Sarcoma & GIST

Palifosfamide added to doxorubicin did not improve survival outcomes in patients with metastatic soft tissue sarcoma, compared with doxorubicin alone, a study showed.

The phase III randomized trial did not meet its amended primary endpoint, as there was no significant difference in progression-free survival (PFS) among patients in the two-drug regimen arm.

“This study represents one of the largest international efforts among sarcoma centers to date,” wrote Christopher W. Ryan, MD, of the Oregon Health & Science University, Knight Cancer Institute, Portland, Ore., and his coauthors (J Clin Oncol. 2016 Sept 12. doi: 10.1200/JCO.2016.67.668).

“Single-agent doxorubicin thus remains a reference standard for the treatment of metastatic soft tissue sarcoma,” they wrote.

Doxorubicin has remained the standard first-line treatment for most sarcoma patients for more than 4 decades. Palifosfamide, a tris salt of isophosphoramide mustard, has previously demonstrated broad activity against sarcoma in experimental models.

In addition, a randomized phase II trial showed improved PFS for combined doxorubicin and palifosfamide, compared with doxorubicin alone, with a hazard ratio (HR) of 0.43 (95% CI, 0.19-0.95).

Based on those promising results, Dr. Ryan and his colleagues conducted a phase III trial that evaluated the two-drug combination with doxorubicin alone as first-line treatment of metastatic soft tissue sarcoma.

The cohort included 447 patients who were randomly assigned 1:1 to receive either doxorubicin 75 mg/m2 IV on day 1 plus palifosfamide 150 mg/m² per day IV on days 1-3, or doxorubicin plus placebo once every 21 days for up to six cycles.

The primary endpoint of the study was PFS by independent radiologic review.

There was no significant difference in PFS between the two cohorts. For the combination therapy group, the median PFS was 6.0 months, compared with 5.2 months for doxorubicin plus placebo (HR, 0.86; 95% CI, 0.68-1.08; P = .19).

Similar results were observed for median overall survival, which was also similar in the two treatment groups: 15.9 months for doxorubicin plus palifosfamide and 16.9 months for doxorubicin plus placebo (HR, 1.05; 95% CI, 0.79-1.39; P = .74).

As for toxicity, all patients had at least one treatment-emergent adverse event, with the most common of any grade being alopecia, nausea, and fatigue.

Grade 3-4 adverse events were more frequently observed in patients receiving doxorubicin plus palifosfamide (63.6%) than in the single-therapy group (50.9%; P = .0075).

“The median PFS of 5.2 months and OS [overall survival] of nearly 17 months with doxorubicin should serve as a reference in the design of future studies in the first-line treatment of metastatic soft tissue sarcoma,” Dr. Ryan and his associates said.

The study was supported by ZIOPHARM Oncology. Dr. Ryan and several of the coauthors reported multiple relationships with industry.

Palifosfamide added to doxorubicin did not improve survival outcomes in patients with metastatic soft tissue sarcoma, compared with doxorubicin alone, a study showed.

The phase III randomized trial did not meet its amended primary endpoint, as there was no significant difference in progression-free survival (PFS) among patients in the two-drug regimen arm.

“This study represents one of the largest international efforts among sarcoma centers to date,” wrote Christopher W. Ryan, MD, of the Oregon Health & Science University, Knight Cancer Institute, Portland, Ore., and his coauthors (J Clin Oncol. 2016 Sept 12. doi: 10.1200/JCO.2016.67.668).

“Single-agent doxorubicin thus remains a reference standard for the treatment of metastatic soft tissue sarcoma,” they wrote.

Doxorubicin has remained the standard first-line treatment for most sarcoma patients for more than 4 decades. Palifosfamide, a tris salt of isophosphoramide mustard, has previously demonstrated broad activity against sarcoma in experimental models.

In addition, a randomized phase II trial showed improved PFS for combined doxorubicin and palifosfamide, compared with doxorubicin alone, with a hazard ratio (HR) of 0.43 (95% CI, 0.19-0.95).

Based on those promising results, Dr. Ryan and his colleagues conducted a phase III trial that evaluated the two-drug combination with doxorubicin alone as first-line treatment of metastatic soft tissue sarcoma.

The cohort included 447 patients who were randomly assigned 1:1 to receive either doxorubicin 75 mg/m2 IV on day 1 plus palifosfamide 150 mg/m² per day IV on days 1-3, or doxorubicin plus placebo once every 21 days for up to six cycles.

The primary endpoint of the study was PFS by independent radiologic review.

There was no significant difference in PFS between the two cohorts. For the combination therapy group, the median PFS was 6.0 months, compared with 5.2 months for doxorubicin plus placebo (HR, 0.86; 95% CI, 0.68-1.08; P = .19).

Similar results were observed for median overall survival, which was also similar in the two treatment groups: 15.9 months for doxorubicin plus palifosfamide and 16.9 months for doxorubicin plus placebo (HR, 1.05; 95% CI, 0.79-1.39; P = .74).

As for toxicity, all patients had at least one treatment-emergent adverse event, with the most common of any grade being alopecia, nausea, and fatigue.

Grade 3-4 adverse events were more frequently observed in patients receiving doxorubicin plus palifosfamide (63.6%) than in the single-therapy group (50.9%; P = .0075).

