ASTRO Annual Meeting 2014

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Use of a shorter, more convenient course of radiation therapy for prostate cancer or a technique that spares blood vessels critical for sexual function yields good long-term quality of life outcomes, according to a pair of studies.

The results were reported at the annual meeting of the American Society for Radiation Oncology.

The first study, a multicenter phase I/II trial, tested hypofractionation among 343 men with low- or intermediate-risk prostate cancer.

Susan London/Frontline Medical News

“Dose escalation, or increasing the total dose delivered, in prostate cancer has been shown to be of benefit. This, however, translates into increased treatment times and patient cost,” lead investigator Jeffrey V. Brower, a radiation oncologist at the University of Wisconsin Carbone Cancer Center in Madison, explained in a press briefing. “Hypofractionation is a method of delivering greater dose per fraction and ultimately shorter treatment times, greater patient convenience, and overall cost benefit,” said Dr. Brower.

In the trial, men underwent intensity-modulated radiation therapy treating the prostate and base of the seminal vesicles, with one of three increasing dose-per-fraction regimens having similar predicted late toxicity: 22 fractions of 2.94 Gy each, 16 fractions of 3.63 Gy each, or 12 fractions of 4.3 Gy each. The schedules yielded a similar equivalent dose in 2-Gy fractions (75-77 Gy) and a similar tumor equivalent dose in 2-Gy fractions (82 to 85 Gy). Seventeen percent of the men also received androgen deprivation therapy.

Results showed the same temporal patterns and no significant differences across groups at 3 years in patient-reported bowel and bladder function, assessed with the Fox Chase Bowel/Bladder Toxicity questionnaire; sexual function, assessed with the International Index of Erectile Function; and overall quality of life, assessed with the Spitzer Quality of Life Index.

The only significant changes from baseline to 3 years were a worsening of bowel function in the 22-fraction group and a worsening of sexual function in the study population overall.

Meanwhile, efficacy results showed that the 5-year probability of biochemical progression-free survival ranged from 91% to 94%, with no significant difference across groups.

“These favorable patient-scored quality of life outcomes are consistent with our previously reported physician-scored acute and late toxicities, providing further support for hypofractionation safety and tolerability,” said Dr. Brower.

“The increased cost-effectiveness and patient convenience of hypofractionation, in conjunction with good quality of life outcomes, may be leveraged to drive implementation of these regimens into clinical practice,” he concluded.

Susan London/Frontline Medical News

The second study tested a vessel-sparing technique that uses magnetic resonance imaging with time-of-flight angiography to identify and minimize irradiation of critical erectile tissues near the prostate, with the aim of preserving sexual quality of life (Int. J. Radiat. Oncol. Biol. Phys. 2005;61:20-31).

“When I started my career 25 years ago, all we wanted to do was cure these very aggressive cancers. I don’t think the quality of life term even came into being until about 15 years ago. But as the cure rates went up, then we turned to quality of life concerns,” said presenting investigator Patrick (Bill) McLaughlin, a radiation oncologist at the University of Michigan Comprehensive Cancer Center, Ann Arbor.

Dr. McLaughlin and his associates tested the vessel-sparing technique among men with any-risk prostate cancer who had minimal erectile dysfunction at baseline; 42 received external beam radiation therapy alone and 49 received a combination of external beam radiation therapy plus brachytherapy.

The external beam radiation therapy, in the form of intensity-modulated radiation therapy, was given to a dose of 75.8 to 79.55 Gy, and the combination was given to a total dose of 90 Gy external equivalent. “We never compromised treatment in an attempt to spare these [critical erectile] structures. We took them into account, we tried to avoid them as much as possible, but we always gave full dose to the prostate,” Dr. McLaughlin stressed.

Sexual function was assessed with two measures: the International Index of Erectile Function, which specifically asks about erections sufficient for intercourse, and the three-item questionnaire (Q3), which asks only about ability to be sexually active, without specifying the nature of that activity.

“We had excellent, maybe even spectacular, function preservation … considering these were very-high-dose treatments on both arms,” he reported. “But interestingly, we had greater preservation on the scale that was not dependent on intercourse.”

Specifically, at 5 years, 64% of men in the external beam group and 63% in the combination group were able to have erection sufficient for intercourse with aids, usually sildenafil (Viagra) or tadalafil (Cialis). But a much higher percentage – 79% and 92%, respectively – were able to be sexually active with aids.

“The difference between those outcomes by metric implies sexual activity apart from intercourse,” Dr. McLaughlin said. “The gap between sexual intercourse and sexual activity demonstrates the limitations of this scale, the International Index of Erectile Function, in this age-group.”

This finding lends support to the new concept of manopause, the male equivalent of menopause, he said. “For many couples, [with aging,] sexual intercourse becomes difficult or even painful, so they shift to other activities. My shorthand for that is 69 at 69, and I usually get a knowing chuckle when I say that to couples. But many couples will say, ‘Well, we still take care of each other even though it’s not sexual intercourse.’ ”

The vessel-sparing radiation therapy also was associated with very high cure rates: 98% for low-risk prostate cancer, 96% for intermediate-risk prostate cancer, and 87% for high-risk prostate cancer.

“Typically, intensive treatments will cause quite a decrement in quality of life,” Dr. McLaughlin noted. “So to have this kind of ‘have your cake and eat it too’ result, of cure and quality of life, I think is very hopeful for men.”

In multivariate analysis, neither radiation therapy group nor any dose parameters predicted sexual outcomes. However, when analyses incorporated data from 44 men treated off protocol who also received hormone therapy, considered to be a major confounder, that therapy was indeed associated with poorer sexual function.

The vessel-sparing technique is probably not ready for routine use, according to Dr. McLaughlin. “I think it’s not the standard and I can’t say it should be the standard based on our study yet, even those these are spectacular sexual function preservation results.”

He and his colleagues have developed an online teaching tool, called Prostadoodle, that shows radiation oncologists how to define these critical vessels if they want to do so. “You can actually do it without doing an MRI if you learn the anatomy, and you can definitely approximate it. But to do it the way we did it actually was what I would consider a research protocol – a lot of effort for each patient, hours and hours even for each patient. It just wasn’t a simple thing to reproduce. I think it’s going to be a while before we can say, ‘You must do this.’ But I do think these results are very promising,” he said.

“Depending on the anatomy and where the disease is, it could really make a difference as to whether you could vessel spare or not,” said Dr. Colleen Lawton, professor and vice chair and clinical director, department of radiation oncology, Medical College of Wisconsin, Milwaukee, and moderator of the press briefing. “If you’ve got disease low in the prostate, what we call the apex, which is close to all of these vessels, you don’t want to miss the disease. So it’s going to be a balancing act.”

SAN FRANCISCO – Chemoradiotherapy is not superior to radiotherapy alone for alleviating dysphagia in patients with advanced esophageal cancer. And it causes more nausea and vomiting.

These were among key findings of a randomized phase III trial reported in a session and a related press briefing at the annual meeting of the American Society for Radiation Oncology.

“This trial was powered to see if there was an improvement with chemotherapy, and it wasn’t powered to show equivalence, so it was a truly negative trial. However, we do know that chemotherapy added some toxicity and didn’t improve the quality of life parameters that we were looking at,” commented lead researcher Dr. Michael G. Penniment, director of Radiation Oncology at both the Royal Adelaide Hospital in Adelaide, Australia, and the Alan Walker Cancer Care Centre in Darwin, Australia.

ASTRO/Adam Donohue

“So I think that we can clearly say that radiotherapy alone remains an excellent tool for palliation of these patients with advanced esophageal cancer and should remain the standard of care,” he maintained. “And if you combine that with the fact that we have a proven role [for radiation] in patients who have curable esophageal cancer, I would say that all patients with esophageal cancer should have the opinion of a radiation oncologist, though I’m a little biased.”

There is no gold standard when it comes to palliative care for patients with advanced esophageal cancer, according to Dr. Penniment. “We can’t even explain to these patients facing a very difficult phase of their life what exactly the results of fairly basic treatments are. We need to give them better information about the chances the treatments we offer will actually help them and perhaps some more evidence about which patients fit into this group,” he said, giving some background to the research.

In the trial, 220 patients from Australia, New Zealand, Canada, and the United Kingdom with advanced esophageal cancer were randomized evenly to receive palliative radiation therapy — 30 Gy in 10 fractions or 35 Gy in 15 fractions, depending on the country — either alone or with concomitant chemotherapy. Three-fourths of the patients had metastases, and the rest had locally advanced tumors.

At 9 weeks after the start of radiation therapy, the proportion of patients whose dysphagia responded to treatment, which was defined as an improvement of at least 1 point on the 5-point Mellow Scale, was 68% with radiation alone and 74% with chemoradiation, a nonsignificant difference.

The respective proportions with a sustained response at 13 weeks, the trial’s primary endpoint, were 42% and 47%, also a nonsignificant difference.

But some patients did not live even this long, Dr. Penniment noted. “So there is a group of people we hope to be able to identify who really do exceedingly badly and it might be that simple radiotherapy, such as a single fraction, might be enough for those patients. Or indeed, unfortunately, there might be some people with such poor prognostic signs that a tube might do them if it’s only a week or something like that,” he said.

The 3-year rates of dysphagia, progression-free survival, and overall survival were statistically indistinguishable between groups. Median overall survival was 203 days with radiation and 210 days with chemoradiation.

