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This year’s annual meeting of The Connective Tissue Oncology Society brought new insights on intimal sarcoma. Four studies in a featured session at the meeting examined both current and novel treatments for this rare and aggressive cancer, and emphasized the need for new therapies.
Anthracycline-based regimens as preferred first-line therapies
Anthracycline-based regimens were the preferred first-line therapies used in 83 adults with intimal sarcomas in a retrospective study of data from the World Sarcoma Network, reported by Anna Maria Frezza, MD, of the, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and her colleagues. The researchers described the experience with anthracycline-based regimens as well as gemcitabine-based regimens and pazopanib among MDM2-positive patients with intimal sarcomas treated at 16 sarcoma reference centers in Europe, the United States, and Japan. Their findings speak to the need for new active drugs, which they said should target the MDM2 and CDK4 overexpression seen in patients with this rare sarcoma.Of the 83 patients studied, nearly all (76 patients) initially received an anthracycline-based regimen. Gemcitabine-based regimens were used in 29 patients and pazopanib in 10 patients; 20 of the 39 patients received more than one treatment.
Anthracycline-based regimens were associated with a 12-month progression-free survival rate of 38% in 76 patients with intimal sarcomas. All of the 76 patients received anthracycline regimens as their initial systemic therapy; 27 were treated for localized disease with a curative intent and the remaining 49 had advanced disease. The researchers also noted that anthracycline regimens were safely used in 22 patients with cardiac intimal sarcomas, as none of them died of cardiotoxicity.
Based on RECIST 1.1 measures, the overall response rate was 37% in 57 evaluable patients: 3 patients had a complete response, 18 had a partial response, 27 had stable disease, and 9 had progressive disease. For those with localized disease, the median time to progression was 14 months, and overall survival time was 51. For patients with advanced disease, the median time to progression was 8 months and overall survival was 22 months.
Outcomes were less favorable when patients were treated with gemcitabine regimens or pazopanib. In most of these cases, however, patients were either on their second (gemcitabine) or third (pazopanib) lines of therapy.
In the gemcitabine group, 2 patients were treated for localized disease with curative intent and 27 for advanced disease. Of 28 evaluable patients, best response was partial remission in 3, stable disease in 8, and progressive disease in 17. In the 27 patients with advanced disease, the median progression free survival time was 3 months and overall survival was 13 months.
All 10 patients in the pazopanib group had advanced disease and had undergone a median of two prior lines of therapy. One patient had a partial remission, 3 had stable disease, and 6 had progressive disease. The median progression free survival was 4 months and median overall survival was 12 months.
Rarest of the rare: Primary malignant sarcoma of the heart
Luke Smith, of the School of Clinical Medicine, University of Cambridge, U.K., detailed the experience of 28 patients diagnosed with sarcomas of the heart or great vessels at the university’s Royal Papworth Hospital and Addenbrooke’s Hospital between 2000 and 2018.
Based on this retrospective review, surgery offers the best chance for long-term survival for these patients, who would otherwise experience progressive heart failure and die. Adjuvant chemotherapy and radiation therapy might be able to extend their survival and improve symptomatic relief, he said, but these outcomes have not been prospectively studied.
Typically, the patients in this series, 20 with pulmonary artery sarcoma and 8 with cardiac sarcoma, presented with symptoms mimicking heart failure, pulmonary hypertension, or thromboembolic disease. Nearly all, 24 patients reported breathlessness. Eight patients had chest pain or tightness, 6 had cough, 6 had peripheral edema, 6 had constitutional symptoms, 3 had hemoptysis, and 1 had a TIA. Only 1 patient had a seriously impaired left ventricular ejection fraction of less than 30%. LVEF was normal at 55% or more in 16 patients, and moderately impaired at 30% or more in 10 patients.
Median overall survival was 17 months. The 19 patients who underwent surgical resection of their primary tumor survived much longer than the 10 patients who did not--median overall survival of 20 months vs. 9 months--but this finding may simply reflect more advanced disease in patients with inoperable disease. There were 3 perioperative deaths among the 19 patients who underwent surgery: 14 with pulmonary artery sarcomas had pulmonary endarterectomy and 4 with cardiac sarcomas underwent resection or maximal debulking of their tumors.