“The median PFS of 5.2 months and OS [overall survival] of nearly 17 months with doxorubicin should serve as a reference in the design of future studies in the first-line treatment of metastatic soft tissue sarcoma,” Dr. Ryan and his associates said.

The study was supported by ZIOPHARM Oncology. Dr. Ryan and several of the coauthors reported multiple relationships with industry.

Palifosfamide added to doxorubicin did not improve survival outcomes in patients with metastatic soft tissue sarcoma, compared with doxorubicin alone, a study showed.

The phase III randomized trial did not meet its amended primary endpoint, as there was no significant difference in progression-free survival (PFS) among patients in the two-drug regimen arm.

“This study represents one of the largest international efforts among sarcoma centers to date,” wrote Christopher W. Ryan, MD, of the Oregon Health & Science University, Knight Cancer Institute, Portland, Ore., and his coauthors (J Clin Oncol. 2016 Sept 12. doi: 10.1200/JCO.2016.67.668).

“Single-agent doxorubicin thus remains a reference standard for the treatment of metastatic soft tissue sarcoma,” they wrote.

Doxorubicin has remained the standard first-line treatment for most sarcoma patients for more than 4 decades. Palifosfamide, a tris salt of isophosphoramide mustard, has previously demonstrated broad activity against sarcoma in experimental models.

In addition, a randomized phase II trial showed improved PFS for combined doxorubicin and palifosfamide, compared with doxorubicin alone, with a hazard ratio (HR) of 0.43 (95% CI, 0.19-0.95).

Based on those promising results, Dr. Ryan and his colleagues conducted a phase III trial that evaluated the two-drug combination with doxorubicin alone as first-line treatment of metastatic soft tissue sarcoma.

The cohort included 447 patients who were randomly assigned 1:1 to receive either doxorubicin 75 mg/m2 IV on day 1 plus palifosfamide 150 mg/m² per day IV on days 1-3, or doxorubicin plus placebo once every 21 days for up to six cycles.

The primary endpoint of the study was PFS by independent radiologic review.

There was no significant difference in PFS between the two cohorts. For the combination therapy group, the median PFS was 6.0 months, compared with 5.2 months for doxorubicin plus placebo (HR, 0.86; 95% CI, 0.68-1.08; P = .19).

Similar results were observed for median overall survival, which was also similar in the two treatment groups: 15.9 months for doxorubicin plus palifosfamide and 16.9 months for doxorubicin plus placebo (HR, 1.05; 95% CI, 0.79-1.39; P = .74).

As for toxicity, all patients had at least one treatment-emergent adverse event, with the most common of any grade being alopecia, nausea, and fatigue.

Grade 3-4 adverse events were more frequently observed in patients receiving doxorubicin plus palifosfamide (63.6%) than in the single-therapy group (50.9%; P = .0075).

“The median PFS of 5.2 months and OS [overall survival] of nearly 17 months with doxorubicin should serve as a reference in the design of future studies in the first-line treatment of metastatic soft tissue sarcoma,” Dr. Ryan and his associates said.

The study was supported by ZIOPHARM Oncology. Dr. Ryan and several of the coauthors reported multiple relationships with industry.

Among patients with Ewing sarcoma, functional imaging with ¹⁸fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging ­modalities were at 6 weeks, results of a retrospective analysis suggest.

A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.

“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].

To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.

Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).

The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.

As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.

“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.

They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.

When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.

The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.

Among patients with Ewing sarcoma, functional imaging with ¹⁸fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging ­modalities were at 6 weeks, results of a retrospective analysis suggest.

A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.

“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].

To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.

Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).

The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.

As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.

“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.

They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.

When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.

The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.

Among patients with Ewing sarcoma, functional imaging with ¹⁸fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging ­modalities were at 6 weeks, results of a retrospective analysis suggest.

A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.

“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].

To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.

Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).

The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.

As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.

“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.

They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.

When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.

The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

The incidence of Kaposi’s sarcoma among HIV patients has declined in the antiretroviral era, but the cancers are now presenting in older patients, after treatment starts, and in patients who have undetectable levels of HIV RNA.

Changes were also seen in the appearance of non-Hodgkin lymphoma, which is now occurring in patients with higher CD4 counts and lower HIV viral loads.

Although the findings of this large database study were largely driven by the fact that more patients are on antiretroviral therapy (ART) and in active clinical care, biological forces may also be at work, wrote Elizabeth L. Yanik, PhD, of the National Cancer Institute, Rockville, Md., and her associates (Am J Clin Oncol. 2016 Aug 9. doi: 10.1200/JCO.2016.67.6999).

“For example, cancers that develop in patients with HIV infection after immune recovery may manifest genetic or epigenetic changes that facilitate evasion from the immune system … [and] given that human herpesvirus-8 and Epstein-Barr virus are genetically heterogeneous, another possibility is that patients in whom Kaposi’s or non-Hodgkin lymphoma develops after immune reconstitution may be infected with more pathogenic strains.”

Dr. Yanik and her colleagues mined data from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). The 24,901 patients have been followed from 1996-2011. Among them, 446 cases of Kaposi’s sarcoma (KS) and 258 cases of non-Hodgkin lymphoma (NHL) developed. Overall, KS and NHL incidence rates decreased 5% and 8% per year, respectively.

