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Partial-breast irradiation alternative to mastectomy following recurrence
BOSTON – In women with in-breast failures following breast-conserving surgery and whole-breast irradiation, partial-breast irradiation with 3D conformal radiation appears to be an effective and safe alternative to mastectomy, results of a phase II trial indicate.
At a median follow-up of 3.6 years, there were only two ipsilateral breast recurrences, and four mastectomies required among 58 women treated with partial-breast irradiation after a second lumpectomy, reported Douglas W. Arthur, MD, chair of radiation oncology at Virginia Commonwealth University in Richmond.
“I think this information adds to the growing data supporting this treatment approach as an alternative to mastectomy for those who continue to want to preserve the breast,” he said at a late-breaking abstracts session at the annual meeting of the American Society of Radiation Oncology.
The NRG/RTOG 1014 study is a prospective phase II trial designed to evaluate skin, breast, and chest wall events occurring within 1 year of re-irradiation. One-year toxicity results from the trial were reported at the 2015 ASTRO annual meeting.
Dr. Arthur presented 3-year efficacy results from the trial. The investigators enrolled women with in-breast recurrences more than 1 year after whole-breast irradiation (WBI), with tumors that were smaller than 3 cm, unifocal, and resected with negative margins. Axillary involvement was limited to pathologic NO or N1 without extracapsular extension.
Partial-breast irradiation was targeted to the surgical cavity with a safety margin of plus 1.5 cm for the clinical target volume, and an additional 1-cm expansion. The prescribed dose was 45 Gy in 1.5-Gy fractions delivered via 3D conformal radiotherapy in 30 treatments.
Of 65 patients accrued, 58 completed treatment and were evaluable for efficacy. The median age was 67.5 years. In all, 23 patients had ductal carcinoma in situ, and 35 had invasive cancers. All patients were node negative.
A total of four patients (6.9%) reported late grade 3 toxicities, which included breast infection, fibrous deep connective tissue, skin induration, and breast atrophy, pain, and volume loss. There were no grade 4 toxicities, and no treatment-related deaths.
Two patients had in-breast recurrences, which translated into a year estimate of 3.7%. Four patients underwent mastectomies, for a 3-year estimated mastectomy failure rate of 5.2%. Two of the mastectomies were for the in-breast recurrences, one for a nonhealing wound, and one occurred in a patient who developed cancer in the contralateral breast and opted for a bilateral mastectomy.
BOSTON – In women with in-breast failures following breast-conserving surgery and whole-breast irradiation, partial-breast irradiation with 3D conformal radiation appears to be an effective and safe alternative to mastectomy, results of a phase II trial indicate.
At a median follow-up of 3.6 years, there were only two ipsilateral breast recurrences, and four mastectomies required among 58 women treated with partial-breast irradiation after a second lumpectomy, reported Douglas W. Arthur, MD, chair of radiation oncology at Virginia Commonwealth University in Richmond.
“I think this information adds to the growing data supporting this treatment approach as an alternative to mastectomy for those who continue to want to preserve the breast,” he said at a late-breaking abstracts session at the annual meeting of the American Society of Radiation Oncology.
The NRG/RTOG 1014 study is a prospective phase II trial designed to evaluate skin, breast, and chest wall events occurring within 1 year of re-irradiation. One-year toxicity results from the trial were reported at the 2015 ASTRO annual meeting.
Dr. Arthur presented 3-year efficacy results from the trial. The investigators enrolled women with in-breast recurrences more than 1 year after whole-breast irradiation (WBI), with tumors that were smaller than 3 cm, unifocal, and resected with negative margins. Axillary involvement was limited to pathologic NO or N1 without extracapsular extension.
Partial-breast irradiation was targeted to the surgical cavity with a safety margin of plus 1.5 cm for the clinical target volume, and an additional 1-cm expansion. The prescribed dose was 45 Gy in 1.5-Gy fractions delivered via 3D conformal radiotherapy in 30 treatments.
Of 65 patients accrued, 58 completed treatment and were evaluable for efficacy. The median age was 67.5 years. In all, 23 patients had ductal carcinoma in situ, and 35 had invasive cancers. All patients were node negative.
A total of four patients (6.9%) reported late grade 3 toxicities, which included breast infection, fibrous deep connective tissue, skin induration, and breast atrophy, pain, and volume loss. There were no grade 4 toxicities, and no treatment-related deaths.
Two patients had in-breast recurrences, which translated into a year estimate of 3.7%. Four patients underwent mastectomies, for a 3-year estimated mastectomy failure rate of 5.2%. Two of the mastectomies were for the in-breast recurrences, one for a nonhealing wound, and one occurred in a patient who developed cancer in the contralateral breast and opted for a bilateral mastectomy.
BOSTON – In women with in-breast failures following breast-conserving surgery and whole-breast irradiation, partial-breast irradiation with 3D conformal radiation appears to be an effective and safe alternative to mastectomy, results of a phase II trial indicate.
At a median follow-up of 3.6 years, there were only two ipsilateral breast recurrences, and four mastectomies required among 58 women treated with partial-breast irradiation after a second lumpectomy, reported Douglas W. Arthur, MD, chair of radiation oncology at Virginia Commonwealth University in Richmond.
“I think this information adds to the growing data supporting this treatment approach as an alternative to mastectomy for those who continue to want to preserve the breast,” he said at a late-breaking abstracts session at the annual meeting of the American Society of Radiation Oncology.
The NRG/RTOG 1014 study is a prospective phase II trial designed to evaluate skin, breast, and chest wall events occurring within 1 year of re-irradiation. One-year toxicity results from the trial were reported at the 2015 ASTRO annual meeting.
Dr. Arthur presented 3-year efficacy results from the trial. The investigators enrolled women with in-breast recurrences more than 1 year after whole-breast irradiation (WBI), with tumors that were smaller than 3 cm, unifocal, and resected with negative margins. Axillary involvement was limited to pathologic NO or N1 without extracapsular extension.
Partial-breast irradiation was targeted to the surgical cavity with a safety margin of plus 1.5 cm for the clinical target volume, and an additional 1-cm expansion. The prescribed dose was 45 Gy in 1.5-Gy fractions delivered via 3D conformal radiotherapy in 30 treatments.
Of 65 patients accrued, 58 completed treatment and were evaluable for efficacy. The median age was 67.5 years. In all, 23 patients had ductal carcinoma in situ, and 35 had invasive cancers. All patients were node negative.
A total of four patients (6.9%) reported late grade 3 toxicities, which included breast infection, fibrous deep connective tissue, skin induration, and breast atrophy, pain, and volume loss. There were no grade 4 toxicities, and no treatment-related deaths.
Two patients had in-breast recurrences, which translated into a year estimate of 3.7%. Four patients underwent mastectomies, for a 3-year estimated mastectomy failure rate of 5.2%. Two of the mastectomies were for the in-breast recurrences, one for a nonhealing wound, and one occurred in a patient who developed cancer in the contralateral breast and opted for a bilateral mastectomy.
