Treatment Outcomes and Sensitivity to Hormone Therapy of Aggressive Angiomyxoma: A Multicenter, International, Retrospective Study.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare, locally aggressive tumor usually arising from pelvis or perineum, with a high local-recurrence rate after complete surgery. Anecdotal responses to hormone therapy have been reported. In the present study we aimed at studying surgical treatment outcomes and sensitivity to hormone therapy of AA. MATERIALS AND METHODS: We conducted a multicenter, international retrospective effort including patients with AA treated at three European referral centers (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy and the Italian Rare Cancer Network; Centre Léon Bérard, Lyon, France; and Hospital Universitario Virgen del Rocio, Seville, Spain). RESULTS: A total of 36 patients were included. Median follow-up was 51.3 months. Thirty-three patients (92%) underwent complete (R0 + R1) surgery, with a local relapse rate of 50% and a median relapse-free survival of 39 months (95% confidence interval [CI], 27-68.1). Thirteen patients received a first-line systemic treatment with hormone therapy for locally advanced disease, with an overall response rate of 62% and a median progression-free survival of 24.6 months (95% CI, 11.0-39.7). In two patients, adding an aromatase inhibitor (AI) on progression to first-line GnRH agonist (GnRHa) resulted in a new tumor response. CONCLUSION: Our findings confirm that in AA, surgical local control may be challenging, with a significant rate of local relapse despite complete surgery. Hormone therapy is an active treatment option, with a potential of disease control and of being combined with surgery. The addition of an AI to first-line GnRHa could be an effective second-line systemic therapy in premenopausal female patients with AA. IMPLICATIONS FOR PRACTICE: In this retrospective effort including 36 patients with aggressive angiomyxoma, local relapse rate after complete surgery was 50%, with a median relapse-free survival of 39 months, confirming that local control is challenging. Overall response rate to first-line hormone therapy was 62%, with a median progression-free survival of 24.6 months. Thus, hormone therapy has a potential of disease control and of being combined with surgery.

Sirolimus in Advanced Epithelioid Hemangioendothelioma: A Retrospective Case-Series Analysis from the Italian Rare Cancer Network Database.

BACKGROUND: The aim of this study was to report on sirolimus activity in a series of patients with hemangioendothelioma (HE) treated at the National Cancer Institute, Milan (Istituto Nazionale Tumori; INT) and within the Italian Rare Cancer Network ("Rete Tumori Rari"; RTR). METHODS: We retrospectively reviewed patients with advanced and progressing epithelioid hemangioendothelioma (EHE) treated with sirolimus at the INT and/or within the RTR. Pathologic review and molecular analysis for WWTR1 rearrangement were performed. Sirolimus was administered until unacceptable toxicity or progression, with the dose being adjusted to reach target plasma levels of 15-20 ng/dL. Responses were assessed using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RESULTS: Since 2005, 18 patients (17 EHE, 1 retiform HE; 1 locally advanced, 17 metastatic; WWTR1 rearrangement: 16) have been identified, with 17/18 patients being evaluable for response. Mean sirolimus daily dose was 4.5 mg. According to RECIST, best responses in EHE were 1 partial response (PR), 12 stable disease (SD), and 3 progressive disease (PD); the patient with retiform HE also achieved a PR, lasting >2 years. Four patients with a reversed interval progression on interruption were observed. Median overall survival was 16 months, and median progression-free survival was 12 months (range 1-45), with four patients progression-free at 24 months. The clinical benefit (complete response [CR] + PR + SD >6 months) was 56 %. Seven patients receiving sirolimus experienced an increase in pleural/peritoneal effusion plus worsening of tumor-related symptoms; six of these patients died within 1-8 months from evidence of effusion progression, while a RECIST PD was assessed in two of seven patients. CONCLUSIONS: A clinical benefit was achieved in 56 % of patients receiving sirolimus, which lasted >24 months in four patients. Most patients with pleural effusion did not benefit from sirolimus and had a poor outcome.

Systemic therapy for selected skull base sarcomas: Chondrosarcoma, chordoma, giant cell tumour and solitary fibrous tumour/hemangiopericytoma.

This review highlights the data currently available on the activity of systemic therapy in chondrosarcoma, chordoma, giant cell tumour of the bone (GCTB) and solitary fibrous tumour, i.e., four rare sarcomas amongst mesenchymal malignancy arising from the skull base.

Medical treatment of advanced chordomas.

Chordoma is a very rare bone sarcoma that can arise from any site along the spine and from the skull base. En bloc resection is the gold standard for treatment while radiation therapy has been shown to provide both curative and palliative benefit. Unfortunately, local recurrences are common, even after a complete surgical resection, and up to 40% of patients suffer from distant metastases, while salvage treatments are challenging. Patients carrying an advanced disease need a systemic treatment. Unluckily, conventional chordoma are insensitive to cytotoxic chemotherapy that is considered the standard treatment option in patients with metastatic sarcoma. In the last decade, innovative therapies have been introduced, positively impacting disease control and patients' quality of life. In addition, a better understanding of the molecular characteristics of chordoma allowed to detect new potential targets. This review is focused on the pharmacological management of patients affected by an advanced disease, starting with a summary of data available on conventional chemotherapy, then moving to a deeper analysis of available data on molecular agents and immunotherapy, and finally providing an update on ongoing clinical trials and future prospective.

Activity of anthracycline- and ifosfamide-based chemotherapy in a series of patients affected by advanced myxofibrosarcoma.