On a bright note, however, there was a tail to the survival curve, with about 10% of patients in each group still alive at 2 years. “I think there is a message here,” Dr. Penniment said. “You don’t want to give people false hope, but there is certainly a group of patients who have advanced esophageal cancer with or without lymph node involvement for whom potential active cancer treatment may actually cause a reasonably long-term survival and local control. I suspect that this tail to the survival curve would probably not be seen in patients who are offered certainly no treatment, but people who are offered bypass with a stent or bypass tubes. And these are clearly patients that we would not go on to see.”

In quality of life assessments, 64% of patients treated with radiation alone and 50% of patients treated with chemoradiation had an improvement in the dysphagia domain on the esophageal module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-OES18), a nonsignificant difference.

However, relative to the radiation group, the chemoradiation group had higher rates of both nausea and vomiting (P less than .01 for each).

Some patients who received radiotherapy alone went on to receive chemotherapy, according to Dr. Penniment, who reported having no financial disclosures. “The majority of those patients had no dysphagia but still got chemotherapy after radiotherapy alone. We will do more analysis on this, but I think there is a fixed belief, which hopefully this trial starts to break, that these people need to have chemotherapy,” he said.

SAN FRANCISCO – Chemoradiotherapy is not superior to radiotherapy alone for alleviating dysphagia in patients with advanced esophageal cancer. And it causes more nausea and vomiting.

These were among key findings of a randomized phase III trial reported in a session and a related press briefing at the annual meeting of the American Society for Radiation Oncology.

“This trial was powered to see if there was an improvement with chemotherapy, and it wasn’t powered to show equivalence, so it was a truly negative trial. However, we do know that chemotherapy added some toxicity and didn’t improve the quality of life parameters that we were looking at,” commented lead researcher Dr. Michael G. Penniment, director of Radiation Oncology at both the Royal Adelaide Hospital in Adelaide, Australia, and the Alan Walker Cancer Care Centre in Darwin, Australia.

ASTRO/Adam Donohue

“So I think that we can clearly say that radiotherapy alone remains an excellent tool for palliation of these patients with advanced esophageal cancer and should remain the standard of care,” he maintained. “And if you combine that with the fact that we have a proven role [for radiation] in patients who have curable esophageal cancer, I would say that all patients with esophageal cancer should have the opinion of a radiation oncologist, though I’m a little biased.”

There is no gold standard when it comes to palliative care for patients with advanced esophageal cancer, according to Dr. Penniment. “We can’t even explain to these patients facing a very difficult phase of their life what exactly the results of fairly basic treatments are. We need to give them better information about the chances the treatments we offer will actually help them and perhaps some more evidence about which patients fit into this group,” he said, giving some background to the research.

In the trial, 220 patients from Australia, New Zealand, Canada, and the United Kingdom with advanced esophageal cancer were randomized evenly to receive palliative radiation therapy — 30 Gy in 10 fractions or 35 Gy in 15 fractions, depending on the country — either alone or with concomitant chemotherapy. Three-fourths of the patients had metastases, and the rest had locally advanced tumors.

At 9 weeks after the start of radiation therapy, the proportion of patients whose dysphagia responded to treatment, which was defined as an improvement of at least 1 point on the 5-point Mellow Scale, was 68% with radiation alone and 74% with chemoradiation, a nonsignificant difference.

The respective proportions with a sustained response at 13 weeks, the trial’s primary endpoint, were 42% and 47%, also a nonsignificant difference.

But some patients did not live even this long, Dr. Penniment noted. “So there is a group of people we hope to be able to identify who really do exceedingly badly and it might be that simple radiotherapy, such as a single fraction, might be enough for those patients. Or indeed, unfortunately, there might be some people with such poor prognostic signs that a tube might do them if it’s only a week or something like that,” he said.

The 3-year rates of dysphagia, progression-free survival, and overall survival were statistically indistinguishable between groups. Median overall survival was 203 days with radiation and 210 days with chemoradiation.

On a bright note, however, there was a tail to the survival curve, with about 10% of patients in each group still alive at 2 years. “I think there is a message here,” Dr. Penniment said. “You don’t want to give people false hope, but there is certainly a group of patients who have advanced esophageal cancer with or without lymph node involvement for whom potential active cancer treatment may actually cause a reasonably long-term survival and local control. I suspect that this tail to the survival curve would probably not be seen in patients who are offered certainly no treatment, but people who are offered bypass with a stent or bypass tubes. And these are clearly patients that we would not go on to see.”

In quality of life assessments, 64% of patients treated with radiation alone and 50% of patients treated with chemoradiation had an improvement in the dysphagia domain on the esophageal module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-OES18), a nonsignificant difference.

However, relative to the radiation group, the chemoradiation group had higher rates of both nausea and vomiting (P less than .01 for each).

Some patients who received radiotherapy alone went on to receive chemotherapy, according to Dr. Penniment, who reported having no financial disclosures. “The majority of those patients had no dysphagia but still got chemotherapy after radiotherapy alone. We will do more analysis on this, but I think there is a fixed belief, which hopefully this trial starts to break, that these people need to have chemotherapy,” he said.

SAN FRANCISCO – Chemoradiotherapy is not superior to radiotherapy alone for alleviating dysphagia in patients with advanced esophageal cancer. And it causes more nausea and vomiting.

These were among key findings of a randomized phase III trial reported in a session and a related press briefing at the annual meeting of the American Society for Radiation Oncology.

“This trial was powered to see if there was an improvement with chemotherapy, and it wasn’t powered to show equivalence, so it was a truly negative trial. However, we do know that chemotherapy added some toxicity and didn’t improve the quality of life parameters that we were looking at,” commented lead researcher Dr. Michael G. Penniment, director of Radiation Oncology at both the Royal Adelaide Hospital in Adelaide, Australia, and the Alan Walker Cancer Care Centre in Darwin, Australia.

ASTRO/Adam Donohue

“So I think that we can clearly say that radiotherapy alone remains an excellent tool for palliation of these patients with advanced esophageal cancer and should remain the standard of care,” he maintained. “And if you combine that with the fact that we have a proven role [for radiation] in patients who have curable esophageal cancer, I would say that all patients with esophageal cancer should have the opinion of a radiation oncologist, though I’m a little biased.”

There is no gold standard when it comes to palliative care for patients with advanced esophageal cancer, according to Dr. Penniment. “We can’t even explain to these patients facing a very difficult phase of their life what exactly the results of fairly basic treatments are. We need to give them better information about the chances the treatments we offer will actually help them and perhaps some more evidence about which patients fit into this group,” he said, giving some background to the research.

In the trial, 220 patients from Australia, New Zealand, Canada, and the United Kingdom with advanced esophageal cancer were randomized evenly to receive palliative radiation therapy — 30 Gy in 10 fractions or 35 Gy in 15 fractions, depending on the country — either alone or with concomitant chemotherapy. Three-fourths of the patients had metastases, and the rest had locally advanced tumors.

At 9 weeks after the start of radiation therapy, the proportion of patients whose dysphagia responded to treatment, which was defined as an improvement of at least 1 point on the 5-point Mellow Scale, was 68% with radiation alone and 74% with chemoradiation, a nonsignificant difference.

The respective proportions with a sustained response at 13 weeks, the trial’s primary endpoint, were 42% and 47%, also a nonsignificant difference.

But some patients did not live even this long, Dr. Penniment noted. “So there is a group of people we hope to be able to identify who really do exceedingly badly and it might be that simple radiotherapy, such as a single fraction, might be enough for those patients. Or indeed, unfortunately, there might be some people with such poor prognostic signs that a tube might do them if it’s only a week or something like that,” he said.

The 3-year rates of dysphagia, progression-free survival, and overall survival were statistically indistinguishable between groups. Median overall survival was 203 days with radiation and 210 days with chemoradiation.

On a bright note, however, there was a tail to the survival curve, with about 10% of patients in each group still alive at 2 years. “I think there is a message here,” Dr. Penniment said. “You don’t want to give people false hope, but there is certainly a group of patients who have advanced esophageal cancer with or without lymph node involvement for whom potential active cancer treatment may actually cause a reasonably long-term survival and local control. I suspect that this tail to the survival curve would probably not be seen in patients who are offered certainly no treatment, but people who are offered bypass with a stent or bypass tubes. And these are clearly patients that we would not go on to see.”

In quality of life assessments, 64% of patients treated with radiation alone and 50% of patients treated with chemoradiation had an improvement in the dysphagia domain on the esophageal module of the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-OES18), a nonsignificant difference.

However, relative to the radiation group, the chemoradiation group had higher rates of both nausea and vomiting (P less than .01 for each).

Some patients who received radiotherapy alone went on to receive chemotherapy, according to Dr. Penniment, who reported having no financial disclosures. “The majority of those patients had no dysphagia but still got chemotherapy after radiotherapy alone. We will do more analysis on this, but I think there is a fixed belief, which hopefully this trial starts to break, that these people need to have chemotherapy,” he said.

SAN FRANCISCO – Men who undergo radiation therapy for high-risk prostate cancer are less likely to have a recurrence and to die if they also receive long-duration androgen deprivation therapy. A long duration roughly half of that typically used appears to strike a good balance between efficacy and quality of life.