Based on the retrospective study, adjuvant chemotherapy and radiation were safe and may lead to better outcomes for these patients. Active chemotherapy regimens in the palliative setting included paclitaxel (angiosarcoma) and anthracycline ± ifosfamide.
Nine patients received post-surgical chemotherapy, and after completion five also had radiotherapy. The 3 cardiac sarcoma patients who had surgical resection with curative intent were treated with adjuvant ifosfamide-based chemotherapy (with close monitoring of fluid balance), and showed no evidence of disease on last follow-ups. One patient received post-operative paclitaxel following maximal debulking of a cardiac angiosarcoma.
Post-surgical anthracycline with and without ifosfamide were used in patients with pulmonary artery sarcomas with no clinical cardiotoxicity. Although the median overall survival for patients who received post-operative chemo- and radio-therapy was 28 months and the median overall survival with surgery alone was 9 months, the difference was not statistically significant.
In the palliative setting, partial responses were observed with paclitaxel and anthracycline (including liposomal doxorubicin) in patients with cardiac angiosarcoma. For pulmonary artery intimal sarcomas, partial responses were achieved with anthracycline with and without ifosfamide. Radiotherapy provided good local control.
The longest surviving pulmonary artery sarcoma patient, at 103 months, had pulmonary artery endarterectomy, followed by adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later and was treated with radiofrequency ablation. The longest surviving cardiac sarcoma patient, at 24 months, remains disease free. He had surgery to resect a high-grade undifferentiated sarcoma with involved margins, followed by adjuvant ifosfamide and radiotherapy to the right atrium.
Therapeutically exploitable genetic aberrations in intimal sarcomas
Imatinib and olaratumab might prove to be therapeutic approaches for some patients with intimal sarcomas, based on a retrospective evaluation of genetic aberrations in 11 patients with intimal sarcomas, Jason Roszik, PhD, MBA, reported at the meeting.
Dr. Roszik and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, analyzed information on 11 patients with intimal sarcomas in the American Association for Cancer Research (AACR) project, Genomics Evidence Neoplasia Information Exchange (GENIE). Sampling was taken from the primary tumor in 8 patients and from the metastatic site in the other 3.
MDM2 amplifications were seen in 8 of 10 patients with available copy number alterations. Amplifications in the CDK pathway were present in 5, PDGFRA gain was seen in 4, and CDKN2A copy number loss was present in 3. Mutations that could be targeted with drugs included ALK, ATM/ATR, PTCH1 and PDGFRB, he said.
Unique genomic rearrangement events included PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion tumor, and PDGFRB mutations in both fusion-positive cases.
The researchers also drew on the published findings of whole-exome sequencing and array-comparative genomic hybridization from an autopsy case of cardiac intimal sarcoma (Virchows Arch. 2017 Sep;471(3):423-428). That study identified concurrent PDGFRA amplification and PDGFRB mutation.
The researchers additionally examined clinical trial enrollments and could find no patient with intimal sarcoma among 406 sarcoma enrolled patients. Intimal sarcomas were not eligible for any clinical trial given the location of the tumors in major blood vessels.
“The somatic mutations and DNA copy number alterations in the PDGFR pathway relevant to the pathogenesis and potential targeted therapy of cardiac intimal sarcoma may be targeted by imatinib or olaratumab. Inclusion of such rare tumors in targeted therapy basket trials with a waiver for inclusion criteria is warranted,” Dr. Roszik and his colleagues concluded in the abstract of their presentation.
The promise of combination therapy
The “largest experience using multimodality therapy with proton based local therapy” for sarcomas involving the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries was reported by Yen-Lin E. Chen, MD, and her colleagues at Massachusetts General Hospital, Boston.
They examined an institutional sarcoma data repository of 13,950 patients and found 37 patients with sarcomas arising from the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries. These included 9 with unclassified pleomorphic sarcoma/malignant fibrous histiocytoma, 8 with angiosarcoma, 4 with spindle cell sarcoma, 4 with sarcoma not otherwise specified, 3 with leiomyosarcoma, 2 with osteosarcoma, 2 with Ewing sarcoma, and 1 each with chondrosarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and intimal sarcoma.
