTON – In addition to causing cavities, oral microbes may be linked to the risk for health care–associated pneumonia, a small study has shown.

In the study, intubated patients in an ICU were found to have oral microbial profiles that were significantly different from those of similar patients who did not develop pneumonia, reported Dr. Samit Joshi of the section of infectious diseases at Yale University in New Haven, Conn.

The study investigators also found that mouth-dwelling microbe profiles of community-dwelling healthy adults differed markedly from those of adults at higher risk for pneumonia, including nursing home residents and patients on mechanical ventilation.

"We showed that as the risk for pneumonia increased among these three groups of adults, that certain types of bacteria living in their mouths decreased. Interestingly, in the adults who actually developed pneumonia, other disease-causing bacteria in their mouths actually increased days before those adults developed pneumonia," Dr. Joshi said in a briefing.

The findings suggest that genetic sequencing of oral microbial communities in patients’ mouths may provide novel methods for targeted prevention of pneumonia, he added.

The investigators took swab samples from the mouths of 19 healthy, community-dwelling adults (mean age, 60.1 years); 10 nursing home residents (86.2 years); and 8 patients in an ICU (51.6 years). The nursing home residents had been living in the facility for a mean of 33.2 months; the ICU patients had been in the unit for a mean of 3.6 days.

Samples of bacteria collected from the palate, buccal mucosa, tongue, and gingival crevice were then analyzed with165 ribosomal RNA pyrosequencing, a sophisticated technology suitable for complex microbiome analyses, but not available for bedside or point of care assays.

"We showed that as the risk for pneumonia increased among these three groups of adults, that certain types of bacteria living in their mouths decreased."

The authors found that bugs in the family Streptococcaceae were the dominant oral residents, but in proportions that differed significantly among the three patient groups: 65% among community dwellers, 43% among nursing home residents, and 33% among the ICU patients, all of whom were on mechanical ventilation.

Three of the patients went on to develop pneumonia at around 1 week of their ICU stay, and these patients had significantly smaller average proportions of oral Steptococcaceae species than did ICU patients who did not develop pneumonia (0.07% vs. 49%).

The authors then looked at the mean weighted UniFrac distance, which allows for phylogenetic comparisons of microbial communities, and found a significant difference between ICU residents who developed pneumonia and those who were spared from it.

"This discovery has implications for how we prevent pneumonia in the future," Dr. Joshi said at the annual meeting of the Infectious Diseases Society of America. "It may lead to new and improved ways that we can prevent pneumonia by maintaining the composition of bacteria which live inside our mouths, or by maintaining our local immune defense mechanisms."

The idea that microbial communities may be markers of disease is "exciting," said Dr. David Relman, professor of medicine at Stanford (Calif.) University. "What we don’t know right now is whether the two are linked causally – these changes in the microbial composition and the onset of disease – but regardless, I think there is value in understanding these novel kinds of markers of pneumococcal disease," he commented. Dr. Relman was not involved in the study, but moderated a briefing where the data were presented.

The study was funded by the National Institute on Aging and the Howard Hughes Medical Institute. Dr. Joshi and Dr. Relman each reported that they had no relevant financial disclosures.

BOSTON – In addition to causing cavities, oral microbes may be linked to the risk for health care–associated pneumonia, a small study has shown.

In the study, intubated patients in an ICU were found to have oral microbial profiles that were significantly different from those of similar patients who did not develop pneumonia, reported Dr. Samit Joshi of the section of infectious diseases at Yale University in New Haven, Conn.

The study investigators also found that mouth-dwelling microbe profiles of community-dwelling healthy adults differed markedly from those of adults at higher risk for pneumonia, including nursing home residents and patients on mechanical ventilation.

"We showed that as the risk for pneumonia increased among these three groups of adults, that certain types of bacteria living in their mouths decreased. Interestingly, in the adults who actually developed pneumonia, other disease-causing bacteria in their mouths actually increased days before those adults developed pneumonia," Dr. Joshi said in a briefing.

The findings suggest that genetic sequencing of oral microbial communities in patients’ mouths may provide novel methods for targeted prevention of pneumonia, he added.

The investigators took swab samples from the mouths of 19 healthy, community-dwelling adults (mean age, 60.1 years); 10 nursing home residents (86.2 years); and 8 patients in an ICU (51.6 years). The nursing home residents had been living in the facility for a mean of 33.2 months; the ICU patients had been in the unit for a mean of 3.6 days.

Samples of bacteria collected from the palate, buccal mucosa, tongue, and gingival crevice were then analyzed with165 ribosomal RNA pyrosequencing, a sophisticated technology suitable for complex microbiome analyses, but not available for bedside or point of care assays.

"We showed that as the risk for pneumonia increased among these three groups of adults, that certain types of bacteria living in their mouths decreased."

The authors found that bugs in the family Streptococcaceae were the dominant oral residents, but in proportions that differed significantly among the three patient groups: 65% among community dwellers, 43% among nursing home residents, and 33% among the ICU patients, all of whom were on mechanical ventilation.

Three of the patients went on to develop pneumonia at around 1 week of their ICU stay, and these patients had significantly smaller average proportions of oral Steptococcaceae species than did ICU patients who did not develop pneumonia (0.07% vs. 49%).

The authors then looked at the mean weighted UniFrac distance, which allows for phylogenetic comparisons of microbial communities, and found a significant difference between ICU residents who developed pneumonia and those who were spared from it.

"This discovery has implications for how we prevent pneumonia in the future," Dr. Joshi said at the annual meeting of the Infectious Diseases Society of America. "It may lead to new and improved ways that we can prevent pneumonia by maintaining the composition of bacteria which live inside our mouths, or by maintaining our local immune defense mechanisms."

The idea that microbial communities may be markers of disease is "exciting," said Dr. David Relman, professor of medicine at Stanford (Calif.) University. "What we don’t know right now is whether the two are linked causally – these changes in the microbial composition and the onset of disease – but regardless, I think there is value in understanding these novel kinds of markers of pneumococcal disease," he commented. Dr. Relman was not involved in the study, but moderated a briefing where the data were presented.

The study was funded by the National Institute on Aging and the Howard Hughes Medical Institute. Dr. Joshi and Dr. Relman each reported that they had no relevant financial disclosures.

BOSTON – Some antimicrobial agents are in such short supply that a majority of physicians surveyed reported having to switch to a more toxic or expensive alternative, and more than half said that the shortage adversely affected patient care, reported investigators at the annual meeting of the Infectious Diseases Society of America.

Among 634 members of the IDSA's Emerging Infections Network, 78% said they had had to modify their antimicrobial choice because of a shortage of the preferred agent within the past 2 years, and 52% reported that the shortage had adversely affected patient care or outcomes, said Dr. Philip M. Polgreen of the University of Iowa in Iowa City.

Fully 70% learned of the shortage from the pharmacy only after they had prescribed the drug, and only 24% said they found out about the shortage from an official source such at the Food and Drug Administration's Drug Shortages website.

"Some of the adverse effects that were reported were exposing a patient to a more toxic drug, exposing them to a much more expensive drug, exposing them to a drug with a much broader spectrum than was needed, and in some cases the physician reported that a patient had to stay longer in the hospital or had a failure of therapy," Dr. Polgreen said at a briefing on Oct. 20.

In a subgroup of 250 respondents, 28% said that patients incurred long-term morbidity from inadequate treatment.

The drugs that are reported to be in short supply tend to be those recommended for less common infections, and their availability may be subject to supply chain issues or local shortages. Although the study was not designed to examine reasons for shortages, several of the agents come from a single supplier, and the shortage of one agent may lead to overuse and subsequent shortage of another, Dr. Polgreen suggested.

The drugs reported most frequently to be unavailable or in short supply include the intravenous formulation of trimethoprim/sulfamethoxazole (Bactrim), amikacin (Amikin), aztreonam (Azactam), foscarnet (Foscavir), and penicillin G.

Other agents in short supply include oseltamivir (Tamiflu) oral suspension, and acyclovir (Zovirax) tablets, as well as injectable biologic agents and vaccines, including intravenous immune globulin, live zoster vaccine, yellow fever vaccine, and inactivated influenza vaccine.

The investigators sent a web-based survey with nine questions to all 1,350 members of the IDSA-EIN, a sentinel network of physicians. They received a total of 634 responses (47% response rate).

Dr. Polgreen acknowledged that that study was limited by self-reporting with no verification and by possible response bias, with members who had encountered a drug shortage being more likely to respond.

He said that physicians need more effective ways of learning about impending or current shortages and about acceptable alternatives to first-line agents. Such efforts are particularly important in light of the fact that there are very few antimicrobial agents in the drug development pipeline, he said.

In a separate presentation, Dr. Helen Boucher, of Tufts Medical Center, Boston, and her colleagues reported that drug companies aren't exactly scrambling to solve the problem of antimicrobial resistance to existing agents.

The researchers identified nine drugs in clinical development for parenteral use against gram-negative bacilli. Of these agents, only two have novel mechanism of action, and none is being studied for efficacy against community-acquired bacterial pneumonia, or hospital- or ventilator-associated pneumonia.

The number of new antibiotics approved for marketing in the United States annually continues to decline, and major pharmaceutical companies – many of which pioneered antimicrobial drug development – are continually slackening both the pace and the quantity of antimicrobial agent development.

"We all know that with antibiotics, attrition happens, so that even in the later stages of development, we can’t count on getting all or even a majority of these compounds to market. Further, and very importantly, none of these drugs is available today, and our patients need new drugs now," Boucher added.

Dr. Polgreen's study was supported by the Centers for Disease Control and Prevention. He reported having no conflicts of interest. Dr. Boucher's study was funded by the participating institutions. She disclosed serving on an adjudication committee for Merck and as a consultant to Merck, Wyeth/Pfizer, Durata, and PolyMedix.

BOSTON – Some antimicrobial agents are in such short supply that a majority of physicians surveyed reported having to switch to a more toxic or expensive alternative, and more than half said that the shortage adversely affected patient care, reported investigators at the annual meeting of the Infectious Diseases Society of America.

Among 634 members of the IDSA's Emerging Infections Network, 78% said they had had to modify their antimicrobial choice because of a shortage of the preferred agent within the past 2 years, and 52% reported that the shortage had adversely affected patient care or outcomes, said Dr. Philip M. Polgreen of the University of Iowa in Iowa City.

Fully 70% learned of the shortage from the pharmacy only after they had prescribed the drug, and only 24% said they found out about the shortage from an official source such at the Food and Drug Administration's Drug Shortages website.

"Some of the adverse effects that were reported were exposing a patient to a more toxic drug, exposing them to a much more expensive drug, exposing them to a drug with a much broader spectrum than was needed, and in some cases the physician reported that a patient had to stay longer in the hospital or had a failure of therapy," Dr. Polgreen said at a briefing on Oct. 20.

In a subgroup of 250 respondents, 28% said that patients incurred long-term morbidity from inadequate treatment.

The drugs that are reported to be in short supply tend to be those recommended for less common infections, and their availability may be subject to supply chain issues or local shortages. Although the study was not designed to examine reasons for shortages, several of the agents come from a single supplier, and the shortage of one agent may lead to overuse and subsequent shortage of another, Dr. Polgreen suggested.

The drugs reported most frequently to be unavailable or in short supply include the intravenous formulation of trimethoprim/sulfamethoxazole (Bactrim), amikacin (Amikin), aztreonam (Azactam), foscarnet (Foscavir), and penicillin G.

Other agents in short supply include oseltamivir (Tamiflu) oral suspension, and acyclovir (Zovirax) tablets, as well as injectable biologic agents and vaccines, including intravenous immune globulin, live zoster vaccine, yellow fever vaccine, and inactivated influenza vaccine.

The investigators sent a web-based survey with nine questions to all 1,350 members of the IDSA-EIN, a sentinel network of physicians. They received a total of 634 responses (47% response rate).

Dr. Polgreen acknowledged that that study was limited by self-reporting with no verification and by possible response bias, with members who had encountered a drug shortage being more likely to respond.

He said that physicians need more effective ways of learning about impending or current shortages and about acceptable alternatives to first-line agents. Such efforts are particularly important in light of the fact that there are very few antimicrobial agents in the drug development pipeline, he said.

In a separate presentation, Dr. Helen Boucher, of Tufts Medical Center, Boston, and her colleagues reported that drug companies aren't exactly scrambling to solve the problem of antimicrobial resistance to existing agents.

The researchers identified nine drugs in clinical development for parenteral use against gram-negative bacilli. Of these agents, only two have novel mechanism of action, and none is being studied for efficacy against community-acquired bacterial pneumonia, or hospital- or ventilator-associated pneumonia.

The number of new antibiotics approved for marketing in the United States annually continues to decline, and major pharmaceutical companies – many of which pioneered antimicrobial drug development – are continually slackening both the pace and the quantity of antimicrobial agent development.

"We all know that with antibiotics, attrition happens, so that even in the later stages of development, we can’t count on getting all or even a majority of these compounds to market. Further, and very importantly, none of these drugs is available today, and our patients need new drugs now," Boucher added.

Dr. Polgreen's study was supported by the Centers for Disease Control and Prevention. He reported having no conflicts of interest. Dr. Boucher's study was funded by the participating institutions. She disclosed serving on an adjudication committee for Merck and as a consultant to Merck, Wyeth/Pfizer, Durata, and PolyMedix.