These were among the key findings of a pair of phase III randomized trials reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Quantity of life became the most important piece for us as we were trying to control prostate cancer. But today, so many of our localized prostate cancer patients are going to survive their illness that quality of life becomes exceedingly important,” said Dr. Colleen Lawton, vice chair and clinical director of the department of radiation oncology at the Medical College of Wisconsin, Milwaukee, and moderator of a related press briefing.

Efficacy data support long-duration ADT

In the first trial, called DART 01/05 (or AADLPC) and supported in part by the AstraZeneca Fund, investigators led by Dr. Almudena Zapatero, a radiation oncologist at Hospital Universitario de la Princesa, Madrid, studied 355 patients with intermediate- or high-risk prostate cancer.

The patients were randomized evenly to high-dose radiation therapy of at least 76 Gy, plus either short-duration ADT (4 months before and during radiation only) or long-duration ADT (4 months before and during radiation and 24 months afterward).

With a median follow-up of 63 months, relative to short-duration ADT, long-duration ADT was associated with better 5-year rates of biochemical disease–free survival according to the Phoenix definition (89.8% vs. 81.3%), overall survival (94.8% vs. 86.1%), and metastasis-free survival (93.6% vs. 83.4%), reported Dr. Zapatero. However, in stratified analyses, these benefits were seen only in the men with high-risk disease.

The two treatment groups did not differ significantly with respect to rates of acute and late rectal and urinary toxicity.

The study is noteworthy as it supports use of more costly high-dose radiation and hormonal therapy, said Dr. Zapatero. “We have demonstrated that we can get a 10% absolute benefit in PSA [prostate-specific antigen] control and overall survival and cancer-specific survival with acceptably low complications for high-risk disease. This is what we know now. We now know that … intermediate-risk disease probably doesn’t need any complementary [hormone therapy],” she said.

“We await longer follow-up to confirm these results and to determine the impact of long-term hormones according to the risk subgroup,” added Dr. Zapatero, noting that high-risk patients can be further stratified according to T3 stage, high Gleason score, and undifferentiated tumor histology. “Probably, if you have one factor, you are going to need less long of a duration of hormones, probably close to 18 months. And if you have two or three, what we call very high risk disease, you are going to need longer hormone therapy and the highest radiation [dose].”

Explaining the importance of the findings, Dr. Lawton, the press briefing moderator, said, “We have shown over time that increasing the dose [of radiation] to the prostate and immediate surrounding tissues improves outcomes. We have also shown for our high-risk patients that adding hormone therapy improves outcomes. But what we have yet to show is … do you really need the hormone therapy if you use dose escalation? And the answer is yes.”

Shortening duration of ADT improves testosterone recovery

In the second trial, known as PCS IV, investigators led by Dr. Abdenour Nabid, a radiation oncologist at Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada, studied 561 men with high-risk prostate cancer who had been treated with radiation therapy (44 Gy to the whole pelvis and 70 Gy to the prostate) and randomized to 18 months or 36 months of ADT. AstraZeneca collaborated on the trial.

Previously reported results suggested that 18 months was just as efficacious as 36 months for overall survival and cancer-specific survival (ASCO 2013 Annual Meeting. Abstract LBA4510).

With a median follow-up of 84 months, relative to counterparts who had received ADT for 36 months, patients who had received ADT for 18 months were more likely to have recovery of testosterone values into the normal range (55.7% vs. 44.9%, P = .01) and had a shorter median time to recovery (47.2 vs. 73.2 months, P less than .001).

Relative to counterparts who did not have testosterone recovery, patients who did had significantly better scores on 18 of 30 items on the European Organization for Research and Treatment of Cancer’s global quality of life questionnaire (EORTC30) (P less than .01 for each) and on 10 of 25 items on the related Prostate Module (PR25) (P less than .01 for each).

Clinically relevant differences, defined as ones of at least 10 points on the 100-point linearly transformed scales, were seen between men who did and did not have testosterone recovery for two of the global quality of life items – trouble doing strenuous activities and trouble taking long walks – and three of the prostate-related quality of life items – hot flushes, interest in sex, and sexual activity.

“In high-risk prostate cancer treated with radiation therapy and ADT, patients who recover normal testosterone levels have a better quality of life,” said Dr. Nabid. “There is a major advantage in the use of 18 months of ADT instead of 36 months since a higher proportion of patients recovered normal testosterone levels in a much shorter time without any apparent detriment in long-term outcomes.”

“If we succeed to demonstrate that 18 months is at least equal to 36 months, it’s a big jump because it’s a matter of quality of life, it’s a matter of cost also,” he added. The investigators expect to be able to publish final efficacy and quality of life results next year.

In the meantime, clinicians can follow national guidelines, according to Dr. Nabid. “If you look at the guidelines, like the NCCN guidelines for the U.S., what is written is that the long-term [ADT] could be between 24 and 36 months. So my advice would be, even if you wait for the final paper, to go for 24 months. It’s a good beginning,” he asserted.

However, “you have to use your clinical judgment,” he added, agreeing that disease factors can be used to further stratify high-risk patients; additionally, age, comorbidities, and other factors will play a role in tailoring the duration of ADT. And importantly, “one has to discuss this with his patients.”

Dr. Lawton noted that the definition of long-duration ADT has varied by world region, and has typically been 28 months in the United States and 36 months in Europe. On the basis of this trial’s findings, “I do think that 18 months is potentially our new long-term hormone therapy option. That data isn’t out in print yet, other than in abstract form, But I think going forward, the question for us should be, can we shorten it from there,” she said. “I don’t know that we’ve nailed [the optimal long duration], but we are certainly heading in the right direction.”

Dr. Zapatero disclosed no conflicts of interest; the trial was supported in part by the AstraZeneca Fund. Dr. Nabid disclosed ties with AstraZeneca and Sanofi; AstraZeneca collaborated on the trial.

SAN FRANCISCO – Men who undergo radiation therapy for high-risk prostate cancer are less likely to have a recurrence and to die if they also receive long-duration androgen deprivation therapy. A long duration roughly half of that typically used appears to strike a good balance between efficacy and quality of life.

These were among the key findings of a pair of phase III randomized trials reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Quantity of life became the most important piece for us as we were trying to control prostate cancer. But today, so many of our localized prostate cancer patients are going to survive their illness that quality of life becomes exceedingly important,” said Dr. Colleen Lawton, vice chair and clinical director of the department of radiation oncology at the Medical College of Wisconsin, Milwaukee, and moderator of a related press briefing.

Efficacy data support long-duration ADT

In the first trial, called DART 01/05 (or AADLPC) and supported in part by the AstraZeneca Fund, investigators led by Dr. Almudena Zapatero, a radiation oncologist at Hospital Universitario de la Princesa, Madrid, studied 355 patients with intermediate- or high-risk prostate cancer.

The patients were randomized evenly to high-dose radiation therapy of at least 76 Gy, plus either short-duration ADT (4 months before and during radiation only) or long-duration ADT (4 months before and during radiation and 24 months afterward).

With a median follow-up of 63 months, relative to short-duration ADT, long-duration ADT was associated with better 5-year rates of biochemical disease–free survival according to the Phoenix definition (89.8% vs. 81.3%), overall survival (94.8% vs. 86.1%), and metastasis-free survival (93.6% vs. 83.4%), reported Dr. Zapatero. However, in stratified analyses, these benefits were seen only in the men with high-risk disease.

The two treatment groups did not differ significantly with respect to rates of acute and late rectal and urinary toxicity.

The study is noteworthy as it supports use of more costly high-dose radiation and hormonal therapy, said Dr. Zapatero. “We have demonstrated that we can get a 10% absolute benefit in PSA [prostate-specific antigen] control and overall survival and cancer-specific survival with acceptably low complications for high-risk disease. This is what we know now. We now know that … intermediate-risk disease probably doesn’t need any complementary [hormone therapy],” she said.

“We await longer follow-up to confirm these results and to determine the impact of long-term hormones according to the risk subgroup,” added Dr. Zapatero, noting that high-risk patients can be further stratified according to T3 stage, high Gleason score, and undifferentiated tumor histology. “Probably, if you have one factor, you are going to need less long of a duration of hormones, probably close to 18 months. And if you have two or three, what we call very high risk disease, you are going to need longer hormone therapy and the highest radiation [dose].”

Explaining the importance of the findings, Dr. Lawton, the press briefing moderator, said, “We have shown over time that increasing the dose [of radiation] to the prostate and immediate surrounding tissues improves outcomes. We have also shown for our high-risk patients that adding hormone therapy improves outcomes. But what we have yet to show is … do you really need the hormone therapy if you use dose escalation? And the answer is yes.”

Shortening duration of ADT improves testosterone recovery

In the second trial, known as PCS IV, investigators led by Dr. Abdenour Nabid, a radiation oncologist at Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada, studied 561 men with high-risk prostate cancer who had been treated with radiation therapy (44 Gy to the whole pelvis and 70 Gy to the prostate) and randomized to 18 months or 36 months of ADT. AstraZeneca collaborated on the trial.

Previously reported results suggested that 18 months was just as efficacious as 36 months for overall survival and cancer-specific survival (ASCO 2013 Annual Meeting. Abstract LBA4510).

With a median follow-up of 84 months, relative to counterparts who had received ADT for 36 months, patients who had received ADT for 18 months were more likely to have recovery of testosterone values into the normal range (55.7% vs. 44.9%, P = .01) and had a shorter median time to recovery (47.2 vs. 73.2 months, P less than .001).

