SUMMARYMetastasis is the primary cause of cancer-related deaths. While The Cancer Genome Atlas (TCGA) has sequenced primary tumor types obtained from surgical resections, much less comprehensive molecular analysis is available from clinically acquired metastatic cancers. Here, we perform whole exome and transcriptome sequencing of 500 adult patients with metastatic solid tumors of diverse lineage and biopsy site. The most prevalent genes somatically altered in metastatic cancer included TP53, CDKN2A, PTEN, PIK3CA, and RB1. Putative pathogenic germline variants were present in 12.2% of cases of which 75% were related to defects in DNA repair. RNA sequencing complemented DNA sequencing for the identification of gene fusions, pathway activation, and immune profiling. Integrative sequence analysis provides a clinically relevant, multi-dimensional view of the complex molecular landscape and microenvironment of metastatic cancers.

No abstract

Chordomas are rare, slowly growing, locally aggressive neoplasms of bone that arise from embryonic remnants of the notochord. These tumors typically occur in the axial skeleton and have a proclivity for the spheno-occipital region of the skull base and sacral regions. In adults, 50% of chordomas involve the sacrococcygeal region, 35% occur at the base of the skull near the spheno-occipital area, and 15% are found in the vertebral column. Craniocervical chordomas most often involve the dorsum sella, clivus, and nasopharynx. Chordomas are divided into conventional, chondroid, and dedifferentiated types. Conventional chordomas are the most common. They are characterized by the absence of cartilaginous or additional mesenchymal components. Chondroid chordomas contain both chordomatous and chondromatous features, and have a predilection for the spheno-occipital region of the skull base. This variant accounts for 5%-15% of all chordomas and up to 33% of cranial chordomas. Dedifferentiation or sarcomatous transformation occurs in 2%-8% of chordomas. This can develop at the onset of the disease or later. Aggressive initial therapy improves overall outcome. Patients who relapse locally have a poor prognosis but both radiation and surgery can be used as salvage therapy. Subtotal resection can result in a stable or improved status in as many as 50% of patients who relapse after primary therapy. Radiation therapy may also salvage some patients with local recurrence. One series reported a 2-year actuarial local control rate of 33% for patients treated with proton beam irradiation. The Oncologist 2007;12:1344 -1350

This combined-modality treatment can be delivered successfully in a multi-institutional setting. Efficacy results are consistent with previous single-institution results.

The NCCN Guidelines for Bone Cancer provide interdisciplinary recommendations for treating chordoma, chondrosarcoma, giant cell tumor of bone, Ewing sarcoma, and osteosarcoma. These NCCN Guidelines Insights summarize the NCCN Bone Cancer Panel's guideline recommendations for treating Ewing sarcoma. The data underlying these treatment recommendations are also discussed.

The significant reduction of late toxicities in patients with extremity STS who were treated with preoperative IGRT and absence of marginal-field recurrences suggest that the target volumes used in the Radiation Therapy Oncology Group RTOG-0630 (A Phase II Trial of Image-Guided Preoperative Radiotherapy for Primary Soft Tissue Sarcomas of the Extremity) study are appropriate for preoperative IGRT for extremity STS.

No abstract

Objectives Expression of strong nuclear STAT6 is thought to be a specific marker for solitary fibrous tumors (SFT). Little is known about subtle expression patterns in other mesenchymal lesions. Methods We performed immunohistochemical studies against the C-terminus of STAT6 in tissue microarrays and whole sections, comprising 2366 mesenchymal lesions. Results Strong nuclear STAT6 was expressed in 285/2021 tumors, including 206/240 SFT, 49/408 well/dedifferentiated liposarcomas, 8/65 unclassified sarcomas, and 14/184 desmoids, among others. Expression in SFT was predominately limited to the nucleus. Other positive tumors typically expressed both nuclear and cytoplasmic STAT6. Complete absence of STAT6 was most common in pleomorphic liposarcoma and alveolar soft part sarcoma (60% and 72% cases negative, respectively). Conclusions Strong nuclear STAT6 is largely specific for SFT. Physiologic low-level cytoplasmic/nuclear expression is common in mesenchymal neoplasia, and is of uncertain significance.