BOSTON – Some antimicrobial agents are in such short supply that a majority of physicians surveyed reported having to switch to a more toxic or expensive alternative, and more than half said that the shortage adversely affected patient care, reported investigators at the annual meeting of the Infectious Diseases Society of America.

Among 634 members of the IDSA's Emerging Infections Network, 78% said they had had to modify their antimicrobial choice because of a shortage of the preferred agent within the past 2 years, and 52% reported that the shortage had adversely affected patient care or outcomes, said Dr. Philip M. Polgreen of the University of Iowa in Iowa City.

Fully 70% learned of the shortage from the pharmacy only after they had prescribed the drug, and only 24% said they found out about the shortage from an official source such at the Food and Drug Administration's Drug Shortages website.

"Some of the adverse effects that were reported were exposing a patient to a more toxic drug, exposing them to a much more expensive drug, exposing them to a drug with a much broader spectrum than was needed, and in some cases the physician reported that a patient had to stay longer in the hospital or had a failure of therapy," Dr. Polgreen said at a briefing on Oct. 20.

In a subgroup of 250 respondents, 28% said that patients incurred long-term morbidity from inadequate treatment.

The drugs that are reported to be in short supply tend to be those recommended for less common infections, and their availability may be subject to supply chain issues or local shortages. Although the study was not designed to examine reasons for shortages, several of the agents come from a single supplier, and the shortage of one agent may lead to overuse and subsequent shortage of another, Dr. Polgreen suggested.

The drugs reported most frequently to be unavailable or in short supply include the intravenous formulation of trimethoprim/sulfamethoxazole (Bactrim), amikacin (Amikin), aztreonam (Azactam), foscarnet (Foscavir), and penicillin G.

Other agents in short supply include oseltamivir (Tamiflu) oral suspension, and acyclovir (Zovirax) tablets, as well as injectable biologic agents and vaccines, including intravenous immune globulin, live zoster vaccine, yellow fever vaccine, and inactivated influenza vaccine.

The investigators sent a web-based survey with nine questions to all 1,350 members of the IDSA-EIN, a sentinel network of physicians. They received a total of 634 responses (47% response rate).

Dr. Polgreen acknowledged that that study was limited by self-reporting with no verification and by possible response bias, with members who had encountered a drug shortage being more likely to respond.

He said that physicians need more effective ways of learning about impending or current shortages and about acceptable alternatives to first-line agents. Such efforts are particularly important in light of the fact that there are very few antimicrobial agents in the drug development pipeline, he said.

In a separate presentation, Dr. Helen Boucher, of Tufts Medical Center, Boston, and her colleagues reported that drug companies aren't exactly scrambling to solve the problem of antimicrobial resistance to existing agents.

The researchers identified nine drugs in clinical development for parenteral use against gram-negative bacilli. Of these agents, only two have novel mechanism of action, and none is being studied for efficacy against community-acquired bacterial pneumonia, or hospital- or ventilator-associated pneumonia.

The number of new antibiotics approved for marketing in the United States annually continues to decline, and major pharmaceutical companies – many of which pioneered antimicrobial drug development – are continually slackening both the pace and the quantity of antimicrobial agent development.

"We all know that with antibiotics, attrition happens, so that even in the later stages of development, we can’t count on getting all or even a majority of these compounds to market. Further, and very importantly, none of these drugs is available today, and our patients need new drugs now," Boucher added.

Dr. Polgreen's study was supported by the Centers for Disease Control and Prevention. He reported having no conflicts of interest. Dr. Boucher's study was funded by the participating institutions. She disclosed serving on an adjudication committee for Merck and as a consultant to Merck, Wyeth/Pfizer, Durata, and PolyMedix.

BOSTON – Some antimicrobial agents are in such short supply that a majority of infectious disease specialists surveyed reported having to switch to a more toxic or expensive alternative, and more than half said that the shortage adversely affected patient care, reported investigators at the annual meeting of the Infectious Diseases Society of America.

Among 634 members of the IDSA’s Emerging Infections Network, 78% said they had had to modify their antimicrobial choice because of a shortage of the preferred agent within the past 2 years, and 52% reported that the shortage had adversely affected patient care or outcomes, said Dr. Philip M. Polgreen of the University of Iowa in Iowa City.

Fully 70% of the ID specialists learned of the shortage from the pharmacy only after they had prescribed the drug, and only 24% said they found out about the shortage from an official source such at the Food and Drug Administration’s Drug Shortages website.

"Some of the adverse effects that were reported were exposing a patient to a more toxic drug, exposing them to a much more expensive drug, exposing them to a drug with a much broader spectrum than was needed, and in some cases the physician reported that a patient had to stay longer in the hospital or had a failure of therapy," Dr. Polgreen said at a briefing on Oct. 20.

In a subgroup of 250 respondents, 28% said that patients incurred long-term morbidity from inadequate treatment.

The drugs that are reported to be in short supply tend to be those recommended for less common infections, and their availability may be subject to supply chain issues or local shortages. Although the study was not designed to examine reasons for shortages, several of the agents come from a single supplier, and the shortage of one agent may lead to overuse and subsequent shortage of another, Dr. Polgreen suggested.

The drugs reported most frequently to be unavailable or in short supply include the intravenous formulation of trimethoprim/sulfamethoxazole (Bactrim), amikacin (Amikin), aztreonam (Azactam), foscarnet (Foscavir), and penicillin G.

Other agents in short supply include oseltamivir (Tamiflu) oral suspension, and acyclovir (Zovirax) tablets, as well as injectable biologic agents and vaccines, including intravenous immune globulin, live zoster vaccine, yellow fever vaccine, and inactivated influenza vaccine.

The investigators sent a web-based survey with nine questions to all 1,350 members of the IDSA-EIN, a sentinel network of physicians. They received a total of 634 responses (47% response rate).

Dr. Polgreen acknowledged that that study was limited by self-reporting with no verification and by possible response bias, with members who had encountered a drug shortage being more likely to respond.

He said that physicians need more effective ways of learning about impending or current shortages and about acceptable alternatives to first-line agents. Such efforts are particularly important in light of the fact that there are very few antimicrobial agents in the drug development pipeline, he said.

In a separate presentation, Dr. Helen Boucher, of Tufts Medical Center, Boston, and her colleagues reported that drug companies aren’t exactly scrambling to solve the problem of antimicrobial resistance to existing agents.

The researchers identified nine drugs in clinical development for parenteral use against gram-negative bacilli. Of these agents, only two have novel mechanism of action, and none is being studied for efficacy against community-acquired bacterial pneumonia, or hospital- or ventilator-associated pneumonia.

The number of new antibiotics approved for marketing in the United States annually continues to decline, and major pharmaceutical companies – many of which pioneered antimicrobial drug development – are continually slackening both the pace and the quantity of antimicrobial agent development.

"We all know that with antibiotics, attrition happens, so that even in the later stages of development, we can’t count on getting all or even a majority of these compounds to market. Further, and very importantly, none of these drugs is available today, and our patients need new drugs now," Boucher added.

Dr. Polgreen’s study was supported by the Centers for Disease Control and Prevention. He reported having no conflicts of interest. Dr. Boucher’s study was funded by the participating institutions. She disclosed serving on an adjudication committee for Merck and as a consultant to Merck, Wyeth/Pfizer, Durata, and PolyMedix.

BOSTON – Some antimicrobial agents are in such short supply that a majority of infectious disease specialists surveyed reported having to switch to a more toxic or expensive alternative, and more than half said that the shortage adversely affected patient care, reported investigators at the annual meeting of the Infectious Diseases Society of America.

Among 634 members of the IDSA’s Emerging Infections Network, 78% said they had had to modify their antimicrobial choice because of a shortage of the preferred agent within the past 2 years, and 52% reported that the shortage had adversely affected patient care or outcomes, said Dr. Philip M. Polgreen of the University of Iowa in Iowa City.

Fully 70% of the ID specialists learned of the shortage from the pharmacy only after they had prescribed the drug, and only 24% said they found out about the shortage from an official source such at the Food and Drug Administration’s Drug Shortages website.

"Some of the adverse effects that were reported were exposing a patient to a more toxic drug, exposing them to a much more expensive drug, exposing them to a drug with a much broader spectrum than was needed, and in some cases the physician reported that a patient had to stay longer in the hospital or had a failure of therapy," Dr. Polgreen said at a briefing on Oct. 20.

In a subgroup of 250 respondents, 28% said that patients incurred long-term morbidity from inadequate treatment.

The drugs that are reported to be in short supply tend to be those recommended for less common infections, and their availability may be subject to supply chain issues or local shortages. Although the study was not designed to examine reasons for shortages, several of the agents come from a single supplier, and the shortage of one agent may lead to overuse and subsequent shortage of another, Dr. Polgreen suggested.

The drugs reported most frequently to be unavailable or in short supply include the intravenous formulation of trimethoprim/sulfamethoxazole (Bactrim), amikacin (Amikin), aztreonam (Azactam), foscarnet (Foscavir), and penicillin G.

Other agents in short supply include oseltamivir (Tamiflu) oral suspension, and acyclovir (Zovirax) tablets, as well as injectable biologic agents and vaccines, including intravenous immune globulin, live zoster vaccine, yellow fever vaccine, and inactivated influenza vaccine.

The investigators sent a web-based survey with nine questions to all 1,350 members of the IDSA-EIN, a sentinel network of physicians. They received a total of 634 responses (47% response rate).

Dr. Polgreen acknowledged that that study was limited by self-reporting with no verification and by possible response bias, with members who had encountered a drug shortage being more likely to respond.

He said that physicians need more effective ways of learning about impending or current shortages and about acceptable alternatives to first-line agents. Such efforts are particularly important in light of the fact that there are very few antimicrobial agents in the drug development pipeline, he said.

In a separate presentation, Dr. Helen Boucher, of Tufts Medical Center, Boston, and her colleagues reported that drug companies aren’t exactly scrambling to solve the problem of antimicrobial resistance to existing agents.

The researchers identified nine drugs in clinical development for parenteral use against gram-negative bacilli. Of these agents, only two have novel mechanism of action, and none is being studied for efficacy against community-acquired bacterial pneumonia, or hospital- or ventilator-associated pneumonia.

The number of new antibiotics approved for marketing in the United States annually continues to decline, and major pharmaceutical companies – many of which pioneered antimicrobial drug development – are continually slackening both the pace and the quantity of antimicrobial agent development.

"We all know that with antibiotics, attrition happens, so that even in the later stages of development, we can’t count on getting all or even a majority of these compounds to market. Further, and very importantly, none of these drugs is available today, and our patients need new drugs now," Boucher added.

Dr. Polgreen’s study was supported by the Centers for Disease Control and Prevention. He reported having no conflicts of interest. Dr. Boucher’s study was funded by the participating institutions. She disclosed serving on an adjudication committee for Merck and as a consultant to Merck, Wyeth/Pfizer, Durata, and PolyMedix.

BOSTON – Some antimicrobial agents are in such short supply that a majority of infectious disease specialists surveyed reported having to switch to a more toxic or expensive alternative, and more than half said that the shortage adversely affected patient care, reported investigators at the annual meeting of the Infectious Diseases Society of America.

Among 634 members of the IDSA’s Emerging Infections Network, 78% said they had had to modify their antimicrobial choice because of a shortage of the preferred agent within the past 2 years, and 52% reported that the shortage had adversely affected patient care or outcomes, said Dr. Philip M. Polgreen of the University of Iowa in Iowa City.

Fully 70% of the ID specialists learned of the shortage from the pharmacy only after they had prescribed the drug, and only 24% said they found out about the shortage from an official source such at the Food and Drug Administration’s Drug Shortages website.

"Some of the adverse effects that were reported were exposing a patient to a more toxic drug, exposing them to a much more expensive drug, exposing them to a drug with a much broader spectrum than was needed, and in some cases the physician reported that a patient had to stay longer in the hospital or had a failure of therapy," Dr. Polgreen said at a briefing on Oct. 20.

In a subgroup of 250 respondents, 28% said that patients incurred long-term morbidity from inadequate treatment.

The drugs that are reported to be in short supply tend to be those recommended for less common infections, and their availability may be subject to supply chain issues or local shortages. Although the study was not designed to examine reasons for shortages, several of the agents come from a single supplier, and the shortage of one agent may lead to overuse and subsequent shortage of another, Dr. Polgreen suggested.

The drugs reported most frequently to be unavailable or in short supply include the intravenous formulation of trimethoprim/sulfamethoxazole (Bactrim), amikacin (Amikin), aztreonam (Azactam), foscarnet (Foscavir), and penicillin G.

Other agents in short supply include oseltamivir (Tamiflu) oral suspension, and acyclovir (Zovirax) tablets, as well as injectable biologic agents and vaccines, including intravenous immune globulin, live zoster vaccine, yellow fever vaccine, and inactivated influenza vaccine.

The investigators sent a web-based survey with nine questions to all 1,350 members of the IDSA-EIN, a sentinel network of physicians. They received a total of 634 responses (47% response rate).

Dr. Polgreen acknowledged that that study was limited by self-reporting with no verification and by possible response bias, with members who had encountered a drug shortage being more likely to respond.

He said that physicians need more effective ways of learning about impending or current shortages and about acceptable alternatives to first-line agents. Such efforts are particularly important in light of the fact that there are very few antimicrobial agents in the drug development pipeline, he said.

In a separate presentation, Dr. Helen Boucher, of Tufts Medical Center, Boston, and her colleagues reported that drug companies aren’t exactly scrambling to solve the problem of antimicrobial resistance to existing agents.