Relative to counterparts who did not have testosterone recovery, patients who did had significantly better scores on 18 of 30 items on the European Organization for Research and Treatment of Cancer’s global quality of life questionnaire (EORTC30) (P less than .01 for each) and on 10 of 25 items on the related Prostate Module (PR25) (P less than .01 for each).

Clinically relevant differences, defined as ones of at least 10 points on the 100-point linearly transformed scales, were seen between men who did and did not have testosterone recovery for two of the global quality of life items – trouble doing strenuous activities and trouble taking long walks – and three of the prostate-related quality of life items – hot flushes, interest in sex, and sexual activity.

“In high-risk prostate cancer treated with radiation therapy and ADT, patients who recover normal testosterone levels have a better quality of life,” said Dr. Nabid. “There is a major advantage in the use of 18 months of ADT instead of 36 months since a higher proportion of patients recovered normal testosterone levels in a much shorter time without any apparent detriment in long-term outcomes.”

“If we succeed to demonstrate that 18 months is at least equal to 36 months, it’s a big jump because it’s a matter of quality of life, it’s a matter of cost also,” he added. The investigators expect to be able to publish final efficacy and quality of life results next year.

In the meantime, clinicians can follow national guidelines, according to Dr. Nabid. “If you look at the guidelines, like the NCCN guidelines for the U.S., what is written is that the long-term [ADT] could be between 24 and 36 months. So my advice would be, even if you wait for the final paper, to go for 24 months. It’s a good beginning,” he asserted.

However, “you have to use your clinical judgment,” he added, agreeing that disease factors can be used to further stratify high-risk patients; additionally, age, comorbidities, and other factors will play a role in tailoring the duration of ADT. And importantly, “one has to discuss this with his patients.”

Dr. Lawton noted that the definition of long-duration ADT has varied by world region, and has typically been 28 months in the United States and 36 months in Europe. On the basis of this trial’s findings, “I do think that 18 months is potentially our new long-term hormone therapy option. That data isn’t out in print yet, other than in abstract form, But I think going forward, the question for us should be, can we shorten it from there,” she said. “I don’t know that we’ve nailed [the optimal long duration], but we are certainly heading in the right direction.”

Dr. Zapatero disclosed no conflicts of interest; the trial was supported in part by the AstraZeneca Fund. Dr. Nabid disclosed ties with AstraZeneca and Sanofi; AstraZeneca collaborated on the trial.

SAN FRANCISCO – Men who undergo radiation therapy for high-risk prostate cancer are less likely to have a recurrence and to die if they also receive long-duration androgen deprivation therapy. A long duration roughly half of that typically used appears to strike a good balance between efficacy and quality of life.

These were among the key findings of a pair of phase III randomized trials reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Quantity of life became the most important piece for us as we were trying to control prostate cancer. But today, so many of our localized prostate cancer patients are going to survive their illness that quality of life becomes exceedingly important,” said Dr. Colleen Lawton, vice chair and clinical director of the department of radiation oncology at the Medical College of Wisconsin, Milwaukee, and moderator of a related press briefing.

Efficacy data support long-duration ADT

In the first trial, called DART 01/05 (or AADLPC) and supported in part by the AstraZeneca Fund, investigators led by Dr. Almudena Zapatero, a radiation oncologist at Hospital Universitario de la Princesa, Madrid, studied 355 patients with intermediate- or high-risk prostate cancer.

The patients were randomized evenly to high-dose radiation therapy of at least 76 Gy, plus either short-duration ADT (4 months before and during radiation only) or long-duration ADT (4 months before and during radiation and 24 months afterward).

With a median follow-up of 63 months, relative to short-duration ADT, long-duration ADT was associated with better 5-year rates of biochemical disease–free survival according to the Phoenix definition (89.8% vs. 81.3%), overall survival (94.8% vs. 86.1%), and metastasis-free survival (93.6% vs. 83.4%), reported Dr. Zapatero. However, in stratified analyses, these benefits were seen only in the men with high-risk disease.

The two treatment groups did not differ significantly with respect to rates of acute and late rectal and urinary toxicity.

The study is noteworthy as it supports use of more costly high-dose radiation and hormonal therapy, said Dr. Zapatero. “We have demonstrated that we can get a 10% absolute benefit in PSA [prostate-specific antigen] control and overall survival and cancer-specific survival with acceptably low complications for high-risk disease. This is what we know now. We now know that … intermediate-risk disease probably doesn’t need any complementary [hormone therapy],” she said.

“We await longer follow-up to confirm these results and to determine the impact of long-term hormones according to the risk subgroup,” added Dr. Zapatero, noting that high-risk patients can be further stratified according to T3 stage, high Gleason score, and undifferentiated tumor histology. “Probably, if you have one factor, you are going to need less long of a duration of hormones, probably close to 18 months. And if you have two or three, what we call very high risk disease, you are going to need longer hormone therapy and the highest radiation [dose].”

Explaining the importance of the findings, Dr. Lawton, the press briefing moderator, said, “We have shown over time that increasing the dose [of radiation] to the prostate and immediate surrounding tissues improves outcomes. We have also shown for our high-risk patients that adding hormone therapy improves outcomes. But what we have yet to show is … do you really need the hormone therapy if you use dose escalation? And the answer is yes.”

Shortening duration of ADT improves testosterone recovery

In the second trial, known as PCS IV, investigators led by Dr. Abdenour Nabid, a radiation oncologist at Centre Hospitalier Universitaire de Sherbrooke, Quebec, Canada, studied 561 men with high-risk prostate cancer who had been treated with radiation therapy (44 Gy to the whole pelvis and 70 Gy to the prostate) and randomized to 18 months or 36 months of ADT. AstraZeneca collaborated on the trial.

Previously reported results suggested that 18 months was just as efficacious as 36 months for overall survival and cancer-specific survival (ASCO 2013 Annual Meeting. Abstract LBA4510).

With a median follow-up of 84 months, relative to counterparts who had received ADT for 36 months, patients who had received ADT for 18 months were more likely to have recovery of testosterone values into the normal range (55.7% vs. 44.9%, P = .01) and had a shorter median time to recovery (47.2 vs. 73.2 months, P less than .001).

Relative to counterparts who did not have testosterone recovery, patients who did had significantly better scores on 18 of 30 items on the European Organization for Research and Treatment of Cancer’s global quality of life questionnaire (EORTC30) (P less than .01 for each) and on 10 of 25 items on the related Prostate Module (PR25) (P less than .01 for each).

Clinically relevant differences, defined as ones of at least 10 points on the 100-point linearly transformed scales, were seen between men who did and did not have testosterone recovery for two of the global quality of life items – trouble doing strenuous activities and trouble taking long walks – and three of the prostate-related quality of life items – hot flushes, interest in sex, and sexual activity.

“In high-risk prostate cancer treated with radiation therapy and ADT, patients who recover normal testosterone levels have a better quality of life,” said Dr. Nabid. “There is a major advantage in the use of 18 months of ADT instead of 36 months since a higher proportion of patients recovered normal testosterone levels in a much shorter time without any apparent detriment in long-term outcomes.”

“If we succeed to demonstrate that 18 months is at least equal to 36 months, it’s a big jump because it’s a matter of quality of life, it’s a matter of cost also,” he added. The investigators expect to be able to publish final efficacy and quality of life results next year.

In the meantime, clinicians can follow national guidelines, according to Dr. Nabid. “If you look at the guidelines, like the NCCN guidelines for the U.S., what is written is that the long-term [ADT] could be between 24 and 36 months. So my advice would be, even if you wait for the final paper, to go for 24 months. It’s a good beginning,” he asserted.

However, “you have to use your clinical judgment,” he added, agreeing that disease factors can be used to further stratify high-risk patients; additionally, age, comorbidities, and other factors will play a role in tailoring the duration of ADT. And importantly, “one has to discuss this with his patients.”

Dr. Lawton noted that the definition of long-duration ADT has varied by world region, and has typically been 28 months in the United States and 36 months in Europe. On the basis of this trial’s findings, “I do think that 18 months is potentially our new long-term hormone therapy option. That data isn’t out in print yet, other than in abstract form, But I think going forward, the question for us should be, can we shorten it from there,” she said. “I don’t know that we’ve nailed [the optimal long duration], but we are certainly heading in the right direction.”

Dr. Zapatero disclosed no conflicts of interest; the trial was supported in part by the AstraZeneca Fund. Dr. Nabid disclosed ties with AstraZeneca and Sanofi; AstraZeneca collaborated on the trial.

SAN FRANCISCO – Patients with extensive small cell lung cancer that responds to chemotherapy fare better when given thoracic radiation in addition to prophylactic cranial irradiation, investigators reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Thoracic radiotherapy ­– 30 Gy in 10 fractions – improves overall survival, progression-free survival, and intrathoracic control,” concluded Dr. Ben J. Slotman, professor and head of the department of radiation oncology at Vrije Universiteit Medical Center, Amsterdam. “We think that this should now be offered in addition to prophylactic cranial irradiation to patients with a response after initial chemotherapy,” he said.

“What are your thoughts about building on these results by using perhaps a higher dose of radiation or perhaps radiation to other extrathoracic sites using [stereotactic body radiation therapy] or other approaches like that?” asked session cochair Dr. Benjamin Movsas, a radiation oncologist at Henry Ford Hospital in Detroit.

