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Primary chest-wall leiomyosarcoma: a rare mimic of a malignant rib lesion
Primary chest-wall leiomyosarcoma (LMS) is an uncommon, malignant, soft-tissue tumor that most often affects the extremities. Malignant LMS originates from mesenchymal cells with smooth muscle differentiation. It is rare in adults, forming only 7% of all soft-tissue sarcomas (STS), but it is the most common STS. In adults, this type of tumor is usually found in the retroperitoneum and extremities.1 Chest-wall LMS is rare and most often occurs in men aged 50-70 years.2 When LMS is associated with rib destruction, it may mimic a primary bone tumor or metastasis. We present here the case of histologically proven chest-wall sarcoma with associated rib destruction that was initially mistaken on imaging for either a metastasis or primary bone tumor.
Case presentation and summary
A 69-year-old man presented to the emergency department complaining of pain over the right side of the chest. The pain, which was pleuritic in nature, had worsened over the previous 6 months and was severe at presentation. The patient had no fever, shortness of breath, or loss of weight. He had no history of chest trauma or chest wall radiation, and nothing noteworthy was discovered in his medical history. Subsequent test results for hemoglobin, white blood cell count, lymphocyte count, and cardiac enzymes were normal.
A frontal chest radiograph showed an osteolytic destructive lesion involving the posterior right 6th rib (Figure 1). A contrast-enhanced computedtomography (CE-CT) scan of the chest showed a heterogeneously enhancing, ovoid, soft-tissue mass of 5.6 x 3.6 cm (2.2 x 1.2 in) centered on the postero- lateral right 6th rib, with associated rib erosion. There was another 2.0-cm (0.8-in) subpleural nodule in the left upper lobe (Figure 2).
Click on the PDF icon below to read the full article.
Primary chest-wall leiomyosarcoma (LMS) is an uncommon, malignant, soft-tissue tumor that most often affects the extremities. Malignant LMS originates from mesenchymal cells with smooth muscle differentiation. It is rare in adults, forming only 7% of all soft-tissue sarcomas (STS), but it is the most common STS. In adults, this type of tumor is usually found in the retroperitoneum and extremities.1 Chest-wall LMS is rare and most often occurs in men aged 50-70 years.2 When LMS is associated with rib destruction, it may mimic a primary bone tumor or metastasis. We present here the case of histologically proven chest-wall sarcoma with associated rib destruction that was initially mistaken on imaging for either a metastasis or primary bone tumor.
Case presentation and summary
A 69-year-old man presented to the emergency department complaining of pain over the right side of the chest. The pain, which was pleuritic in nature, had worsened over the previous 6 months and was severe at presentation. The patient had no fever, shortness of breath, or loss of weight. He had no history of chest trauma or chest wall radiation, and nothing noteworthy was discovered in his medical history. Subsequent test results for hemoglobin, white blood cell count, lymphocyte count, and cardiac enzymes were normal.
A frontal chest radiograph showed an osteolytic destructive lesion involving the posterior right 6th rib (Figure 1). A contrast-enhanced computedtomography (CE-CT) scan of the chest showed a heterogeneously enhancing, ovoid, soft-tissue mass of 5.6 x 3.6 cm (2.2 x 1.2 in) centered on the postero- lateral right 6th rib, with associated rib erosion. There was another 2.0-cm (0.8-in) subpleural nodule in the left upper lobe (Figure 2).
Click on the PDF icon below to read the full article.
Primary chest-wall leiomyosarcoma (LMS) is an uncommon, malignant, soft-tissue tumor that most often affects the extremities. Malignant LMS originates from mesenchymal cells with smooth muscle differentiation. It is rare in adults, forming only 7% of all soft-tissue sarcomas (STS), but it is the most common STS. In adults, this type of tumor is usually found in the retroperitoneum and extremities.1 Chest-wall LMS is rare and most often occurs in men aged 50-70 years.2 When LMS is associated with rib destruction, it may mimic a primary bone tumor or metastasis. We present here the case of histologically proven chest-wall sarcoma with associated rib destruction that was initially mistaken on imaging for either a metastasis or primary bone tumor.