The proportion of KS diagnosed during routine care increased significantly, from 32% to 49%, reflecting the fact that more HIV patients continue to enter active clinical settings. The diagnostic setting of NHL did not change significantly over the study period, with 64% of cases being diagnosed in routine care in the latter years. From the beginning to the end of the study period, patient median age at diagnosis increased for both KS (from 37 to 42 years) and NHL (from 40 to 46 years).

The authors said this is a direct result of changing care patterns. “The proportion of KS cases diagnosed among patients who received ART increased not because KS incidence increased in patients who received ART but because of the growing fraction of the HIV population administered ART.”

As the study period progressed, more cases of KS appeared 6 months or longer after ART initiation, from 26% in the early years to 60% in the latter years. This change didn’t occur with NHL cases; 68% of them were diagnosed at least 6 months after ART began.

The mean CD4 count at diagnosis increased with time for both KS and NHL. During 2007-2011, 15% of KS cases and 24% of NHL cases were diagnosed at CD4 counts of 500 cells/mL or more, whereas less than half were diagnosed at CD4 counts less than 200 cells/mL, the authors observed.

Both cancers began to appear during periods of decreased viral load as the study progressed, although the decrease was only significant for NHL. However, from 2007 to 2011, 29% of KS cases and 51% of NHL cases were diagnosed when HIV RNA was suppressed to 500 copies/mL or lower.

Again, the authors related this to improved clinical care. “These clinical characteristics and the changes in the underlying HIV population are inherently related. Improvements in ART access and earlier initiation lead to earlier suppression of HIV RNA and, ultimately, higher CD4 counts,” they said.

[email protected]

On Twitter @Alz_Gal

Survivors of fusion-negative sarcomas have a higher risk of developing second malignant neoplasms, report Philip J. Lupo, PhD, and his coauthors from the Baylor College of Medicine in Houston.

Investigators evaluated 4,822 survivors of fusion-positive (F+) sarcomas and 3,963 survivors of fusion-negative (F–) sarcomas aged birth-39 years. Patients were diagnosed between 1992 and 2012, and were included in the Surveillance, Epidemiology, and End Results (SEER) database.

Results showed that second malignancy risk was almost two times higher in F+ sarcoma patients, compared with the reference population (standardized incidence ratio = 1.86; 95% confidence interval, 1.48-2.30), and almost three times higher in survivors of F– sarcomas (SIR = 2.89; 95% CI, 2.30-3.59).

Second malignancy types were similar between F+ and F– survivors. However, the second malignant neoplasm rate was greater among survivors of F– sarcomas (adjusted hazard ratio = 1.38; 95% CI, 1.01-1.89) when compared with survivors of F+ sarcomas, Dr. Lupo and his colleagues reported.

Read the full study in Cancer.

Survivors of fusion-negative sarcomas have a higher risk of developing second malignant neoplasms, report Philip J. Lupo, PhD, and his coauthors from the Baylor College of Medicine in Houston.

Investigators evaluated 4,822 survivors of fusion-positive (F+) sarcomas and 3,963 survivors of fusion-negative (F–) sarcomas aged birth-39 years. Patients were diagnosed between 1992 and 2012, and were included in the Surveillance, Epidemiology, and End Results (SEER) database.

Results showed that second malignancy risk was almost two times higher in F+ sarcoma patients, compared with the reference population (standardized incidence ratio = 1.86; 95% confidence interval, 1.48-2.30), and almost three times higher in survivors of F– sarcomas (SIR = 2.89; 95% CI, 2.30-3.59).

Second malignancy types were similar between F+ and F– survivors. However, the second malignant neoplasm rate was greater among survivors of F– sarcomas (adjusted hazard ratio = 1.38; 95% CI, 1.01-1.89) when compared with survivors of F+ sarcomas, Dr. Lupo and his colleagues reported.

Read the full study in Cancer.

Survivors of fusion-negative sarcomas have a higher risk of developing second malignant neoplasms, report Philip J. Lupo, PhD, and his coauthors from the Baylor College of Medicine in Houston.

Investigators evaluated 4,822 survivors of fusion-positive (F+) sarcomas and 3,963 survivors of fusion-negative (F–) sarcomas aged birth-39 years. Patients were diagnosed between 1992 and 2012, and were included in the Surveillance, Epidemiology, and End Results (SEER) database.

Results showed that second malignancy risk was almost two times higher in F+ sarcoma patients, compared with the reference population (standardized incidence ratio = 1.86; 95% confidence interval, 1.48-2.30), and almost three times higher in survivors of F– sarcomas (SIR = 2.89; 95% CI, 2.30-3.59).

Second malignancy types were similar between F+ and F– survivors. However, the second malignant neoplasm rate was greater among survivors of F– sarcomas (adjusted hazard ratio = 1.38; 95% CI, 1.01-1.89) when compared with survivors of F+ sarcomas, Dr. Lupo and his colleagues reported.

Read the full study in Cancer.

When trabectedin was administered to soft tissue sarcoma (STS) patients receiving doxorubicin, neither progression-free nor overall survival significantly improved, investigators found.

In addition, patients who received both drugs were significantly more likely to experience adverse events.

“The combination of trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS patients, at least under this schedule. Moreover, the experimental arm was significantly more toxic than the control arm, especially regarding thrombocytopenia, vomiting, liver toxicity, and asthenia,” wrote Dr. Javier Martin-Broto of the Virgen del Rocio Hospital and Biomedicine Institute, Seville (Spain) and his associates (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.65.3329).