“That’s an excellent point. The dose was chosen on the safe side – 10 times 3 Gy – and was given without much toxicity, so I think the next step would be to move … to a higher dose, perhaps 15 times 3 Gy,” Dr. Slotman replied. The findings also support use of radiation therapy to manage other sites of metastases. “I think this study really shows that if you give local treatment to this group of patients with disseminated disease, that you are still able to make a great impact,” he maintained.

In this patient population, prophylactic cranial irradiation alone reduces the risk of symptomatic brain metastases and improves overall survival, he noted, giving some background to the trial (N. Engl. J. Med. 2007;357:664-72). The large majority of patients, however, have persistent intrathoracic disease (76%) and experience intrathoracic progression (89%).

Patients from the Netherlands, United Kingdom, Norway, and Belgium were eligible for the phase III trial, known as the Chest Radiotherapy Extensive Stage Trial (CREST), if they had extensive-stage small cell lung cancer (disease beyond the hemithorax, hilar, mediastinal, and supraclavicular nodes) and had experienced a complete, partial, or good response to platinum-based chemotherapy. Additionally, they could not have any brain, leptomeningeal, or pleural metastases and could not have previously received radiation therapy to the thorax or brain.

The 498 patients were randomized evenly to receive thoracic radiation or no thoracic radiation. All received prophylactic cranial irradiation.

Overall survival curves for the two groups first began to diverge at about 9 months, Dr. Slotman noted.

Thoracic radiation was associated with a trend toward better 1-year overall survival (33% vs. 28%; hazard ratio, 0.84; P = .066) and significantly better 2-year overall survival (13% vs. 3%, P = .004), according to results reported at the meeting and simultaneously published online (Lancet 2014 Sept. 14 [doi:10.1016/S0140-6736(14)61085-0]).

Subgroup analyses suggested that thoracic radiation was similarly efficacious regardless of a variety of disease, clinical, and demographic characteristics, except for possibly having less benefit in patients who had had a complete response to chemotherapy and in patients who did not have intrathoracic disease, he said.

Thoracic radiation also was associated with better progression-free survival (HR, 0.73; P = .001).

The rate of intrathoracic progression was significantly lower in the thoracic radiation group as well, regardless of whether this applied to intrathoracic progression events overall (44% vs. 80%), to those that were the first site relapse (42% vs. 78%), or to those that were the only site of relapse (20% vs. 46%), Dr. Slotman reported.

The thorax was the leading site of first relapse in the control group. In contrast, sites outside the thorax and brain were most often the site of first relapse in the thoracic radiation group.

About 8% of patients overall experienced grade 3 or worse toxicity, with no significant difference between groups in the rate or nature of the events.

Dr. Slotman disclosed no relevant conflicts of interest.

SAN FRANCISCO – Patients with extensive small cell lung cancer that responds to chemotherapy fare better when given thoracic radiation in addition to prophylactic cranial irradiation, investigators reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Thoracic radiotherapy ­– 30 Gy in 10 fractions – improves overall survival, progression-free survival, and intrathoracic control,” concluded Dr. Ben J. Slotman, professor and head of the department of radiation oncology at Vrije Universiteit Medical Center, Amsterdam. “We think that this should now be offered in addition to prophylactic cranial irradiation to patients with a response after initial chemotherapy,” he said.

“What are your thoughts about building on these results by using perhaps a higher dose of radiation or perhaps radiation to other extrathoracic sites using [stereotactic body radiation therapy] or other approaches like that?” asked session cochair Dr. Benjamin Movsas, a radiation oncologist at Henry Ford Hospital in Detroit.

“That’s an excellent point. The dose was chosen on the safe side – 10 times 3 Gy – and was given without much toxicity, so I think the next step would be to move … to a higher dose, perhaps 15 times 3 Gy,” Dr. Slotman replied. The findings also support use of radiation therapy to manage other sites of metastases. “I think this study really shows that if you give local treatment to this group of patients with disseminated disease, that you are still able to make a great impact,” he maintained.

In this patient population, prophylactic cranial irradiation alone reduces the risk of symptomatic brain metastases and improves overall survival, he noted, giving some background to the trial (N. Engl. J. Med. 2007;357:664-72). The large majority of patients, however, have persistent intrathoracic disease (76%) and experience intrathoracic progression (89%).

Patients from the Netherlands, United Kingdom, Norway, and Belgium were eligible for the phase III trial, known as the Chest Radiotherapy Extensive Stage Trial (CREST), if they had extensive-stage small cell lung cancer (disease beyond the hemithorax, hilar, mediastinal, and supraclavicular nodes) and had experienced a complete, partial, or good response to platinum-based chemotherapy. Additionally, they could not have any brain, leptomeningeal, or pleural metastases and could not have previously received radiation therapy to the thorax or brain.

The 498 patients were randomized evenly to receive thoracic radiation or no thoracic radiation. All received prophylactic cranial irradiation.

Overall survival curves for the two groups first began to diverge at about 9 months, Dr. Slotman noted.

Thoracic radiation was associated with a trend toward better 1-year overall survival (33% vs. 28%; hazard ratio, 0.84; P = .066) and significantly better 2-year overall survival (13% vs. 3%, P = .004), according to results reported at the meeting and simultaneously published online (Lancet 2014 Sept. 14 [doi:10.1016/S0140-6736(14)61085-0]).

Subgroup analyses suggested that thoracic radiation was similarly efficacious regardless of a variety of disease, clinical, and demographic characteristics, except for possibly having less benefit in patients who had had a complete response to chemotherapy and in patients who did not have intrathoracic disease, he said.

Thoracic radiation also was associated with better progression-free survival (HR, 0.73; P = .001).

The rate of intrathoracic progression was significantly lower in the thoracic radiation group as well, regardless of whether this applied to intrathoracic progression events overall (44% vs. 80%), to those that were the first site relapse (42% vs. 78%), or to those that were the only site of relapse (20% vs. 46%), Dr. Slotman reported.

The thorax was the leading site of first relapse in the control group. In contrast, sites outside the thorax and brain were most often the site of first relapse in the thoracic radiation group.

About 8% of patients overall experienced grade 3 or worse toxicity, with no significant difference between groups in the rate or nature of the events.

Dr. Slotman disclosed no relevant conflicts of interest.

SAN FRANCISCO – Patients with extensive small cell lung cancer that responds to chemotherapy fare better when given thoracic radiation in addition to prophylactic cranial irradiation, investigators reported at the annual scientific meeting of the American Society for Radiation Oncology.

“Thoracic radiotherapy ­– 30 Gy in 10 fractions – improves overall survival, progression-free survival, and intrathoracic control,” concluded Dr. Ben J. Slotman, professor and head of the department of radiation oncology at Vrije Universiteit Medical Center, Amsterdam. “We think that this should now be offered in addition to prophylactic cranial irradiation to patients with a response after initial chemotherapy,” he said.

“What are your thoughts about building on these results by using perhaps a higher dose of radiation or perhaps radiation to other extrathoracic sites using [stereotactic body radiation therapy] or other approaches like that?” asked session cochair Dr. Benjamin Movsas, a radiation oncologist at Henry Ford Hospital in Detroit.

“That’s an excellent point. The dose was chosen on the safe side – 10 times 3 Gy – and was given without much toxicity, so I think the next step would be to move … to a higher dose, perhaps 15 times 3 Gy,” Dr. Slotman replied. The findings also support use of radiation therapy to manage other sites of metastases. “I think this study really shows that if you give local treatment to this group of patients with disseminated disease, that you are still able to make a great impact,” he maintained.

In this patient population, prophylactic cranial irradiation alone reduces the risk of symptomatic brain metastases and improves overall survival, he noted, giving some background to the trial (N. Engl. J. Med. 2007;357:664-72). The large majority of patients, however, have persistent intrathoracic disease (76%) and experience intrathoracic progression (89%).

Patients from the Netherlands, United Kingdom, Norway, and Belgium were eligible for the phase III trial, known as the Chest Radiotherapy Extensive Stage Trial (CREST), if they had extensive-stage small cell lung cancer (disease beyond the hemithorax, hilar, mediastinal, and supraclavicular nodes) and had experienced a complete, partial, or good response to platinum-based chemotherapy. Additionally, they could not have any brain, leptomeningeal, or pleural metastases and could not have previously received radiation therapy to the thorax or brain.

The 498 patients were randomized evenly to receive thoracic radiation or no thoracic radiation. All received prophylactic cranial irradiation.

Overall survival curves for the two groups first began to diverge at about 9 months, Dr. Slotman noted.

Thoracic radiation was associated with a trend toward better 1-year overall survival (33% vs. 28%; hazard ratio, 0.84; P = .066) and significantly better 2-year overall survival (13% vs. 3%, P = .004), according to results reported at the meeting and simultaneously published online (Lancet 2014 Sept. 14 [doi:10.1016/S0140-6736(14)61085-0]).

Subgroup analyses suggested that thoracic radiation was similarly efficacious regardless of a variety of disease, clinical, and demographic characteristics, except for possibly having less benefit in patients who had had a complete response to chemotherapy and in patients who did not have intrathoracic disease, he said.

Thoracic radiation also was associated with better progression-free survival (HR, 0.73; P = .001).