Case presentation and summary
A 69-year-old man presented to the emergency department complaining of pain over the right side of the chest. The pain, which was pleuritic in nature, had worsened over the previous 6 months and was severe at presentation. The patient had no fever, shortness of breath, or loss of weight. He had no history of chest trauma or chest wall radiation, and nothing noteworthy was discovered in his medical history. Subsequent test results for hemoglobin, white blood cell count, lymphocyte count, and cardiac enzymes were normal.
A frontal chest radiograph showed an osteolytic destructive lesion involving the posterior right 6th rib (Figure 1). A contrast-enhanced computedtomography (CE-CT) scan of the chest showed a heterogeneously enhancing, ovoid, soft-tissue mass of 5.6 x 3.6 cm (2.2 x 1.2 in) centered on the postero- lateral right 6th rib, with associated rib erosion. There was another 2.0-cm (0.8-in) subpleural nodule in the left upper lobe (Figure 2).
Click on the PDF icon below to read the full article.
FDA grants accelerated approval to olaratumab for soft tissue sarcoma
The Food and Drug Administration has granted accelerated approval to olaratumab with doxorubicin for the treatment of adult patients with certain types of soft tissue sarcoma.
“This is the first new therapy approved by the FDA for the initial treatment of soft tissue sarcoma since doxorubicin’s approval more than 40 years ago,” Richard Pazdur, MD, director of the office of hematology and oncology products in the FDA Center for Drug Evaluation and Research and acting director of the FDA Oncology Center of Excellence, said in a statement.
Approval was based on a statistically significant improvement in survival in a randomized trial involving 133 patients with more than 25 different subtypes of metastatic soft tissue sarcoma. Patients received olaratumab (Lartruvo) with doxorubicin or doxorubicin alone. Median survival was 26.5 months for patients who received both drugs, compared with 14.7 months for patients who received doxorubicin alone. Median progression-free survival was 8.2 months for patients who received both drugs and 4.4 months for patients who received doxorubicin alone.
The most common adverse reactions from olaratumab were nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache. There are serious risks of infusion-related reactions and embryo-fetal harm, the FDA warned.
Olaratumab was approved under the FDA’s accelerated approval program after receiving fast track designation, breakthrough therapy designation, and a priority review status. The drug also received an orphan drug designation. Drug maker Eli Lilly is currently conducting a larger study of olaratumab across multiple subtypes of soft tissue sarcoma.
[email protected]
On Twitter @nikolaideslaura
The Food and Drug Administration has granted accelerated approval to olaratumab with doxorubicin for the treatment of adult patients with certain types of soft tissue sarcoma.
“This is the first new therapy approved by the FDA for the initial treatment of soft tissue sarcoma since doxorubicin’s approval more than 40 years ago,” Richard Pazdur, MD, director of the office of hematology and oncology products in the FDA Center for Drug Evaluation and Research and acting director of the FDA Oncology Center of Excellence, said in a statement.
Approval was based on a statistically significant improvement in survival in a randomized trial involving 133 patients with more than 25 different subtypes of metastatic soft tissue sarcoma. Patients received olaratumab (Lartruvo) with doxorubicin or doxorubicin alone. Median survival was 26.5 months for patients who received both drugs, compared with 14.7 months for patients who received doxorubicin alone. Median progression-free survival was 8.2 months for patients who received both drugs and 4.4 months for patients who received doxorubicin alone.
The most common adverse reactions from olaratumab were nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache. There are serious risks of infusion-related reactions and embryo-fetal harm, the FDA warned.
Olaratumab was approved under the FDA’s accelerated approval program after receiving fast track designation, breakthrough therapy designation, and a priority review status. The drug also received an orphan drug designation. Drug maker Eli Lilly is currently conducting a larger study of olaratumab across multiple subtypes of soft tissue sarcoma.
[email protected]
On Twitter @nikolaideslaura
The Food and Drug Administration has granted accelerated approval to olaratumab with doxorubicin for the treatment of adult patients with certain types of soft tissue sarcoma.