BACKGROUND: We report on the activity of anthracycline-based and high-dose prolonged-infusion ifosfamide chemotherapy in a retrospective series of patients affected by advanced myxofibrosarcoma treated at Istituto Nazionale Tumori in Milan, Italy, and within the Italian Rare Cancer Network (RTR). METHODS: Advanced myxofibrosarcoma patients treated with anthracycline + ifosfamide and high-dose prolonged-infusion ifosfamide as a single agent from November 2001 to December 2016 were retrospectively reviewed. All pathological diagnosis were centrally reviewed by at least two expert pathologists. Response was evaluated by RECIST, and survival functions were computed. RESULTS: Among 34 advanced myxofibrosarcoma patients, 13 were treated with front-line anthracycline + ifosfamide chemotherapy (male/female = 6/7, median age 54 years, range 33-72). Overall best response was: 4 partial responses, 3 stable diseases and 6 progressive diseases, with a median progression-free survival of 4 months. Twenty-eight patients received second/further line high-dose prolonged-infusion ifosfamide (male/female = 17/11, median age 55 years, range 27-75 years). We observed 10 partial responses, 4 stable diseases and 14 progressive diseases, with a median progression-free survival of 4 months. Median overall survival was 12 months. CONCLUSIONS: This retrospective analysis suggests that the combination of anthracyclines and ifosfamide is active in myxofibrosarcoma. In patients already treated with a combination of anthracyclines and ifosfamide, high-dose prolonged-infusion ifosfamide showed activity as well.

High-Dose Ifosfamide Chemotherapy in a Series of Patients Affected by Myxoid Liposarcoma.

BACKGROUND: To report on the activity of high-dose prolonged-infusion ifosfamide (HDIFX) chemotherapy in a retrospective series of patients affected by myxoid liposarcoma treated at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. PATIENTS AND METHODS: Patients with an advanced myxoid liposarcoma treated with HDIFX (14 g/sqm, i.v., prolonged infusion of 14 days every 28 days) as a single agent between May 2002 and April 2017 were retrospectively reviewed. All pathologic diagnoses were centrally reviewed and molecularly confirmed. Response was evaluated by RECIST, and survival functions were computed by the Kaplan-Meier method. RESULTS: Eleven patients with advanced myxoid liposarcoma were treated with HDIFX (male/female = 9/2, median age 33 years, range 31-75). Among these, 1/11 received HDIFX in first line, 5/11 in second line, 3/11 in third line, and 2/11 in fourth line for a median course number of 3 (range 2-7). No RECIST objective responses were observed. Overall median progression-free survival was 1,9 months. Median overall survival was 37 months. At a median follow-up of 115 months, 1 patient is alive. CONCLUSIONS: In this series of patients affected by advanced myxoid liposarcoma, chemotherapy with HDIFX was essentially inactive.

Response to isolated limb perfusion and chemotherapy with epirubicin plus ifosfamide in a metastatic malignant ossifying fibromyxoid tumor.

BACKGROUND: Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain lineage and intermediate biological potential. It is more common in middle-aged men, usually arising from the deep tissues of the extremities. It is now established that it is a translocation related tumor, most often marked by translocation of PHF1 gene. Surgery is the mainstay of treatment and proves usually curative, although, in rarer cases the disease shows malignant features and tendency to recur both locally and at distant sites. In such cases, no standard treatment exists. CASE PRESENTATION: We report on a case of malignant advanced OFMT of the hand with lung metastases responding to isolated limb perfusion with human recombinant tumor necrosis factor and melphalan and chemotherapy with epirubicin and ifosfamide. CONCLUSIONS: To our knowledge, this is the first report of activity of soft tissue sarcoma-oriented chemotherapy in advanced OFMT.

Solitary fibrous tumour presenting with a single bone metastasis: report of six cases and literature review.

BACKGROUND: Solitary fibrous tumour (SFT) is a rare soft tissue sarcoma with a low metastatic potential. A higher metastatic rate is observed in the high-grade/dedifferentiated variant. The most common expected site of distant spread are the lungs and the liver. Bone involvement is generally viewed as a late stage of disease spread. We report on a retrospective series of SFT patients relapsing with a single distant bone recurrence as first metastatic event, without evidence of other organ involvement. CASE PRESENTATION: All patients affected by a single distant bone metastasis from SFT as first distant event, without any evidence of other site of metastasis, observed at our Institution, were considered. Bone involvement from SFT was pathologically assessed in all cases and confirmed by expert pathologists. A total of six patients were retrospectively identified. Primary tumour arose from the meninges in four patients, from soft tissues in two. Bone metastases were located to the vertebrae, the hip, the acetabulum and the rib. In all cases, bone relapse was the first event, with one patient presenting a local relapse. Median time from the primary tumour and the evidence of bone relapse was 40 months (range 0-58). In 2/6 patients bone metastasis was treated with radiotherapy (RT), in 2/6 with surgery, in 2/6 with surgery plus RT. At a median follow-up of 55 months (range 23-88), 5/6 patients are alive (2/5 without disease, 3/5 with multicentric metastatic disease) and one is dead of disease. 2/6 patients did not relapse after the treatment of the bone metastasis. CONCLUSIONS: This small series in a relatively rare histology suggests that isolated, possibly late, bone metastases are a plausible scenario, in particular in meningeal SFT. Notably, new bone lesions in a patient with a history of SFT should be always investigated. Exclusive local treatments may be an option, though collection of such series would be needed to define the best treatment strategy.