AT ASTRO 2016
Key clinical point: Re-irradiation following second lumpectomy after in-breast cancer recurrences appears to be a safe and effective alternative to mastectomy.
Major finding: The 3-year estimated in-breast recurrence rate was 3.7%.
Data source: Phase II nonrandomized study in 58 women with in-breast failures following breast-conserving surgery and whole-breast irradiation.
Disclosures: The study was supported by the National Cancer Institute. Dr. Arthur reported formerly serving on the medical advisory board of Impedimed,
Limit primary site radiation, but not craniospinal dose in medulloblastoma
BOSTON – For children with average-risk medulloblastoma, it is safe to limit the radiation boost to the posterior fossa, but reducing doses to the craniospinal axis results in worse outcomes among younger children, and is not advisable, according to results from the largest trial conducted in this population.
There were no significant differences in either 5-year event-free survival (EFS) or overall survival (OS) between children who received an involved field radiation therapy boost (boost to the tumor bed only) or a standard volume boost (to the whole posterior fossa) in a phase III randomized trial, reported lead author Jeff M. Michalski, MD, MBA, FASTRO, professor of radiation oncology at Washington University, St. Louis.
“We conclude that the survival rates and event-free survival rates following reduced boost volumes were comparable to standard radiation treatment volumes for the primary tumor site. This is the first trial to state definitively that there is no survival difference between these two approaches,” he said at a briefing following his presentation of the data in an oral abstract session at the annual meeting of the American Society for Radiation Oncology.
“However, the reduced craniospinal axis irradiation was associated with a higher event rate and worse survival. We believe that physicians can adopt smaller boost volumes to the posterior fossa in children with average-risk medulloblastoma, average risk being no evidence of spread at the time of diagnosis and near-complete or complete resection. But for all children, the standard of 23.4 Gy remains necessary to retain high-level tumor control,” he added.
Aggressive malignancy
Medulloblastoma, an aggressive tumor with the propensity to spread from the lower brain to the upper brain and spine, is the most common brain malignancy in children. The current standard of care for children with average-risk disease is surgical resection followed by systemic chemotherapy followed by irradiation to both the posterior fossa and to the craniospinal axis.
“Unfortunately, this strategy has significant negative consequences for the patients’ neurocognitive abilities, endocrine function, and hearing,” Dr. Michalski said.
The Children’s Oncology Group ACNS0331 trial was designed to determine whether reducing the volume of the boost from the whole posterior to the tumor bed only would compromise EFS and OS, and whether reducing the dose to the craniospinal axis from the current 23.4 Gy to 18 Gy in children aged 3-7 years would compromise survival measures.
The trial had two randomizations, both at the time of study enrollment. In the first, children from the ages of 3 to 7 years were randomly assigned to either low-dose craniospinal irradiation (18 Gy, 116 children) or to the standard dose (23.4 Gy, 110 children). All children aged 8 and older were assigned to receive the standard dose.
For the second randomization, all children were randomly allocated to either involved field RT boost or to standard volume boost to the whole posterior fossa.
Following radiation, all children were assigned to nine cycles of maintenance chemotherapy.
At a median follow-up of 6.6 years, 5-year EFS estimates for the primary site irradiation endpoint were 82.2% for 227 patients who received the involved-field radiation, compared with 80.8% for 237 patients who received whole posterior fossa irradiation.
Respective 5-year OS estimates were 84.1% and 85.2%. The upper limit of the hazard ratio confidence interval (CI) for the involved field therapy was lower than the prespecified limit, indicating that involved-field radiation was noninferior.
For the endpoint of low- vs. standard-dose craniospinal irradiation, the 5-year EFS estimates were 72.1% and 82.6%, respectively. The upper limit of the hazard ratio CI exceeded the prespecified limit, indicating that EFS was worse with the low-dose strategy.
Similarly, respective 5-year OS estimates were 78.1% and 85.9%, with the upper limit of the CI also higher than the prespecified upper limit.
When the investigators looked at the patterns of failure among the children in the two randomizations, they saw that there was no significant difference in the rate of isolated local failure between the involved-field or whole posterior fossa groups, or between the low-dose or high-dose craniospinal irradiation groups.
The finding that radiation volume to the primary site can be reduced is likely to be practice changing, said Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown. Dr. Jacobson moderated the briefing.
However, the worse survival with the low-dose craniospinal radiation “leaves the COG investigators with the challenge to explore other avenues for reducing toxicity of craniospinal irradiation,” she said.
BOSTON – For children with average-risk medulloblastoma, it is safe to limit the radiation boost to the posterior fossa, but reducing doses to the craniospinal axis results in worse outcomes among younger children, and is not advisable, according to results from the largest trial conducted in this population.
There were no significant differences in either 5-year event-free survival (EFS) or overall survival (OS) between children who received an involved field radiation therapy boost (boost to the tumor bed only) or a standard volume boost (to the whole posterior fossa) in a phase III randomized trial, reported lead author Jeff M. Michalski, MD, MBA, FASTRO, professor of radiation oncology at Washington University, St. Louis.
“We conclude that the survival rates and event-free survival rates following reduced boost volumes were comparable to standard radiation treatment volumes for the primary tumor site. This is the first trial to state definitively that there is no survival difference between these two approaches,” he said at a briefing following his presentation of the data in an oral abstract session at the annual meeting of the American Society for Radiation Oncology.
“However, the reduced craniospinal axis irradiation was associated with a higher event rate and worse survival. We believe that physicians can adopt smaller boost volumes to the posterior fossa in children with average-risk medulloblastoma, average risk being no evidence of spread at the time of diagnosis and near-complete or complete resection. But for all children, the standard of 23.4 Gy remains necessary to retain high-level tumor control,” he added.
Aggressive malignancy
Medulloblastoma, an aggressive tumor with the propensity to spread from the lower brain to the upper brain and spine, is the most common brain malignancy in children. The current standard of care for children with average-risk disease is surgical resection followed by systemic chemotherapy followed by irradiation to both the posterior fossa and to the craniospinal axis.
“Unfortunately, this strategy has significant negative consequences for the patients’ neurocognitive abilities, endocrine function, and hearing,” Dr. Michalski said.
The Children’s Oncology Group ACNS0331 trial was designed to determine whether reducing the volume of the boost from the whole posterior to the tumor bed only would compromise EFS and OS, and whether reducing the dose to the craniospinal axis from the current 23.4 Gy to 18 Gy in children aged 3-7 years would compromise survival measures.
The trial had two randomizations, both at the time of study enrollment. In the first, children from the ages of 3 to 7 years were randomly assigned to either low-dose craniospinal irradiation (18 Gy, 116 children) or to the standard dose (23.4 Gy, 110 children). All children aged 8 and older were assigned to receive the standard dose.
For the second randomization, all children were randomly allocated to either involved field RT boost or to standard volume boost to the whole posterior fossa.
Following radiation, all children were assigned to nine cycles of maintenance chemotherapy.
At a median follow-up of 6.6 years, 5-year EFS estimates for the primary site irradiation endpoint were 82.2% for 227 patients who received the involved-field radiation, compared with 80.8% for 237 patients who received whole posterior fossa irradiation.