Of 115 adult patients with advanced nonresectable or metastatic STS, 59 received doxorubicin only, 55 received both doxorubicin and trabectedin, and one patient was not treated. In the experimental group, doxorubicin was administered before trabectedin. Both the experimental and control groups underwent six cycles of their respective drug regime unless disease progression or unacceptable toxicity was observed.

A Cox proportional hazard regression model revealed that the progression-free survival was not significantly higher among patients receiving trabectedin and doxorubicin compared to patients only receiving doxorubicin (5.7 months vs. 5.5 months; hazard ratio, 1.16; 95% confidence interval, 0.79-1.71; P = .45). Overall survival was also not significantly different between the groups (13.3 months vs. 13.7 months; HR, 1.21; 95% CI, .77-1.92, P = .41).

However, compared with patients who only received doxorubicin, patients who received both trabectedin and doxorubicin experienced significantly more adverse events such as grade 3 or 4 thrombocytopenia (2% vs. 18%, P = .016), grade 3 or 4 liver toxicity (12% vs. 29%, P = .002), AST (0% vs. 8%, P = .007), ALT (0% vs. 19%, P less than .001), and grade 3 or 4 asthenia (4% vs. 25%, P = .002).

[email protected]

On Twitter @jess_craig94

When trabectedin was administered to soft tissue sarcoma (STS) patients receiving doxorubicin, neither progression-free nor overall survival significantly improved, investigators found.

In addition, patients who received both drugs were significantly more likely to experience adverse events.

“The combination of trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS patients, at least under this schedule. Moreover, the experimental arm was significantly more toxic than the control arm, especially regarding thrombocytopenia, vomiting, liver toxicity, and asthenia,” wrote Dr. Javier Martin-Broto of the Virgen del Rocio Hospital and Biomedicine Institute, Seville (Spain) and his associates (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.65.3329).

Of 115 adult patients with advanced nonresectable or metastatic STS, 59 received doxorubicin only, 55 received both doxorubicin and trabectedin, and one patient was not treated. In the experimental group, doxorubicin was administered before trabectedin. Both the experimental and control groups underwent six cycles of their respective drug regime unless disease progression or unacceptable toxicity was observed.

A Cox proportional hazard regression model revealed that the progression-free survival was not significantly higher among patients receiving trabectedin and doxorubicin compared to patients only receiving doxorubicin (5.7 months vs. 5.5 months; hazard ratio, 1.16; 95% confidence interval, 0.79-1.71; P = .45). Overall survival was also not significantly different between the groups (13.3 months vs. 13.7 months; HR, 1.21; 95% CI, .77-1.92, P = .41).

However, compared with patients who only received doxorubicin, patients who received both trabectedin and doxorubicin experienced significantly more adverse events such as grade 3 or 4 thrombocytopenia (2% vs. 18%, P = .016), grade 3 or 4 liver toxicity (12% vs. 29%, P = .002), AST (0% vs. 8%, P = .007), ALT (0% vs. 19%, P less than .001), and grade 3 or 4 asthenia (4% vs. 25%, P = .002).

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On Twitter @jess_craig94

When trabectedin was administered to soft tissue sarcoma (STS) patients receiving doxorubicin, neither progression-free nor overall survival significantly improved, investigators found.

In addition, patients who received both drugs were significantly more likely to experience adverse events.

“The combination of trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS patients, at least under this schedule. Moreover, the experimental arm was significantly more toxic than the control arm, especially regarding thrombocytopenia, vomiting, liver toxicity, and asthenia,” wrote Dr. Javier Martin-Broto of the Virgen del Rocio Hospital and Biomedicine Institute, Seville (Spain) and his associates (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.65.3329).

Of 115 adult patients with advanced nonresectable or metastatic STS, 59 received doxorubicin only, 55 received both doxorubicin and trabectedin, and one patient was not treated. In the experimental group, doxorubicin was administered before trabectedin. Both the experimental and control groups underwent six cycles of their respective drug regime unless disease progression or unacceptable toxicity was observed.

A Cox proportional hazard regression model revealed that the progression-free survival was not significantly higher among patients receiving trabectedin and doxorubicin compared to patients only receiving doxorubicin (5.7 months vs. 5.5 months; hazard ratio, 1.16; 95% confidence interval, 0.79-1.71; P = .45). Overall survival was also not significantly different between the groups (13.3 months vs. 13.7 months; HR, 1.21; 95% CI, .77-1.92, P = .41).

However, compared with patients who only received doxorubicin, patients who received both trabectedin and doxorubicin experienced significantly more adverse events such as grade 3 or 4 thrombocytopenia (2% vs. 18%, P = .016), grade 3 or 4 liver toxicity (12% vs. 29%, P = .002), AST (0% vs. 8%, P = .007), ALT (0% vs. 19%, P less than .001), and grade 3 or 4 asthenia (4% vs. 25%, P = .002).

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On Twitter @jess_craig94

The Food and Drug Administration has granted priority review of olaratumab, in combination with doxorubicin, for the treatment of patients with advanced soft tissue sarcoma who unsuccessfully underwent prior radiotherapy or surgery for their cancer.

Olaratumab is a human IgG1 monoclonal antibody that directly targets tumor cells by disrupting the platelet-derived growth factor receptor alpha, a receptor that is believed to play a role in tumor growth and progression.