The researchers identified nine drugs in clinical development for parenteral use against gram-negative bacilli. Of these agents, only two have novel mechanism of action, and none is being studied for efficacy against community-acquired bacterial pneumonia, or hospital- or ventilator-associated pneumonia.

The number of new antibiotics approved for marketing in the United States annually continues to decline, and major pharmaceutical companies – many of which pioneered antimicrobial drug development – are continually slackening both the pace and the quantity of antimicrobial agent development.

"We all know that with antibiotics, attrition happens, so that even in the later stages of development, we can’t count on getting all or even a majority of these compounds to market. Further, and very importantly, none of these drugs is available today, and our patients need new drugs now," Boucher added.

Dr. Polgreen’s study was supported by the Centers for Disease Control and Prevention. He reported having no conflicts of interest. Dr. Boucher’s study was funded by the participating institutions. She disclosed serving on an adjudication committee for Merck and as a consultant to Merck, Wyeth/Pfizer, Durata, and PolyMedix.

BOSTON – Born in an era when vaccine-preventable diseases are rare, newly minted physicians appear to have less faith in the efficacy and safety of vaccinations than do their older colleagues – and this skepticism may rub off on patients, with potentially harmful consequences, said investigators at the annual meeting of the Infectious Diseases Society of America.

Recent medical school graduates were about 15% less likely to say that vaccines are efficacious than were their more mature counterparts. The younger providers also were less likely to say they believe that live attenuated or inactivated vaccines against poliomyelitis, measles, mumps, rubella, and varicella were safe, and more likely to say that vaccines do more harm than good, said Dr. Saad B. Omer of the Rollins School of Public Health at Emory University, Atlanta, at a briefing and in a poster to be presented Oct. 21.

Overall support for vaccinations among physicians of all ages is generally strong, Omer said. But the data reveal trends that seem to mirror those seen among parents. Younger physicians, like younger parents, rarely encounter once-commonplace childhood ailments, and therefore may be less sanguine about the benefits of immunization than more seasoned providers, Dr. Omer noted.

"If you are a health care provider, and you have seen a case of whooping cough and have heard a child whoop, or if you have treated Haemophilus influenzae B meningitis, that experience is a little more visceral; and that possibly could have an impact not only on the individual level, but also at the institutional level in terms of training," he said.

In terms of parent and physician attitudes, vaccinations have been victims of their own success, suggested Dr. Bruce Gellin of the National Vaccine Program Office at the U.S. Department of Health and Human Services.

"I think it reflects the power that vaccines have had to make these diseases go away, which now [calls into question] their ‘value’ to the people who are receiving them, because they don’t understand how society has changed because of them," Dr. Gellin said.

"As the familiarity with the disease goes away, then [providers] are only hearing about vaccines and don’t link up with what the vaccines are designed to do," noted Dr. Gellin while moderated a briefing at which the data were presented.

To gauge physician attitudes, Dr. Omer and his colleague Michelle J. Mergler of the National Vaccine Program Office at the U.S. Department of Health and Human Services surveyed physicians who had been identified by parents participating in a vaccine attitudes survey. The children were either fully vaccinated or had parents who were vaccine refuseniks, choosing to opt out of their schools’ immunization requirements.

A total of 551 providers (84.3% response rate) returned completed surveys. The responses were stratified by physicians caring for vaccine-exempt and nonexempt patients, and by year of graduate clinical training in 5-year intervals, from 1954 through 2002.

The researchers found that every 5-year increase in the graduation date was associated with a 20% increase in the odds ratio (OR) that physicians would agree with the statement that "children get more immunizations than are good for them."

In addition, for every 5-year-later graduation date, there was a 20% decrease in the OR that providers would agree with the statement that "immunizations are getting better and safer all the time as the result of medical research."

Parental Attitudes

In a second study, Dr. Thomas Tryon and his colleagues from Children’s Mercy Hospitals and Clinics in Kansas City, Mo., surveyed 909 pediatricians in nine Midwestern states about patients’ reasons for refusing or questioning vaccinations.

They found that parents most frequently refuse or ask the pediatrician to defer administration of the measles, mumps, and rubella (MMR) vaccine, human papillomavirus (HPV) vaccine, and influenza vaccine. The most frequent reasons given were fear of causing autism, too many shots, and serious side effects.

Nearly all of the respondents (95%) said they engaged the family in discussion of or presentation of options, 66% referred families to evidence-based Web sites, and 63% handed out or referred patients to evidence-based literature as a means of intervention.

Overall, 21% of practitioners said they discharged vaccine-refusing families from their practices. Minnesota-based practitioners were least likely (0.9%) to report kicking out a family that had consistently refused vaccinations. In contrast, 38% of pediatricians in Iowa said they had given vaccine-refusing families the boot.

Dr. Omer’s study was internally funded. He reported having no relevant disclosures. Ms. Mergler reported having no relevant disclosures. Dr. Tryon’s study was supported by a research grant from GlaxoSmithKline to coauthor Dr. Christopher Harrison. Dr. Tryon reported no relevant disclosures.

BOSTON – Born in an era when vaccine-preventable diseases are rare, newly minted physicians appear to have less faith in the efficacy and safety of vaccinations than do their older colleagues – and this skepticism may rub off on patients, with potentially harmful consequences, said investigators at the annual meeting of the Infectious Diseases Society of America.

Recent medical school graduates were about 15% less likely to say that vaccines are efficacious than were their more mature counterparts. The younger providers also were less likely to say they believe that live attenuated or inactivated vaccines against poliomyelitis, measles, mumps, rubella, and varicella were safe, and more likely to say that vaccines do more harm than good, said Dr. Saad B. Omer of the Rollins School of Public Health at Emory University, Atlanta, at a briefing and in a poster to be presented Oct. 21.

Overall support for vaccinations among physicians of all ages is generally strong, Omer said. But the data reveal trends that seem to mirror those seen among parents. Younger physicians, like younger parents, rarely encounter once-commonplace childhood ailments, and therefore may be less sanguine about the benefits of immunization than more seasoned providers, Dr. Omer noted.

"If you are a health care provider, and you have seen a case of whooping cough and have heard a child whoop, or if you have treated Haemophilus influenzae B meningitis, that experience is a little more visceral; and that possibly could have an impact not only on the individual level, but also at the institutional level in terms of training," he said.

In terms of parent and physician attitudes, vaccinations have been victims of their own success, suggested Dr. Bruce Gellin of the National Vaccine Program Office at the U.S. Department of Health and Human Services.

"I think it reflects the power that vaccines have had to make these diseases go away, which now [calls into question] their ‘value’ to the people who are receiving them, because they don’t understand how society has changed because of them," Dr. Gellin said.

"As the familiarity with the disease goes away, then [providers] are only hearing about vaccines and don’t link up with what the vaccines are designed to do," noted Dr. Gellin while moderated a briefing at which the data were presented.

To gauge physician attitudes, Dr. Omer and his colleague Michelle J. Mergler of the National Vaccine Program Office at the U.S. Department of Health and Human Services surveyed physicians who had been identified by parents participating in a vaccine attitudes survey. The children were either fully vaccinated or had parents who were vaccine refuseniks, choosing to opt out of their schools’ immunization requirements.

A total of 551 providers (84.3% response rate) returned completed surveys. The responses were stratified by physicians caring for vaccine-exempt and nonexempt patients, and by year of graduate clinical training in 5-year intervals, from 1954 through 2002.

The researchers found that every 5-year increase in the graduation date was associated with a 20% increase in the odds ratio (OR) that physicians would agree with the statement that "children get more immunizations than are good for them."

In addition, for every 5-year-later graduation date, there was a 20% decrease in the OR that providers would agree with the statement that "immunizations are getting better and safer all the time as the result of medical research."

Parental Attitudes

In a second study, Dr. Thomas Tryon and his colleagues from Children’s Mercy Hospitals and Clinics in Kansas City, Mo., surveyed 909 pediatricians in nine Midwestern states about patients’ reasons for refusing or questioning vaccinations.

They found that parents most frequently refuse or ask the pediatrician to defer administration of the measles, mumps, and rubella (MMR) vaccine, human papillomavirus (HPV) vaccine, and influenza vaccine. The most frequent reasons given were fear of causing autism, too many shots, and serious side effects.

Nearly all of the respondents (95%) said they engaged the family in discussion of or presentation of options, 66% referred families to evidence-based Web sites, and 63% handed out or referred patients to evidence-based literature as a means of intervention.

Overall, 21% of practitioners said they discharged vaccine-refusing families from their practices. Minnesota-based practitioners were least likely (0.9%) to report kicking out a family that had consistently refused vaccinations. In contrast, 38% of pediatricians in Iowa said they had given vaccine-refusing families the boot.

Dr. Omer’s study was internally funded. He reported having no relevant disclosures. Ms. Mergler reported having no relevant disclosures. Dr. Tryon’s study was supported by a research grant from GlaxoSmithKline to coauthor Dr. Christopher Harrison. Dr. Tryon reported no relevant disclosures.

BOSTON – Born in an era when vaccine-preventable diseases are rare, newly minted physicians appear to have less faith in the efficacy and safety of vaccinations than do their older colleagues – and this skepticism may rub off on patients, with potentially harmful consequences, said investigators at the annual meeting of the Infectious Diseases Society of America.

Recent medical school graduates were about 15% less likely to say that vaccines are efficacious than were their more mature counterparts. The younger providers also were less likely to say they believe that live attenuated or inactivated vaccines against poliomyelitis, measles, mumps, rubella, and varicella were safe, and more likely to say that vaccines do more harm than good, said Dr. Saad B. Omer of the Rollins School of Public Health at Emory University, Atlanta, at a briefing and in a poster to be presented Oct. 21.

Overall support for vaccinations among physicians of all ages is generally strong, Omer said. But the data reveal trends that seem to mirror those seen among parents. Younger physicians, like younger parents, rarely encounter once-commonplace childhood ailments, and therefore may be less sanguine about the benefits of immunization than more seasoned providers, Dr. Omer noted.

"If you are a health care provider, and you have seen a case of whooping cough and have heard a child whoop, or if you have treated Haemophilus influenzae B meningitis, that experience is a little more visceral; and that possibly could have an impact not only on the individual level, but also at the institutional level in terms of training," he said.

In terms of parent and physician attitudes, vaccinations have been victims of their own success, suggested Dr. Bruce Gellin of the National Vaccine Program Office at the U.S. Department of Health and Human Services.

"I think it reflects the power that vaccines have had to make these diseases go away, which now [calls into question] their ‘value’ to the people who are receiving them, because they don’t understand how society has changed because of them," Dr. Gellin said.

"As the familiarity with the disease goes away, then [providers] are only hearing about vaccines and don’t link up with what the vaccines are designed to do," noted Dr. Gellin while moderated a briefing at which the data were presented.

To gauge physician attitudes, Dr. Omer and his colleague Michelle J. Mergler of the National Vaccine Program Office at the U.S. Department of Health and Human Services surveyed physicians who had been identified by parents participating in a vaccine attitudes survey. The children were either fully vaccinated or had parents who were vaccine refuseniks, choosing to opt out of their schools’ immunization requirements.

A total of 551 providers (84.3% response rate) returned completed surveys. The responses were stratified by physicians caring for vaccine-exempt and nonexempt patients, and by year of graduate clinical training in 5-year intervals, from 1954 through 2002.

The researchers found that every 5-year increase in the graduation date was associated with a 20% increase in the odds ratio (OR) that physicians would agree with the statement that "children get more immunizations than are good for them."

In addition, for every 5-year-later graduation date, there was a 20% decrease in the OR that providers would agree with the statement that "immunizations are getting better and safer all the time as the result of medical research."

Parental Attitudes

In a second study, Dr. Thomas Tryon and his colleagues from Children’s Mercy Hospitals and Clinics in Kansas City, Mo., surveyed 909 pediatricians in nine Midwestern states about patients’ reasons for refusing or questioning vaccinations.

They found that parents most frequently refuse or ask the pediatrician to defer administration of the measles, mumps, and rubella (MMR) vaccine, human papillomavirus (HPV) vaccine, and influenza vaccine. The most frequent reasons given were fear of causing autism, too many shots, and serious side effects.

Nearly all of the respondents (95%) said they engaged the family in discussion of or presentation of options, 66% referred families to evidence-based Web sites, and 63% handed out or referred patients to evidence-based literature as a means of intervention.

Overall, 21% of practitioners said they discharged vaccine-refusing families from their practices. Minnesota-based practitioners were least likely (0.9%) to report kicking out a family that had consistently refused vaccinations. In contrast, 38% of pediatricians in Iowa said they had given vaccine-refusing families the boot.

Dr. Omer’s study was internally funded. He reported having no relevant disclosures. Ms. Mergler reported having no relevant disclosures. Dr. Tryon’s study was supported by a research grant from GlaxoSmithKline to coauthor Dr. Christopher Harrison. Dr. Tryon reported no relevant disclosures.

MIAMI BEACH – An x-ray tube about the size of a sewing needle can safely deliver radiation to nonmelanoma skin tumors on the nose, scalp, or other highly visible areas of skin with good efficacy and good to excellent cosmetic results, an investigator reported at the annual meeting of the American Society for Radiation Oncology.

About 93% of patients treated with an electronic brachytherapy system from Xoft had cosmetic results judged to meet Radiation Therapy Oncology Group (RTOG) criteria for "excellent" at 1 year, said Dr. Ajay Bhatnagar of Cancer Treatment Services Arizona, Casa Grande.