Respective 5-year OS estimates were 84.1% and 85.2%. The upper limit of the hazard ratio confidence interval (CI) for the involved field therapy was lower than the prespecified limit, indicating that involved-field radiation was noninferior.
For the endpoint of low- vs. standard-dose craniospinal irradiation, the 5-year EFS estimates were 72.1% and 82.6%, respectively. The upper limit of the hazard ratio CI exceeded the prespecified limit, indicating that EFS was worse with the low-dose strategy.
Similarly, respective 5-year OS estimates were 78.1% and 85.9%, with the upper limit of the CI also higher than the prespecified upper limit.
When the investigators looked at the patterns of failure among the children in the two randomizations, they saw that there was no significant difference in the rate of isolated local failure between the involved-field or whole posterior fossa groups, or between the low-dose or high-dose craniospinal irradiation groups.
The finding that radiation volume to the primary site can be reduced is likely to be practice changing, said Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown. Dr. Jacobson moderated the briefing.
However, the worse survival with the low-dose craniospinal radiation “leaves the COG investigators with the challenge to explore other avenues for reducing toxicity of craniospinal irradiation,” she said.
BOSTON – For children with average-risk medulloblastoma, it is safe to limit the radiation boost to the posterior fossa, but reducing doses to the craniospinal axis results in worse outcomes among younger children, and is not advisable, according to results from the largest trial conducted in this population.
There were no significant differences in either 5-year event-free survival (EFS) or overall survival (OS) between children who received an involved field radiation therapy boost (boost to the tumor bed only) or a standard volume boost (to the whole posterior fossa) in a phase III randomized trial, reported lead author Jeff M. Michalski, MD, MBA, FASTRO, professor of radiation oncology at Washington University, St. Louis.
“We conclude that the survival rates and event-free survival rates following reduced boost volumes were comparable to standard radiation treatment volumes for the primary tumor site. This is the first trial to state definitively that there is no survival difference between these two approaches,” he said at a briefing following his presentation of the data in an oral abstract session at the annual meeting of the American Society for Radiation Oncology.
“However, the reduced craniospinal axis irradiation was associated with a higher event rate and worse survival. We believe that physicians can adopt smaller boost volumes to the posterior fossa in children with average-risk medulloblastoma, average risk being no evidence of spread at the time of diagnosis and near-complete or complete resection. But for all children, the standard of 23.4 Gy remains necessary to retain high-level tumor control,” he added.
Aggressive malignancy
Medulloblastoma, an aggressive tumor with the propensity to spread from the lower brain to the upper brain and spine, is the most common brain malignancy in children. The current standard of care for children with average-risk disease is surgical resection followed by systemic chemotherapy followed by irradiation to both the posterior fossa and to the craniospinal axis.
“Unfortunately, this strategy has significant negative consequences for the patients’ neurocognitive abilities, endocrine function, and hearing,” Dr. Michalski said.
The Children’s Oncology Group ACNS0331 trial was designed to determine whether reducing the volume of the boost from the whole posterior to the tumor bed only would compromise EFS and OS, and whether reducing the dose to the craniospinal axis from the current 23.4 Gy to 18 Gy in children aged 3-7 years would compromise survival measures.
The trial had two randomizations, both at the time of study enrollment. In the first, children from the ages of 3 to 7 years were randomly assigned to either low-dose craniospinal irradiation (18 Gy, 116 children) or to the standard dose (23.4 Gy, 110 children). All children aged 8 and older were assigned to receive the standard dose.
For the second randomization, all children were randomly allocated to either involved field RT boost or to standard volume boost to the whole posterior fossa.
Following radiation, all children were assigned to nine cycles of maintenance chemotherapy.
At a median follow-up of 6.6 years, 5-year EFS estimates for the primary site irradiation endpoint were 82.2% for 227 patients who received the involved-field radiation, compared with 80.8% for 237 patients who received whole posterior fossa irradiation.
Respective 5-year OS estimates were 84.1% and 85.2%. The upper limit of the hazard ratio confidence interval (CI) for the involved field therapy was lower than the prespecified limit, indicating that involved-field radiation was noninferior.
For the endpoint of low- vs. standard-dose craniospinal irradiation, the 5-year EFS estimates were 72.1% and 82.6%, respectively. The upper limit of the hazard ratio CI exceeded the prespecified limit, indicating that EFS was worse with the low-dose strategy.
Similarly, respective 5-year OS estimates were 78.1% and 85.9%, with the upper limit of the CI also higher than the prespecified upper limit.
When the investigators looked at the patterns of failure among the children in the two randomizations, they saw that there was no significant difference in the rate of isolated local failure between the involved-field or whole posterior fossa groups, or between the low-dose or high-dose craniospinal irradiation groups.
The finding that radiation volume to the primary site can be reduced is likely to be practice changing, said Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown. Dr. Jacobson moderated the briefing.
However, the worse survival with the low-dose craniospinal radiation “leaves the COG investigators with the challenge to explore other avenues for reducing toxicity of craniospinal irradiation,” she said.
Key clinical point: Primary site irradiation in children with medulloblastoma can be limited to the tumor bed rather than the whole posterior fossa.
Major finding: There were no differences in EFS or OS when radiation was limited to the tumor bed, but reduced dose to the craniospinal axis was associated with worse survival.
Data source: Randomized phase III trial of 690 children with average-risk medulloblastoma.
Disclosures: The National Cancer Institute funded the study. Dr. Michalski and Dr. Jacobson reported no relevant conflicts of interest.
Boost dose pays off long term after surgery, WBRT for DCIS
BOSTON – Adding a boost dose after surgery and whole-breast radiation therapy (WBRT) for ductal carcinoma in situ offers a small but significant reduction in long-term risk of same-breast recurrence, according to results of a multicenter study.
An analysis of pooled data from 10 institutions showed that after 15 years of follow-up, 91.6% of women who had been treated with breast-conserving surgery, WBRT, and a boost dose remained free of ipsilateral breast tumor recurrence (IBTR), compared with 88% of women who received WBRT alone, reported Meena Savur Moran, MD, director of the breast cancer radiotherapy program at Smilow Cancer Hospital, Yale New Haven, Connecticut.
The absolute differences between the groups – 3% at 10 years, and 4% at 15 years – “don’t seem like a lot, but it is clinically important for patients, because what we’ve learned from the invasive cancer data is that this small, incremental decrease results in about a 40% less mastectomy rate for salvage mastectomies for recurrences,” she said.
It is common practice in many centers to give a radiation boost to the tumor bed of 8-16 Gy in 4-8 additional fractions following breast-conserving surgery and WBRT. This has been shown in invasive cancers to be associated with a statistically significant decrease in risk for IBTR in all age groups of about 4% at 20 years.
Yet because DCIS generally has an excellent prognosis with very few recurrences after whole-breast irradiation, it has been harder to determine whether radiation boosting would offer similar benefit to that seen in invasive cancers,
In an attempt to answer this question, investigators from 10 centers collaborated to create a DCIS database of patients treated with WBRT either with or without boost, and then analyzed the results.
