Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer.

Purpose: Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have poor prognosis. We report efficacy and safety of sacituzumab govitecan (SG), a trophoblast cell-surface antigen 2 (Trop-2)-directed antibody-drug conjugate, in patients with advanced EC.

Methods: TROPiCS-03 (ClinicalTrials.

Results of a Randomized, Double-Blinded, Placebo-Controlled, Phase 2.5 Study of Saracatinib (AZD0530), in Patients with Recurrent Osteosarcoma Localized to the Lung.

Purpose: Osteosarcoma is a rare cancer and a third of patients who have completed primary treatment will develop osteosarcoma recurrence. The Src pathway has been implicated in the metastatic behavior of osteosarcoma; about 95% of samples examined express Src or have evidence of downstream activation of this pathway. Saracatinib (AZD0530) is a potent and selective Src kinase inhibitor that was evaluated in adults in Phase 1 studies.

Phase 1 study of oral abexinostat, a histone deacetylase inhibitor, in combination with doxorubicin in patients with metastatic sarcoma.

Background: It has been demonstrated that several inhibitors of histone deacetylase (HDAC) can enhance chemotherapy-induced apoptosis and reduce sarcoma tumor volume in preclinical models. The authors sought to determine the maximum tolerated dose, pharmacokinetics/pharmacodynamics, safety, and toxicity of the HDAC inhibitor abexinostat (PCI-24781) when administered with doxorubicin to patients with metastatic sarcomas.

Methods: Participants were enrolled in a standard, phase 1, 3 + 3, dose-escalation study design.

Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy.

Background: Preclinical studies have documented antitumor activity of PARP inhibition both in vitro and in vivo, against Ewing sarcoma cells. This study aimed to translate that observation into a clinical trial to assess the efficacy and tolerability of olaparib, a PARP inhibitor, in patients with advanced Ewing sarcoma (EWS) progressing after prior chemotherapy.

Methods: In this nonrandomized phase II trial, adult participants with radiographically measureable metastatic EWS received olaparib tablets, 400 mg orally twice daily, until disease progression or drug intolerance.

Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

Purpose: TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability.

Patients And Methods: In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle.

An assessment of risk factors associated with ifosfamide-induced encephalopathy in a large academic cancer center.

Purpose: Ifosfamide-induced encephalopathy is a neurotoxic adverse effect of ifosfamide chemotherapy. The objective of this study was to determine the incidence of encephalopathy in patients with lymphoma and sarcoma receiving ifosfamide chemotherapy and assess for potential risk factors that influence the incidence of encephalopathy.

Methods: A retrospective study of sarcoma and lymphoma patients receiving ifosfamide chemotherapy was performed at the participating institutions.

Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors.

Background: Advanced uterine leiomyosarcoma (ULMS) is an incurable disease. A significant percentage of cases of ULMS express estrogen and/or progesterone receptors (ER and/or PR). To the authors' knowledge, the role of estrogen suppression in disease management is not known.

Bone cancer.

Primary bone cancers are extremely rare neoplasms, accounting for fewer than 0.2% of all cancers. The evaluation and treatment of patients with bone cancers requires a multidisciplinary team of physicians, including musculoskeletal, medical, and radiation oncologists, and surgeons and radiologists with demonstrated expertise in the management of these tumors.

Cutaneous radiation-associated angiosarcoma of the breast: poor prognosis in a rare secondary malignancy.

Background: Cutaneous radiation-associated angiosarcoma of the breast (CRAASBr) is a rare complication of radiation therapy (RT) administered for primary breast cancer treatment. Although case series have provided clinical and histological descriptions of this disease, to our knowledge, none have identified trends in presentation and treatments that may contribute to outcomes.

Methods: Demographic, clinical, histopathologic, and outcomes data for all patients presenting with CRAASBr for treatment or consultation at our institution from 1987 to 2009 were reviewed.

Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial.

Purpose: Metastatic GI stromal tumor (GIST) is a life-threatening disease with no therapy of proven efficacy after failure of imatinib and sunitinib. Regorafenib is a structurally unique inhibitor of multiple cancer-associated kinases, including KIT and platelet-derived growth factor receptor (PDGFR), with broad-spectrum anticancer activity in preclinical and early-phase trials. Because KIT and PDGFR-α remain drivers of GIST after resistance to imatinib and sunitinib, we performed a multicenter single-stage phase II trial of regorafenib in patients with advanced GIST after failure of at least imatinib and sunitinib.

Cardiac angiosarcoma management and outcomes: 20-year single-institution experience.

Purpose: To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS).

Methods: This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed.

Extraskeletal osteosarcoma: spectrum of imaging findings.

Objective: The purpose of this article is to present the spectrum of imaging findings of primary and metastatic extraskeletal osteosarcoma and highlight the differences from primary osteogenic osteosarcoma in bone.

Conclusion: Extraskeletal osteosarcoma is a rare mesenchymal malignancy of soft tissue, histologically indistinguishable from primary osteosarcoma of bone. However, there are distinct differences in demographics, imaging features, prognosis, and management compared with osteogenic osteosarcoma.

A to Z of desmoid tumors.

Objective: The purpose of this article is to illustrate the common locations of desmoid tumors (deep fibromatosis), complications of intra- and extraabdominal desmoids, and treatment-related changes in their imaging appearance.