Courtesy Cancer Treatment Services Arizona

"To date, the treatment of nonmelanoma skin cancer with electronic brachytherapy is comparable to traditional brachytherapy, with excellent cosmesis, acceptable acute toxicities, and no recurrences to date. Brachytherapy is an excellent modality for elderly patients with nonmelanoma skin cancers in cosmetically sensitive locations," he said.

The electronic brachytherapy system delivers a radiation dose to tumors equivalent to that of an iridium-192, high dose rate surface (Leipzig) applicator, but without the need for a radioisotope. The electronic device is a miniature, high dose rate, low-energy x-ray tube that produces x-rays with a maximum of 50 keV of energy.

Dr. Bhatnagar looked at data on 102 patients treated with the device for 120 nonmelanoma skin cancer lesions. All patients received 5 Gy in eight dose fractions for a total of 40 Gy delivered in two fractions per week for 4 weeks. The prescription depth, based on CT simulation, varied from 3 to 7 mm. The treatment goal was to achieve a minimum 5-mm treatment margin wherever possible.

The device was placed with the patient immobilized and wearing a flex shield that prevents excessive radiation exposure to the clinician. Skin care included application of petrolatum ointment during treatment and aloe vera gel for 1 month afterward.

Of the 120 lesions treated, 59% had basal cell histology, 36% were squamous cell, 2% were Merkel cell carcinomas, 3% were cutaneous T-cell lymphoma lesions, and 1% had a mixed basal-squamous histology.

About one-third of the lesions were on the nose, another third on the face, with the remainder on the ears, extremities, scalp, and torso.

Nearly all patients (91%) experienced an acute rash with treatment, and 25% had itching of the treatment site. The most frequent late adverse effect was hypopigmentation of the treated skin, which occurred in 11% of lesions from 3 to 6 months.

At 1 month post treatment, cosmesis was rated as excellent (no change to slight atrophy or pigment change; slight hair loss; or no changes to slight induration or loss of subcutaneous fat) in about 77% of 81 patients evaluated; the remainder had "good" cosmesis (patch atrophy, moderate telangiectasia, total hair loss; moderate fibrosis but asymptomatic, slight field contracture with less than 10% linear reduction).

A physician who was not involved in the study commented that radiation therapy offers certain advantages over surgery when tumors are located in prominent locations, such as the face.

"We’ve been treating these lesions for close to 100 years now, and radiation does very well," said Dr. Keith A. Cengel, of the University of Pennsylvania School of Medicine in Philadelphia. "The one drawback – and I tell this to my patients when I treat with radiation – is that [subsequent] surgery can be more difficult and have a higher complication rate if you have a recurrence."

Mohs surgery, the most common form of treatment for basal or squamous cell skin cancers, may itself leave a comparatively deep and wide wound that may not heal as smoothly as a radiation-treated lesion, he added.

Dr. Cengel comoderated the session in which the electronic brachytherapy data were presented.

The study was sponsored by Xoft, manufacturer of the brachytherapy device. Dr. Bhatnagar receives funding for serving as principal investigator of a prospective multicenter study of the device.

MIAMI BEACH – An x-ray tube about the size of a sewing needle can safely deliver radiation to nonmelanoma skin tumors on the nose, scalp, or other highly visible areas of skin with good efficacy and good to excellent cosmetic results, an investigator reported at the annual meeting of the American Society for Radiation Oncology.

About 93% of patients treated with an electronic brachytherapy system from Xoft had cosmetic results judged to meet Radiation Therapy Oncology Group (RTOG) criteria for "excellent" at 1 year, said Dr. Ajay Bhatnagar of Cancer Treatment Services Arizona, Casa Grande.

Courtesy Cancer Treatment Services Arizona

"To date, the treatment of nonmelanoma skin cancer with electronic brachytherapy is comparable to traditional brachytherapy, with excellent cosmesis, acceptable acute toxicities, and no recurrences to date. Brachytherapy is an excellent modality for elderly patients with nonmelanoma skin cancers in cosmetically sensitive locations," he said.

The electronic brachytherapy system delivers a radiation dose to tumors equivalent to that of an iridium-192, high dose rate surface (Leipzig) applicator, but without the need for a radioisotope. The electronic device is a miniature, high dose rate, low-energy x-ray tube that produces x-rays with a maximum of 50 keV of energy.

Dr. Bhatnagar looked at data on 102 patients treated with the device for 120 nonmelanoma skin cancer lesions. All patients received 5 Gy in eight dose fractions for a total of 40 Gy delivered in two fractions per week for 4 weeks. The prescription depth, based on CT simulation, varied from 3 to 7 mm. The treatment goal was to achieve a minimum 5-mm treatment margin wherever possible.

The device was placed with the patient immobilized and wearing a flex shield that prevents excessive radiation exposure to the clinician. Skin care included application of petrolatum ointment during treatment and aloe vera gel for 1 month afterward.

Of the 120 lesions treated, 59% had basal cell histology, 36% were squamous cell, 2% were Merkel cell carcinomas, 3% were cutaneous T-cell lymphoma lesions, and 1% had a mixed basal-squamous histology.

About one-third of the lesions were on the nose, another third on the face, with the remainder on the ears, extremities, scalp, and torso.

Nearly all patients (91%) experienced an acute rash with treatment, and 25% had itching of the treatment site. The most frequent late adverse effect was hypopigmentation of the treated skin, which occurred in 11% of lesions from 3 to 6 months.

At 1 month post treatment, cosmesis was rated as excellent (no change to slight atrophy or pigment change; slight hair loss; or no changes to slight induration or loss of subcutaneous fat) in about 77% of 81 patients evaluated; the remainder had "good" cosmesis (patch atrophy, moderate telangiectasia, total hair loss; moderate fibrosis but asymptomatic, slight field contracture with less than 10% linear reduction).

A physician who was not involved in the study commented that radiation therapy offers certain advantages over surgery when tumors are located in prominent locations, such as the face.

"We’ve been treating these lesions for close to 100 years now, and radiation does very well," said Dr. Keith A. Cengel, of the University of Pennsylvania School of Medicine in Philadelphia. "The one drawback – and I tell this to my patients when I treat with radiation – is that [subsequent] surgery can be more difficult and have a higher complication rate if you have a recurrence."

Mohs surgery, the most common form of treatment for basal or squamous cell skin cancers, may itself leave a comparatively deep and wide wound that may not heal as smoothly as a radiation-treated lesion, he added.

Dr. Cengel comoderated the session in which the electronic brachytherapy data were presented.

The study was sponsored by Xoft, manufacturer of the brachytherapy device. Dr. Bhatnagar receives funding for serving as principal investigator of a prospective multicenter study of the device.

MIAMI BEACH – An x-ray tube about the size of a sewing needle can safely deliver radiation to nonmelanoma skin tumors on the nose, scalp, or other highly visible areas of skin with good efficacy and good to excellent cosmetic results, an investigator reported at the annual meeting of the American Society for Radiation Oncology.

About 93% of patients treated with an electronic brachytherapy system from Xoft had cosmetic results judged to meet Radiation Therapy Oncology Group (RTOG) criteria for "excellent" at 1 year, said Dr. Ajay Bhatnagar of Cancer Treatment Services Arizona, Casa Grande.

Courtesy Cancer Treatment Services Arizona

"To date, the treatment of nonmelanoma skin cancer with electronic brachytherapy is comparable to traditional brachytherapy, with excellent cosmesis, acceptable acute toxicities, and no recurrences to date. Brachytherapy is an excellent modality for elderly patients with nonmelanoma skin cancers in cosmetically sensitive locations," he said.

The electronic brachytherapy system delivers a radiation dose to tumors equivalent to that of an iridium-192, high dose rate surface (Leipzig) applicator, but without the need for a radioisotope. The electronic device is a miniature, high dose rate, low-energy x-ray tube that produces x-rays with a maximum of 50 keV of energy.

Dr. Bhatnagar looked at data on 102 patients treated with the device for 120 nonmelanoma skin cancer lesions. All patients received 5 Gy in eight dose fractions for a total of 40 Gy delivered in two fractions per week for 4 weeks. The prescription depth, based on CT simulation, varied from 3 to 7 mm. The treatment goal was to achieve a minimum 5-mm treatment margin wherever possible.

The device was placed with the patient immobilized and wearing a flex shield that prevents excessive radiation exposure to the clinician. Skin care included application of petrolatum ointment during treatment and aloe vera gel for 1 month afterward.

Of the 120 lesions treated, 59% had basal cell histology, 36% were squamous cell, 2% were Merkel cell carcinomas, 3% were cutaneous T-cell lymphoma lesions, and 1% had a mixed basal-squamous histology.

About one-third of the lesions were on the nose, another third on the face, with the remainder on the ears, extremities, scalp, and torso.

Nearly all patients (91%) experienced an acute rash with treatment, and 25% had itching of the treatment site. The most frequent late adverse effect was hypopigmentation of the treated skin, which occurred in 11% of lesions from 3 to 6 months.

At 1 month post treatment, cosmesis was rated as excellent (no change to slight atrophy or pigment change; slight hair loss; or no changes to slight induration or loss of subcutaneous fat) in about 77% of 81 patients evaluated; the remainder had "good" cosmesis (patch atrophy, moderate telangiectasia, total hair loss; moderate fibrosis but asymptomatic, slight field contracture with less than 10% linear reduction).

A physician who was not involved in the study commented that radiation therapy offers certain advantages over surgery when tumors are located in prominent locations, such as the face.

"We’ve been treating these lesions for close to 100 years now, and radiation does very well," said Dr. Keith A. Cengel, of the University of Pennsylvania School of Medicine in Philadelphia. "The one drawback – and I tell this to my patients when I treat with radiation – is that [subsequent] surgery can be more difficult and have a higher complication rate if you have a recurrence."

Mohs surgery, the most common form of treatment for basal or squamous cell skin cancers, may itself leave a comparatively deep and wide wound that may not heal as smoothly as a radiation-treated lesion, he added.

Dr. Cengel comoderated the session in which the electronic brachytherapy data were presented.

The study was sponsored by Xoft, manufacturer of the brachytherapy device. Dr. Bhatnagar receives funding for serving as principal investigator of a prospective multicenter study of the device.

MIAMI BEACH – An x-ray tube about the size of a sewing needle can safely deliver radiation to nonmelanoma skin tumors on the nose, scalp, or other highly visible areas of skin with good efficacy and good to excellent cosmetic results, an investigator reported at the annual meeting of the American Society for Radiation Oncology.

About 93% of patients treated with an electronic brachytherapy system from Xoft had cosmetic results judged to meet Radiation Therapy Oncology Group (RTOG) criteria for "excellent" at 1 year, said Dr. Ajay Bhatnagar of Cancer Treatment Services Arizona, Casa Grande.

Courtesy Cancer Treatment Services Arizona

"To date, the treatment of nonmelanoma skin cancer with electronic brachytherapy is comparable to traditional brachytherapy, with excellent cosmesis, acceptable acute toxicities, and no recurrences to date. Brachytherapy is an excellent modality for elderly patients with nonmelanoma skin cancers in cosmetically sensitive locations," he said.

The electronic brachytherapy system delivers a radiation dose to tumors equivalent to that of an iridium-192, high dose rate surface (Leipzig) applicator, but without the need for a radioisotope. The electronic device is a miniature, high dose rate, low-energy x-ray tube that produces x-rays with a maximum of 50 keV of energy.

Dr. Bhatnagar looked at data on 102 patients treated with the device for 120 nonmelanoma skin cancer lesions. All patients received 5 Gy in eight dose fractions for a total of 40 Gy delivered in two fractions per week for 4 weeks. The prescription depth, based on CT simulation, varied from 3 to 7 mm. The treatment goal was to achieve a minimum 5-mm treatment margin wherever possible.

The device was placed with the patient immobilized and wearing a flex shield that prevents excessive radiation exposure to the clinician. Skin care included application of petrolatum ointment during treatment and aloe vera gel for 1 month afterward.

Of the 120 lesions treated, 59% had basal cell histology, 36% were squamous cell, 2% were Merkel cell carcinomas, 3% were cutaneous T-cell lymphoma lesions, and 1% had a mixed basal-squamous histology.

About one-third of the lesions were on the nose, another third on the face, with the remainder on the ears, extremities, scalp, and torso.

Nearly all patients (91%) experienced an acute rash with treatment, and 25% had itching of the treatment site. The most frequent late adverse effect was hypopigmentation of the treated skin, which occurred in 11% of lesions from 3 to 6 months.

At 1 month post treatment, cosmesis was rated as excellent (no change to slight atrophy or pigment change; slight hair loss; or no changes to slight induration or loss of subcutaneous fat) in about 77% of 81 patients evaluated; the remainder had "good" cosmesis (patch atrophy, moderate telangiectasia, total hair loss; moderate fibrosis but asymptomatic, slight field contracture with less than 10% linear reduction).

Dr. Bhatnagar also launched a salvo in the turf battle between radiation oncologists and surgeons by urging his colleagues to take on more skin cancer cases. "Despite skin cancer being the most common malignancy in the world, it’s under-represented in our radiation oncology clinics. As radiation oncologists, we need to play a more prominent role in the treatment of nonmelanoma skin cancers," he said in his presentation.

A radiation oncologist who was not involved in the study commented that radiation therapy offers certain advantages over surgery when tumors are located in prominent locations, such as the face.