The rate of intrathoracic progression was significantly lower in the thoracic radiation group as well, regardless of whether this applied to intrathoracic progression events overall (44% vs. 80%), to those that were the first site relapse (42% vs. 78%), or to those that were the only site of relapse (20% vs. 46%), Dr. Slotman reported.

The thorax was the leading site of first relapse in the control group. In contrast, sites outside the thorax and brain were most often the site of first relapse in the thoracic radiation group.

About 8% of patients overall experienced grade 3 or worse toxicity, with no significant difference between groups in the rate or nature of the events.

Dr. Slotman disclosed no relevant conflicts of interest.

SAN FRANCISCO – Directing radiation therapy to lymph nodes in the breast or chest wall as part of treatment for early node-negative breast cancer does not increase lymphedema risk, according to a secondary analysis of the National Surgical Adjuvant Breast and Bowel Project’s B-32 trial.

“There was no evidence to suggest a detrimental impact of nonregional nodal breast or chest wall radiation on the risk of lymphedema beyond surgery,” lead author Dr. Susan A. McCloskey of the University of California, Los Angeles, said at the annual scientific meeting of the American Society for Radiation Oncology.

The results also showed that subjectively perceived lymphedema was less common than objectively measured lymphedema, and the two were poorly correlated. “Additional analyses of our objective data are currently in progress to evaluate quantification methods that may better correlate with the subjective assessment,” she said.

In the trial, women with clinically node-negative breast cancer were randomized to sentinel node resection followed by routine axillary lymph node dissection (ALND) – the standard when the trial began – or to sentinel node resection followed by ALND only if that node was positive.

Previously reported results showed that the two strategies yielded statistically equivalent overall survival, disease-free survival, and regional control (Lancet Oncol. 2010;11:927-933) and that ALND increased the risk of lymphedema (J. Surg. Oncol. 2010;102:111-8).

“In large part, on the basis of these findings, sentinel node resection alone became [the] standard of care for women presenting with clinically negative axillary nodes,” Dr. McCloskey noted.

The new analysis compared lymphedema outcomes according to receipt of radiation among the 3,894 women with pathologically negative sentinel nodes. Most underwent breast-conserving surgery, and 83% received radiation therapy as part of their treatment, nearly always breast or chest wall–only radiation (that is, nonregional nodal radiation).

The women were evaluated for the presence of lymphedema every 6 months. Subjective lymphedema, assessed with a questionnaire, was defined as a report that swelling was somewhat, quite, or very bothersome. Objective lymphedema, assessed with a water displacement test, was defined as a relative difference in volumes between arms exceeding 10%.

During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively, reported Dr. McCloskey. The findings were the same when women were stratified by the extent of nodal surgery.

The rate of subjective lymphedema was consistently lower than the rate of objective lymphedema, both among women who had only sentinel node resection (averaging roughly 2.5% vs. 7.5%) and among women who had sentinel node resection followed by ALND (averaging roughly 10% vs. 15%). Overall, there was poor agreement between objectively and subjectively measured lymphedema, with kappa values ranging from just 0.02 to 0.21, where 1.0 would represent perfect agreement.

“Some considerations that we view as hypothesis generating at this point are that a relative arm volume difference of less than 10% is bothersome to some women, and conversely, a relative arm volume difference of greater than 10% is not bothersome to all women. So there may be issues of body habitus or handedness that may affect these metrics,” Dr. McCloskey commented. “Also, I think the jury is still out on exactly what the best metric is to measure lymphedema, both in terms of water displacement and the relative arm volume difference equation.”

In a related press briefing, she said that the findings could affect treatment decisions, given that some women with early breast cancer opt for mastectomy in part because of fears about radiation therapy.

“Where I practice, we run a multidisciplinary breast clinic where all women who are newly diagnosed come to see a team of physicians at the time of their diagnosis. I find that one of the most feared topics for discussion is radiation, and many women will talk about a litany of potential side effects that they are fearful of. And as many of you know, there have been dramatic increases in rates of mastectomy in the United States,” she said. “So it’s an opportunity, I think, to reassure women who are particularly fearful of lymphedema that yes, there is still a risk from the surgery and the type of surgery that’s done, but it doesn’t appear that choice of breast conservation and having routine breast radiation is going to impact that risk beyond the surgery. So I think it can affect what women choose.”

The findings are good news when it comes to quality of life after breast cancer treatment, agreed Dr. Tracy Balboni, a radiation oncologist at the Dana-Farber Cancer Institute in Boston and moderator of the press briefing. The evidence suggesting that conventional radiation therapy doesn’t add to the risk of lymphedema for patients “help[s] us feel assured that we’re not going to be reducing the quality of life of our cancer patients through the addition of conventional radiation therapy to the whole breast,” she said.

Dr. McCloskey disclosed no relevant conflicts of interest.

SAN FRANCISCO – Directing radiation therapy to lymph nodes in the breast or chest wall as part of treatment for early node-negative breast cancer does not increase lymphedema risk, according to a secondary analysis of the National Surgical Adjuvant Breast and Bowel Project’s B-32 trial.

“There was no evidence to suggest a detrimental impact of nonregional nodal breast or chest wall radiation on the risk of lymphedema beyond surgery,” lead author Dr. Susan A. McCloskey of the University of California, Los Angeles, said at the annual scientific meeting of the American Society for Radiation Oncology.

The results also showed that subjectively perceived lymphedema was less common than objectively measured lymphedema, and the two were poorly correlated. “Additional analyses of our objective data are currently in progress to evaluate quantification methods that may better correlate with the subjective assessment,” she said.

In the trial, women with clinically node-negative breast cancer were randomized to sentinel node resection followed by routine axillary lymph node dissection (ALND) – the standard when the trial began – or to sentinel node resection followed by ALND only if that node was positive.

Previously reported results showed that the two strategies yielded statistically equivalent overall survival, disease-free survival, and regional control (Lancet Oncol. 2010;11:927-933) and that ALND increased the risk of lymphedema (J. Surg. Oncol. 2010;102:111-8).

“In large part, on the basis of these findings, sentinel node resection alone became [the] standard of care for women presenting with clinically negative axillary nodes,” Dr. McCloskey noted.

The new analysis compared lymphedema outcomes according to receipt of radiation among the 3,894 women with pathologically negative sentinel nodes. Most underwent breast-conserving surgery, and 83% received radiation therapy as part of their treatment, nearly always breast or chest wall–only radiation (that is, nonregional nodal radiation).

The women were evaluated for the presence of lymphedema every 6 months. Subjective lymphedema, assessed with a questionnaire, was defined as a report that swelling was somewhat, quite, or very bothersome. Objective lymphedema, assessed with a water displacement test, was defined as a relative difference in volumes between arms exceeding 10%.

During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively, reported Dr. McCloskey. The findings were the same when women were stratified by the extent of nodal surgery.

The rate of subjective lymphedema was consistently lower than the rate of objective lymphedema, both among women who had only sentinel node resection (averaging roughly 2.5% vs. 7.5%) and among women who had sentinel node resection followed by ALND (averaging roughly 10% vs. 15%). Overall, there was poor agreement between objectively and subjectively measured lymphedema, with kappa values ranging from just 0.02 to 0.21, where 1.0 would represent perfect agreement.

“Some considerations that we view as hypothesis generating at this point are that a relative arm volume difference of less than 10% is bothersome to some women, and conversely, a relative arm volume difference of greater than 10% is not bothersome to all women. So there may be issues of body habitus or handedness that may affect these metrics,” Dr. McCloskey commented. “Also, I think the jury is still out on exactly what the best metric is to measure lymphedema, both in terms of water displacement and the relative arm volume difference equation.”

In a related press briefing, she said that the findings could affect treatment decisions, given that some women with early breast cancer opt for mastectomy in part because of fears about radiation therapy.

“Where I practice, we run a multidisciplinary breast clinic where all women who are newly diagnosed come to see a team of physicians at the time of their diagnosis. I find that one of the most feared topics for discussion is radiation, and many women will talk about a litany of potential side effects that they are fearful of. And as many of you know, there have been dramatic increases in rates of mastectomy in the United States,” she said. “So it’s an opportunity, I think, to reassure women who are particularly fearful of lymphedema that yes, there is still a risk from the surgery and the type of surgery that’s done, but it doesn’t appear that choice of breast conservation and having routine breast radiation is going to impact that risk beyond the surgery. So I think it can affect what women choose.”

The findings are good news when it comes to quality of life after breast cancer treatment, agreed Dr. Tracy Balboni, a radiation oncologist at the Dana-Farber Cancer Institute in Boston and moderator of the press briefing. The evidence suggesting that conventional radiation therapy doesn’t add to the risk of lymphedema for patients “help[s] us feel assured that we’re not going to be reducing the quality of life of our cancer patients through the addition of conventional radiation therapy to the whole breast,” she said.

Dr. McCloskey disclosed no relevant conflicts of interest.

SAN FRANCISCO – Directing radiation therapy to lymph nodes in the breast or chest wall as part of treatment for early node-negative breast cancer does not increase lymphedema risk, according to a secondary analysis of the National Surgical Adjuvant Breast and Bowel Project’s B-32 trial.

“There was no evidence to suggest a detrimental impact of nonregional nodal breast or chest wall radiation on the risk of lymphedema beyond surgery,” lead author Dr. Susan A. McCloskey of the University of California, Los Angeles, said at the annual scientific meeting of the American Society for Radiation Oncology.

