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Purpose. Practice patterns for treatment of localized adult pleomorphic rhabdomyosarcoma (PRMS) remain quite variable given its rarity. Current national guidelines recommend management similar to that of other high-grade soft tissue sarcomas (STS), which include surgery with perioperative radiation (RT) with or without chemotherapy. Using the National Cancer Database (NCDB), we assessed practice patterns and overall outcomes of patients with localized PRMS. Patients and Methods. Patients with stage II/III PRMS treated with surgical resection from 2004 to 2015 were identified from the NCDB. Predictors of RT and chemotherapy use were assessed using multivariable logistic regression analysis. The association of radiation and chemotherapy status on overall survival was assessed using Kaplan–Meier and Cox proportional hazards analyses. Results. Of 243 total patients, RT and chemotherapy were not uniformly utilized, with 44% receiving chemotherapy and in those who did not undergo amputation 62% receiving RT. In those who did not undergo amputation, RT was associated with improved survival on both univariate (HR: 0.49, 95% CI 0.32–0.73, P < 0.001 ) and multivariate analysis (HR: 0.40, 95% CI 0.26–0.62, P < 0.001 ), corresponding to greater 5-year overall survival (59% vs. 38%, P < 0.001 ). Chemotherapy was associated with a higher rate of 5-year overall survival (63% vs. 39%, P < 0.001 ). However, the survival benefit of chemotherapy did not reach statistical significance on multivariate analysis (HR: 0.65, 95% CI 0.41–1.03, P = 0.064 ). Notable predictors of omission of RT included female gender (OR: 0.40, 95% CI 0.22–0.74, P < 0.01 ) and age ≥ 70 (OR: 0.55, 95% CI 0.30–1.00, P = 0.05 ). Correspondingly, factors associated with omission of chemotherapy included age ≥70 (OR: 0.17, 95% CI 0.08–0.39, P < 0.001 ). Conclusions. A significant proportion of patients with localized adult PRMS are not receiving RT. Likewise, use of chemotherapy was heterogeneous. Our findings note potential benefits and underutilization of RT, for which further investigation is warranted.

Background. Patients with recurrent synovial sarcomas have few options for systemic therapy. Since they express large amounts of endogenous CT (cancer testis) antigens such as NY-ESO-1, we investigated the clinical activity of single agent anti-CTLA4 antibody ipilimumab in patients with advanced or metastatic synovial sarcoma.Methods. A Simon two-stage phase II design was used to determine if there was sufficient activity to pursue further. The primary endpoint was tumor response rate by RECIST 1.0. Patients were treated with ipilimumab 3 mg/kg intravenously every 3 weeks for three cycles and then restaged. Retreatment was possible for patients receiving an extra three-week break from therapy. Sera and peripheral blood mononuclear cells were collected before and during therapy to assess NY-ESO-1-specific immunity.Results. Six patients were enrolled and received 1–3 cycles of ipilimumab. All patients showed clinical or radiological evidence of disease progression after no more than three cycles of therapy, for a RECIST response rate of 0%. The study was stopped for slow accrual, lack of activity, and lack of immune response. There was no evidence of clinically significant either serologic or delayed type hypersensitivity responses to NY-ESO-1 before or after therapy.Conclusion. Despite high expression of CT antigens by synovial sarcomas of patients treated in this study, there was neither clinical benefit nor evidence of anti-CT antigen serological responses. Assessment of the ability of synovial sarcoma cell lines to present cancer-germ cell antigens may be useful in determining the reason for the observed lack of immunological or clinical activity.

Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sarcoma. This study tested the hypothesis that outcomes would be improved by addition of bevacizumab (B). The initial design was randomized double-blind trial of G + D + B versus G + D + placebo. Due to slow accrual this was modified to single-arm open-label G + D + B. Eligible patients had diagnosis of leiomyosarcoma, pleomorphic undifferentiated sarcoma, pleomorphic liposarcoma, or angiosarcoma. Treatment was B 15 mg/kg on d1, G 900 mg/m2 on d1 and d8, and D 75 mg/m2 on d8, q21d. Primary endpoint was progression-free survival (PFS) at 6 months and would be met if ≥17 patients were progression-free at 6 m. Secondary endpoints are response rate, PFS at 3 m, overall survival, and toxicity. Of 44 patients enrolled, 35 were treated with GDB and evaluable for safety and efficacy. Median age was 55, 50% male, most ECOG 0. Toxicity is mostly myelosuppression with one deep vein thrombosis and one small bowel perforation possibly related to B. There were 17 partial responses (49%) by RECIST 1.1. Among 35 patients, the number who remained on study and progression-free was 24 at 3 m and 15 at 6 m. 9 withdrew prior to 6 m for reasons other than toxicity or progression. PFS at 6 m was 65% (95% CI: 51–85%). The primary endpoint of 6 m PFS was not met due to censoring of patients who withdrew. However PFS at 3 m (76%) was promising and response rate was higher than expected from G + D.