"We’ve been treating these lesions for close to 100 years now, and radiation does very well," said Dr. Keith A. Cengel, of the University of Pennsylvania School of Medicine in Philadelphia. "The one drawback – and I tell this to my patients when I treat with radiation – is that [subsequent] surgery can be more difficult and have a higher complication rate if you have a recurrence."

Mohs surgery, the most common form of treatment for basal or squamous cell skin cancers, may itself leave a comparatively deep and wide wound that may not heal as smoothly as a radiation-treated lesion, he added.

Dr. Cengel comoderated the session in which the electronic brachytherapy data were presented.

The study was sponsored by Xoft, manufacturer of the brachytherapy device. Dr. Bhatnagar receives funding for serving as principal investigator of a prospective multicenter study of the device.

MIAMI BEACH – An x-ray tube about the size of a sewing needle can safely deliver radiation to nonmelanoma skin tumors on the nose, scalp, or other highly visible areas of skin with good efficacy and good to excellent cosmetic results, an investigator reported at the annual meeting of the American Society for Radiation Oncology.

About 93% of patients treated with an electronic brachytherapy system from Xoft had cosmetic results judged to meet Radiation Therapy Oncology Group (RTOG) criteria for "excellent" at 1 year, said Dr. Ajay Bhatnagar of Cancer Treatment Services Arizona, Casa Grande.

Courtesy Cancer Treatment Services Arizona

"To date, the treatment of nonmelanoma skin cancer with electronic brachytherapy is comparable to traditional brachytherapy, with excellent cosmesis, acceptable acute toxicities, and no recurrences to date. Brachytherapy is an excellent modality for elderly patients with nonmelanoma skin cancers in cosmetically sensitive locations," he said.

The electronic brachytherapy system delivers a radiation dose to tumors equivalent to that of an iridium-192, high dose rate surface (Leipzig) applicator, but without the need for a radioisotope. The electronic device is a miniature, high dose rate, low-energy x-ray tube that produces x-rays with a maximum of 50 keV of energy.

Dr. Bhatnagar looked at data on 102 patients treated with the device for 120 nonmelanoma skin cancer lesions. All patients received 5 Gy in eight dose fractions for a total of 40 Gy delivered in two fractions per week for 4 weeks. The prescription depth, based on CT simulation, varied from 3 to 7 mm. The treatment goal was to achieve a minimum 5-mm treatment margin wherever possible.

The device was placed with the patient immobilized and wearing a flex shield that prevents excessive radiation exposure to the clinician. Skin care included application of petrolatum ointment during treatment and aloe vera gel for 1 month afterward.

Of the 120 lesions treated, 59% had basal cell histology, 36% were squamous cell, 2% were Merkel cell carcinomas, 3% were cutaneous T-cell lymphoma lesions, and 1% had a mixed basal-squamous histology.

About one-third of the lesions were on the nose, another third on the face, with the remainder on the ears, extremities, scalp, and torso.

Nearly all patients (91%) experienced an acute rash with treatment, and 25% had itching of the treatment site. The most frequent late adverse effect was hypopigmentation of the treated skin, which occurred in 11% of lesions from 3 to 6 months.

At 1 month post treatment, cosmesis was rated as excellent (no change to slight atrophy or pigment change; slight hair loss; or no changes to slight induration or loss of subcutaneous fat) in about 77% of 81 patients evaluated; the remainder had "good" cosmesis (patch atrophy, moderate telangiectasia, total hair loss; moderate fibrosis but asymptomatic, slight field contracture with less than 10% linear reduction).

Dr. Bhatnagar also launched a salvo in the turf battle between radiation oncologists and surgeons by urging his colleagues to take on more skin cancer cases. "Despite skin cancer being the most common malignancy in the world, it’s under-represented in our radiation oncology clinics. As radiation oncologists, we need to play a more prominent role in the treatment of nonmelanoma skin cancers," he said in his presentation.

A radiation oncologist who was not involved in the study commented that radiation therapy offers certain advantages over surgery when tumors are located in prominent locations, such as the face.

"We’ve been treating these lesions for close to 100 years now, and radiation does very well," said Dr. Keith A. Cengel, of the University of Pennsylvania School of Medicine in Philadelphia. "The one drawback – and I tell this to my patients when I treat with radiation – is that [subsequent] surgery can be more difficult and have a higher complication rate if you have a recurrence."

Mohs surgery, the most common form of treatment for basal or squamous cell skin cancers, may itself leave a comparatively deep and wide wound that may not heal as smoothly as a radiation-treated lesion, he added.

Dr. Cengel comoderated the session in which the electronic brachytherapy data were presented.

The study was sponsored by Xoft, manufacturer of the brachytherapy device. Dr. Bhatnagar receives funding for serving as principal investigator of a prospective multicenter study of the device.

MIAMI BEACH – An x-ray tube about the size of a sewing needle can safely deliver radiation to nonmelanoma skin tumors on the nose, scalp, or other highly visible areas of skin with good efficacy and good to excellent cosmetic results, an investigator reported at the annual meeting of the American Society for Radiation Oncology.

About 93% of patients treated with an electronic brachytherapy system from Xoft had cosmetic results judged to meet Radiation Therapy Oncology Group (RTOG) criteria for "excellent" at 1 year, said Dr. Ajay Bhatnagar of Cancer Treatment Services Arizona, Casa Grande.

Courtesy Cancer Treatment Services Arizona

"To date, the treatment of nonmelanoma skin cancer with electronic brachytherapy is comparable to traditional brachytherapy, with excellent cosmesis, acceptable acute toxicities, and no recurrences to date. Brachytherapy is an excellent modality for elderly patients with nonmelanoma skin cancers in cosmetically sensitive locations," he said.

The electronic brachytherapy system delivers a radiation dose to tumors equivalent to that of an iridium-192, high dose rate surface (Leipzig) applicator, but without the need for a radioisotope. The electronic device is a miniature, high dose rate, low-energy x-ray tube that produces x-rays with a maximum of 50 keV of energy.

Dr. Bhatnagar looked at data on 102 patients treated with the device for 120 nonmelanoma skin cancer lesions. All patients received 5 Gy in eight dose fractions for a total of 40 Gy delivered in two fractions per week for 4 weeks. The prescription depth, based on CT simulation, varied from 3 to 7 mm. The treatment goal was to achieve a minimum 5-mm treatment margin wherever possible.

The device was placed with the patient immobilized and wearing a flex shield that prevents excessive radiation exposure to the clinician. Skin care included application of petrolatum ointment during treatment and aloe vera gel for 1 month afterward.

Of the 120 lesions treated, 59% had basal cell histology, 36% were squamous cell, 2% were Merkel cell carcinomas, 3% were cutaneous T-cell lymphoma lesions, and 1% had a mixed basal-squamous histology.

About one-third of the lesions were on the nose, another third on the face, with the remainder on the ears, extremities, scalp, and torso.

Nearly all patients (91%) experienced an acute rash with treatment, and 25% had itching of the treatment site. The most frequent late adverse effect was hypopigmentation of the treated skin, which occurred in 11% of lesions from 3 to 6 months.

At 1 month post treatment, cosmesis was rated as excellent (no change to slight atrophy or pigment change; slight hair loss; or no changes to slight induration or loss of subcutaneous fat) in about 77% of 81 patients evaluated; the remainder had "good" cosmesis (patch atrophy, moderate telangiectasia, total hair loss; moderate fibrosis but asymptomatic, slight field contracture with less than 10% linear reduction).

Dr. Bhatnagar also launched a salvo in the turf battle between radiation oncologists and surgeons by urging his colleagues to take on more skin cancer cases. "Despite skin cancer being the most common malignancy in the world, it’s under-represented in our radiation oncology clinics. As radiation oncologists, we need to play a more prominent role in the treatment of nonmelanoma skin cancers," he said in his presentation.

A radiation oncologist who was not involved in the study commented that radiation therapy offers certain advantages over surgery when tumors are located in prominent locations, such as the face.

"We’ve been treating these lesions for close to 100 years now, and radiation does very well," said Dr. Keith A. Cengel, of the University of Pennsylvania School of Medicine in Philadelphia. "The one drawback – and I tell this to my patients when I treat with radiation – is that [subsequent] surgery can be more difficult and have a higher complication rate if you have a recurrence."

Mohs surgery, the most common form of treatment for basal or squamous cell skin cancers, may itself leave a comparatively deep and wide wound that may not heal as smoothly as a radiation-treated lesion, he added.

Dr. Cengel comoderated the session in which the electronic brachytherapy data were presented.

The study was sponsored by Xoft, manufacturer of the brachytherapy device. Dr. Bhatnagar receives funding for serving as principal investigator of a prospective multicenter study of the device.

MIAMI BEACH – Where conventional radiation and surgery often fail, high-dose proton–based radiation therapy can succeed at providing local control of spinal chordomas, according to investigators at the annual meeting of the American Society for Radiation Oncology.

Among 126 patients with 127 localized chordomas, those who received a combination of pre- and postoperative radiation with protons added to photon radiation had a 5-year local control rate of 85%, reported Dr. Ronny L. Rotondo of the Stephen Harris Chordoma Center at Massachusetts General Hospital in Boston and his colleagues.

"Local control of spinal chordomas remains quite poor with surgery and photon-radiation therapy at conventional doses less than 60 Gy, with a number of series reporting local failure rates as high as 75%-100%. More recently, a number of centers have reported encouraging results with particle therapy, including protons and carbon ions," Dr. Rotondo said.

Chordomas are rare cancers that arise from the remnants of the fetal notochord, a structure that normally exists only during embryonic development. Although they do not tend to metastasize, chordomas incapacitate patients with locally aggressive growth.

Surgical resection is the mainstay of treatment, but local recurrences are common, and salvage therapy after local failure is often unsuccessful, hence the need for adjuvant radiation therapy, Dr. Rotondo said.

The unique physical properties of proton energy deposition in tissue makes proton therapy well suited for treatment of chordomas; most of the dose is deposited in the target tissue with little or no exit dose, allowing for higher doses and better local control than is possible with conventional photon therapy, he said.

He and his colleagues looked at clinical outcomes and clinical and pathologic prognostic factors in patients who underwent high-dose proton–based therapy with or without surgery for primary or recurrent chordomas of the thoracic, lumbar, or sacrococcygeal spine.

The patients were treated from 1982 through 2011 at either the Harvard Cyclotron Laboratory in Cambridge, Mass., or more recently at Massachusetts General Hospital’s proton therapy center in Boston. Their mean age at diagnosis was 53 years (range, 5-88 years), and the mean maximum size of lesions was 7 cm (range, 1.6 cm-21.7 cm).

In all, 45% of patients had surgery followed by radiation; 48% had preoperative radiation and surgery, followed by postoperative radiation; and 7% had radiation for recurrent tumors. About half of all of the surgeries (49%) were performed with en bloc resection, and 49% were intralesional (in the remaining 2% the surgery type was unknown).

Clear surgical margins (R0) were achieved in 27% of patients, with 45% having R1 resections, 24% having R2 margins, and 4% having unknown margin status.

Although some received protons* exclusively, most patients received a combination of photons and protons, with the protons comprising about 45% of the energy delivered in both pre- and postoperative treatment. The mean total dose delivered was 72.4 Gy.

Among patients still alive, median follow-up was 47 months with a median of 5.7 months since the last follow-up.

For the entire cohort, overall survival was 81% at 5 years and 53% at 10 years. The local control rate was 62% at 5 years and 49% at 10 years. Distant control was 77% at 5 years and 63% at 10 years.

Comparing patients by presentation, the investigators found that the 5-year local rate was 68% for patients with primary tumors, compared with 49% for those with recurrent tumors (P = .058). Respective 5-year event-free survival rates by presentation were 51% and 34% (P = .035).

Local control rates were also significantly better among patients who had undergone en bloc resection, at 72% at 5 years, compared with 55% for those who underwent an intralesional procedure (P = .016).

There were no significant differences in local control by surgical margin size, although there was a trend favoring R0, compared with R1 or R2, resections.

Preoperative radiotherapy also offered a significant benefit in both local and locoregional control of primary tumors. Local control at 5 years was 85% for those who received preoperative radiation in addition to postoperative, compared with 56% for those who did not (P = .019). Respective locoregional control rates were 79% and 56% at 5 years (P = .034).

The review was internally funded. Dr. Rotondo reported having no relevant conflicts of interest.

*Correction, 10/25/2011: An earlier version of this story incorrectly stated that some patients received photons exclusively.

MIAMI BEACH – Where conventional radiation and surgery often fail, high-dose proton–based radiation therapy can succeed at providing local control of spinal chordomas, according to investigators at the annual meeting of the American Society for Radiation Oncology.

Among 126 patients with 127 localized chordomas, those who received a combination of pre- and postoperative radiation with protons added to photon radiation had a 5-year local control rate of 85%, reported Dr. Ronny L. Rotondo of the Stephen Harris Chordoma Center at Massachusetts General Hospital in Boston and his colleagues.

"Local control of spinal chordomas remains quite poor with surgery and photon-radiation therapy at conventional doses less than 60 Gy, with a number of series reporting local failure rates as high as 75%-100%. More recently, a number of centers have reported encouraging results with particle therapy, including protons and carbon ions," Dr. Rotondo said.

Chordomas are rare cancers that arise from the remnants of the fetal notochord, a structure that normally exists only during embryonic development. Although they do not tend to metastasize, chordomas incapacitate patients with locally aggressive growth.

