Background Lung cancer is the leading cancer cause of mortality worldwide; large-scale trials have failed to improve clinical outcomes of patients with chemorefractory non-small-cell lung cancer (NSCLC). Methods Following an initial equal randomization period, BATTLE adaptively randomized patients with chemorefractory NSCLC to erlotinib, vandetanib, erlotinib plus bexarotene, or sorafenib based on molecular biomarkers of NSCLC pathogenesis in fresh core needle biopsy specimens. The primary end point was disease control rate (DCR) at 8 weeks. Results Of 255 patients randomly assigned to erlotinib (59 patients), vandetanib (54), erlotinib plus bexarotene (37), and sorafenib (105), 244 were eligible for the DCR analysis. Pneumothorax after lung biopsy occurred in 11.5% and treatment-related toxicities grade 3–4 in 6.5% of patients. Overall results were a 46% 8-week DCR, 1.9-month median progression-free survival, 9-month median overall survival, and 35% 1-year survival. Individual markers predicting a significantly superior DCR for a treatment included: epidermal growth factor receptor (EGFR) mutation (P=0.04) for erlotinib; cyclin D1 positivity (P=0.01) or EGFR amplification (P=0.006) for erlotinib plus bexarotene; vascular endothelial growth factor receptor 2 positivity (P=0.05) for vandetanib; and absence of EGFR mutation (P=0.01) or of EGFR high polysomy (P=0.05) for sorafenib. A better 8-week DCR occurred with sorafenib versus all other regimens (64% versus 33%; P<0.001) among EGFR wild-type patients and versus all other regimens (61% versus 32%; P=0.11) among mutant-KRAS patients. The prespecified biomarker groups were less predictive than the individual biomarkers analyzed in this study. Conclusions The first completed biopsy-mandated study in pretreated NSCLC, BATTLE confirmed our pre-specified hypotheses regarding biomarker and targeted treatment interactions, establishing a new paradigm for personalizing therapy for patients with NSCLC. (ClinicalTrials.gov numbers, NCT00409968, NCT00411671, NCT00411632, NCT00410059, NCT00410189.)

The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.

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This treatment does not increase the risks associated with major liver resection. It may be indicated in selected patients before major resection. Future prospective studies are needed to define more clearly the indications for this evolving technique.

BACKGROUND.The objective of this study was to determine the prognostic variables that influence response and survival in patients with metastatic neuroendocrine tumors who are treated with hepatic arterial embolization (HAE) or chemoembolization (HACE). METHODS.Patients with metastatic neuroendocrine tumors who underwent HAE or HACE were included in this retrospective study. Follow-up imaging studies were compared with baseline imaging to determine the radiologic response. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to assess the prognostic variables that affected response and survival. RESULTS.The study included 69 patients with carcinoid tumors and 54 patients with pancreatic islet cell carcinomas. Patients who had carcinoid tumors had a higher response rate (66.7% vs. 35.2%; P ϭ 0.0001) and had longer PFS (22.7 mos vs. 16.1 mos; P ϭ 0.046) and OS (33.8 mos vs. 23.2 mos; P ϭ 0.012) compared with patients who had islet cell carcinomas. For patients with carcinoid tumors, multivariate analysis identified male gender as the only independent risk factor for poor survival (P ϭ 0.05). Octreotide was predictive marginally for PFS (P ϭ 0.06). Patients who were treated with HAE had a higher response rate than patients who were treated with HACE (P ϭ 0.004). For patients with islet cell carcinoma, an intact primary tumor, Ն 75% liver involvement, and extrahepatic metastases were associated with reduced OS in the univariate analysis; the presence of bone metastases was the only risk factor (P ϭ 0.031) in the multivariate analysis. Patients who were treated with HACE had a prolonged OS (31.5 mos vs. 18.2 mos) and improved response (50% vs. 25%) compared with patients who were treated with HAE, although the differences did not reach statistical significance. CONCLUSIONS.Patients with carcinoid tumors had better outcomes than patients with islet cell carcinomas. The addition of intraarterial chemotherapy to HAE did not improve the outcome of patients with carcinoid tumors, but it seemed to benefit patients with islet cell carcinomas. In patients who had carcinoid tumors, male gender predicted a poor outcome, and a trend toward prolonged PFS was observed in patients who received concomitant octreotide.An intact primary tumor, extensive liver disease, and bone metastases were associated with reduced survival in patients with islet cell carcinomas. Cancer