The final cohort included 4,131 patients, far exceeding the minimum sample size the statisticians calculated would be needed to detect a benefit.
The median age of patients at the time of therapy was 56.1 years, median follow-up was 9 years, and the median boost dose was 14 Gy. In all, 4% of patients had positive tumor margins after surgery.
Rates of IBTR-free survival with boost vs. no boost were 97.1% vs. 96.3% at 5 years, 94.1% vs. 92.5% at 10 years, and, as noted before, 91.6% vs. 88% at 15 years (P = .0389).
In both univariate and in multivariate analysis controlling for tumor grade, comedo carcinoma, tamoxifen use, margin status, and age, IBTR was significantly associated with lower risk for recurrence.
The investigators also conducted a boost/no boost analysis stratified by margin status using both the National Surgical Adjuvant Breast and Bowel Project (NSABP) definition of negative margins as no ink on tumor, and the joint Society of Surgical Oncology, ASTRO, and American Society of Clinical Oncology guideline definition as less than 2 mm, and in each case found that among patients with negative margins, boosting offered a significant recurrence-free advantage.
Finally, they found that boosting offered a significant advantage both for patients 50 and older (P = .0073) and those 49 and younger (P = .0166).
“For DCIS, most of who treat breast cancer have used a boost, but we really extrapolated from the treatment from invasive breast cancer. Evidence for this practice until now in specific for DCIS has been lacking,” said Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown. Dr. Jacobson moderated the briefing.
She noted that the large sample size and long follow-up of the study was necessary for the treatment benefit to emerge.
BOSTON – Adding a boost dose after surgery and whole-breast radiation therapy (WBRT) for ductal carcinoma in situ offers a small but significant reduction in long-term risk of same-breast recurrence, according to results of a multicenter study.
An analysis of pooled data from 10 institutions showed that after 15 years of follow-up, 91.6% of women who had been treated with breast-conserving surgery, WBRT, and a boost dose remained free of ipsilateral breast tumor recurrence (IBTR), compared with 88% of women who received WBRT alone, reported Meena Savur Moran, MD, director of the breast cancer radiotherapy program at Smilow Cancer Hospital, Yale New Haven, Connecticut.
The absolute differences between the groups – 3% at 10 years, and 4% at 15 years – “don’t seem like a lot, but it is clinically important for patients, because what we’ve learned from the invasive cancer data is that this small, incremental decrease results in about a 40% less mastectomy rate for salvage mastectomies for recurrences,” she said.
It is common practice in many centers to give a radiation boost to the tumor bed of 8-16 Gy in 4-8 additional fractions following breast-conserving surgery and WBRT. This has been shown in invasive cancers to be associated with a statistically significant decrease in risk for IBTR in all age groups of about 4% at 20 years.
Yet because DCIS generally has an excellent prognosis with very few recurrences after whole-breast irradiation, it has been harder to determine whether radiation boosting would offer similar benefit to that seen in invasive cancers,
In an attempt to answer this question, investigators from 10 centers collaborated to create a DCIS database of patients treated with WBRT either with or without boost, and then analyzed the results.
The final cohort included 4,131 patients, far exceeding the minimum sample size the statisticians calculated would be needed to detect a benefit.
The median age of patients at the time of therapy was 56.1 years, median follow-up was 9 years, and the median boost dose was 14 Gy. In all, 4% of patients had positive tumor margins after surgery.
Rates of IBTR-free survival with boost vs. no boost were 97.1% vs. 96.3% at 5 years, 94.1% vs. 92.5% at 10 years, and, as noted before, 91.6% vs. 88% at 15 years (P = .0389).
In both univariate and in multivariate analysis controlling for tumor grade, comedo carcinoma, tamoxifen use, margin status, and age, IBTR was significantly associated with lower risk for recurrence.
The investigators also conducted a boost/no boost analysis stratified by margin status using both the National Surgical Adjuvant Breast and Bowel Project (NSABP) definition of negative margins as no ink on tumor, and the joint Society of Surgical Oncology, ASTRO, and American Society of Clinical Oncology guideline definition as less than 2 mm, and in each case found that among patients with negative margins, boosting offered a significant recurrence-free advantage.
Finally, they found that boosting offered a significant advantage both for patients 50 and older (P = .0073) and those 49 and younger (P = .0166).
“For DCIS, most of who treat breast cancer have used a boost, but we really extrapolated from the treatment from invasive breast cancer. Evidence for this practice until now in specific for DCIS has been lacking,” said Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown. Dr. Jacobson moderated the briefing.
She noted that the large sample size and long follow-up of the study was necessary for the treatment benefit to emerge.
BOSTON – Adding a boost dose after surgery and whole-breast radiation therapy (WBRT) for ductal carcinoma in situ offers a small but significant reduction in long-term risk of same-breast recurrence, according to results of a multicenter study.
An analysis of pooled data from 10 institutions showed that after 15 years of follow-up, 91.6% of women who had been treated with breast-conserving surgery, WBRT, and a boost dose remained free of ipsilateral breast tumor recurrence (IBTR), compared with 88% of women who received WBRT alone, reported Meena Savur Moran, MD, director of the breast cancer radiotherapy program at Smilow Cancer Hospital, Yale New Haven, Connecticut.
The absolute differences between the groups – 3% at 10 years, and 4% at 15 years – “don’t seem like a lot, but it is clinically important for patients, because what we’ve learned from the invasive cancer data is that this small, incremental decrease results in about a 40% less mastectomy rate for salvage mastectomies for recurrences,” she said.
It is common practice in many centers to give a radiation boost to the tumor bed of 8-16 Gy in 4-8 additional fractions following breast-conserving surgery and WBRT. This has been shown in invasive cancers to be associated with a statistically significant decrease in risk for IBTR in all age groups of about 4% at 20 years.
Yet because DCIS generally has an excellent prognosis with very few recurrences after whole-breast irradiation, it has been harder to determine whether radiation boosting would offer similar benefit to that seen in invasive cancers,
In an attempt to answer this question, investigators from 10 centers collaborated to create a DCIS database of patients treated with WBRT either with or without boost, and then analyzed the results.
The final cohort included 4,131 patients, far exceeding the minimum sample size the statisticians calculated would be needed to detect a benefit.
The median age of patients at the time of therapy was 56.1 years, median follow-up was 9 years, and the median boost dose was 14 Gy. In all, 4% of patients had positive tumor margins after surgery.
Rates of IBTR-free survival with boost vs. no boost were 97.1% vs. 96.3% at 5 years, 94.1% vs. 92.5% at 10 years, and, as noted before, 91.6% vs. 88% at 15 years (P = .0389).
In both univariate and in multivariate analysis controlling for tumor grade, comedo carcinoma, tamoxifen use, margin status, and age, IBTR was significantly associated with lower risk for recurrence.
The investigators also conducted a boost/no boost analysis stratified by margin status using both the National Surgical Adjuvant Breast and Bowel Project (NSABP) definition of negative margins as no ink on tumor, and the joint Society of Surgical Oncology, ASTRO, and American Society of Clinical Oncology guideline definition as less than 2 mm, and in each case found that among patients with negative margins, boosting offered a significant recurrence-free advantage.