“We are hopeful that, if approved, olaratumab will provide a meaningful addition to the limited treatment options for this rare and difficult-to-treat disease,” Dr. Richard Gaynor, senior vice president of product development and medical affairs for Lilly Oncology, the maker of the drug, said in a written statement issued by company.

The biologics license application submission for olaratumab was based on a phase II clinical trial of 129 patients with metastatic or unresectable soft tissue sarcoma. Sixty-four patients were assigned to the treatment group and received both doxorubicin and olaratumab. Patients in this group continued to receive olaratumab through observed disease progression. Sixty-five patients were assigned to the control group and received only doxorubicin until disease progression was first observed. Patients who received olaratumab in addition to doxorubicin experienced a longer median progression-free survival, compared with patients who only received doxorubicin (6.6 months vs. 4.1 months; stratified hazard ratio, 0.672; 95% confidence interval, 0.442 to 1.021; P = .0615). The results of the phase II clinical trial were reported at the 2015 American Society of Clinical Oncology annual meeting and the 2015 Connective Tissue Oncology Society annual meeting.

The FDA previously granted olaratumab breakthrough therapy, fast track, and orphan drug designation.

[email protected]

On Twitter @jess_craig94

The Food and Drug Administration has granted priority review of olaratumab, in combination with doxorubicin, for the treatment of patients with advanced soft tissue sarcoma who unsuccessfully underwent prior radiotherapy or surgery for their cancer.

Olaratumab is a human IgG1 monoclonal antibody that directly targets tumor cells by disrupting the platelet-derived growth factor receptor alpha, a receptor that is believed to play a role in tumor growth and progression.

“We are hopeful that, if approved, olaratumab will provide a meaningful addition to the limited treatment options for this rare and difficult-to-treat disease,” Dr. Richard Gaynor, senior vice president of product development and medical affairs for Lilly Oncology, the maker of the drug, said in a written statement issued by company.

The biologics license application submission for olaratumab was based on a phase II clinical trial of 129 patients with metastatic or unresectable soft tissue sarcoma. Sixty-four patients were assigned to the treatment group and received both doxorubicin and olaratumab. Patients in this group continued to receive olaratumab through observed disease progression. Sixty-five patients were assigned to the control group and received only doxorubicin until disease progression was first observed. Patients who received olaratumab in addition to doxorubicin experienced a longer median progression-free survival, compared with patients who only received doxorubicin (6.6 months vs. 4.1 months; stratified hazard ratio, 0.672; 95% confidence interval, 0.442 to 1.021; P = .0615). The results of the phase II clinical trial were reported at the 2015 American Society of Clinical Oncology annual meeting and the 2015 Connective Tissue Oncology Society annual meeting.

The FDA previously granted olaratumab breakthrough therapy, fast track, and orphan drug designation.

[email protected]

On Twitter @jess_craig94

The Food and Drug Administration has granted priority review of olaratumab, in combination with doxorubicin, for the treatment of patients with advanced soft tissue sarcoma who unsuccessfully underwent prior radiotherapy or surgery for their cancer.

Olaratumab is a human IgG1 monoclonal antibody that directly targets tumor cells by disrupting the platelet-derived growth factor receptor alpha, a receptor that is believed to play a role in tumor growth and progression.

“We are hopeful that, if approved, olaratumab will provide a meaningful addition to the limited treatment options for this rare and difficult-to-treat disease,” Dr. Richard Gaynor, senior vice president of product development and medical affairs for Lilly Oncology, the maker of the drug, said in a written statement issued by company.

The biologics license application submission for olaratumab was based on a phase II clinical trial of 129 patients with metastatic or unresectable soft tissue sarcoma. Sixty-four patients were assigned to the treatment group and received both doxorubicin and olaratumab. Patients in this group continued to receive olaratumab through observed disease progression. Sixty-five patients were assigned to the control group and received only doxorubicin until disease progression was first observed. Patients who received olaratumab in addition to doxorubicin experienced a longer median progression-free survival, compared with patients who only received doxorubicin (6.6 months vs. 4.1 months; stratified hazard ratio, 0.672; 95% confidence interval, 0.442 to 1.021; P = .0615). The results of the phase II clinical trial were reported at the 2015 American Society of Clinical Oncology annual meeting and the 2015 Connective Tissue Oncology Society annual meeting.

The FDA previously granted olaratumab breakthrough therapy, fast track, and orphan drug designation.

[email protected]

On Twitter @jess_craig94

Entrectinib, an investigational drug that targets several abnormal fusion proteins, showed antitumor activity and was safe in patients with several different types of advanced solid tumors. The patients had never before been exposed to drugs targeting these same genetic alterations.

“Responses can be very rapid and durable … which include colorectal, primary brain tumor, astrocytoma, fibrosarcoma, lung, and mammary analog secretory carcinoma,” Dr. Alexander Drilon of Memorial Sloan Kettering Cancer Center in New York said in a news conference at the annual meeting of the American Association for Cancer Research. “Dramatic intracranial activity … has been demonstrated both in primary brain tumor and also in metastatic.”

NTRK1/2/3, ROS1, and ALK gene–rearranged cancers produce fusion proteins that are ligand independent for their activity and thus constitutively active, driving tumor growth. Entrectinib is a pan-TRK, ROS1, ALK tyrosine kinase inhibitor that targets the abnormal fusion protein products of the genes, is highly potent at low concentrations, and has been designed to cross the blood-brain barrier (BBB). The targeted proteins are present across multiple cancers and are especially prevalent (greater than 80%) among some rare adult and pediatric cancers.