The results also showed that subjectively perceived lymphedema was less common than objectively measured lymphedema, and the two were poorly correlated. “Additional analyses of our objective data are currently in progress to evaluate quantification methods that may better correlate with the subjective assessment,” she said.

In the trial, women with clinically node-negative breast cancer were randomized to sentinel node resection followed by routine axillary lymph node dissection (ALND) – the standard when the trial began – or to sentinel node resection followed by ALND only if that node was positive.

Previously reported results showed that the two strategies yielded statistically equivalent overall survival, disease-free survival, and regional control (Lancet Oncol. 2010;11:927-933) and that ALND increased the risk of lymphedema (J. Surg. Oncol. 2010;102:111-8).

“In large part, on the basis of these findings, sentinel node resection alone became [the] standard of care for women presenting with clinically negative axillary nodes,” Dr. McCloskey noted.

The new analysis compared lymphedema outcomes according to receipt of radiation among the 3,894 women with pathologically negative sentinel nodes. Most underwent breast-conserving surgery, and 83% received radiation therapy as part of their treatment, nearly always breast or chest wall–only radiation (that is, nonregional nodal radiation).

The women were evaluated for the presence of lymphedema every 6 months. Subjective lymphedema, assessed with a questionnaire, was defined as a report that swelling was somewhat, quite, or very bothersome. Objective lymphedema, assessed with a water displacement test, was defined as a relative difference in volumes between arms exceeding 10%.

During 36 months of follow-up, there was no significant difference at any time point between women who did and did not receive radiation in the adjusted rate of lymphedema, whether it was assessed subjectively or objectively, reported Dr. McCloskey. The findings were the same when women were stratified by the extent of nodal surgery.

The rate of subjective lymphedema was consistently lower than the rate of objective lymphedema, both among women who had only sentinel node resection (averaging roughly 2.5% vs. 7.5%) and among women who had sentinel node resection followed by ALND (averaging roughly 10% vs. 15%). Overall, there was poor agreement between objectively and subjectively measured lymphedema, with kappa values ranging from just 0.02 to 0.21, where 1.0 would represent perfect agreement.

“Some considerations that we view as hypothesis generating at this point are that a relative arm volume difference of less than 10% is bothersome to some women, and conversely, a relative arm volume difference of greater than 10% is not bothersome to all women. So there may be issues of body habitus or handedness that may affect these metrics,” Dr. McCloskey commented. “Also, I think the jury is still out on exactly what the best metric is to measure lymphedema, both in terms of water displacement and the relative arm volume difference equation.”

In a related press briefing, she said that the findings could affect treatment decisions, given that some women with early breast cancer opt for mastectomy in part because of fears about radiation therapy.

“Where I practice, we run a multidisciplinary breast clinic where all women who are newly diagnosed come to see a team of physicians at the time of their diagnosis. I find that one of the most feared topics for discussion is radiation, and many women will talk about a litany of potential side effects that they are fearful of. And as many of you know, there have been dramatic increases in rates of mastectomy in the United States,” she said. “So it’s an opportunity, I think, to reassure women who are particularly fearful of lymphedema that yes, there is still a risk from the surgery and the type of surgery that’s done, but it doesn’t appear that choice of breast conservation and having routine breast radiation is going to impact that risk beyond the surgery. So I think it can affect what women choose.”

The findings are good news when it comes to quality of life after breast cancer treatment, agreed Dr. Tracy Balboni, a radiation oncologist at the Dana-Farber Cancer Institute in Boston and moderator of the press briefing. The evidence suggesting that conventional radiation therapy doesn’t add to the risk of lymphedema for patients “help[s] us feel assured that we’re not going to be reducing the quality of life of our cancer patients through the addition of conventional radiation therapy to the whole breast,” she said.

Dr. McCloskey disclosed no relevant conflicts of interest.

SAN FRANCISCO – Stereotactic body radiation therapy has durable safety and efficacy when used to treat early lung cancer in patients who can’t undergo surgery for medical reasons, according to updated results of the Radiation Therapy Oncology Group’s 0236 trial (RTOG 0236), reported at the annual scientific meeting of the American Society for Radiation Oncology.

The trial was the first North American cooperative group trial to test this image-guided, highly focused form of radiation. The 59 patients studied all had stage 1 non–small cell lung cancer, but were frail and unable to undergo surgery because of comorbidities such as emphysema, heart disease, and stroke.

“Patients like this are typically not allowed into clinical trials because their prognosis is so bad. But these were exactly the patients that we selected,” lead investigator Dr. Robert Timmerman, professor and vice chair of the Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, commented in a press briefing.

Susan London/Frontline Medical News

Initial findings, reported after a median follow-up of about 3 years, led to “a fairly significant transition of care. The results at that time were frankly astounding, with nearly perfect tumor control at the treated site,” he said (JAMA 2010;303:1070-6). “There was skepticism, however, that led to sort of incomplete market penetration throughout cancer centers due to a concern about late toxicity that might occur with longer follow-up, or additional recurrences.”

But the updated results, now after a median follow-up of 4 years (7.2 years for survivors), showed that the 5-year rate of primary tumor recurrence in the radiation field was just 7%. “This is on par with surgery,” Dr. Timmerman noted.

Five-year overall survival was 40% (down from the initial 3-year rate of 56%). “Survival continues to decline as we might expect for a very frail population with competing causes of death but is still very impressive,” he maintained.

In terms of recurrences outside of the radiation field, seven patients had a regional failure (up from two initially), leading to a locoregional failure rate of 38% (up from 13%). “This indicates that our staging at the time of diagnosis was probably incorrect in that there were micrometastases. It did take a long time for many of these to appear, and most of them were in the involved lobe outside of the treated area,” Dr. Timmerman elaborated. “So, in response to that, we’ll need to look carefully at better staging and more effective adjuvant therapy to address this problem.”

Additionally, 15 patients developed disseminated metastases (up from 11). Five-year disease-free survival was therefore 26% (down from 48%).

“The really exciting news though was that there really wasn’t any significant difference in the toxicity with longer follow-up. This was something that many thought was going to happen,” Dr. Timmerman commented. Specifically, there were no treatment-related deaths. Seventeen patients experienced high-grade toxicity, consisting mainly of pulmonary toxicity.

The trial’s findings are pertinent to the roughly 10,000 patients in the United States each year who receive a diagnosis of stage I lung cancer and are not surgical candidates, according to Dr. Timmerman.

A survey done after the initial report suggested that although 70%-80% of centers have stereotactic body radiation therapy (SBRT) capability, only 40%-50% are actually using it. “These results, though, I think will change that dynamic. There were people who were skeptical, and in fact, there were a lot of notable people in our field who told everybody, ‘Pull the horses back,’ because there could be these late terrible side effects that were observed 100 years ago when similar treatment was done with low-tech treatments,” he said. “So that’s probably the biggest message from this long-term report: We did not see those horrible late side effects that were predicted.”

Lack of training may also explain in part the limited use of SBRT, he added. “You can buy the equipment if you have the money, but that doesn’t mean you have the training to run the equipment. So the big challenge that we will have as a profession – and I think ASTRO is really going to have to address this – is facilitating the training so that people can get this treatment where they live. Not everybody can go to the big academic medical centers and get treatment.”

“We are about to embark on a phase III trial that will randomize centers to treat with either SBRT or surgery for high-risk operable patients in clusters of three to five patients,” noted Dr. Timmerman. “This is very innovative. There have been several randomized trials that failed to accrue when the operable patients were randomized on a per-patient basis because there is such a disparity between the two treatments that the patient just couldn’t accept the randomization.”

Dr. Benjamin Movsas, a radiation oncologist at the Henry Ford Hospital in Detroit and moderator of the press briefing, noted that, historically, conventional radiation therapy in patients with inoperable stage I disease has yielded a tumor control rate of only about 40%-50%, contrasting to the nearly 90% seen with SBRT. “Having a 40% 5-year survival in this group of patients is actually a very, very positive result, even though clearly we are always working to do better and improve on that,” he said.

Susan London/Frontline Medical News

“We find this to be a very promising approach [at our institution]. We are offering a very precise, localized, millimeter-accurate treatment, which for the most part is extremely well tolerated,” he noted. “We primarily use it for the medically inoperable patients. However, there are also patients who, for their own reasons, may decide to decline surgery. So we’ll tell those patients that they should first consider surgery, but if they decline surgery, this is a secondary alternative.

“All these cases, though, are first presented at a multidisciplinary tumor board where we have thoracic surgeons, medical oncologists, radiation oncologists sitting around the table discussing it before we treat any patients,” Dr. Movsas stressed. “So these decisions are made as part of the multidisciplinary team approach.”

Dr. Timmerman disclosed no conflicts of interest relevant to the research.

SAN FRANCISCO – Stereotactic body radiation therapy has durable safety and efficacy when used to treat early lung cancer in patients who can’t undergo surgery for medical reasons, according to updated results of the Radiation Therapy Oncology Group’s 0236 trial (RTOG 0236), reported at the annual scientific meeting of the American Society for Radiation Oncology.

The trial was the first North American cooperative group trial to test this image-guided, highly focused form of radiation. The 59 patients studied all had stage 1 non–small cell lung cancer, but were frail and unable to undergo surgery because of comorbidities such as emphysema, heart disease, and stroke.