Surgical resection is the mainstay of treatment, but local recurrences are common, and salvage therapy after local failure is often unsuccessful, hence the need for adjuvant radiation therapy, Dr. Rotondo said.

The unique physical properties of proton energy deposition in tissue makes proton therapy well suited for treatment of chordomas; most of the dose is deposited in the target tissue with little or no exit dose, allowing for higher doses and better local control than is possible with conventional photon therapy, he said.

He and his colleagues looked at clinical outcomes and clinical and pathologic prognostic factors in patients who underwent high-dose proton–based therapy with or without surgery for primary or recurrent chordomas of the thoracic, lumbar, or sacrococcygeal spine.

The patients were treated from 1982 through 2011 at either the Harvard Cyclotron Laboratory in Cambridge, Mass., or more recently at Massachusetts General Hospital’s proton therapy center in Boston. Their mean age at diagnosis was 53 years (range, 5-88 years), and the mean maximum size of lesions was 7 cm (range, 1.6 cm-21.7 cm).

In all, 45% of patients had surgery followed by radiation; 48% had preoperative radiation and surgery, followed by postoperative radiation; and 7% had radiation for recurrent tumors. About half of all of the surgeries (49%) were performed with en bloc resection, and 49% were intralesional (in the remaining 2% the surgery type was unknown).

Clear surgical margins (R0) were achieved in 27% of patients, with 45% having R1 resections, 24% having R2 margins, and 4% having unknown margin status.

Although some received protons* exclusively, most patients received a combination of photons and protons, with the protons comprising about 45% of the energy delivered in both pre- and postoperative treatment. The mean total dose delivered was 72.4 Gy.

Among patients still alive, median follow-up was 47 months with a median of 5.7 months since the last follow-up.

For the entire cohort, overall survival was 81% at 5 years and 53% at 10 years. The local control rate was 62% at 5 years and 49% at 10 years. Distant control was 77% at 5 years and 63% at 10 years.

Comparing patients by presentation, the investigators found that the 5-year local rate was 68% for patients with primary tumors, compared with 49% for those with recurrent tumors (P = .058). Respective 5-year event-free survival rates by presentation were 51% and 34% (P = .035).

Local control rates were also significantly better among patients who had undergone en bloc resection, at 72% at 5 years, compared with 55% for those who underwent an intralesional procedure (P = .016).

There were no significant differences in local control by surgical margin size, although there was a trend favoring R0, compared with R1 or R2, resections.

Preoperative radiotherapy also offered a significant benefit in both local and locoregional control of primary tumors. Local control at 5 years was 85% for those who received preoperative radiation in addition to postoperative, compared with 56% for those who did not (P = .019). Respective locoregional control rates were 79% and 56% at 5 years (P = .034).

The review was internally funded. Dr. Rotondo reported having no relevant conflicts of interest.

*Correction, 10/25/2011: An earlier version of this story incorrectly stated that some patients received photons exclusively.

MIAMI BEACH – Where conventional radiation and surgery often fail, high-dose proton–based radiation therapy can succeed at providing local control of spinal chordomas, according to investigators at the annual meeting of the American Society for Radiation Oncology.

Among 126 patients with 127 localized chordomas, those who received a combination of pre- and postoperative radiation with protons added to photon radiation had a 5-year local control rate of 85%, reported Dr. Ronny L. Rotondo of the Stephen Harris Chordoma Center at Massachusetts General Hospital in Boston and his colleagues.

"Local control of spinal chordomas remains quite poor with surgery and photon-radiation therapy at conventional doses less than 60 Gy, with a number of series reporting local failure rates as high as 75%-100%. More recently, a number of centers have reported encouraging results with particle therapy, including protons and carbon ions," Dr. Rotondo said.

Chordomas are rare cancers that arise from the remnants of the fetal notochord, a structure that normally exists only during embryonic development. Although they do not tend to metastasize, chordomas incapacitate patients with locally aggressive growth.

Surgical resection is the mainstay of treatment, but local recurrences are common, and salvage therapy after local failure is often unsuccessful, hence the need for adjuvant radiation therapy, Dr. Rotondo said.

The unique physical properties of proton energy deposition in tissue makes proton therapy well suited for treatment of chordomas; most of the dose is deposited in the target tissue with little or no exit dose, allowing for higher doses and better local control than is possible with conventional photon therapy, he said.

He and his colleagues looked at clinical outcomes and clinical and pathologic prognostic factors in patients who underwent high-dose proton–based therapy with or without surgery for primary or recurrent chordomas of the thoracic, lumbar, or sacrococcygeal spine.

The patients were treated from 1982 through 2011 at either the Harvard Cyclotron Laboratory in Cambridge, Mass., or more recently at Massachusetts General Hospital’s proton therapy center in Boston. Their mean age at diagnosis was 53 years (range, 5-88 years), and the mean maximum size of lesions was 7 cm (range, 1.6 cm-21.7 cm).

In all, 45% of patients had surgery followed by radiation; 48% had preoperative radiation and surgery, followed by postoperative radiation; and 7% had radiation for recurrent tumors. About half of all of the surgeries (49%) were performed with en bloc resection, and 49% were intralesional (in the remaining 2% the surgery type was unknown).

Clear surgical margins (R0) were achieved in 27% of patients, with 45% having R1 resections, 24% having R2 margins, and 4% having unknown margin status.

Although some received protons* exclusively, most patients received a combination of photons and protons, with the protons comprising about 45% of the energy delivered in both pre- and postoperative treatment. The mean total dose delivered was 72.4 Gy.

Among patients still alive, median follow-up was 47 months with a median of 5.7 months since the last follow-up.

For the entire cohort, overall survival was 81% at 5 years and 53% at 10 years. The local control rate was 62% at 5 years and 49% at 10 years. Distant control was 77% at 5 years and 63% at 10 years.

Comparing patients by presentation, the investigators found that the 5-year local rate was 68% for patients with primary tumors, compared with 49% for those with recurrent tumors (P = .058). Respective 5-year event-free survival rates by presentation were 51% and 34% (P = .035).

Local control rates were also significantly better among patients who had undergone en bloc resection, at 72% at 5 years, compared with 55% for those who underwent an intralesional procedure (P = .016).

There were no significant differences in local control by surgical margin size, although there was a trend favoring R0, compared with R1 or R2, resections.

Preoperative radiotherapy also offered a significant benefit in both local and locoregional control of primary tumors. Local control at 5 years was 85% for those who received preoperative radiation in addition to postoperative, compared with 56% for those who did not (P = .019). Respective locoregional control rates were 79% and 56% at 5 years (P = .034).

The review was internally funded. Dr. Rotondo reported having no relevant conflicts of interest.

*Correction, 10/25/2011: An earlier version of this story incorrectly stated that some patients received photons exclusively.

MIAMI BEACH – Bevacizumab added to docetaxel and definitive radiotherapy was an effective and safe non–platinum-based regimen for locoregionally advanced squamous cell carcinoma of the head and neck in a small phase II trial that was presented at the annual meeting of the American Society for Radiation Oncology.

The disease-free survival rate at 2 years (the primary end point) was 75% among 28 patients who had completed the full course of chemoradiation in the phase II study, said Dr. Nicholas Galanopoulos of University Hospitals Seidman Cancer Center in Cleveland. In this as-treated population, 85% of patients were alive at 2 years, locoregional control was achieved in 85% of patients, and 81.5% were free of distant metastases at 2 years.

The numbers were slightly lower when two additional patients who dropped out of the study (one for unspecified reasons and one who developed aspiration pneumonia and was hospitalized) were included in an intention-to-treat analysis. Among all 30 patients, the disease-free survival rate at 2 years was 63% and overall survival was 72%, although locoregional control and distant-metastasis-free rates remained unchanged at 85% and 81.5%, respectively.

"Future trials of concurrent chemoradiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer," Dr. Galanopoulos said.

The rationale for trying bevacizumab (Avastin) in chemoradiation regimens for head and neck tumors is based on its demonstrated ability to inhibit endothelial cell proliferation and blood vessel formation, and to increase radiosensitivity of tumors when administered concurrently with radiation, he noted.

In all, 30 treatment-naive patients (26 men, 4 women) with locally advanced stage III (6 patients) or IV (24 patients) squamous cell carcinoma of the head and neck were enrolled. The patients had good performance status and a life expectancy greater than 12 weeks.

They received 70.2 Gy radiation in 1.8-Gy fractions, docetaxel (Taxotere) 20 mg/m² per week, and bevacizumab 5 mg/kg every 2 weeks, with bevacizumab continued for up to 1 year following chemoradiation (median, 7 months).

"Future trials of concurrent chemo-radiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer."

Results were reported as of a median follow-up of 24.4 months.

Adjuvant bevacizumab was stopped 4 weeks before surgery in those patients who required neck dissection, and the drug was discontinued in three patients (one for radiation necrosis of the larynx requiring laryngectomy, one for severe pharyngoesophageal stenosis, and one for hemorrhagic cholecystits requiring cholecystectomy).

Major toxicities associated with the regimen included grade 4 bleeding in two patients (the episode of hemorrhagic cholecystitis already noted), and one oropharyngeal hemorrhage in field during chemoradiation.

Late grade 3 or 4 dysphagia occurred in 7 of 19 patients who had been treated with 3-D conformal radiation therapy, but in none of 11 patients who received intensity-modulated radiation (P less than .05). Patients with laryngeal primary tumors were more likely to develop serious late dysphagia, compared with patients with oropharyngeal primaries (58%% vs. 15%; P less than .05).

The study was funded in part by grants from the National Institutes of Health, Genentech, and Sanofi-Aventis. Dr. Galanopoulos reported having no relevant financial disclosures. Coauthor Dr. Panayiotis Savvides disclosed receiving research grants or support from Genentech and Sanofi-Aventis.

MIAMI BEACH – Bevacizumab added to docetaxel and definitive radiotherapy was an effective and safe non–platinum-based regimen for locoregionally advanced squamous cell carcinoma of the head and neck in a small phase II trial that was presented at the annual meeting of the American Society for Radiation Oncology.

The disease-free survival rate at 2 years (the primary end point) was 75% among 28 patients who had completed the full course of chemoradiation in the phase II study, said Dr. Nicholas Galanopoulos of University Hospitals Seidman Cancer Center in Cleveland. In this as-treated population, 85% of patients were alive at 2 years, locoregional control was achieved in 85% of patients, and 81.5% were free of distant metastases at 2 years.

The numbers were slightly lower when two additional patients who dropped out of the study (one for unspecified reasons and one who developed aspiration pneumonia and was hospitalized) were included in an intention-to-treat analysis. Among all 30 patients, the disease-free survival rate at 2 years was 63% and overall survival was 72%, although locoregional control and distant-metastasis-free rates remained unchanged at 85% and 81.5%, respectively.

"Future trials of concurrent chemoradiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer," Dr. Galanopoulos said.

The rationale for trying bevacizumab (Avastin) in chemoradiation regimens for head and neck tumors is based on its demonstrated ability to inhibit endothelial cell proliferation and blood vessel formation, and to increase radiosensitivity of tumors when administered concurrently with radiation, he noted.

In all, 30 treatment-naive patients (26 men, 4 women) with locally advanced stage III (6 patients) or IV (24 patients) squamous cell carcinoma of the head and neck were enrolled. The patients had good performance status and a life expectancy greater than 12 weeks.

They received 70.2 Gy radiation in 1.8-Gy fractions, docetaxel (Taxotere) 20 mg/m² per week, and bevacizumab 5 mg/kg every 2 weeks, with bevacizumab continued for up to 1 year following chemoradiation (median, 7 months).

"Future trials of concurrent chemo-radiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer."

Results were reported as of a median follow-up of 24.4 months.

Adjuvant bevacizumab was stopped 4 weeks before surgery in those patients who required neck dissection, and the drug was discontinued in three patients (one for radiation necrosis of the larynx requiring laryngectomy, one for severe pharyngoesophageal stenosis, and one for hemorrhagic cholecystits requiring cholecystectomy).

Major toxicities associated with the regimen included grade 4 bleeding in two patients (the episode of hemorrhagic cholecystitis already noted), and one oropharyngeal hemorrhage in field during chemoradiation.

Late grade 3 or 4 dysphagia occurred in 7 of 19 patients who had been treated with 3-D conformal radiation therapy, but in none of 11 patients who received intensity-modulated radiation (P less than .05). Patients with laryngeal primary tumors were more likely to develop serious late dysphagia, compared with patients with oropharyngeal primaries (58%% vs. 15%; P less than .05).

The study was funded in part by grants from the National Institutes of Health, Genentech, and Sanofi-Aventis. Dr. Galanopoulos reported having no relevant financial disclosures. Coauthor Dr. Panayiotis Savvides disclosed receiving research grants or support from Genentech and Sanofi-Aventis.

MIAMI BEACH – Bevacizumab added to docetaxel and definitive radiotherapy was an effective and safe non–platinum-based regimen for locoregionally advanced squamous cell carcinoma of the head and neck in a small phase II trial that was presented at the annual meeting of the American Society for Radiation Oncology.

The disease-free survival rate at 2 years (the primary end point) was 75% among 28 patients who had completed the full course of chemoradiation in the phase II study, said Dr. Nicholas Galanopoulos of University Hospitals Seidman Cancer Center in Cleveland. In this as-treated population, 85% of patients were alive at 2 years, locoregional control was achieved in 85% of patients, and 81.5% were free of distant metastases at 2 years.