Combined data on 119 patients in two phase I trials established 600 mg orally once daily as the recommended dose to go into phase II trials. Among the 24 patients meeting eligibility criteria for a phase II trial (presence of the targeted gene fusions in their tumors, no prior treatment against these targets, and treatment at or above 600 mg daily), the confirmed response rate was 79% (19/24). Most were partial responses in terms of tumor shrinkage, but two patients had complete responses. Response rates appeared to vary according to the specific fusion protein defect.

All three cases of CNS disease with NTRK-rearranged cancers had intracranial responses, demonstrating that the drug crosses the BBB and is active. In one case, a 46-year-old man with brain metastases heavily pretreated for non–small cell lung cancer with an NTRK1 rearrangement experienced a dramatic response.

“The patient at that point was actually on hospice and was doing extremely poorly on supplemental oxygen,” Dr. Drilon said. “Within a few weeks, the patient had a dramatic clinical response to therapy … At day 26 there was almost a 50% reduction in tumor burden.” At day 317 scans showed he had a complete intracranial response to entrectinib, but he still has visceral disease on therapy past 1 year.

Responses often occurred within the first month of therapy, and many persisted for several months without disease progression, with one patient being followed for more than 2 years with clinical benefit. Nineteen of 24 patients have been on the therapy for more than 6 months, and the therapy appears to be safe and well tolerated.

Commenting on this study and others targeting specific genetic alterations leading to cancer, Dr. Louis Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, said, “You’re seeing a series of clinical trials described that aren’t necessarily targeting people with a particular cancer but rather people who have cancers characterized by particular molecular abnormalities.” Not all cancers will have identified molecular abnormalities driving them. “However, I think where you have these drivers, the proper thing to do is not to worry about whether [a drug] works in a given disease but rather whether it works for people with that particular abnormality,” he said.

For the future, the investigators plan a phase II trial called STARTRK-2. It is a multicenter, open-label, global basket study to include any solid tumors with the targeted rearrangements.

Dr. Drilon disclosed ties with Ignyta, which funded the study, and has received research funding from Foundation Medicine. Dr. Weiner disclosed ties with several pharmaceutical companies.

Entrectinib, an investigational drug that targets several abnormal fusion proteins, showed antitumor activity and was safe in patients with several different types of advanced solid tumors. The patients had never before been exposed to drugs targeting these same genetic alterations.

“Responses can be very rapid and durable … which include colorectal, primary brain tumor, astrocytoma, fibrosarcoma, lung, and mammary analog secretory carcinoma,” Dr. Alexander Drilon of Memorial Sloan Kettering Cancer Center in New York said in a news conference at the annual meeting of the American Association for Cancer Research. “Dramatic intracranial activity … has been demonstrated both in primary brain tumor and also in metastatic.”

NTRK1/2/3, ROS1, and ALK gene–rearranged cancers produce fusion proteins that are ligand independent for their activity and thus constitutively active, driving tumor growth. Entrectinib is a pan-TRK, ROS1, ALK tyrosine kinase inhibitor that targets the abnormal fusion protein products of the genes, is highly potent at low concentrations, and has been designed to cross the blood-brain barrier (BBB). The targeted proteins are present across multiple cancers and are especially prevalent (greater than 80%) among some rare adult and pediatric cancers.

Combined data on 119 patients in two phase I trials established 600 mg orally once daily as the recommended dose to go into phase II trials. Among the 24 patients meeting eligibility criteria for a phase II trial (presence of the targeted gene fusions in their tumors, no prior treatment against these targets, and treatment at or above 600 mg daily), the confirmed response rate was 79% (19/24). Most were partial responses in terms of tumor shrinkage, but two patients had complete responses. Response rates appeared to vary according to the specific fusion protein defect.

All three cases of CNS disease with NTRK-rearranged cancers had intracranial responses, demonstrating that the drug crosses the BBB and is active. In one case, a 46-year-old man with brain metastases heavily pretreated for non–small cell lung cancer with an NTRK1 rearrangement experienced a dramatic response.

“The patient at that point was actually on hospice and was doing extremely poorly on supplemental oxygen,” Dr. Drilon said. “Within a few weeks, the patient had a dramatic clinical response to therapy … At day 26 there was almost a 50% reduction in tumor burden.” At day 317 scans showed he had a complete intracranial response to entrectinib, but he still has visceral disease on therapy past 1 year.

Responses often occurred within the first month of therapy, and many persisted for several months without disease progression, with one patient being followed for more than 2 years with clinical benefit. Nineteen of 24 patients have been on the therapy for more than 6 months, and the therapy appears to be safe and well tolerated.

Commenting on this study and others targeting specific genetic alterations leading to cancer, Dr. Louis Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, said, “You’re seeing a series of clinical trials described that aren’t necessarily targeting people with a particular cancer but rather people who have cancers characterized by particular molecular abnormalities.” Not all cancers will have identified molecular abnormalities driving them. “However, I think where you have these drivers, the proper thing to do is not to worry about whether [a drug] works in a given disease but rather whether it works for people with that particular abnormality,” he said.