“This is the first new therapy approved by the FDA for the initial treatment of soft tissue sarcoma since doxorubicin’s approval more than 40 years ago,” Richard Pazdur, MD, director of the office of hematology and oncology products in the FDA Center for Drug Evaluation and Research and acting director of the FDA Oncology Center of Excellence, said in a statement.
Approval was based on a statistically significant improvement in survival in a randomized trial involving 133 patients with more than 25 different subtypes of metastatic soft tissue sarcoma. Patients received olaratumab (Lartruvo) with doxorubicin or doxorubicin alone. Median survival was 26.5 months for patients who received both drugs, compared with 14.7 months for patients who received doxorubicin alone. Median progression-free survival was 8.2 months for patients who received both drugs and 4.4 months for patients who received doxorubicin alone.
The most common adverse reactions from olaratumab were nausea, fatigue, neutropenia, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, and headache. There are serious risks of infusion-related reactions and embryo-fetal harm, the FDA warned.
Olaratumab was approved under the FDA’s accelerated approval program after receiving fast track designation, breakthrough therapy designation, and a priority review status. The drug also received an orphan drug designation. Drug maker Eli Lilly is currently conducting a larger study of olaratumab across multiple subtypes of soft tissue sarcoma.
[email protected]
On Twitter @nikolaideslaura
Yes, neoadjuvant chemo improves survival in soft tissue sarcomas
COPENHAGEN – Hard data are hard to come by in sarcoma, but interim results from a randomized trial show that combination chemotherapy with an anthracycline and an alkylating agent offers both a relapse-free and overall survival benefit for patients with soft tissue sarcomas of the trunk wall or extremities, compared with histology-driven therapies.
In a study comparing three cycles of a full-dose epirubicin and ifosfamide combination with three cycles of one of five regimens tailored to specific sarcoma subtypes, there was an average absolute benefit in both relapse-free survival (RFS) and overall survival (OS) of approximately 20% with the combination regimen, reported Alessandro Gronchi, MD, chair of sarcoma surgery at the National Cancer Institute of Italy in Milan.
The findings come as a surprise, however, because the trial was originally designed to detect a benefit for the tailored, histology-driven therapies, and is therefore, technically, a failure, Dr. Gronchi said at the European Society for Medical Oncology Congress.
“In a population of soft-tissue sarcoma patients selected by a risk of relapse averaging 60%-70%, the neoadjuvant administration of a short full-dose anthracycline plus ifosfamide chemotherapy increases relapse-free survival of more than 20% and overall survival of at least 10%,” he said.
Chemotherapy in both the neoadjuvant and adjuvant setting for patients with high-risk soft-tissue sarcomas has been controversial, with a wide range of practices worldwide. Some centers administer neoadjuvant chemotherapy and/or radiation, followed by surgery and adjuvant radiation and/or chemotherapy, whereas other centers do not use chemotherapy, either out of concerns about toxicities, or because the evidence supporting the practice has been equivocal.
The best argument in favor of neoadjuvant chemotherapy in this setting until now has been that it can increase the chances of successful surgery (R0 resection), which is associated with longer progression-free survival and better control of both recurrence and distant metastasis, Dr. Gronchi said at a briefing prior to his presentation of the data in a symposium session.
The multicenter trial compared a regimen of epirubicin 120 mg/m2 plus ifosfamide 9 g/m2 (standard combination arm) with one of five different regimens based on the following sarcoma histologies, which comprise approximately 80% of all sarcomas of the trunk wall or extremities:
• Undifferentiated pleomorphic sarcoma (UPS): gemcitabine+docetaxel.
• High grade myxoid liposarcoma: trabectedin (Yondelis).
• Synovial sarcoma: high-dose prolonged-infusion ifosfamide.
• Malignant peripheral nerve sheath tumors (MPNST): etoposide plus ifosfamide.
• Leiomyosarcoma: gemcitabine+dacarbazine in leiomyosarcoma.
All patients had localized, high-risk soft tissue sarcomas defined as grade 3, size greater than 5 cm, and deep tumor site; the median tumor size was 10 cm in each arm.