The numbers were slightly lower when two additional patients who dropped out of the study (one for unspecified reasons and one who developed aspiration pneumonia and was hospitalized) were included in an intention-to-treat analysis. Among all 30 patients, the disease-free survival rate at 2 years was 63% and overall survival was 72%, although locoregional control and distant-metastasis-free rates remained unchanged at 85% and 81.5%, respectively.

"Future trials of concurrent chemoradiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer," Dr. Galanopoulos said.

The rationale for trying bevacizumab (Avastin) in chemoradiation regimens for head and neck tumors is based on its demonstrated ability to inhibit endothelial cell proliferation and blood vessel formation, and to increase radiosensitivity of tumors when administered concurrently with radiation, he noted.

In all, 30 treatment-naive patients (26 men, 4 women) with locally advanced stage III (6 patients) or IV (24 patients) squamous cell carcinoma of the head and neck were enrolled. The patients had good performance status and a life expectancy greater than 12 weeks.

They received 70.2 Gy radiation in 1.8-Gy fractions, docetaxel (Taxotere) 20 mg/m² per week, and bevacizumab 5 mg/kg every 2 weeks, with bevacizumab continued for up to 1 year following chemoradiation (median, 7 months).

"Future trials of concurrent chemo-radiotherapy with or without bevacizumab are justified for local-regionally advanced head and neck cancer."

Results were reported as of a median follow-up of 24.4 months.

Adjuvant bevacizumab was stopped 4 weeks before surgery in those patients who required neck dissection, and the drug was discontinued in three patients (one for radiation necrosis of the larynx requiring laryngectomy, one for severe pharyngoesophageal stenosis, and one for hemorrhagic cholecystits requiring cholecystectomy).

Major toxicities associated with the regimen included grade 4 bleeding in two patients (the episode of hemorrhagic cholecystitis already noted), and one oropharyngeal hemorrhage in field during chemoradiation.

Late grade 3 or 4 dysphagia occurred in 7 of 19 patients who had been treated with 3-D conformal radiation therapy, but in none of 11 patients who received intensity-modulated radiation (P less than .05). Patients with laryngeal primary tumors were more likely to develop serious late dysphagia, compared with patients with oropharyngeal primaries (58%% vs. 15%; P less than .05).

The study was funded in part by grants from the National Institutes of Health, Genentech, and Sanofi-Aventis. Dr. Galanopoulos reported having no relevant financial disclosures. Coauthor Dr. Panayiotis Savvides disclosed receiving research grants or support from Genentech and Sanofi-Aventis.

MIAMI BEACH – Preoperative chemotherapy or radiation – take your pick or both – improves overall survival of patients with large, soft-tissue sarcomas of the extremities, retrospective studies from two cancer centers suggest.

Looking at a cohort of 112 patients, investigators at the Mayo Clinic in Scottsdale, Ariz., saw no significant differences by treatment type in local control rates or overall survival.

But among patients with tumors measuring longer than 5 cm, the 3-year overall survival rate was 63% for those who had neoadjuvant radiation and surgery and 70% for those who had chemoradiotherapy and surgery, versus 40% with surgery alone (P = .03), radiation oncologist Jonathan B. Ashman and colleagues reported at the annual meeting of the American Society for Radiation Oncology.

"We found that patients who are treated with either neoadjuvant strategy – either radiation or chemotherapy/radiation – have bigger tumors, so they’re more aggressive tumors, but the local control is the same, so we think that the neoadjuvant therapy is helping more than we would expect from surgery alone," Dr. Ashman said in an interview.

In a separate study, Johns Hopkins Hospital investigators reported excellent local control and good overall survival rates for patients with large sarcomas of the extremities that were treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy.

The estimated 3-year overall survival rate was 66%, the estimated disease-free survival rate 58%, and estimated the local control rate 100% among 16 patients treated with interdigitated neoadjuvant chemotherapy and radiation using the MAID protocol (mesna, doxorubicin, ifosfamide and dacarbazine), reported radiation oncologist Dr. Raju Raval and colleagues from Johns Hopkins Hospital in Baltimore.

The Mayo Experience

The Mayo investigators retrospectively looked at whether adding chemotherapy to external beam radiation therapy and limb-sparing surgery added benefit for patients with stage II or III soft-tissue sarcomas of the extremities. The center’s sarcoma team recommends either neoadjuvant radiation or chemoradiotherapy for patients who have high-grade tumors and are likely to have narrow resection margins based on preoperative MRI imaging showing large tumor size or unfavorable location of the tumor relative to bone or to neurovascular structures.

"We found that patients who are treated with either neoadjuvant strategy – either radiation or chemotherapy/ radiation – have bigger tumors."

The investigators reviewed the charts of 91 patients treated for primary disease, and 21 treated for tumor recurrence from 1998 through 2009. Median follow-up was 22.1 months. Overall, 39 of the patients received neoadjuvant chemoradiotherapy, 37 neoadjuvant radiation, and 36 surgery alone. The majority of tumors in each treatment group were pathologic grade 3 or 4, and most were 5 cm or greater in their longest dimension.

Of the 39 patients who received some form of chemotherapy, 20 had concurrent weekly cisplatin 20-40 mg/m2, with the remainder receiving other protocols, including MAID and MAP (methotrexate, doxorubicin, and cisplatin).

Dr. Ashman said that although there is no clear evidence to support the use of weekly cisplatin in sarcoma, "our practice has been over the last 5-8 years to have patients who have large and high-risk tumors but otherwise have good performance status, with good renal function and no other contraindications to receive weekly cisplatin, because it’s such a well-tolerated regimen. The rationale is that there hasn’t been really good data to show a benefit from the more toxic protocols."

Cisplatin is known to sensitize tumor cells to radiation, he noted. "When you’re looking at just radiosensitization, and you’re looking at just local outcomes and not trying to affect the distant metastasis rate, then let’s try to use a therapy that’s less toxic, so that patients don’t have to break therapy."

In all, 92 patients had surgery with limb-preservation attempt, and the majority (88%) had disease-free surgical margins (R0 resections); rates of R0 resections did not differ among the treatment groups.

The overall 3-year local control rate was 87%, distant metastasis-free survival was 69%, and overall survival was 68%. Patients who received a neoadjuvant therapy had higher rates of wound complications, which occurred in 11% of surgery-only patients, compared with 50% of patients who received chemoradiotherapy (P = .003) and 42% of those who received radiation (P = .02). There was no significant difference in wound complications between the two neoadjuvant therapy types, however, and no factors predicted these complications.

The Johns Hopkins Experience

Dr. Raval and colleagues from Johns Hopkins reported on 16 patients with high-grade soft-tissue sarcomas treated with interdigitated neoadjuvant chemotherapy and radiation, surgery, and adjuvant chemotherapy.

The therapy consists of three cycles of chemotherapy, with 44 Gy radiation divided into 22 fractions, 11 of which are delivered following the first chemotherapy cycle, and 11 following the second cycle. Surgery is performed about 80 days after the start of therapy, and an additional 11 Gy or radiation is given if an R0 resection was not achieved. If the patient can tolerate it, three additional adjuvant chemotherapy cycles are given.

Estimated 3-year overall survival was 66%, disease-free survival was 58%, and the local control rate was 100%. No local recurrences had been seen at the longest follow-up of 160 months.

The Hopkins investigators compared their results with those from a pilot study using the same protocol at Massachusetts General Hospital in Boston. The MGH investigators had an 87% 5-year overall survival rate, 70% disease-free survival rate, and 92% local-control rate. Among MGH historical controls treated with surgery only, the respective rates were 58%, 42%, and 86%.

"This combined-modality approach to high grade soft-tissue sarcoma continues to play a role in the treatment of patients with this rare soft tissue neoplasm," the investigators concluded.

Both studies were internally funded. Dr. Ashman and Dr. Raval reported that they had no relevant financial disclosures.

MIAMI BEACH – Preoperative chemotherapy or radiation – take your pick or both – improves overall survival of patients with large, soft-tissue sarcomas of the extremities, retrospective studies from two cancer centers suggest.

Looking at a cohort of 112 patients, investigators at the Mayo Clinic in Scottsdale, Ariz., saw no significant differences by treatment type in local control rates or overall survival.

But among patients with tumors measuring longer than 5 cm, the 3-year overall survival rate was 63% for those who had neoadjuvant radiation and surgery and 70% for those who had chemoradiotherapy and surgery, versus 40% with surgery alone (P = .03), radiation oncologist Jonathan B. Ashman and colleagues reported at the annual meeting of the American Society for Radiation Oncology.

"We found that patients who are treated with either neoadjuvant strategy – either radiation or chemotherapy/radiation – have bigger tumors, so they’re more aggressive tumors, but the local control is the same, so we think that the neoadjuvant therapy is helping more than we would expect from surgery alone," Dr. Ashman said in an interview.

In a separate study, Johns Hopkins Hospital investigators reported excellent local control and good overall survival rates for patients with large sarcomas of the extremities that were treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy.

The estimated 3-year overall survival rate was 66%, the estimated disease-free survival rate 58%, and estimated the local control rate 100% among 16 patients treated with interdigitated neoadjuvant chemotherapy and radiation using the MAID protocol (mesna, doxorubicin, ifosfamide and dacarbazine), reported radiation oncologist Dr. Raju Raval and colleagues from Johns Hopkins Hospital in Baltimore.

The Mayo Experience

The Mayo investigators retrospectively looked at whether adding chemotherapy to external beam radiation therapy and limb-sparing surgery added benefit for patients with stage II or III soft-tissue sarcomas of the extremities. The center’s sarcoma team recommends either neoadjuvant radiation or chemoradiotherapy for patients who have high-grade tumors and are likely to have narrow resection margins based on preoperative MRI imaging showing large tumor size or unfavorable location of the tumor relative to bone or to neurovascular structures.

"We found that patients who are treated with either neoadjuvant strategy – either radiation or chemotherapy/ radiation – have bigger tumors."

The investigators reviewed the charts of 91 patients treated for primary disease, and 21 treated for tumor recurrence from 1998 through 2009. Median follow-up was 22.1 months. Overall, 39 of the patients received neoadjuvant chemoradiotherapy, 37 neoadjuvant radiation, and 36 surgery alone. The majority of tumors in each treatment group were pathologic grade 3 or 4, and most were 5 cm or greater in their longest dimension.

Of the 39 patients who received some form of chemotherapy, 20 had concurrent weekly cisplatin 20-40 mg/m2, with the remainder receiving other protocols, including MAID and MAP (methotrexate, doxorubicin, and cisplatin).

Dr. Ashman said that although there is no clear evidence to support the use of weekly cisplatin in sarcoma, "our practice has been over the last 5-8 years to have patients who have large and high-risk tumors but otherwise have good performance status, with good renal function and no other contraindications to receive weekly cisplatin, because it’s such a well-tolerated regimen. The rationale is that there hasn’t been really good data to show a benefit from the more toxic protocols."

Cisplatin is known to sensitize tumor cells to radiation, he noted. "When you’re looking at just radiosensitization, and you’re looking at just local outcomes and not trying to affect the distant metastasis rate, then let’s try to use a therapy that’s less toxic, so that patients don’t have to break therapy."

In all, 92 patients had surgery with limb-preservation attempt, and the majority (88%) had disease-free surgical margins (R0 resections); rates of R0 resections did not differ among the treatment groups.

The overall 3-year local control rate was 87%, distant metastasis-free survival was 69%, and overall survival was 68%. Patients who received a neoadjuvant therapy had higher rates of wound complications, which occurred in 11% of surgery-only patients, compared with 50% of patients who received chemoradiotherapy (P = .003) and 42% of those who received radiation (P = .02). There was no significant difference in wound complications between the two neoadjuvant therapy types, however, and no factors predicted these complications.

The Johns Hopkins Experience

Dr. Raval and colleagues from Johns Hopkins reported on 16 patients with high-grade soft-tissue sarcomas treated with interdigitated neoadjuvant chemotherapy and radiation, surgery, and adjuvant chemotherapy.

The therapy consists of three cycles of chemotherapy, with 44 Gy radiation divided into 22 fractions, 11 of which are delivered following the first chemotherapy cycle, and 11 following the second cycle. Surgery is performed about 80 days after the start of therapy, and an additional 11 Gy or radiation is given if an R0 resection was not achieved. If the patient can tolerate it, three additional adjuvant chemotherapy cycles are given.

Estimated 3-year overall survival was 66%, disease-free survival was 58%, and the local control rate was 100%. No local recurrences had been seen at the longest follow-up of 160 months.

The Hopkins investigators compared their results with those from a pilot study using the same protocol at Massachusetts General Hospital in Boston. The MGH investigators had an 87% 5-year overall survival rate, 70% disease-free survival rate, and 92% local-control rate. Among MGH historical controls treated with surgery only, the respective rates were 58%, 42%, and 86%.

"This combined-modality approach to high grade soft-tissue sarcoma continues to play a role in the treatment of patients with this rare soft tissue neoplasm," the investigators concluded.

Both studies were internally funded. Dr. Ashman and Dr. Raval reported that they had no relevant financial disclosures.

MIAMI BEACH – Preoperative chemotherapy or radiation – take your pick or both – improves overall survival of patients with large, soft-tissue sarcomas of the extremities, retrospective studies from two cancer centers suggest.

Looking at a cohort of 112 patients, investigators at the Mayo Clinic in Scottsdale, Ariz., saw no significant differences by treatment type in local control rates or overall survival.