Conclusion: Desmoids are locally aggressive fibrous tumors with a tendency to recur. Desmoids can be intraabdominal, in the abdominal wall, or extraabdominal.

Clinical presentation and management of mTOR inhibitor-associated stomatitis.

Anti-cancer agents that inhibit the mTOR pathway are associated with a number of unique toxicities, with one of the most significant and potentially dose-limiting being stomatitis. The objective of this study was to report the clinical features and management outcomes of a series of cancer patients who developed painful mTOR inhibitor-associated stomatitis (mIAS). Seventeen cancer patients developed mIAS while being treated with everolimus- or ridaforolimus-containing protocols at the Dana-Farber Cancer Institute and were referred to the oral medicine clinic for evaluation and management.

Imaging of radiation-associated sarcoma.

Objective: The objective of this article is to show the imaging features of radiation-associated sarcoma arising after radiation therapy using multiple imaging modalities.

Conclusion: A multimodality imaging strategy and collaboration between multidisciplinary teams are important for the management of radiation-associated sarcoma. Because radiation-associated sarcoma often displays locally aggressive behavior and may metastasize, resulting in a poor prognosis, it is important to consider this diagnosis in any patient previously treated with radiation therapy and to recognize the imaging findings.

PML expression in soft tissue sarcoma: prognostic and predictive value in alkylating agents/antracycline-based first line therapy.

Soft tissue sarcomas are aggressive tumors representing <1% of all adult neoplasms. Aim of our study was to evaluate promyelocytic leukemia gene expression value as prognostic factor and as a factor predicting response to alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected.

A phase I study of the safety and pharmacokinetics of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

Purpose: The purpose of this study was to determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), safety, pharmacokinetics and preliminary activity of TH-302, a hypoxia-activated prodrug, in combination with doxorubicin in patients with advanced soft tissue sarcoma.

Patients And Methods: TH-302 was administered intravenously on days 1 and 8 and doxorubicin 75 mg/m² on day 1 (2 h after TH-302) of every 3-week cycle. TH-302 starting dose was 240 mg/m² with a classic 3 + 3 dose escalation.

Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors.

Purpose: Preclinical models demonstrate synergistic antitumor activity with combination blockade of mTOR and IGF-1R signaling. We aimed to determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of figitumumab, a fully human IgG(2) anti-insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody (Pfizer) and the mTOR inhibitor, everolimus (Novartis). Pharmacokinetics and preliminary antitumor effects of the combination were evaluated.

The neuroblastoma-associated F1174L ALK mutation causes resistance to an ALK kinase inhibitor in ALK-translocated cancers.

The ALK kinase inhibitor crizotinib (PF-02341066) is clinically effective in patients with ALK-translocated cancers, but its efficacy will ultimately be limited by acquired drug resistance. Here we report the identification of a secondary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory myofibroblastic tumor (IMT) harboring a RANBP2-ALK translocation who progressed while on crizotinib therapy. When present in cis with an ALK translocation, this mutation (also detected in neuroblastomas) causes an increase in ALK phosphorylation, cell growth, and downstream signaling.

Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation.

Primary extragastrointestinal stromal tumor of the pleura: report of a unique case with genetic confirmation.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the tubular gastrointestinal tract, usually originate in the wall of the stomach or small intestine. Most GISTs harbor oncogenic mutations in either the KIT or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinase receptor genes and show differentiation along the lines of the interstitial cells of Cajal. Rarely, GISTs arise primarily in the omentum, mesentery, or retroperitoneum, at which sites they are referred to as "extragastrointestinal stromal tumors" (EGISTs).

Management of adult soft-tissue sarcoma of the extremities and trunk.

Soft-tissue sarcomas are a heterogeneous group of tumors consisting of approximately 100 distinct diagnoses. Management requires a multimodality approach with the input of pathologists, surgeons, radiation oncologists, medical oncologists and radiologists. In localized disease, the primary modality of treatment is wide-resection surgery, and the use of radiation therapy has improved local control rates for high-grade tumors.

Cytoreductive surgery in patients with metastatic gastrointestinal stromal tumor treated with sunitinib malate.

Background: In patients with metastatic gastrointestinal stromal tumor (GIST) on first-line imatinib (IM) undergoing cytoreductive surgery, response to IM at time of surgery correlates with completeness of resection and progression-free and overall survival (PFS, OS). Impact of surgery in IM-resistant patients on second-line sunitinib (SU) is unknown.

Methods: Patients on SU undergoing surgery for metastatic GIST at our institution were reviewed.

[F-18]-fluorodeoxy-D-glucose-positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults.

Background: Response to neoadjuvant chemotherapy is 1 of the most powerful prognostic factors for extremity osteosarcoma. [F-18]-fluorodeoxy-D-glucose-positron emission tomography (FDG-PET) is a noninvasive imaging modality that is used to predict histopathologic response. To determine the prognostic value of FDG-PET response for progression-free survival (PFS) in osteosarcoma, the authors of this report reviewed the University of Washington Medical Center experience.

Multicenter phase II trial of sunitinib in the treatment of nongastrointestinal stromal tumor sarcomas.

PURPOSE To evaluate the potential benefit of continuous daily dosing sunitinib in patients with advanced nongastrointestinal stromal tumor (GIST) sarcomas. PATIENTS AND METHODS A total of 53 patients with advanced non-GIST soft tissue sarcomas received sunitinib 37.5 mg daily.