Two-thirds of the patients had induction chemotherapy with or without maintenance therapy. Adriamycin, ifosfamide, and taxol therapies were most common. Two-thirds received proton based radiotherapy. Of the 23 patients who underwent resection, 11 were R2 (macroscopic positive margins), 3 were R1 (microscopic positive margins), and 9 were R0 (clear margins).
The 1-year overall survival rate was 64%, which fell to 37% at 3 years and to 28% at 5 years. Median survival was 28 months, twice that typically seen in the literature, Dr. Chen said.
For patients receiving proton based radiotherapy to a median dose of 64.8 GyRBE (range 63-72 GyRBE, 3 with additional intraoperative electrons), local failure free survivals were 80%, 64%, and 52% at 1, 3, and 5 years, respectively. For patients who did not receive radiotherapy, local failure free survival rates were 13%, 10%, 10%, respectively.
Overall, the 1, 3, and 5 year metastatic free survival rates were 25%, 14%, and 14%.
Survival rate was significantly better for patients with tumors smaller than 5 cm ( P =0.036), those over 40 years old ( P =0.028), those able to have surgery ( P =0.011), and those with non-angiosarcoma histologies ( P = 0.002).
This year’s annual meeting of The Connective Tissue Oncology Society brought new insights on intimal sarcoma. Four studies in a featured session at the meeting examined both current and novel treatments for this rare and aggressive cancer, and emphasized the need for new therapies.
Anthracycline-based regimens as preferred first-line therapies
Anthracycline-based regimens were the preferred first-line therapies used in 83 adults with intimal sarcomas in a retrospective study of data from the World Sarcoma Network, reported by Anna Maria Frezza, MD, of the, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and her colleagues. The researchers described the experience with anthracycline-based regimens as well as gemcitabine-based regimens and pazopanib among MDM2-positive patients with intimal sarcomas treated at 16 sarcoma reference centers in Europe, the United States, and Japan. Their findings speak to the need for new active drugs, which they said should target the MDM2 and CDK4 overexpression seen in patients with this rare sarcoma.Of the 83 patients studied, nearly all (76 patients) initially received an anthracycline-based regimen. Gemcitabine-based regimens were used in 29 patients and pazopanib in 10 patients; 20 of the 39 patients received more than one treatment.
Anthracycline-based regimens were associated with a 12-month progression-free survival rate of 38% in 76 patients with intimal sarcomas. All of the 76 patients received anthracycline regimens as their initial systemic therapy; 27 were treated for localized disease with a curative intent and the remaining 49 had advanced disease. The researchers also noted that anthracycline regimens were safely used in 22 patients with cardiac intimal sarcomas, as none of them died of cardiotoxicity.
Based on RECIST 1.1 measures, the overall response rate was 37% in 57 evaluable patients: 3 patients had a complete response, 18 had a partial response, 27 had stable disease, and 9 had progressive disease. For those with localized disease, the median time to progression was 14 months, and overall survival time was 51. For patients with advanced disease, the median time to progression was 8 months and overall survival was 22 months.
Outcomes were less favorable when patients were treated with gemcitabine regimens or pazopanib. In most of these cases, however, patients were either on their second (gemcitabine) or third (pazopanib) lines of therapy.
In the gemcitabine group, 2 patients were treated for localized disease with curative intent and 27 for advanced disease. Of 28 evaluable patients, best response was partial remission in 3, stable disease in 8, and progressive disease in 17. In the 27 patients with advanced disease, the median progression free survival time was 3 months and overall survival was 13 months.
All 10 patients in the pazopanib group had advanced disease and had undergone a median of two prior lines of therapy. One patient had a partial remission, 3 had stable disease, and 6 had progressive disease. The median progression free survival was 4 months and median overall survival was 12 months.
Rarest of the rare: Primary malignant sarcoma of the heart
Luke Smith, of the School of Clinical Medicine, University of Cambridge, U.K., detailed the experience of 28 patients diagnosed with sarcomas of the heart or great vessels at the university’s Royal Papworth Hospital and Addenbrooke’s Hospital between 2000 and 2018.
