Patient-derived xenografts for individualized care in advanced sarcoma.

BACKGROUND: Patients with advanced, metastatic sarcoma have a poor prognosis, and the overall benefit from the few standard-of-care therapeutics available is small. The rarity of this tumor, combined with the wide range of subtypes, leads to difficulties in conducting clinical trials. The authors previously reported the outcome of patients with a variety of common solid tumors who received treatment with drug regimens that were first tested in patient-derived xenografts using a proprietary method ("TumorGrafts"). METHODS: Tumors resected from 29 patients with sarcoma were implanted into immunodeficient mice to identify drug targets and drugs for clinical use. The results of drug sensitivity testing in the TumorGrafts were used to personalize cancer treatment. RESULTS: Of 29 implanted tumors, 22 (76%) successfully engrafted, permitting the identification of treatment regimens for these patients. Although 6 patients died before the completion of TumorGraft testing, a correlation between TumorGraft results and clinical outcome was observed in 13 of 16 (81%) of the remaining individuals. No patients progressed during the TumorGraft-predicted therapy. CONCLUSIONS: The current data support the use of the personalized TumorGraft model as an investigational platform for therapeutic decision-making that can guide treatment for rare tumors such as sarcomas. A randomized phase 3 trial versus physician's choice is warranted.

The flow-metabolic phenotype of primary colorectal cancer: assessment by integrated 18F-FDG PET/perfusion CT with histopathologic correlation.

UNLABELLED: The aim of this study was to assess the in vivo flow-metabolic phenotype in primary colorectal cancer with integrated (18)F-FDG PET/perfusion CT and its relationship to gold standard histopathologic assessment of angiogenesis and hypoxia. METHODS: 45 patients (26 male and 19 female; mean age, 67.6 y) with primary colorectal cancer underwent integrated (18)F-FDG PET/perfusion CT, deriving tumor glucose metabolism (maximum standardized uptake value) and regional blood flow. From this cohort, 35 underwent surgery subsequently, without intervening neoadjuvant treatment, allowing histopathologic correlation with tumor stage, CD105 microvessel density, vascular endothelial growth factor (VEGF), glucose transporter protein 1 (Glut-1), and hypoxia-inducible factor 1 expression. RESULTS: The flow-metabolic ratio was significantly lower for tumors with higher VEGF (3.65 vs. 5.98; P = 0.01) or hypoxia-inducible factor 1 expression (3.63 vs. 5.48; P = 0.04) versus tumors with lower expression. There were significant negative correlations between the tumor flow-metabolic ratio and VEGF expression (r = -0.55, P = 0.0008), indicating that tumors with low blood flow but higher metabolism were associated with higher VEGF expression. Flow and metabolism were coupled in higher-stage (stage III/IV) tumors but not lower-stage tumors (stage I/II) (r = 0.47, P = 0.03, vs. r = 0.09, P = 0.65, respectively. CONCLUSION: Tumors with a low-flow-high-metabolism phenotype demonstrated higher VEGF expression and may reflect a more angiogenic phenotype.

Numb chin syndrome: a nonmetastatic neurological manifestation of malignancy.

Numb chin syndrome, sometimes called numb lip syndrome, is an uncommon but well-recognized symptom in medical oncology. It may be a nonmetastatic neurological manifestation of malignancy, often with no clinically visible pathology. We report a case of a 79-year-old woman with widespread metastatic disease secondary to breast carcinoma who presented with a left-sided numb lip and chin. The patient had no clinical or radiographic pathology within the head and neck region. Numb chin syndrome is almost unknown within the dental and oral and maxillofacial community, despite being well reported in the medical literature. We urge all general dentists, oral medicine specialists, and oral and maxillofacial surgeons to consider metastatic cancer in patients with unexplained facial hypoesthesia.

Survival benefits of lung cancer patients undergoing laser and brachytherapy.

We aimed to compare the duration of survival among subjects receiving brachytherapy (BT) in combination with Nd:YAG laser therapy (LT), and those receiving LT or BT alone. The medical records of subjects who received endobronchial treatment for unresectable tracheobronchial malignancies between January 1997 and December 1999 in a single center were reviewed retrospectively. A total of 80 patients were evaluated. The overall symptomatic response rate after treatment was 86.5%. Median survival durations for the LT, BT, and combined therapy (CT) group were 111, 115, and 264 days, respectively. The survival duration was significantly longer in the CT group than in the BT group (p=0.0078), but the difference was not statistically significant between the CT and the LT group. The bronchoscopic finding of endobronchial polypoid lesion was associated with a longer survival time than extraluminal with compression type (p=0.0023) by univariate analysis. Other factors associated with the better prognosis included hemoglobin > or = 12.5 g/dL, serum albumin level > or = 37 g/L, and BT dose > or = 15 Gy at 1 cm distance. Of these factors, specific bronchoscopic findings, serum albumin level, CT modality, and dose of BT retained statistical significance in multivariate analysis. In conclusion, combined LT and BT is associated with increased patient survival compared with BT alone. Combined therapy may improve survival time in selected patients with endobronchial malignancies.