Objectives. To report the prevalence of consumptive coagulopathy in angiosarcoma patients seen at a single center.Methods. We retrospectively reviewed case records of 42 patients diagnosed with angiosarcoma at Mount Sinai Hospital between 2000 and 2013.Results. Seven patients (17%) met clinical criteria for disseminated intravascular coagulation (DIC) in absence of concomitant clinical states known to cause coagulopathy or myelosuppression. In all patients who received systemic antineoplastic therapy with resultant disease response or stability, DIC resolved in tandem with clinical improvement. DIC recurred at time of disease progression in all cases. Two patients had bulky disease, defined as diameter of largest single or contiguous tumor mass measuring 5 cm or more. All patients demonstrated an aggressive clinical course with short duration of disease control and demise within 1 year. In contrast, evaluation over the same period of 17 epithelioid hemangioendothelioma patients serving as a clinical control group revealed no evidence of DIC.Conclusion. Angiosarcomas can be associated with a consumptive coagulopathy arising in tandem with disease activity. Vigilance for this complication will be needed in the course of often aggressive multimodality therapy. The potential utility of coagulopathy as a prognostic biomarker will need to be explored in future studies.

Background. Pharmacokinetic data on clearance of ifosfamide in hemodialysis patients are limited. Consequently, these patients are excluded from therapy with this agent. We review the outcomes for patients at our institution with end stage renal disease on dialysis who received ifosfamide for metastatic sarcoma.Patients and Methods. We treated three patients with end stage renal disease on hemodialysis with escalating doses of ifosfamide. Data on radiographic response to therapy, WBC and platelet counts, signs or symptoms of infection, neuropathy and bladder toxicity are reported. Starting doses of ifosfamide were based on review of the literature available with subsequent modifications based on each patient's prior exposure to myelosuppressive agents and on symptoms of neurotoxicity and the degree of myelosuppression following each cycle of chemotherapy.Results. Myelosuppression was the most common side effect from therapy, but no patient developed a life threatening infection, neurotoxicity, or hematuria. One patient developed epistaxis in the setting of thrombocytopenia while on warfarin therapy. All patients had clinical evidence for therapeutic response and two had documented radiographic improvement following ifosfamide administration.Conclusion. Ifosfamide can be used safely in combination with hemodialysis in patients with end stage renal disease.

Background. Epstein-Barr virus (EBV)-related smooth muscle neoplasms (SMNs) have been associated with immune dysregulation, most notably in patients who have undergone solid organ transplantation or in patients with HIV/AIDS.Objective. to report our experience with EBV-related neoplasms as well as describing the first EBV-related SMN in the setting of administration of glucocorticoids and the tumor necrosis factor inhibitor etanercept.Design. We have case reports, of minimum 3-year follow-up, 2002–2005.Setting. It was held in an academic and tertiary referral cancer center.Patients. Patients are with dysregulated immunity after solid organ transplantation, HIV/AIDS, or with psoriasis after treatment with etanercept.Interventions. There were discontinuation of etanercept, right hepatic trisegmentectomy, and chemotherapy.Measurements. We use survival as a measurement here.Results. Patients who were able to withstand reduction in immunosuppression survived. Surgical resection or chemotherapy was successful in delaying progression of disease.Limitations. There was a relatively short follow-up for these slow-growing neoplasms.Conclusion. EBV-related SMNs have variable aggressiveness. While chemotherapy may slow disease progression, resection and improving the host immune status provide the best opportunity for primary tumor control.

Introduction. The role of vinorelbine in specific soft tissue sarcoma subtypes is unclear. We present retrospective single institution experience with single-agent vinorelbine in subjects with metastatic soft tissue malignancies.Methods. Fifty-eight patients were treated with single agent intravenous vinorelbine between April 1997 and December 2004. Doxorubicin had been administered previously to 53 subjects (91%), and the median number of lines of previous chemotherapy was 3 (range 0–7).Results. Patients received a median 6 doses of vinorelbine (range 1–65). The overall response rate was 6%(3 patients: 1 angiosarcoma, 1 epithelioid sarcoma, and 1 embryonal rhabdomyosarcoma). Fourteen patients (26%) experienced a best result of stable disease. Median time to progression was 1.8 months (95%confidence intervals 1.5–2.1 months, Kaplan-Meier estimate). Eight patients experienced grade 3 or 4 toxicity, most commonly febrile neutropenia.Conclusion. Vinorelbine demonstrates limited activity in a heavily pretreated group of soft-tissue sarcoma patients. Prospective investigation may be considered for selected sarcoma subtypes.