Based on this retrospective review, surgery offers the best chance for long-term survival for these patients, who would otherwise experience progressive heart failure and die. Adjuvant chemotherapy and radiation therapy might be able to extend their survival and improve symptomatic relief, he said, but these outcomes have not been prospectively studied.
Typically, the patients in this series, 20 with pulmonary artery sarcoma and 8 with cardiac sarcoma, presented with symptoms mimicking heart failure, pulmonary hypertension, or thromboembolic disease. Nearly all, 24 patients reported breathlessness. Eight patients had chest pain or tightness, 6 had cough, 6 had peripheral edema, 6 had constitutional symptoms, 3 had hemoptysis, and 1 had a TIA. Only 1 patient had a seriously impaired left ventricular ejection fraction of less than 30%. LVEF was normal at 55% or more in 16 patients, and moderately impaired at 30% or more in 10 patients.
Median overall survival was 17 months. The 19 patients who underwent surgical resection of their primary tumor survived much longer than the 10 patients who did not--median overall survival of 20 months vs. 9 months--but this finding may simply reflect more advanced disease in patients with inoperable disease. There were 3 perioperative deaths among the 19 patients who underwent surgery: 14 with pulmonary artery sarcomas had pulmonary endarterectomy and 4 with cardiac sarcomas underwent resection or maximal debulking of their tumors.
Based on the retrospective study, adjuvant chemotherapy and radiation were safe and may lead to better outcomes for these patients. Active chemotherapy regimens in the palliative setting included paclitaxel (angiosarcoma) and anthracycline ± ifosfamide.
Nine patients received post-surgical chemotherapy, and after completion five also had radiotherapy. The 3 cardiac sarcoma patients who had surgical resection with curative intent were treated with adjuvant ifosfamide-based chemotherapy (with close monitoring of fluid balance), and showed no evidence of disease on last follow-ups. One patient received post-operative paclitaxel following maximal debulking of a cardiac angiosarcoma.
Post-surgical anthracycline with and without ifosfamide were used in patients with pulmonary artery sarcomas with no clinical cardiotoxicity. Although the median overall survival for patients who received post-operative chemo- and radio-therapy was 28 months and the median overall survival with surgery alone was 9 months, the difference was not statistically significant.
In the palliative setting, partial responses were observed with paclitaxel and anthracycline (including liposomal doxorubicin) in patients with cardiac angiosarcoma. For pulmonary artery intimal sarcomas, partial responses were achieved with anthracycline with and without ifosfamide. Radiotherapy provided good local control.
The longest surviving pulmonary artery sarcoma patient, at 103 months, had pulmonary artery endarterectomy, followed by adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later and was treated with radiofrequency ablation. The longest surviving cardiac sarcoma patient, at 24 months, remains disease free. He had surgery to resect a high-grade undifferentiated sarcoma with involved margins, followed by adjuvant ifosfamide and radiotherapy to the right atrium.
Therapeutically exploitable genetic aberrations in intimal sarcomas
Imatinib and olaratumab might prove to be therapeutic approaches for some patients with intimal sarcomas, based on a retrospective evaluation of genetic aberrations in 11 patients with intimal sarcomas, Jason Roszik, PhD, MBA, reported at the meeting.
Dr. Roszik and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, analyzed information on 11 patients with intimal sarcomas in the American Association for Cancer Research (AACR) project, Genomics Evidence Neoplasia Information Exchange (GENIE). Sampling was taken from the primary tumor in 8 patients and from the metastatic site in the other 3.
MDM2 amplifications were seen in 8 of 10 patients with available copy number alterations. Amplifications in the CDK pathway were present in 5, PDGFRA gain was seen in 4, and CDKN2A copy number loss was present in 3. Mutations that could be targeted with drugs included ALK, ATM/ATR, PTCH1 and PDGFRB, he said.
Unique genomic rearrangement events included PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion tumor, and PDGFRB mutations in both fusion-positive cases.
The researchers also drew on the published findings of whole-exome sequencing and array-comparative genomic hybridization from an autopsy case of cardiac intimal sarcoma (Virchows Arch. 2017 Sep;471(3):423-428). That study identified concurrent PDGFRA amplification and PDGFRB mutation.
