Despite improvements in early detection and treatment, cancer remains a major cause of mortality. Death from cancer is largely due to metastasis, which results in spreading of tumor cells to other parts of the body. The metastatic process is poorly understood, is often unpredictable, and usually results in incurable disease. There are no therapies specifically designed to target metastases or to block the metastatic process. Development and pre-clinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically reproduce human tumor growth and metastatic progression. Here, we report development of novel models for breast tumor growth and metastasis, which exist in the form of transplantable tumors derived directly from patients. These tumor grafts not only represent the diversity of human breast cancer, but also maintain essential features of the original patients’ tumors, including histopathology, clinical markers, hormone responsiveness, and metastasis to specific sites. Genomic features, such as gene expression profiles and DNA copy number variants, are also well maintained between the original specimens and the tumor grafts. We found that co-engraftment of primary human mesenchymal stem cells with tumor grafts helps to maintain the phenotypic stability of the tumors, and increases tumor growth by promoting angiogenesis and reducing necrosis. Remarkably, tumor engraftment is also a prognostic indicator of disease outcome: newly diagnosed women whose primary breast tumor successfully engrafted in mouse mammary glands had significantly reduced survival compared to patients whose tumors did not engraft. Thus, orthotopic breast tumor grafting marks a first step toward personalized medicine by replicating the diversity of human breast cancer through patient-centric models for tumor growth, metastasis, drug efficacy, and prognosis.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

Background High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aiming to improve outcomes of this rare disease by facilitating randomised controlled trials. Methods Patients eligible for EURAMOS-1 were aged ≤40 years with M0 or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients. Results For all registered patients at a median follow-up of 54 months (interquartile range: 38–73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval [CI]: 57–61%) and 54% (95% CI: 52–56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio [HR] = 2.34, 95% CI: 1.95–2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38–2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10–2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33–0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52–0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77–81%) and 71% (95% CI: 68–73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76–2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. Conclusions In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.