Finally, they found that boosting offered a significant advantage both for patients 50 and older (P = .0073) and those 49 and younger (P = .0166).
“For DCIS, most of who treat breast cancer have used a boost, but we really extrapolated from the treatment from invasive breast cancer. Evidence for this practice until now in specific for DCIS has been lacking,” said Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown. Dr. Jacobson moderated the briefing.
She noted that the large sample size and long follow-up of the study was necessary for the treatment benefit to emerge.
AT THE ASTRO ANNUAL MEETING 2016
Key clinical point: This study shows a significant benefit for adding a boost radiation dose following breast-conserving surgery and whole-breast radiation for ductal carcinoma in situ (DCIS).
Major finding: After 15 years of follow-up, 91.6% of women who had received a boost dose were free of ipsilateral breast recurrence, compared with 88% of women who did not have a boost.
Data source: Analysis of pooled data on 4,131 patients with DCIS treated at 10 academic medical centers.
Disclosures: The study was supported by participating institutions. Dr. Moran and Dr. Jacobson reported no conflicts of interest.
Database review supports chemoradiation for high-risk sarcomas
BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.
The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.
In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.
“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.
He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.
They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.
They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)
In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.
Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).
Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).
There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.
Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).
Drop the ‘D’ in MAID?
In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.
The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.
To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.
In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.
At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.
The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.
“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
Better Agents Needed
Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.
“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.
Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.
Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”
Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.
BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.
The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.
In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.
“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.
He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.
They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.
They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)
In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.
Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).
Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).
There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.
Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).
Drop the ‘D’ in MAID?
In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.
The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.
To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.
In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.
At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.
The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.
“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
Better Agents Needed
Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.
“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.
Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.
Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”
Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.
BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.
The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.
In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.
“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.
He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.
They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.
They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)
In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.
Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).
Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).
There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.
Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).
Drop the ‘D’ in MAID?
In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.
The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.
To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.
In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.
At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.
The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.
“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
Better Agents Needed
Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.
“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.
Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.
Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”
Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.
Key clinical point: Sarcoma specialists do not agree on whether neoadjuvant or adjuvant chemotherapy adds benefit in patients with high-risk soft-tissue sarcomas.
Major finding: In a cancer database, chemotherapy was associated with 57% 5-year overall survival, compared with 45% with no chemotherapy (P less than .001)
Data source: A National Cancer Database review of 3,840 patients with grade 3 or 4 soft-tissue sarcomas and a retrospective case series of 26 patients with large STS of the extremities or abdominal wall.
Disclosures: The studies were internally supported. The authors, Dr. Baldini and Dr. Chen, reported no relevant disclosures. Dr. Chen is the reporter’s personal radiation oncologist.
NSCLC survival comparable with accelerated and conventional RT
BOSTON – Patients with stage II or III non–small-cell lung cancer with comorbidities that make them poor candidates for surgery or chemotherapy may still benefit from accelerated hypofractionated radiation, an interim analysis of a randomized trial suggests.
Among 48 patients followed for a median of 24 months, there were no statistical differences in either overall survival (OS) or progression-free survival between patients with stage II or III NSCLC and poor performance status treated with either conventional radiation delivered over 6 weeks, or image-guided radiation therapy (IGRT) delivered over 3 weeks, reported Puneeth Iyengar, MD, PhD, of the University of Texas Southwestern in Dallas.
“There is limited grade 3-5 toxicity, and as importantly, and more important to patients, is that the treatment time is cut in half and may be acceptable to the patient as well as to the treating physician,” he added.
The investigators are hopeful that the study, when completed, will “change the paradigm of how we treat these patients who can’t receive the standard-of-care treatment.”
The UT Southwestern investigators had previously shown in a phase I dose-escalation study that treating patients with 60 Gy delivered in 15 fractions instead of the conventional 30 fractions did not increase treatment-related toxicity,
In the current study, they explored the question of whether accelerated hypofractionated radiation therapy could improve survival in a difficult-to-treat population.
They have enrolled to date 60 patients with stage II or III NSCLC and Zubrod performance status of 2 or greater.
In arm A, 28 patients were assigned to receive conventional radiation at total doses of 60 to 66 Gy delivered in 30-33 fractions of 2 Gy each, In arm B, 32 patients were assigned to receive a total dose of 60 Gy delivered in 15 fractions of 4 Gy each.
The median age was 68 in both arms. The male-to-female ratio was equal in arm A, but 4:1 in arm B, The distribution of tumor types was equally weighted in each arm, with squamous cell carcinomas accounting for 53% of lesions, and adenocarcinomas accounting for the remainder.
Among all 60 patients, 53 presented with stage III disease, and 7 with stage II.
Of the 60 patients, 48 had follow-up sufficient for interim evaluation, and of this group, 27 (56%) were alive at last follow-up.
Median OS on Kaplan-Meier analysis was 11.5 months, with no statistical differences between the groups (per-group rates were not shown), Median PFS was 14 months, also with no statistical differences.
There were three deaths from hypoxia possibly related to radiation, two in the conventional fractionation arm, and one in the IGRT, accelerated fractionation arm. There were 10 grade 3 radiation-associated toxicities in arm A, and 6 in Arm B. There were no grade 4 toxicities in either group.
George Rodrigues, MD, of London (Ontario) Health Sciences Center, who moderated the briefing, said that in addition to patients with poor performance status, there are some patients who simply do not want to undergo chemotherapy, and for these patients the efficacy, low side effects, and convenience of accelerated fractionation radiation therapy may prove to be a good treatment option.
BOSTON – Patients with stage II or III non–small-cell lung cancer with comorbidities that make them poor candidates for surgery or chemotherapy may still benefit from accelerated hypofractionated radiation, an interim analysis of a randomized trial suggests.
Among 48 patients followed for a median of 24 months, there were no statistical differences in either overall survival (OS) or progression-free survival between patients with stage II or III NSCLC and poor performance status treated with either conventional radiation delivered over 6 weeks, or image-guided radiation therapy (IGRT) delivered over 3 weeks, reported Puneeth Iyengar, MD, PhD, of the University of Texas Southwestern in Dallas.
“There is limited grade 3-5 toxicity, and as importantly, and more important to patients, is that the treatment time is cut in half and may be acceptable to the patient as well as to the treating physician,” he added.
The investigators are hopeful that the study, when completed, will “change the paradigm of how we treat these patients who can’t receive the standard-of-care treatment.”
The UT Southwestern investigators had previously shown in a phase I dose-escalation study that treating patients with 60 Gy delivered in 15 fractions instead of the conventional 30 fractions did not increase treatment-related toxicity,
In the current study, they explored the question of whether accelerated hypofractionated radiation therapy could improve survival in a difficult-to-treat population.
They have enrolled to date 60 patients with stage II or III NSCLC and Zubrod performance status of 2 or greater.
In arm A, 28 patients were assigned to receive conventional radiation at total doses of 60 to 66 Gy delivered in 30-33 fractions of 2 Gy each, In arm B, 32 patients were assigned to receive a total dose of 60 Gy delivered in 15 fractions of 4 Gy each.