The researchers additionally examined clinical trial enrollments and could find no patient with intimal sarcoma among 406 sarcoma enrolled patients. Intimal sarcomas were not eligible for any clinical trial given the location of the tumors in major blood vessels.
“The somatic mutations and DNA copy number alterations in the PDGFR pathway relevant to the pathogenesis and potential targeted therapy of cardiac intimal sarcoma may be targeted by imatinib or olaratumab. Inclusion of such rare tumors in targeted therapy basket trials with a waiver for inclusion criteria is warranted,” Dr. Roszik and his colleagues concluded in the abstract of their presentation.
The promise of combination therapy
The “largest experience using multimodality therapy with proton based local therapy” for sarcomas involving the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries was reported by Yen-Lin E. Chen, MD, and her colleagues at Massachusetts General Hospital, Boston.
They examined an institutional sarcoma data repository of 13,950 patients and found 37 patients with sarcomas arising from the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries. These included 9 with unclassified pleomorphic sarcoma/malignant fibrous histiocytoma, 8 with angiosarcoma, 4 with spindle cell sarcoma, 4 with sarcoma not otherwise specified, 3 with leiomyosarcoma, 2 with osteosarcoma, 2 with Ewing sarcoma, and 1 each with chondrosarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and intimal sarcoma.
Two-thirds of the patients had induction chemotherapy with or without maintenance therapy. Adriamycin, ifosfamide, and taxol therapies were most common. Two-thirds received proton based radiotherapy. Of the 23 patients who underwent resection, 11 were R2 (macroscopic positive margins), 3 were R1 (microscopic positive margins), and 9 were R0 (clear margins).
The 1-year overall survival rate was 64%, which fell to 37% at 3 years and to 28% at 5 years. Median survival was 28 months, twice that typically seen in the literature, Dr. Chen said.
For patients receiving proton based radiotherapy to a median dose of 64.8 GyRBE (range 63-72 GyRBE, 3 with additional intraoperative electrons), local failure free survivals were 80%, 64%, and 52% at 1, 3, and 5 years, respectively. For patients who did not receive radiotherapy, local failure free survival rates were 13%, 10%, 10%, respectively.
Overall, the 1, 3, and 5 year metastatic free survival rates were 25%, 14%, and 14%.
Survival rate was significantly better for patients with tumors smaller than 5 cm ( P =0.036), those over 40 years old ( P =0.028), those able to have surgery ( P =0.011), and those with non-angiosarcoma histologies ( P = 0.002).
This year’s annual meeting of The Connective Tissue Oncology Society brought new insights on intimal sarcoma. Four studies in a featured session at the meeting examined both current and novel treatments for this rare and aggressive cancer, and emphasized the need for new therapies.
Anthracycline-based regimens as preferred first-line therapies
Anthracycline-based regimens were the preferred first-line therapies used in 83 adults with intimal sarcomas in a retrospective study of data from the World Sarcoma Network, reported by Anna Maria Frezza, MD, of the, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, and her colleagues. The researchers described the experience with anthracycline-based regimens as well as gemcitabine-based regimens and pazopanib among MDM2-positive patients with intimal sarcomas treated at 16 sarcoma reference centers in Europe, the United States, and Japan. Their findings speak to the need for new active drugs, which they said should target the MDM2 and CDK4 overexpression seen in patients with this rare sarcoma.Of the 83 patients studied, nearly all (76 patients) initially received an anthracycline-based regimen. Gemcitabine-based regimens were used in 29 patients and pazopanib in 10 patients; 20 of the 39 patients received more than one treatment.
Anthracycline-based regimens were associated with a 12-month progression-free survival rate of 38% in 76 patients with intimal sarcomas. All of the 76 patients received anthracycline regimens as their initial systemic therapy; 27 were treated for localized disease with a curative intent and the remaining 49 had advanced disease. The researchers also noted that anthracycline regimens were safely used in 22 patients with cardiac intimal sarcomas, as none of them died of cardiotoxicity.
Based on RECIST 1.1 measures, the overall response rate was 37% in 57 evaluable patients: 3 patients had a complete response, 18 had a partial response, 27 had stable disease, and 9 had progressive disease. For those with localized disease, the median time to progression was 14 months, and overall survival time was 51. For patients with advanced disease, the median time to progression was 8 months and overall survival was 22 months.