But among patients with tumors measuring longer than 5 cm, the 3-year overall survival rate was 63% for those who had neoadjuvant radiation and surgery and 70% for those who had chemoradiotherapy and surgery, versus 40% with surgery alone (P = .03), radiation oncologist Jonathan B. Ashman and colleagues reported at the annual meeting of the American Society for Radiation Oncology.

"We found that patients who are treated with either neoadjuvant strategy – either radiation or chemotherapy/radiation – have bigger tumors, so they’re more aggressive tumors, but the local control is the same, so we think that the neoadjuvant therapy is helping more than we would expect from surgery alone," Dr. Ashman said in an interview.

In a separate study, Johns Hopkins Hospital investigators reported excellent local control and good overall survival rates for patients with large sarcomas of the extremities that were treated with neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy.

The estimated 3-year overall survival rate was 66%, the estimated disease-free survival rate 58%, and estimated the local control rate 100% among 16 patients treated with interdigitated neoadjuvant chemotherapy and radiation using the MAID protocol (mesna, doxorubicin, ifosfamide and dacarbazine), reported radiation oncologist Dr. Raju Raval and colleagues from Johns Hopkins Hospital in Baltimore.

The Mayo Experience

The Mayo investigators retrospectively looked at whether adding chemotherapy to external beam radiation therapy and limb-sparing surgery added benefit for patients with stage II or III soft-tissue sarcomas of the extremities. The center’s sarcoma team recommends either neoadjuvant radiation or chemoradiotherapy for patients who have high-grade tumors and are likely to have narrow resection margins based on preoperative MRI imaging showing large tumor size or unfavorable location of the tumor relative to bone or to neurovascular structures.

"We found that patients who are treated with either neoadjuvant strategy – either radiation or chemotherapy/ radiation – have bigger tumors."

The investigators reviewed the charts of 91 patients treated for primary disease, and 21 treated for tumor recurrence from 1998 through 2009. Median follow-up was 22.1 months. Overall, 39 of the patients received neoadjuvant chemoradiotherapy, 37 neoadjuvant radiation, and 36 surgery alone. The majority of tumors in each treatment group were pathologic grade 3 or 4, and most were 5 cm or greater in their longest dimension.

Of the 39 patients who received some form of chemotherapy, 20 had concurrent weekly cisplatin 20-40 mg/m2, with the remainder receiving other protocols, including MAID and MAP (methotrexate, doxorubicin, and cisplatin).

Dr. Ashman said that although there is no clear evidence to support the use of weekly cisplatin in sarcoma, "our practice has been over the last 5-8 years to have patients who have large and high-risk tumors but otherwise have good performance status, with good renal function and no other contraindications to receive weekly cisplatin, because it’s such a well-tolerated regimen. The rationale is that there hasn’t been really good data to show a benefit from the more toxic protocols."

Cisplatin is known to sensitize tumor cells to radiation, he noted. "When you’re looking at just radiosensitization, and you’re looking at just local outcomes and not trying to affect the distant metastasis rate, then let’s try to use a therapy that’s less toxic, so that patients don’t have to break therapy."

In all, 92 patients had surgery with limb-preservation attempt, and the majority (88%) had disease-free surgical margins (R0 resections); rates of R0 resections did not differ among the treatment groups.

The overall 3-year local control rate was 87%, distant metastasis-free survival was 69%, and overall survival was 68%. Patients who received a neoadjuvant therapy had higher rates of wound complications, which occurred in 11% of surgery-only patients, compared with 50% of patients who received chemoradiotherapy (P = .003) and 42% of those who received radiation (P = .02). There was no significant difference in wound complications between the two neoadjuvant therapy types, however, and no factors predicted these complications.

The Johns Hopkins Experience

Dr. Raval and colleagues from Johns Hopkins reported on 16 patients with high-grade soft-tissue sarcomas treated with interdigitated neoadjuvant chemotherapy and radiation, surgery, and adjuvant chemotherapy.

The therapy consists of three cycles of chemotherapy, with 44 Gy radiation divided into 22 fractions, 11 of which are delivered following the first chemotherapy cycle, and 11 following the second cycle. Surgery is performed about 80 days after the start of therapy, and an additional 11 Gy or radiation is given if an R0 resection was not achieved. If the patient can tolerate it, three additional adjuvant chemotherapy cycles are given.

Estimated 3-year overall survival was 66%, disease-free survival was 58%, and the local control rate was 100%. No local recurrences had been seen at the longest follow-up of 160 months.

The Hopkins investigators compared their results with those from a pilot study using the same protocol at Massachusetts General Hospital in Boston. The MGH investigators had an 87% 5-year overall survival rate, 70% disease-free survival rate, and 92% local-control rate. Among MGH historical controls treated with surgery only, the respective rates were 58%, 42%, and 86%.

"This combined-modality approach to high grade soft-tissue sarcoma continues to play a role in the treatment of patients with this rare soft tissue neoplasm," the investigators concluded.

Both studies were internally funded. Dr. Ashman and Dr. Raval reported that they had no relevant financial disclosures.

MIAMI BEACH – Head and neck cancer patients treated with radiation should be screened routinely for carotid artery stenosis, investigators recommended at the annual meeting of the American Society for Radiation Oncology.

Among 225 patients who had received radiation and were screened, an estimated 18% had significant asymptomatic stenosis (50% or greater narrowing) of one or both carotid arteries 3 years after treatment said Dr. Jennifer Dorth, a resident in radiation oncology at Duke University Medical Center in Durham, N.C.

"We recommend screening for head and neck cancer patients given that there are high rates of stenosis as well as high rates of progression of stenosis," she said.

Factors significantly associated with risk for stenosis included Framingham risk factors (smoking history, hypertension, hyperlipidemia, diabetes mellitus, cardiovascular/peripheral vascular disease, and atrial fibrillation) and radiation dose.

The investigators retrospectively reviewed outcomes of asymptomatic, disease-free head and neck cancer patients who had received radiation with curative intent to the neck. The patients were screened with carotid Doppler ultrasound at or after the 1-year follow-up visit, and this was repeated every 2-3 years. Patients with ultrasound evidence of 50% or greater stenosis were referred to vascular surgery.

The study identified 225 patients, 139 of whom had received intensity-modulated radiation therapy (IMRT), with the dose calculated separately for each side of the neck. Because of the separate treatment planning, the investigators analyzed the data by creating two separate models: one looking at all patients, and the other looking at 278 treatments in the 139 patients with IMRT.

In each model, about 85% of patients had stage III or IV disease and about 58% had cancer in the oropharynx, followed in order of frequency by the larynx, oral cavity, nasopharynx, or other sites.

A total of 33 patients had stenosis in 51 arteries. The median time between completion of radiation therapy and the last follow-up screening was 2 years. The median time to stenosis was 3 years.

Actuarial estimates of carotid artery stenosis were 2% at 1 year, 6% at 2 years, and 18% at 3 years.

In univariate analysis, factors associated with stenosis included male gender (P = .02), hypertension (P = .003), vascular disease (P less than .001), and Framingham score (P less than .001).

In the multivariate model looking at all patients, each Framingham risk factor was associated with a near doubling of stenosis risk (hazard ratio 1.8, P = .0003). In the model focusing on the IMRT population (adjusted for Framingham score), only radiation dose was significantly associated with stenosis (HR 1.07/Gy, P = .02).

Of the 33 patients with stenosis, 8 had no further follow-up imaging, 8 had stable stenosis, and 17 had progressive stenosis, 2 of whom had a cerebrovascular event. Eight patients with progressive stenosis received medical management only, and nine went on to surgery (three endarterectomies and six stent placements).

"Of the nine patients who underwent surgical management, there was a high rate of restenosis in 30% of patients at a year median follow-up, and this is consistent, unfortunately, with other series looking at rates of restenosis," Dr. Dorth said.

The study was internally funded. Dr. Dorth reported having no relevant financial disclosures.

MIAMI BEACH – Head and neck cancer patients treated with radiation should be screened routinely for carotid artery stenosis, investigators recommended at the annual meeting of the American Society for Radiation Oncology.

Among 225 patients who had received radiation and were screened, an estimated 18% had significant asymptomatic stenosis (50% or greater narrowing) of one or both carotid arteries 3 years after treatment said Dr. Jennifer Dorth, a resident in radiation oncology at Duke University Medical Center in Durham, N.C.

"We recommend screening for head and neck cancer patients given that there are high rates of stenosis as well as high rates of progression of stenosis," she said.

Factors significantly associated with risk for stenosis included Framingham risk factors (smoking history, hypertension, hyperlipidemia, diabetes mellitus, cardiovascular/peripheral vascular disease, and atrial fibrillation) and radiation dose.

The investigators retrospectively reviewed outcomes of asymptomatic, disease-free head and neck cancer patients who had received radiation with curative intent to the neck. The patients were screened with carotid Doppler ultrasound at or after the 1-year follow-up visit, and this was repeated every 2-3 years. Patients with ultrasound evidence of 50% or greater stenosis were referred to vascular surgery.

The study identified 225 patients, 139 of whom had received intensity-modulated radiation therapy (IMRT), with the dose calculated separately for each side of the neck. Because of the separate treatment planning, the investigators analyzed the data by creating two separate models: one looking at all patients, and the other looking at 278 treatments in the 139 patients with IMRT.

In each model, about 85% of patients had stage III or IV disease and about 58% had cancer in the oropharynx, followed in order of frequency by the larynx, oral cavity, nasopharynx, or other sites.

A total of 33 patients had stenosis in 51 arteries. The median time between completion of radiation therapy and the last follow-up screening was 2 years. The median time to stenosis was 3 years.

Actuarial estimates of carotid artery stenosis were 2% at 1 year, 6% at 2 years, and 18% at 3 years.

In univariate analysis, factors associated with stenosis included male gender (P = .02), hypertension (P = .003), vascular disease (P less than .001), and Framingham score (P less than .001).

In the multivariate model looking at all patients, each Framingham risk factor was associated with a near doubling of stenosis risk (hazard ratio 1.8, P = .0003). In the model focusing on the IMRT population (adjusted for Framingham score), only radiation dose was significantly associated with stenosis (HR 1.07/Gy, P = .02).

Of the 33 patients with stenosis, 8 had no further follow-up imaging, 8 had stable stenosis, and 17 had progressive stenosis, 2 of whom had a cerebrovascular event. Eight patients with progressive stenosis received medical management only, and nine went on to surgery (three endarterectomies and six stent placements).

"Of the nine patients who underwent surgical management, there was a high rate of restenosis in 30% of patients at a year median follow-up, and this is consistent, unfortunately, with other series looking at rates of restenosis," Dr. Dorth said.

The study was internally funded. Dr. Dorth reported having no relevant financial disclosures.

MIAMI BEACH – Head and neck cancer patients treated with radiation should be screened routinely for carotid artery stenosis, investigators recommended at the annual meeting of the American Society for Radiation Oncology.

Among 225 patients who had received radiation and were screened, an estimated 18% had significant asymptomatic stenosis (50% or greater narrowing) of one or both carotid arteries 3 years after treatment said Dr. Jennifer Dorth, a resident in radiation oncology at Duke University Medical Center in Durham, N.C.

"We recommend screening for head and neck cancer patients given that there are high rates of stenosis as well as high rates of progression of stenosis," she said.

Factors significantly associated with risk for stenosis included Framingham risk factors (smoking history, hypertension, hyperlipidemia, diabetes mellitus, cardiovascular/peripheral vascular disease, and atrial fibrillation) and radiation dose.

The investigators retrospectively reviewed outcomes of asymptomatic, disease-free head and neck cancer patients who had received radiation with curative intent to the neck. The patients were screened with carotid Doppler ultrasound at or after the 1-year follow-up visit, and this was repeated every 2-3 years. Patients with ultrasound evidence of 50% or greater stenosis were referred to vascular surgery.

The study identified 225 patients, 139 of whom had received intensity-modulated radiation therapy (IMRT), with the dose calculated separately for each side of the neck. Because of the separate treatment planning, the investigators analyzed the data by creating two separate models: one looking at all patients, and the other looking at 278 treatments in the 139 patients with IMRT.

In each model, about 85% of patients had stage III or IV disease and about 58% had cancer in the oropharynx, followed in order of frequency by the larynx, oral cavity, nasopharynx, or other sites.

A total of 33 patients had stenosis in 51 arteries. The median time between completion of radiation therapy and the last follow-up screening was 2 years. The median time to stenosis was 3 years.

Actuarial estimates of carotid artery stenosis were 2% at 1 year, 6% at 2 years, and 18% at 3 years.

In univariate analysis, factors associated with stenosis included male gender (P = .02), hypertension (P = .003), vascular disease (P less than .001), and Framingham score (P less than .001).

In the multivariate model looking at all patients, each Framingham risk factor was associated with a near doubling of stenosis risk (hazard ratio 1.8, P = .0003). In the model focusing on the IMRT population (adjusted for Framingham score), only radiation dose was significantly associated with stenosis (HR 1.07/Gy, P = .02).

Of the 33 patients with stenosis, 8 had no further follow-up imaging, 8 had stable stenosis, and 17 had progressive stenosis, 2 of whom had a cerebrovascular event. Eight patients with progressive stenosis received medical management only, and nine went on to surgery (three endarterectomies and six stent placements).

"Of the nine patients who underwent surgical management, there was a high rate of restenosis in 30% of patients at a year median follow-up, and this is consistent, unfortunately, with other series looking at rates of restenosis," Dr. Dorth said.

The study was internally funded. Dr. Dorth reported having no relevant financial disclosures.