The median age was 68 in both arms. The male-to-female ratio was equal in arm A, but 4:1 in arm B, The distribution of tumor types was equally weighted in each arm, with squamous cell carcinomas accounting for 53% of lesions, and adenocarcinomas accounting for the remainder.
Among all 60 patients, 53 presented with stage III disease, and 7 with stage II.
Of the 60 patients, 48 had follow-up sufficient for interim evaluation, and of this group, 27 (56%) were alive at last follow-up.
Median OS on Kaplan-Meier analysis was 11.5 months, with no statistical differences between the groups (per-group rates were not shown), Median PFS was 14 months, also with no statistical differences.
There were three deaths from hypoxia possibly related to radiation, two in the conventional fractionation arm, and one in the IGRT, accelerated fractionation arm. There were 10 grade 3 radiation-associated toxicities in arm A, and 6 in Arm B. There were no grade 4 toxicities in either group.
George Rodrigues, MD, of London (Ontario) Health Sciences Center, who moderated the briefing, said that in addition to patients with poor performance status, there are some patients who simply do not want to undergo chemotherapy, and for these patients the efficacy, low side effects, and convenience of accelerated fractionation radiation therapy may prove to be a good treatment option.
BOSTON – Patients with stage II or III non–small-cell lung cancer with comorbidities that make them poor candidates for surgery or chemotherapy may still benefit from accelerated hypofractionated radiation, an interim analysis of a randomized trial suggests.
Among 48 patients followed for a median of 24 months, there were no statistical differences in either overall survival (OS) or progression-free survival between patients with stage II or III NSCLC and poor performance status treated with either conventional radiation delivered over 6 weeks, or image-guided radiation therapy (IGRT) delivered over 3 weeks, reported Puneeth Iyengar, MD, PhD, of the University of Texas Southwestern in Dallas.
“There is limited grade 3-5 toxicity, and as importantly, and more important to patients, is that the treatment time is cut in half and may be acceptable to the patient as well as to the treating physician,” he added.
The investigators are hopeful that the study, when completed, will “change the paradigm of how we treat these patients who can’t receive the standard-of-care treatment.”
The UT Southwestern investigators had previously shown in a phase I dose-escalation study that treating patients with 60 Gy delivered in 15 fractions instead of the conventional 30 fractions did not increase treatment-related toxicity,
In the current study, they explored the question of whether accelerated hypofractionated radiation therapy could improve survival in a difficult-to-treat population.
They have enrolled to date 60 patients with stage II or III NSCLC and Zubrod performance status of 2 or greater.
In arm A, 28 patients were assigned to receive conventional radiation at total doses of 60 to 66 Gy delivered in 30-33 fractions of 2 Gy each, In arm B, 32 patients were assigned to receive a total dose of 60 Gy delivered in 15 fractions of 4 Gy each.
The median age was 68 in both arms. The male-to-female ratio was equal in arm A, but 4:1 in arm B, The distribution of tumor types was equally weighted in each arm, with squamous cell carcinomas accounting for 53% of lesions, and adenocarcinomas accounting for the remainder.
Among all 60 patients, 53 presented with stage III disease, and 7 with stage II.
Of the 60 patients, 48 had follow-up sufficient for interim evaluation, and of this group, 27 (56%) were alive at last follow-up.
Median OS on Kaplan-Meier analysis was 11.5 months, with no statistical differences between the groups (per-group rates were not shown), Median PFS was 14 months, also with no statistical differences.
There were three deaths from hypoxia possibly related to radiation, two in the conventional fractionation arm, and one in the IGRT, accelerated fractionation arm. There were 10 grade 3 radiation-associated toxicities in arm A, and 6 in Arm B. There were no grade 4 toxicities in either group.
George Rodrigues, MD, of London (Ontario) Health Sciences Center, who moderated the briefing, said that in addition to patients with poor performance status, there are some patients who simply do not want to undergo chemotherapy, and for these patients the efficacy, low side effects, and convenience of accelerated fractionation radiation therapy may prove to be a good treatment option.
Key clinical point: Accelerated hypofractionated radiation therapy offers survival and safety comparable to that of conventional radiation in non–small-cell lung cancer in half the time.
Major finding: There were no differences in overall or progression-free survival among patients with NSCLC treated with either accelerated or conventional fractionation radiation.
Data source: Interim analysis of randomized phase III trial in 48 of 60 evaluable patients with stage II or III NSCLC and poor performance status.
Disclosures: UT Southwestern Medical Center, Dallas, sponsored the trial. Dr. Iyengar and Dr. Rodrigues reported having no conflicts of interest.
Hypofractionated RT safe, convenient in low-risk prostate cancer
BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.
Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.
“The International Atomic Energy [Agency] in its prostate cancer guidelines still lists hypofractionated radiation therapy as investigational, but I think we are at the stage where there is a ton of evidence, and this is really no leap of faith anymore that this can become the standard of care,” said Deborah W. Bruner, PhD, of Emory University and the Winship Cancer Institute in Atlanta.
In the treatment of patients with low-risk prostate cancer who opt for therapy over active surveillance, it is essential that “we treat them with the absolute minimum amount of treatment, with minimum side effects, and with minimum cost,” she said at a plenary session.
As reported by the investigators in 2015, there were small but significant increases in clinician-reported adverse gastrointestinal and genitourinary adverse events in the hypofractionation arm compared with the conventional fractionation arm in the trial, prompting the researchers to see whether patients were actually experiencing what clinicians thought they were seeing.
The investigators examined health-related quality of life and symptoms using the Expanded Prostate Index Composite (EPIC instrument).
They used a 50-item patient-reported outcomes questionnaire using a scale of 0 (no problem) to 4 (big problem), with responses transferred to a 0-100 scale. The questionnaire asked about symptoms in four domains: bowel, urinary, sexual, and hormonal. Patients filled out the questionnaire at baseline and at 6 and 12 months of follow-up.
At 1 year, there were no changes from baseline in hormonal scores in either study arm, but sexual function scores declined by approximately 15 points among patients treated with conventional fractionation and by 11 points among patients treated with hypofractionation (between-group difference nonsignificant).
There was a small decline in urinary scores in both arms, but this difference was not significant.
Patients treated with hypofractionation had a statistically larger decline in bowel scores compared with patients treated with conventional fractionation, a 1.8-point difference, but this difference did not translate into a clinically significant difference; that is, patients themselves could not detect a significant decline in bowel function, Dr. Bruner said.
The invited discussant, Ronald Chen, MD, MPH, director of the comparative effectiveness research program at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, agreed that a difference of only 1.8 points on a 0-100 scale, while technically significant, is clinically meaningless.
“So now we have the complete story and a better understanding of perhaps the value of hypofractionation versus standard fractionation from the patient’s perspective,” he said.
He also emphasized that “quality of life is a central component of any value framework in cancer care, and we must hear the patient’s voice. For clinical trials to truly inform patient decision making and allow patients to assess the value of their treatment options, quality of life must be studied.”
BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.
Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.
“The International Atomic Energy [Agency] in its prostate cancer guidelines still lists hypofractionated radiation therapy as investigational, but I think we are at the stage where there is a ton of evidence, and this is really no leap of faith anymore that this can become the standard of care,” said Deborah W. Bruner, PhD, of Emory University and the Winship Cancer Institute in Atlanta.
In the treatment of patients with low-risk prostate cancer who opt for therapy over active surveillance, it is essential that “we treat them with the absolute minimum amount of treatment, with minimum side effects, and with minimum cost,” she said at a plenary session.
As reported by the investigators in 2015, there were small but significant increases in clinician-reported adverse gastrointestinal and genitourinary adverse events in the hypofractionation arm compared with the conventional fractionation arm in the trial, prompting the researchers to see whether patients were actually experiencing what clinicians thought they were seeing.
The investigators examined health-related quality of life and symptoms using the Expanded Prostate Index Composite (EPIC instrument).
They used a 50-item patient-reported outcomes questionnaire using a scale of 0 (no problem) to 4 (big problem), with responses transferred to a 0-100 scale. The questionnaire asked about symptoms in four domains: bowel, urinary, sexual, and hormonal. Patients filled out the questionnaire at baseline and at 6 and 12 months of follow-up.
At 1 year, there were no changes from baseline in hormonal scores in either study arm, but sexual function scores declined by approximately 15 points among patients treated with conventional fractionation and by 11 points among patients treated with hypofractionation (between-group difference nonsignificant).
There was a small decline in urinary scores in both arms, but this difference was not significant.
Patients treated with hypofractionation had a statistically larger decline in bowel scores compared with patients treated with conventional fractionation, a 1.8-point difference, but this difference did not translate into a clinically significant difference; that is, patients themselves could not detect a significant decline in bowel function, Dr. Bruner said.
The invited discussant, Ronald Chen, MD, MPH, director of the comparative effectiveness research program at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, agreed that a difference of only 1.8 points on a 0-100 scale, while technically significant, is clinically meaningless.
“So now we have the complete story and a better understanding of perhaps the value of hypofractionation versus standard fractionation from the patient’s perspective,” he said.
He also emphasized that “quality of life is a central component of any value framework in cancer care, and we must hear the patient’s voice. For clinical trials to truly inform patient decision making and allow patients to assess the value of their treatment options, quality of life must be studied.”
BOSTON – Shortening the radiation dosing schedule by 3 weeks in men with early-stage, low-risk prostate cancer does not appear to result in worse outcomes or diminished quality of life, according to investigators in the NRG Oncology/RTOG 0415 trial.
Efficacy results from the trial, reported at the annual meeting of the American Society for Radiation Oncology, showed that a radiation schedule of 70 Gy in 28 fractions delivered over 5.6 weeks was not inferior to 73.8 Gy delivered in 41 fractions over 8.2 weeks in terms of disease-free, progression-free, or overall survival.
“The International Atomic Energy [Agency] in its prostate cancer guidelines still lists hypofractionated radiation therapy as investigational, but I think we are at the stage where there is a ton of evidence, and this is really no leap of faith anymore that this can become the standard of care,” said Deborah W. Bruner, PhD, of Emory University and the Winship Cancer Institute in Atlanta.
In the treatment of patients with low-risk prostate cancer who opt for therapy over active surveillance, it is essential that “we treat them with the absolute minimum amount of treatment, with minimum side effects, and with minimum cost,” she said at a plenary session.
As reported by the investigators in 2015, there were small but significant increases in clinician-reported adverse gastrointestinal and genitourinary adverse events in the hypofractionation arm compared with the conventional fractionation arm in the trial, prompting the researchers to see whether patients were actually experiencing what clinicians thought they were seeing.
The investigators examined health-related quality of life and symptoms using the Expanded Prostate Index Composite (EPIC instrument).
They used a 50-item patient-reported outcomes questionnaire using a scale of 0 (no problem) to 4 (big problem), with responses transferred to a 0-100 scale. The questionnaire asked about symptoms in four domains: bowel, urinary, sexual, and hormonal. Patients filled out the questionnaire at baseline and at 6 and 12 months of follow-up.
At 1 year, there were no changes from baseline in hormonal scores in either study arm, but sexual function scores declined by approximately 15 points among patients treated with conventional fractionation and by 11 points among patients treated with hypofractionation (between-group difference nonsignificant).
There was a small decline in urinary scores in both arms, but this difference was not significant.
Patients treated with hypofractionation had a statistically larger decline in bowel scores compared with patients treated with conventional fractionation, a 1.8-point difference, but this difference did not translate into a clinically significant difference; that is, patients themselves could not detect a significant decline in bowel function, Dr. Bruner said.
The invited discussant, Ronald Chen, MD, MPH, director of the comparative effectiveness research program at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, agreed that a difference of only 1.8 points on a 0-100 scale, while technically significant, is clinically meaningless.
“So now we have the complete story and a better understanding of perhaps the value of hypofractionation versus standard fractionation from the patient’s perspective,” he said.
He also emphasized that “quality of life is a central component of any value framework in cancer care, and we must hear the patient’s voice. For clinical trials to truly inform patient decision making and allow patients to assess the value of their treatment options, quality of life must be studied.”
Key clinical point: There were no clinically significant differences in survival or patient-reported outcomes between hypofractionated or conventional radiation schedules for patients with low-risk prostate cancer.
Major finding: There was statistically but not clinically significant difference of 1.8 out of 100 patients on a quality-of-life scale.
Data source: Analysis of patient-reported QoL in the NRG//RTOG 0415 trial.
Disclosures: The National Cancer Institute supported the study. Dr. Bruner and Dr. Chen reported having no conflicts of interest.
Better GI, urinary function after pelvic radiation with IMRT
BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.
Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.
The trial, nicknamed TIME-C, was specifically designed to determine whether IMRT could reduce acute GI toxicities relative to standard therapy in the 5th week of treatment, after 23 to 25 radiation fractions had been delivered, with urinary toxicities and quality of life measures as secondary endpoints.
Eligible patients were women with pathologically proven diagnoses of endometrial and/or cervical cancer who required postoperative radiation or chemoradiation and had good performance statuses.
Following stratification by dose level (45 or 50.4 Gy), chemotherapy (five cycles of weekly cisplatin 40 mg/m2) or no chemotherapy, and disease site, the patients were randomly assigned to undergo either IMRT (129 patients) or standard 4-field radiation (149) to the pelvis.
Patients were evaluated for symptoms at baseline, 3 and 5 weeks after the start of radiation, and 4-5 weeks after completion, and follow-up is planned for 1 and 3 years after the start of radiation therapy.
EPIC findings
For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.
Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.
For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)
Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).
The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.
But Supriya Chopra, MD, a radiation oncologist at the Tata Memorial Centre in Mumbai, India, the invited discussant at the plenary, said that the evidence in favor of IMRT is not so clear.
