Characterization of a novel radiation-induced sarcoma cell line.

BACKGROUND: Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. METHODS: We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. RESULTS: Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. CONCLUSION: Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS.

Radiation-induced sarcoma of the breast: a systematic review.

INTRODUCTION: Radiation-induced sarcoma (RIS) is a rare, aggressive malignancy. Breast cancer survivors treated with radiotherapy constitute a large fraction of RIS patients. To evaluate evidenced-based practices for RIS treatment, we performed a systematic review of the published English-language literature. METHODS: We performed a systematic keyword search of PubMed for original research articles pertaining to RIS of the breast. We classified and evaluated the articles based on hierarchical levels of scientific evidence. RESULTS: We identified 124 original articles available for analysis, which included 1,831 patients. No randomized controlled trials involving RIS patients were found. We present the best available evidence for the etiology, comparative biology to primary sarcoma, prognostic factors, and treatment options for RIS of the breast. CONCLUSION: Although the evidence to guide clinical practice is limited to single institutional cohort studies, registry studies, case-control studies, and case reports, we applied the available evidence to address clinically relevant questions related to best practice in patient management. Surgery with widely negative margins remains the primary treatment of RIS. Unfortunately, the role of adjuvant and neoadjuvant chemotherapy remains uncertain. This systematic review highlights the need for additional well-designed studies to inform the management of RIS.

Randomized phase II study of cetuximab and bevacizumab in combination with two regimens of paclitaxel and carboplatin in chemonaive patients with stage IIIB/IV non-small-cell lung cancer.

INTRODUCTION: We conducted a phase II study of dual-agent monoclonal antibody therapy consisting of cetuximab and bevacizumab in combination with paclitaxel and carboplatin chemotherapy in non-small-cell lung cancer. METHODS: Patients with stage IIIB/IV nonsquamous non-small-cell lung cancer randomly received cetuximab (400 mg/m initially, 250 mg/m weekly thereafter) plus bevacizumab (15 mg/kg) for six cycles combined with paclitaxel (200 mg/m) and carboplatin (area under the curve 6) for either six cycles (six-cycle arm) or the first three cycles (three-cycle arm) (one cycle = 3 weeks). The primary objective was progression-free survival (PFS), estimated separately for each treatment arm. RESULTS: In 121 patients, the median PFS was 6.05 months (95% confidence interval [CI]: 5.65, 7.03) in the six-cycle arm and 4.50 months (95% CI: 4.01, 5.42) in the three-cycle arm. Respective median overall survival times were 12.06 months (95% CI: 9.40, 19.25) and 11.63 months (95% CI: 6.64, 17.61). The tumor response rate was 51.7% (95% CI: 39.0%, 64.3%) and 44.3% (95% CI: 31.8%, 56.7%) in the six-cycle and three-cycle arms, respectively, with corresponding median response durations of 4.86 months (95% CI: 4.30, 7.16) and 3.94 months (95% CI: 2.92, 4.47). Quality of life was consistent across arms. Cetuximab-related grade 3/4 events in greater than 5% of patients (six-cycle arm, three-cycle arm) were dermatitis acneiform (6.9%; 8.6%) and fatigue (13.8%; 5.2%). Three patients died during the study from drug-related adverse events (one in the six-cycle arm and two in the three-cycle arm). CONCLUSIONS: Both the regimens showed expected PFS and numerically comparable overall survival. Quality of life was similar in the two arms, and both the regimens were well tolerated.