For the future, the investigators plan a phase II trial called STARTRK-2. It is a multicenter, open-label, global basket study to include any solid tumors with the targeted rearrangements.

Dr. Drilon disclosed ties with Ignyta, which funded the study, and has received research funding from Foundation Medicine. Dr. Weiner disclosed ties with several pharmaceutical companies.

Entrectinib, an investigational drug that targets several abnormal fusion proteins, showed antitumor activity and was safe in patients with several different types of advanced solid tumors. The patients had never before been exposed to drugs targeting these same genetic alterations.

“Responses can be very rapid and durable … which include colorectal, primary brain tumor, astrocytoma, fibrosarcoma, lung, and mammary analog secretory carcinoma,” Dr. Alexander Drilon of Memorial Sloan Kettering Cancer Center in New York said in a news conference at the annual meeting of the American Association for Cancer Research. “Dramatic intracranial activity … has been demonstrated both in primary brain tumor and also in metastatic.”

NTRK1/2/3, ROS1, and ALK gene–rearranged cancers produce fusion proteins that are ligand independent for their activity and thus constitutively active, driving tumor growth. Entrectinib is a pan-TRK, ROS1, ALK tyrosine kinase inhibitor that targets the abnormal fusion protein products of the genes, is highly potent at low concentrations, and has been designed to cross the blood-brain barrier (BBB). The targeted proteins are present across multiple cancers and are especially prevalent (greater than 80%) among some rare adult and pediatric cancers.

Combined data on 119 patients in two phase I trials established 600 mg orally once daily as the recommended dose to go into phase II trials. Among the 24 patients meeting eligibility criteria for a phase II trial (presence of the targeted gene fusions in their tumors, no prior treatment against these targets, and treatment at or above 600 mg daily), the confirmed response rate was 79% (19/24). Most were partial responses in terms of tumor shrinkage, but two patients had complete responses. Response rates appeared to vary according to the specific fusion protein defect.

All three cases of CNS disease with NTRK-rearranged cancers had intracranial responses, demonstrating that the drug crosses the BBB and is active. In one case, a 46-year-old man with brain metastases heavily pretreated for non–small cell lung cancer with an NTRK1 rearrangement experienced a dramatic response.

“The patient at that point was actually on hospice and was doing extremely poorly on supplemental oxygen,” Dr. Drilon said. “Within a few weeks, the patient had a dramatic clinical response to therapy … At day 26 there was almost a 50% reduction in tumor burden.” At day 317 scans showed he had a complete intracranial response to entrectinib, but he still has visceral disease on therapy past 1 year.

Responses often occurred within the first month of therapy, and many persisted for several months without disease progression, with one patient being followed for more than 2 years with clinical benefit. Nineteen of 24 patients have been on the therapy for more than 6 months, and the therapy appears to be safe and well tolerated.

Commenting on this study and others targeting specific genetic alterations leading to cancer, Dr. Louis Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, said, “You’re seeing a series of clinical trials described that aren’t necessarily targeting people with a particular cancer but rather people who have cancers characterized by particular molecular abnormalities.” Not all cancers will have identified molecular abnormalities driving them. “However, I think where you have these drivers, the proper thing to do is not to worry about whether [a drug] works in a given disease but rather whether it works for people with that particular abnormality,” he said.

For the future, the investigators plan a phase II trial called STARTRK-2. It is a multicenter, open-label, global basket study to include any solid tumors with the targeted rearrangements.

Dr. Drilon disclosed ties with Ignyta, which funded the study, and has received research funding from Foundation Medicine. Dr. Weiner disclosed ties with several pharmaceutical companies.

Older patients appeared to receive greater benefit from adjuvant radiotherapy (RT) for soft tissue sarcoma (STS) than younger patients, according an analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

Several STS subtypes were associated with significant RT benefits to overall survival (OS) and disease-specific survival (DSS) in patients older than 65 years, but survival differences were not significant in younger patients. These seven subtypes included leiomyosarcoma (hazard ratio, 0.84; P = .04), sarcoma not otherwise specified (HR, 0.66; P less than or equal to .001), liposarcoma not otherwise specified (HR, 0.72; P = .05), myxoid liposarcoma (HR, 0.50; P = .02), rhabdomyosarcoma (HR, 0.23; P less than or equal to .001), epithelioid (HR, 0.01; P less than .01) and myxoid chondrosarcoma (HR, 0.02; P = .04). One STS subtype, synovial sarcoma, was associated with significant RT benefit only in younger patients (HR, 0.73; P = .04). Malignant fibrous histiocytoma was the only subtype to show significant benefit in the overall cohort as well as both age groups.

“We observed a statistically significant improvement in OS and DSS in all patients receiving RT compared to surgery alone across the majority of histological subgroups. More importantly, there was no significant improvement in younger patients compared to a significant improvement in older patients, suggesting that survival benefits in response to RT are significantly affected by age-related differences,” wrote Dr. Noah K. Yuen of the Department of Surgery, University of California, Davis, and his colleagues (Anticancer Res. 2016 Apr;36(4):1745-50). The findings suggest that older patients may benefit more than previously appreciated, and while implementation of RT among the elderly may present challenges, according to the investigators, “our data suggest that this approach deserves greater attention.”