Background While the incorporation of research biopsies into clinical trials is increasing, limited information is available on how study protocols and informed consents integrate and describe their use. Methods All therapeutic clinical trials where image-guided research biopsies were performed from January 1, 2005 to October 1, 2010 were identified from an Interventional Radiology database. Data from study protocols and informed consents was extracted and analyzed. Procedural complications were recorded. Results A total of 57 clinical trials were identified, of which 38 (67%) contained at least one mandatory biopsy. Analysis of the research biopsy tumor tissue was a study endpoint in 95% of trials. The primary indication for research biopsy was for integral biomarker analysis in 32% and for correlative science in 68% of trials. A statistical analytic plan for the correlative science research biopsy tumor tissue was mentioned in 26%, described as exploratory in 51% and not mentioned in 23% of trials. For studies with mandatory biopsies, “biopsy” was an eligibility criterion in 71% of trials and a statistical justification for the research biopsy sample size was present in 50% of trials. 745 research biopsies were performed on 576 patients. The overall and major complication rates were 5.2% (39/745) and 0.8% (6/745), respectively. Complication rates for intra-thoracic and abdominal/pelvic solid organ biopsies were 17.1% (36/211) and 1.6% (3/189), respectively. Site stratified research biopsy-related risks were discussed in 5 consents. Conclusion A better representation of the risks and benefits of research biopsies in study protocols and informed consents is needed.

Management of hepatic malignancies is a ubiquitous medical problem. Surgical resection of primary or metastatic liver cancer, with or without adjuvant chemotherapy, is the most effective method for enhancing survival; however, hepatic malignancies in the vast majority of patients are unresectable both at initial manifestation and at recurrence. In these patients, palliative cytoreductive therapies may help to retard tumor progression and therefore favorably alter the course of the disease. Since hepatic neoplasms are principally supplied by the hepatic artery, various arterially delivered cytotoxic agents have been developed to achieve these objectives. Recently, the Food and Drug Administration approved the transarterial administration of yttrium-90 microspheres for liver-directed therapy. Effective use of these devices requires knowledge of the accumulated clinical experience and a dedicated multidisciplinary effort to ensure optimal outcomes and avoid therapy-specific life-threatening complications.

Splenic arterial interventions are increasingly performed to treat various clinical conditions, including abdominal trauma, hypersplenism, splenic arterial aneurysm, portal hypertension, and splenic neoplasm. When clinically appropriate, these procedures may provide an alternative to open surgery. They may help to salvage splenic function in patients with posttraumatic injuries or hypersplenism and to improve hematologic parameters in those who otherwise would be unable to undergo high-dose chemotherapy or immunosuppressive therapy. Splenic arterial interventions also may be performed to exclude splenic artery aneurysms from the parent vessel lumen and prevent aneurysm rupture; to reduce portal pressure and prevent sequelae in patients with portal hypertension; to treat splenic artery steal syndrome and improve liver perfusion in liver transplant recipients; and to administer targeted treatment to areas of neoplastic disease in the splenic parenchyma. As the use of splenic arterial interventions increases in interventional radiology practice, clinicians must be familiar with the splenic vascular anatomy, the indications and contraindications for performing interventional procedures, the technical considerations involved, and the potential use of other interventional procedures, such as radiofrequency ablation, in combination with splenic arterial interventions. Familiarity with the complications that can result from these interventional procedures, including abscess formation and pancreatitis, also is important.