Outcomes were less favorable when patients were treated with gemcitabine regimens or pazopanib. In most of these cases, however, patients were either on their second (gemcitabine) or third (pazopanib) lines of therapy.
In the gemcitabine group, 2 patients were treated for localized disease with curative intent and 27 for advanced disease. Of 28 evaluable patients, best response was partial remission in 3, stable disease in 8, and progressive disease in 17. In the 27 patients with advanced disease, the median progression free survival time was 3 months and overall survival was 13 months.
All 10 patients in the pazopanib group had advanced disease and had undergone a median of two prior lines of therapy. One patient had a partial remission, 3 had stable disease, and 6 had progressive disease. The median progression free survival was 4 months and median overall survival was 12 months.
Rarest of the rare: Primary malignant sarcoma of the heart
Luke Smith, of the School of Clinical Medicine, University of Cambridge, U.K., detailed the experience of 28 patients diagnosed with sarcomas of the heart or great vessels at the university’s Royal Papworth Hospital and Addenbrooke’s Hospital between 2000 and 2018.
Based on this retrospective review, surgery offers the best chance for long-term survival for these patients, who would otherwise experience progressive heart failure and die. Adjuvant chemotherapy and radiation therapy might be able to extend their survival and improve symptomatic relief, he said, but these outcomes have not been prospectively studied.
Typically, the patients in this series, 20 with pulmonary artery sarcoma and 8 with cardiac sarcoma, presented with symptoms mimicking heart failure, pulmonary hypertension, or thromboembolic disease. Nearly all, 24 patients reported breathlessness. Eight patients had chest pain or tightness, 6 had cough, 6 had peripheral edema, 6 had constitutional symptoms, 3 had hemoptysis, and 1 had a TIA. Only 1 patient had a seriously impaired left ventricular ejection fraction of less than 30%. LVEF was normal at 55% or more in 16 patients, and moderately impaired at 30% or more in 10 patients.
Median overall survival was 17 months. The 19 patients who underwent surgical resection of their primary tumor survived much longer than the 10 patients who did not--median overall survival of 20 months vs. 9 months--but this finding may simply reflect more advanced disease in patients with inoperable disease. There were 3 perioperative deaths among the 19 patients who underwent surgery: 14 with pulmonary artery sarcomas had pulmonary endarterectomy and 4 with cardiac sarcomas underwent resection or maximal debulking of their tumors.
Based on the retrospective study, adjuvant chemotherapy and radiation were safe and may lead to better outcomes for these patients. Active chemotherapy regimens in the palliative setting included paclitaxel (angiosarcoma) and anthracycline ± ifosfamide.
Nine patients received post-surgical chemotherapy, and after completion five also had radiotherapy. The 3 cardiac sarcoma patients who had surgical resection with curative intent were treated with adjuvant ifosfamide-based chemotherapy (with close monitoring of fluid balance), and showed no evidence of disease on last follow-ups. One patient received post-operative paclitaxel following maximal debulking of a cardiac angiosarcoma.
Post-surgical anthracycline with and without ifosfamide were used in patients with pulmonary artery sarcomas with no clinical cardiotoxicity. Although the median overall survival for patients who received post-operative chemo- and radio-therapy was 28 months and the median overall survival with surgery alone was 9 months, the difference was not statistically significant.
In the palliative setting, partial responses were observed with paclitaxel and anthracycline (including liposomal doxorubicin) in patients with cardiac angiosarcoma. For pulmonary artery intimal sarcomas, partial responses were achieved with anthracycline with and without ifosfamide. Radiotherapy provided good local control.
The longest surviving pulmonary artery sarcoma patient, at 103 months, had pulmonary artery endarterectomy, followed by adjuvant epirubicin and radiotherapy. She developed lung metastases 7 years later and was treated with radiofrequency ablation. The longest surviving cardiac sarcoma patient, at 24 months, remains disease free. He had surgery to resect a high-grade undifferentiated sarcoma with involved margins, followed by adjuvant ifosfamide and radiotherapy to the right atrium.