Following chemotherapy, all resectable patients went on to surgery with or without radiation therapy.
A total of 287 patients, median age 50, were randomized either to the regimen tailored to their tumor type (142 patients), or to the combination (145). A total of 240 patients were evaluable for response.
At a median follow-up of 12.34 months, RFS rates were 62% for patients who received epirubicin-ifosfamide, compared with 38% for those who received tailored therapy, In univariate analysis, the hazard ratio for tailored therapy was 1.955 (P = .007).
Overall survival rates were 89% vs. 64%, respectively (P = .033).
An analysis of responses by RECIST (Response Evaluation Criteria in Solid Tumors) showed that more patients in the standard arm had partial responses (16% vs. 10%). Stable disease rates were comparable, at 81% and 82%, respectively. Fewer patients on the standard arm had disease progression, at 3% vs. 8%. There were no complete responses in either group.
A look at RFS by histology subtype showed that for four of the five tumor types, standard chemotherapy was better. For patients with myxoid round cell liposarcoma, however, trabecdetin was equivalent in efficacy to combination chemotherapy.
“Since the safety profile of trabecdetin is much better, it’s a much better-tolerated drug than combination epirubicin and ifosfamide, we are now aiming to reopen that strata and looking into possibly moving the drug into the first line,” Dr. Gronchi said in an interview.
He recommended that based on these results, ESMO guidelines for soft tissue and visceral sarcoma guidelines should be updated to read as follows (additions or substitution to the existing text shown in italics):
“If the decision is made to use CT as upfront treatment, it may well be used preoperatively. A benefit may be gained when 3 full-dose anthracycline ifosfamide chemotherapy cycles is used as upfront treatment, facilitating surgery. This regimen has ‘proven’ to give a positive impact on RFS/OS in selected high-risk soft-tissue sarcomas of extremity/trunk wall.”
He added that the guidelines should emphasize management of patients with discussion in multidisciplinary tumor boards in specialized or “reference” sarcoma centers or within reference networks sharing multidisciplinary expertise and treating a high number of patients.
Eurosarc funded the study. Dr. Gronchi and Dr. Le Cesne disclosed ties with several companies
COPENHAGEN – Hard data are hard to come by in sarcoma, but interim results from a randomized trial show that combination chemotherapy with an anthracycline and an alkylating agent offers both a relapse-free and overall survival benefit for patients with soft tissue sarcomas of the trunk wall or extremities, compared with histology-driven therapies.
In a study comparing three cycles of a full-dose epirubicin and ifosfamide combination with three cycles of one of five regimens tailored to specific sarcoma subtypes, there was an average absolute benefit in both relapse-free survival (RFS) and overall survival (OS) of approximately 20% with the combination regimen, reported Alessandro Gronchi, MD, chair of sarcoma surgery at the National Cancer Institute of Italy in Milan.
The findings come as a surprise, however, because the trial was originally designed to detect a benefit for the tailored, histology-driven therapies, and is therefore, technically, a failure, Dr. Gronchi said at the European Society for Medical Oncology Congress.
“In a population of soft-tissue sarcoma patients selected by a risk of relapse averaging 60%-70%, the neoadjuvant administration of a short full-dose anthracycline plus ifosfamide chemotherapy increases relapse-free survival of more than 20% and overall survival of at least 10%,” he said.
Chemotherapy in both the neoadjuvant and adjuvant setting for patients with high-risk soft-tissue sarcomas has been controversial, with a wide range of practices worldwide. Some centers administer neoadjuvant chemotherapy and/or radiation, followed by surgery and adjuvant radiation and/or chemotherapy, whereas other centers do not use chemotherapy, either out of concerns about toxicities, or because the evidence supporting the practice has been equivocal.
The best argument in favor of neoadjuvant chemotherapy in this setting until now has been that it can increase the chances of successful surgery (R0 resection), which is associated with longer progression-free survival and better control of both recurrence and distant metastasis, Dr. Gronchi said at a briefing prior to his presentation of the data in a symposium session.