At the 2015 ASTRO annual meeting, Dr. Chopra and colleagues presented interim results of the PARCER study, in which grade III or higher radiation-induced bowel toxicity was lower with IMRT than with 3D-conformal radiation therapy. However, the 14.6% absolute difference, while significant (P = .02) was an exploratory endpoint only, and the observed differences in grade II or greater toxicities was not significant.
Differences in results between PARCER and TIME-C may be explained by the fact that patients in the PARCER trial had a higher proportion of concurrent cisplatin-based chemotherapy (about 88%) than patients in TIME-C (about 75%), with the excess cisplatin in the former trial possibly contributing to a worse symptom burden, she suggested.
“Pooled data from both trials is needed to assess the impact of IMRT for at least physician-reported acute GI toxicity, which both trials have captured. Long-term data from TIME-C and the final analysis of PARCER is awaited to assess the impact of late GI toxicity, and in my opinion, postoperative IMRT for gynecological cancers continues to be investigational,” she said.
BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.
Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.
The trial, nicknamed TIME-C, was specifically designed to determine whether IMRT could reduce acute GI toxicities relative to standard therapy in the 5th week of treatment, after 23 to 25 radiation fractions had been delivered, with urinary toxicities and quality of life measures as secondary endpoints.
Eligible patients were women with pathologically proven diagnoses of endometrial and/or cervical cancer who required postoperative radiation or chemoradiation and had good performance statuses.
Following stratification by dose level (45 or 50.4 Gy), chemotherapy (five cycles of weekly cisplatin 40 mg/m2) or no chemotherapy, and disease site, the patients were randomly assigned to undergo either IMRT (129 patients) or standard 4-field radiation (149) to the pelvis.
Patients were evaluated for symptoms at baseline, 3 and 5 weeks after the start of radiation, and 4-5 weeks after completion, and follow-up is planned for 1 and 3 years after the start of radiation therapy.
EPIC findings
For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.
Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.
For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)
Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).
The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.
But Supriya Chopra, MD, a radiation oncologist at the Tata Memorial Centre in Mumbai, India, the invited discussant at the plenary, said that the evidence in favor of IMRT is not so clear.
At the 2015 ASTRO annual meeting, Dr. Chopra and colleagues presented interim results of the PARCER study, in which grade III or higher radiation-induced bowel toxicity was lower with IMRT than with 3D-conformal radiation therapy. However, the 14.6% absolute difference, while significant (P = .02) was an exploratory endpoint only, and the observed differences in grade II or greater toxicities was not significant.
Differences in results between PARCER and TIME-C may be explained by the fact that patients in the PARCER trial had a higher proportion of concurrent cisplatin-based chemotherapy (about 88%) than patients in TIME-C (about 75%), with the excess cisplatin in the former trial possibly contributing to a worse symptom burden, she suggested.
“Pooled data from both trials is needed to assess the impact of IMRT for at least physician-reported acute GI toxicity, which both trials have captured. Long-term data from TIME-C and the final analysis of PARCER is awaited to assess the impact of late GI toxicity, and in my opinion, postoperative IMRT for gynecological cancers continues to be investigational,” she said.
BOSTON – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.
Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite (EPIC) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD, from the University of Texas MD Anderson Cancer in Houston.
The trial, nicknamed TIME-C, was specifically designed to determine whether IMRT could reduce acute GI toxicities relative to standard therapy in the 5th week of treatment, after 23 to 25 radiation fractions had been delivered, with urinary toxicities and quality of life measures as secondary endpoints.
Eligible patients were women with pathologically proven diagnoses of endometrial and/or cervical cancer who required postoperative radiation or chemoradiation and had good performance statuses.
Following stratification by dose level (45 or 50.4 Gy), chemotherapy (five cycles of weekly cisplatin 40 mg/m2) or no chemotherapy, and disease site, the patients were randomly assigned to undergo either IMRT (129 patients) or standard 4-field radiation (149) to the pelvis.
Patients were evaluated for symptoms at baseline, 3 and 5 weeks after the start of radiation, and 4-5 weeks after completion, and follow-up is planned for 1 and 3 years after the start of radiation therapy.
EPIC findings
For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.
Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure (PRO-CTCAE), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.
For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)
Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).
The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH, professor and chair of radiation oncology at West Virginia University, Morgantown.
But Supriya Chopra, MD, a radiation oncologist at the Tata Memorial Centre in Mumbai, India, the invited discussant at the plenary, said that the evidence in favor of IMRT is not so clear.
At the 2015 ASTRO annual meeting, Dr. Chopra and colleagues presented interim results of the PARCER study, in which grade III or higher radiation-induced bowel toxicity was lower with IMRT than with 3D-conformal radiation therapy. However, the 14.6% absolute difference, while significant (P = .02) was an exploratory endpoint only, and the observed differences in grade II or greater toxicities was not significant.
Differences in results between PARCER and TIME-C may be explained by the fact that patients in the PARCER trial had a higher proportion of concurrent cisplatin-based chemotherapy (about 88%) than patients in TIME-C (about 75%), with the excess cisplatin in the former trial possibly contributing to a worse symptom burden, she suggested.
“Pooled data from both trials is needed to assess the impact of IMRT for at least physician-reported acute GI toxicity, which both trials have captured. Long-term data from TIME-C and the final analysis of PARCER is awaited to assess the impact of late GI toxicity, and in my opinion, postoperative IMRT for gynecological cancers continues to be investigational,” she said.
Key clinical point: Pelvic irradiation with intensity-modulated radiation therapy was associated with lower acute bowel toxicity than standard radiation.
Major finding: The decline in EPIC bowel summary scores was smaller with IMRT than with four-field pelvic irradiation.
Data source: Randomized phase III trial in 278 patients with cervical or endometrial cancers.
Disclosures: TIME-C was supported by the National Cancer Institute. Dr. Klopp, Dr. Jacobson, and Dr. Chopra reported no relevant conflicts of interest.
Less cognitive decline with stereotactic radiosurgery after brain metastases resection
BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.
In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.
In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.
“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.
WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.
The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.
WBRT vs. SRS
To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.
Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.
Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.
After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.
There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).
The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).
Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).
Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.
Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.
SRS vs. observation
In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.
The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.
“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.
The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.
In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.
In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.
“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.
WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.
The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.
WBRT vs. SRS
To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.
Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.
Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.
After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.
There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).
The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).
Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).
Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.
Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.
SRS vs. observation
In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.
The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.
“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.
The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.
In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.
In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.
“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.
WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.
The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.
WBRT vs. SRS
To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.
Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.
Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.
After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.
There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).
The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).
Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).
Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.
Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.
SRS vs. observation
In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.
The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.
“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.
The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
AT ASTRO ANNUAL MEETING 2016
Key clinical point: Stereotactic radiosurgery following brain metastases resection was associated with similar survival but less toxicity than was whole-brain radiation therapy.
Major finding: WBRT was associated with a twofold greater risk for cognitive deterioration than SRS in one study, and SRS provided better local control than observation alone in another study.
Data source: A randomized, phase III trial in 194 patients from 48 centers in the United States and Canada, and a randomized trial in 128 patients from the MD Anderson Cancer Center.
Disclosures: The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.