Therapeutically exploitable genetic aberrations in intimal sarcomas
Imatinib and olaratumab might prove to be therapeutic approaches for some patients with intimal sarcomas, based on a retrospective evaluation of genetic aberrations in 11 patients with intimal sarcomas, Jason Roszik, PhD, MBA, reported at the meeting.
Dr. Roszik and his colleagues at the University of Texas MD Anderson Cancer Center, Houston, analyzed information on 11 patients with intimal sarcomas in the American Association for Cancer Research (AACR) project, Genomics Evidence Neoplasia Information Exchange (GENIE). Sampling was taken from the primary tumor in 8 patients and from the metastatic site in the other 3.
MDM2 amplifications were seen in 8 of 10 patients with available copy number alterations. Amplifications in the CDK pathway were present in 5, PDGFRA gain was seen in 4, and CDKN2A copy number loss was present in 3. Mutations that could be targeted with drugs included ALK, ATM/ATR, PTCH1 and PDGFRB, he said.
Unique genomic rearrangement events included PDE4DIP-NOTCH2 and MRPS30-ARID2 fusions. Co-occurring alterations included a NOTCH2 copy number gain in the PDE4DIP-NOTCH2 fusion tumor, and PDGFRB mutations in both fusion-positive cases.
The researchers also drew on the published findings of whole-exome sequencing and array-comparative genomic hybridization from an autopsy case of cardiac intimal sarcoma (Virchows Arch. 2017 Sep;471(3):423-428). That study identified concurrent PDGFRA amplification and PDGFRB mutation.
The researchers additionally examined clinical trial enrollments and could find no patient with intimal sarcoma among 406 sarcoma enrolled patients. Intimal sarcomas were not eligible for any clinical trial given the location of the tumors in major blood vessels.
“The somatic mutations and DNA copy number alterations in the PDGFR pathway relevant to the pathogenesis and potential targeted therapy of cardiac intimal sarcoma may be targeted by imatinib or olaratumab. Inclusion of such rare tumors in targeted therapy basket trials with a waiver for inclusion criteria is warranted,” Dr. Roszik and his colleagues concluded in the abstract of their presentation.
The promise of combination therapy
The “largest experience using multimodality therapy with proton based local therapy” for sarcomas involving the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries was reported by Yen-Lin E. Chen, MD, and her colleagues at Massachusetts General Hospital, Boston.
They examined an institutional sarcoma data repository of 13,950 patients and found 37 patients with sarcomas arising from the pericardium, myocardium, valves, pulmonary veins, or pulmonary arteries. These included 9 with unclassified pleomorphic sarcoma/malignant fibrous histiocytoma, 8 with angiosarcoma, 4 with spindle cell sarcoma, 4 with sarcoma not otherwise specified, 3 with leiomyosarcoma, 2 with osteosarcoma, 2 with Ewing sarcoma, and 1 each with chondrosarcoma, malignant peripheral nerve sheath tumor, rhabdomyosarcoma, synovial sarcoma, and intimal sarcoma.
Two-thirds of the patients had induction chemotherapy with or without maintenance therapy. Adriamycin, ifosfamide, and taxol therapies were most common. Two-thirds received proton based radiotherapy. Of the 23 patients who underwent resection, 11 were R2 (macroscopic positive margins), 3 were R1 (microscopic positive margins), and 9 were R0 (clear margins).
The 1-year overall survival rate was 64%, which fell to 37% at 3 years and to 28% at 5 years. Median survival was 28 months, twice that typically seen in the literature, Dr. Chen said.
For patients receiving proton based radiotherapy to a median dose of 64.8 GyRBE (range 63-72 GyRBE, 3 with additional intraoperative electrons), local failure free survivals were 80%, 64%, and 52% at 1, 3, and 5 years, respectively. For patients who did not receive radiotherapy, local failure free survival rates were 13%, 10%, 10%, respectively.
Overall, the 1, 3, and 5 year metastatic free survival rates were 25%, 14%, and 14%.
Survival rate was significantly better for patients with tumors smaller than 5 cm ( P =0.036), those over 40 years old ( P =0.028), those able to have surgery ( P =0.011), and those with non-angiosarcoma histologies ( P = 0.002).