The multicenter trial compared a regimen of epirubicin 120 mg/m2 plus ifosfamide 9 g/m2 (standard combination arm) with one of five different regimens based on the following sarcoma histologies, which comprise approximately 80% of all sarcomas of the trunk wall or extremities:
• Undifferentiated pleomorphic sarcoma (UPS): gemcitabine+docetaxel.
• High grade myxoid liposarcoma: trabectedin (Yondelis).
• Synovial sarcoma: high-dose prolonged-infusion ifosfamide.
• Malignant peripheral nerve sheath tumors (MPNST): etoposide plus ifosfamide.
• Leiomyosarcoma: gemcitabine+dacarbazine in leiomyosarcoma.
All patients had localized, high-risk soft tissue sarcomas defined as grade 3, size greater than 5 cm, and deep tumor site; the median tumor size was 10 cm in each arm.
Following chemotherapy, all resectable patients went on to surgery with or without radiation therapy.
A total of 287 patients, median age 50, were randomized either to the regimen tailored to their tumor type (142 patients), or to the combination (145). A total of 240 patients were evaluable for response.
At a median follow-up of 12.34 months, RFS rates were 62% for patients who received epirubicin-ifosfamide, compared with 38% for those who received tailored therapy, In univariate analysis, the hazard ratio for tailored therapy was 1.955 (P = .007).
Overall survival rates were 89% vs. 64%, respectively (P = .033).
An analysis of responses by RECIST (Response Evaluation Criteria in Solid Tumors) showed that more patients in the standard arm had partial responses (16% vs. 10%). Stable disease rates were comparable, at 81% and 82%, respectively. Fewer patients on the standard arm had disease progression, at 3% vs. 8%. There were no complete responses in either group.
A look at RFS by histology subtype showed that for four of the five tumor types, standard chemotherapy was better. For patients with myxoid round cell liposarcoma, however, trabecdetin was equivalent in efficacy to combination chemotherapy.
“Since the safety profile of trabecdetin is much better, it’s a much better-tolerated drug than combination epirubicin and ifosfamide, we are now aiming to reopen that strata and looking into possibly moving the drug into the first line,” Dr. Gronchi said in an interview.
He recommended that based on these results, ESMO guidelines for soft tissue and visceral sarcoma guidelines should be updated to read as follows (additions or substitution to the existing text shown in italics):
“If the decision is made to use CT as upfront treatment, it may well be used preoperatively. A benefit may be gained when 3 full-dose anthracycline ifosfamide chemotherapy cycles is used as upfront treatment, facilitating surgery. This regimen has ‘proven’ to give a positive impact on RFS/OS in selected high-risk soft-tissue sarcomas of extremity/trunk wall.”
He added that the guidelines should emphasize management of patients with discussion in multidisciplinary tumor boards in specialized or “reference” sarcoma centers or within reference networks sharing multidisciplinary expertise and treating a high number of patients.
Eurosarc funded the study. Dr. Gronchi and Dr. Le Cesne disclosed ties with several companies
COPENHAGEN – Hard data are hard to come by in sarcoma, but interim results from a randomized trial show that combination chemotherapy with an anthracycline and an alkylating agent offers both a relapse-free and overall survival benefit for patients with soft tissue sarcomas of the trunk wall or extremities, compared with histology-driven therapies.
In a study comparing three cycles of a full-dose epirubicin and ifosfamide combination with three cycles of one of five regimens tailored to specific sarcoma subtypes, there was an average absolute benefit in both relapse-free survival (RFS) and overall survival (OS) of approximately 20% with the combination regimen, reported Alessandro Gronchi, MD, chair of sarcoma surgery at the National Cancer Institute of Italy in Milan.
The findings come as a surprise, however, because the trial was originally designed to detect a benefit for the tailored, histology-driven therapies, and is therefore, technically, a failure, Dr. Gronchi said at the European Society for Medical Oncology Congress.