“Patients like this are typically not allowed into clinical trials because their prognosis is so bad. But these were exactly the patients that we selected,” lead investigator Dr. Robert Timmerman, professor and vice chair of the Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, commented in a press briefing.

Susan London/Frontline Medical News

Initial findings, reported after a median follow-up of about 3 years, led to “a fairly significant transition of care. The results at that time were frankly astounding, with nearly perfect tumor control at the treated site,” he said (JAMA 2010;303:1070-6). “There was skepticism, however, that led to sort of incomplete market penetration throughout cancer centers due to a concern about late toxicity that might occur with longer follow-up, or additional recurrences.”

But the updated results, now after a median follow-up of 4 years (7.2 years for survivors), showed that the 5-year rate of primary tumor recurrence in the radiation field was just 7%. “This is on par with surgery,” Dr. Timmerman noted.

Five-year overall survival was 40% (down from the initial 3-year rate of 56%). “Survival continues to decline as we might expect for a very frail population with competing causes of death but is still very impressive,” he maintained.

In terms of recurrences outside of the radiation field, seven patients had a regional failure (up from two initially), leading to a locoregional failure rate of 38% (up from 13%). “This indicates that our staging at the time of diagnosis was probably incorrect in that there were micrometastases. It did take a long time for many of these to appear, and most of them were in the involved lobe outside of the treated area,” Dr. Timmerman elaborated. “So, in response to that, we’ll need to look carefully at better staging and more effective adjuvant therapy to address this problem.”

Additionally, 15 patients developed disseminated metastases (up from 11). Five-year disease-free survival was therefore 26% (down from 48%).

“The really exciting news though was that there really wasn’t any significant difference in the toxicity with longer follow-up. This was something that many thought was going to happen,” Dr. Timmerman commented. Specifically, there were no treatment-related deaths. Seventeen patients experienced high-grade toxicity, consisting mainly of pulmonary toxicity.

The trial’s findings are pertinent to the roughly 10,000 patients in the United States each year who receive a diagnosis of stage I lung cancer and are not surgical candidates, according to Dr. Timmerman.

A survey done after the initial report suggested that although 70%-80% of centers have stereotactic body radiation therapy (SBRT) capability, only 40%-50% are actually using it. “These results, though, I think will change that dynamic. There were people who were skeptical, and in fact, there were a lot of notable people in our field who told everybody, ‘Pull the horses back,’ because there could be these late terrible side effects that were observed 100 years ago when similar treatment was done with low-tech treatments,” he said. “So that’s probably the biggest message from this long-term report: We did not see those horrible late side effects that were predicted.”

Lack of training may also explain in part the limited use of SBRT, he added. “You can buy the equipment if you have the money, but that doesn’t mean you have the training to run the equipment. So the big challenge that we will have as a profession – and I think ASTRO is really going to have to address this – is facilitating the training so that people can get this treatment where they live. Not everybody can go to the big academic medical centers and get treatment.”

“We are about to embark on a phase III trial that will randomize centers to treat with either SBRT or surgery for high-risk operable patients in clusters of three to five patients,” noted Dr. Timmerman. “This is very innovative. There have been several randomized trials that failed to accrue when the operable patients were randomized on a per-patient basis because there is such a disparity between the two treatments that the patient just couldn’t accept the randomization.”

Dr. Benjamin Movsas, a radiation oncologist at the Henry Ford Hospital in Detroit and moderator of the press briefing, noted that, historically, conventional radiation therapy in patients with inoperable stage I disease has yielded a tumor control rate of only about 40%-50%, contrasting to the nearly 90% seen with SBRT. “Having a 40% 5-year survival in this group of patients is actually a very, very positive result, even though clearly we are always working to do better and improve on that,” he said.

Susan London/Frontline Medical News

“We find this to be a very promising approach [at our institution]. We are offering a very precise, localized, millimeter-accurate treatment, which for the most part is extremely well tolerated,” he noted. “We primarily use it for the medically inoperable patients. However, there are also patients who, for their own reasons, may decide to decline surgery. So we’ll tell those patients that they should first consider surgery, but if they decline surgery, this is a secondary alternative.

“All these cases, though, are first presented at a multidisciplinary tumor board where we have thoracic surgeons, medical oncologists, radiation oncologists sitting around the table discussing it before we treat any patients,” Dr. Movsas stressed. “So these decisions are made as part of the multidisciplinary team approach.”

Dr. Timmerman disclosed no conflicts of interest relevant to the research.

SAN FRANCISCO – Stereotactic body radiation therapy has durable safety and efficacy when used to treat early lung cancer in patients who can’t undergo surgery for medical reasons, according to updated results of the Radiation Therapy Oncology Group’s 0236 trial (RTOG 0236), reported at the annual scientific meeting of the American Society for Radiation Oncology.

The trial was the first North American cooperative group trial to test this image-guided, highly focused form of radiation. The 59 patients studied all had stage 1 non–small cell lung cancer, but were frail and unable to undergo surgery because of comorbidities such as emphysema, heart disease, and stroke.

“Patients like this are typically not allowed into clinical trials because their prognosis is so bad. But these were exactly the patients that we selected,” lead investigator Dr. Robert Timmerman, professor and vice chair of the Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, commented in a press briefing.

Susan London/Frontline Medical News

Initial findings, reported after a median follow-up of about 3 years, led to “a fairly significant transition of care. The results at that time were frankly astounding, with nearly perfect tumor control at the treated site,” he said (JAMA 2010;303:1070-6). “There was skepticism, however, that led to sort of incomplete market penetration throughout cancer centers due to a concern about late toxicity that might occur with longer follow-up, or additional recurrences.”

But the updated results, now after a median follow-up of 4 years (7.2 years for survivors), showed that the 5-year rate of primary tumor recurrence in the radiation field was just 7%. “This is on par with surgery,” Dr. Timmerman noted.

Five-year overall survival was 40% (down from the initial 3-year rate of 56%). “Survival continues to decline as we might expect for a very frail population with competing causes of death but is still very impressive,” he maintained.

In terms of recurrences outside of the radiation field, seven patients had a regional failure (up from two initially), leading to a locoregional failure rate of 38% (up from 13%). “This indicates that our staging at the time of diagnosis was probably incorrect in that there were micrometastases. It did take a long time for many of these to appear, and most of them were in the involved lobe outside of the treated area,” Dr. Timmerman elaborated. “So, in response to that, we’ll need to look carefully at better staging and more effective adjuvant therapy to address this problem.”

Additionally, 15 patients developed disseminated metastases (up from 11). Five-year disease-free survival was therefore 26% (down from 48%).

“The really exciting news though was that there really wasn’t any significant difference in the toxicity with longer follow-up. This was something that many thought was going to happen,” Dr. Timmerman commented. Specifically, there were no treatment-related deaths. Seventeen patients experienced high-grade toxicity, consisting mainly of pulmonary toxicity.

The trial’s findings are pertinent to the roughly 10,000 patients in the United States each year who receive a diagnosis of stage I lung cancer and are not surgical candidates, according to Dr. Timmerman.

A survey done after the initial report suggested that although 70%-80% of centers have stereotactic body radiation therapy (SBRT) capability, only 40%-50% are actually using it. “These results, though, I think will change that dynamic. There were people who were skeptical, and in fact, there were a lot of notable people in our field who told everybody, ‘Pull the horses back,’ because there could be these late terrible side effects that were observed 100 years ago when similar treatment was done with low-tech treatments,” he said. “So that’s probably the biggest message from this long-term report: We did not see those horrible late side effects that were predicted.”

Lack of training may also explain in part the limited use of SBRT, he added. “You can buy the equipment if you have the money, but that doesn’t mean you have the training to run the equipment. So the big challenge that we will have as a profession – and I think ASTRO is really going to have to address this – is facilitating the training so that people can get this treatment where they live. Not everybody can go to the big academic medical centers and get treatment.”

“We are about to embark on a phase III trial that will randomize centers to treat with either SBRT or surgery for high-risk operable patients in clusters of three to five patients,” noted Dr. Timmerman. “This is very innovative. There have been several randomized trials that failed to accrue when the operable patients were randomized on a per-patient basis because there is such a disparity between the two treatments that the patient just couldn’t accept the randomization.”

Dr. Benjamin Movsas, a radiation oncologist at the Henry Ford Hospital in Detroit and moderator of the press briefing, noted that, historically, conventional radiation therapy in patients with inoperable stage I disease has yielded a tumor control rate of only about 40%-50%, contrasting to the nearly 90% seen with SBRT. “Having a 40% 5-year survival in this group of patients is actually a very, very positive result, even though clearly we are always working to do better and improve on that,” he said.

Susan London/Frontline Medical News

“We find this to be a very promising approach [at our institution]. We are offering a very precise, localized, millimeter-accurate treatment, which for the most part is extremely well tolerated,” he noted. “We primarily use it for the medically inoperable patients. However, there are also patients who, for their own reasons, may decide to decline surgery. So we’ll tell those patients that they should first consider surgery, but if they decline surgery, this is a secondary alternative.

“All these cases, though, are first presented at a multidisciplinary tumor board where we have thoracic surgeons, medical oncologists, radiation oncologists sitting around the table discussing it before we treat any patients,” Dr. Movsas stressed. “So these decisions are made as part of the multidisciplinary team approach.”

Dr. Timmerman disclosed no conflicts of interest relevant to the research.