Previous population-based retrospective studies have demonstrated a similar benefit with surgery and adjuvant RT; however, randomized clinical trials have shown significant improvement in local control but have failed to show significant improvement in OS. The authors acknowledged the potential impact of unmeasured confounding factors on the retrospective study. Selection bias may be present if healthier older patients preferentially received RT; a subpopulation of healthier individuals would be expected to have better survival.

The SEER database analysis included 15,380 patients with non-metastatic STS who underwent surgery during 1990 to 2011. The mean age of the cohort was 56.6 years and one-third were age 65 years or more. As the most common histologic subtype, leiomyosarcoma accounted for 30.1% of all tumors. Most of the patients treated with RT (68.3%) had high-grade tumors.

Older patients appeared to receive greater benefit from adjuvant radiotherapy (RT) for soft tissue sarcoma (STS) than younger patients, according an analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

Several STS subtypes were associated with significant RT benefits to overall survival (OS) and disease-specific survival (DSS) in patients older than 65 years, but survival differences were not significant in younger patients. These seven subtypes included leiomyosarcoma (hazard ratio, 0.84; P = .04), sarcoma not otherwise specified (HR, 0.66; P less than or equal to .001), liposarcoma not otherwise specified (HR, 0.72; P = .05), myxoid liposarcoma (HR, 0.50; P = .02), rhabdomyosarcoma (HR, 0.23; P less than or equal to .001), epithelioid (HR, 0.01; P less than .01) and myxoid chondrosarcoma (HR, 0.02; P = .04). One STS subtype, synovial sarcoma, was associated with significant RT benefit only in younger patients (HR, 0.73; P = .04). Malignant fibrous histiocytoma was the only subtype to show significant benefit in the overall cohort as well as both age groups.

“We observed a statistically significant improvement in OS and DSS in all patients receiving RT compared to surgery alone across the majority of histological subgroups. More importantly, there was no significant improvement in younger patients compared to a significant improvement in older patients, suggesting that survival benefits in response to RT are significantly affected by age-related differences,” wrote Dr. Noah K. Yuen of the Department of Surgery, University of California, Davis, and his colleagues (Anticancer Res. 2016 Apr;36(4):1745-50). The findings suggest that older patients may benefit more than previously appreciated, and while implementation of RT among the elderly may present challenges, according to the investigators, “our data suggest that this approach deserves greater attention.”

Previous population-based retrospective studies have demonstrated a similar benefit with surgery and adjuvant RT; however, randomized clinical trials have shown significant improvement in local control but have failed to show significant improvement in OS. The authors acknowledged the potential impact of unmeasured confounding factors on the retrospective study. Selection bias may be present if healthier older patients preferentially received RT; a subpopulation of healthier individuals would be expected to have better survival.

The SEER database analysis included 15,380 patients with non-metastatic STS who underwent surgery during 1990 to 2011. The mean age of the cohort was 56.6 years and one-third were age 65 years or more. As the most common histologic subtype, leiomyosarcoma accounted for 30.1% of all tumors. Most of the patients treated with RT (68.3%) had high-grade tumors.

Older patients appeared to receive greater benefit from adjuvant radiotherapy (RT) for soft tissue sarcoma (STS) than younger patients, according an analysis of the Surveillance, Epidemiology, and End Results (SEER) database.

Several STS subtypes were associated with significant RT benefits to overall survival (OS) and disease-specific survival (DSS) in patients older than 65 years, but survival differences were not significant in younger patients. These seven subtypes included leiomyosarcoma (hazard ratio, 0.84; P = .04), sarcoma not otherwise specified (HR, 0.66; P less than or equal to .001), liposarcoma not otherwise specified (HR, 0.72; P = .05), myxoid liposarcoma (HR, 0.50; P = .02), rhabdomyosarcoma (HR, 0.23; P less than or equal to .001), epithelioid (HR, 0.01; P less than .01) and myxoid chondrosarcoma (HR, 0.02; P = .04). One STS subtype, synovial sarcoma, was associated with significant RT benefit only in younger patients (HR, 0.73; P = .04). Malignant fibrous histiocytoma was the only subtype to show significant benefit in the overall cohort as well as both age groups.

“We observed a statistically significant improvement in OS and DSS in all patients receiving RT compared to surgery alone across the majority of histological subgroups. More importantly, there was no significant improvement in younger patients compared to a significant improvement in older patients, suggesting that survival benefits in response to RT are significantly affected by age-related differences,” wrote Dr. Noah K. Yuen of the Department of Surgery, University of California, Davis, and his colleagues (Anticancer Res. 2016 Apr;36(4):1745-50). The findings suggest that older patients may benefit more than previously appreciated, and while implementation of RT among the elderly may present challenges, according to the investigators, “our data suggest that this approach deserves greater attention.”

Previous population-based retrospective studies have demonstrated a similar benefit with surgery and adjuvant RT; however, randomized clinical trials have shown significant improvement in local control but have failed to show significant improvement in OS. The authors acknowledged the potential impact of unmeasured confounding factors on the retrospective study. Selection bias may be present if healthier older patients preferentially received RT; a subpopulation of healthier individuals would be expected to have better survival.

The SEER database analysis included 15,380 patients with non-metastatic STS who underwent surgery during 1990 to 2011. The mean age of the cohort was 56.6 years and one-third were age 65 years or more. As the most common histologic subtype, leiomyosarcoma accounted for 30.1% of all tumors. Most of the patients treated with RT (68.3%) had high-grade tumors.