“In a population of soft-tissue sarcoma patients selected by a risk of relapse averaging 60%-70%, the neoadjuvant administration of a short full-dose anthracycline plus ifosfamide chemotherapy increases relapse-free survival of more than 20% and overall survival of at least 10%,” he said.
Chemotherapy in both the neoadjuvant and adjuvant setting for patients with high-risk soft-tissue sarcomas has been controversial, with a wide range of practices worldwide. Some centers administer neoadjuvant chemotherapy and/or radiation, followed by surgery and adjuvant radiation and/or chemotherapy, whereas other centers do not use chemotherapy, either out of concerns about toxicities, or because the evidence supporting the practice has been equivocal.
The best argument in favor of neoadjuvant chemotherapy in this setting until now has been that it can increase the chances of successful surgery (R0 resection), which is associated with longer progression-free survival and better control of both recurrence and distant metastasis, Dr. Gronchi said at a briefing prior to his presentation of the data in a symposium session.
The multicenter trial compared a regimen of epirubicin 120 mg/m2 plus ifosfamide 9 g/m2 (standard combination arm) with one of five different regimens based on the following sarcoma histologies, which comprise approximately 80% of all sarcomas of the trunk wall or extremities:
• Undifferentiated pleomorphic sarcoma (UPS): gemcitabine+docetaxel.
• High grade myxoid liposarcoma: trabectedin (Yondelis).
• Synovial sarcoma: high-dose prolonged-infusion ifosfamide.
• Malignant peripheral nerve sheath tumors (MPNST): etoposide plus ifosfamide.
• Leiomyosarcoma: gemcitabine+dacarbazine in leiomyosarcoma.
All patients had localized, high-risk soft tissue sarcomas defined as grade 3, size greater than 5 cm, and deep tumor site; the median tumor size was 10 cm in each arm.
Following chemotherapy, all resectable patients went on to surgery with or without radiation therapy.
A total of 287 patients, median age 50, were randomized either to the regimen tailored to their tumor type (142 patients), or to the combination (145). A total of 240 patients were evaluable for response.
At a median follow-up of 12.34 months, RFS rates were 62% for patients who received epirubicin-ifosfamide, compared with 38% for those who received tailored therapy, In univariate analysis, the hazard ratio for tailored therapy was 1.955 (P = .007).
Overall survival rates were 89% vs. 64%, respectively (P = .033).
An analysis of responses by RECIST (Response Evaluation Criteria in Solid Tumors) showed that more patients in the standard arm had partial responses (16% vs. 10%). Stable disease rates were comparable, at 81% and 82%, respectively. Fewer patients on the standard arm had disease progression, at 3% vs. 8%. There were no complete responses in either group.
A look at RFS by histology subtype showed that for four of the five tumor types, standard chemotherapy was better. For patients with myxoid round cell liposarcoma, however, trabecdetin was equivalent in efficacy to combination chemotherapy.
“Since the safety profile of trabecdetin is much better, it’s a much better-tolerated drug than combination epirubicin and ifosfamide, we are now aiming to reopen that strata and looking into possibly moving the drug into the first line,” Dr. Gronchi said in an interview.
He recommended that based on these results, ESMO guidelines for soft tissue and visceral sarcoma guidelines should be updated to read as follows (additions or substitution to the existing text shown in italics):
“If the decision is made to use CT as upfront treatment, it may well be used preoperatively. A benefit may be gained when 3 full-dose anthracycline ifosfamide chemotherapy cycles is used as upfront treatment, facilitating surgery. This regimen has ‘proven’ to give a positive impact on RFS/OS in selected high-risk soft-tissue sarcomas of extremity/trunk wall.”
He added that the guidelines should emphasize management of patients with discussion in multidisciplinary tumor boards in specialized or “reference” sarcoma centers or within reference networks sharing multidisciplinary expertise and treating a high number of patients.
Eurosarc funded the study. Dr. Gronchi and Dr. Le Cesne disclosed ties with several companies
Key clinical point: This study provides the first clear randomized evidence for a survival benefit with neoadjuvant chemotherapy in the five most common types of soft-tissue sarcomas of the extremities or trunk wall.
Major finding: Combined epirubicin/ifosfamide was associated with 30% better relapse-free survival and 10% better overall survival compared with histology-tailored therapies.
Data source: Randomized trial of 240 patients with sarcomas of the extremities or trunk wall.
Disclosures: Eurosarc funded the study. Dr. Gronchi and Dr. Le Cesne disclosed ties with several companies.
Database review supports chemoradiation for high-risk sarcomas
BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.
The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.
In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.
“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.
He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.
They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.
They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)
In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.
Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).
Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).
There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.
Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).
Drop the ‘D’ in MAID?
In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.
The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.
To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.
In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.
At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.
The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.
“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
Better Agents Needed
Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.
“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.
Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.
Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”
Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.
BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.
The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.
In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.
“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.
He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.
They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.
They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)
In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.
Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).
Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).
There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.
Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).
Drop the ‘D’ in MAID?
In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.
The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.
To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.
In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.
At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.
The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.
“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
Better Agents Needed
Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.
“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.
Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.
Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”
Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.
BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.
The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.
In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.
“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.
He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.
They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.
They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)
In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.
Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).
Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).
There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.
Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).
Drop the ‘D’ in MAID?
In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.
The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.
To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.
In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.
At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.
The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.
“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
Better Agents Needed
Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.
“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.
Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.
Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”
Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.
Key clinical point: Sarcoma specialists do not agree on whether neoadjuvant or adjuvant chemotherapy adds benefit in patients with high-risk soft-tissue sarcomas.
Major finding: In a cancer database, chemotherapy was associated with 57% 5-year overall survival, compared with 45% with no chemotherapy (P less than .001)
Data source: A National Cancer Database review of 3,840 patients with grade 3 or 4 soft-tissue sarcomas and a retrospective case series of 26 patients with large STS of the extremities or abdominal wall.
Disclosures: The studies were internally supported. The authors, Dr. Baldini and Dr. Chen, reported no relevant disclosures. Dr. Chen is the reporter’s personal radiation oncologist.
Palifosfamide plus doxorubicin does not improve survival in sarcoma
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.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Palifosfamide combined with doxorubicin did not improve survival in metastatic soft tissue sarcoma.
Major finding: The median progression-free survival was 6.0 months for palifosfamide/doxorubicin vs. 5.2 months for doxorubicin plus placebo (HR, 0.86; 95% CI, 0.68-1.08; P = 0.19).
Data source: A phase III randomized trial that included 447 patients with metastatic soft tissue sarcoma.
Disclosures: The study was supported by ZIOPHARM Oncology. Dr. Ryan and several of his coauthors reported multiple relationships with industry.
FDG-PET gives early indication of response to therapy for Ewing sarcoma
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.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: FDG-PET predicted response to Ewing sarcoma therapy significantly earlier than MRI or CT.
Major finding: Day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001).
Data source: Retrospective analysis of data on 76 patients enrolled in the SARC 011 trial.
Disclosures: The study was supported by the Radiological Society of North America; Quantitative Imaging Biomarker Alliance; the Sarcoma Alliance for Research Through Collaboration (SARC), and the National Institutes of Health. Vadim S. Koshkin and three coauthors reported no conflicts of interest. Seven coauthors reported financial relationships with various drug and/or device companies.
Changes in HIV-related cancers reflect changes in HIV patient care
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.
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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.
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.
On Twitter @Alz_Gal
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Kaposi’s sarcoma and non-Hodgkin lymphoma are appearing in older, less- immunosuppressed patients.
Major finding: From 1996-2011, median patient age at diagnosis increased for both Kaposi’s sarcoma (from 37 to 42 years) and non-Hodgkin lymphoma (from 40 to 46 years).
Data source: The database study examined 446 cases of Kaposi’s sarcoma and 258 cases of non-Hodgkin lymphoma.
Disclosures: The National Cancer Institute headed the study; Dr. Yanik had no financial disclosures.
Second malignancy risk higher in patients with fusion-negative sarcoma
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.
FROM CANCER
Trabectedin expands treatment options for some forms of advanced soft tissue sarcoma
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Mining for information, participation in clinical trials
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