Venous obstruction in the cancer population can result in substantial morbidity and, in extreme cases, mortality. While venous obstruction can be caused by both benign and malignant etiologies in this population, the management of malignant venous obstruction as a palliative measure can be somewhat nuanced with respect to nonprocedural and procedural management, both with respect to treatment of the underlying malignancy as well as treatment of venous hypertension, which may be associated with venous thrombosis. Symptom severity, primary malignancy, functional status, and prognosis are all fundamental to the patient workup and dictate both the timing and extent of endovascular intervention. The morbidity and mortality associated with malignant obstructions of central venous structures, specifically the superior vena cava and inferior vena cava, can be significantly improved with endovascular management in appropriately selected patients. Thus, the pertinent literature regarding the clinical presentation, workup, and endovascular management of malignant central venous obstruction syndromes, with directed attention to superior vena cava syndrome and inferior vena cava syndrome, will be reviewed in this article.

While surface-enhanced Raman scattering (SERS) spectroscopy has traditionally been employed as an in vitro analytical tool, in the past few years the first reports of the feasibility of in vivo imaging of cancer with biocompatible SERS probes have emerged. SERS imaging has great potential in the field of medical imaging because it offers several major theoretical advantages over other molecular imaging methods. Medical imaging using SERS nanoprobes can yield higher sensitivity and higher signal specificity than other imaging modalities while also offering multiplexing capabilities that allow for unique applications. This review article explains the principles of SERS and highlights recent advances for in vivo cancer imaging. In order to present the abilities of the method as accurate as possible, the discussion is limited to studies in which the imaging data were confirmed by histological correlation.

Hepatocellular carcinoma (HCC) represents a significant contributor to cancer-related morbidity and mortality with increasing incidence in both developing and developed countries. Embolotherapy as a locoregional therapeutic strategy consists of trans-arterial or “bland” embolization (TAE), trans-arterial chemoembolization (TACE), and selective internal radiotherapy (SIRT). Trans-catheter arterial therapies can be applied along all stages of HCC, either as an alternative or neoadjuvant to surgical resection/transplantation in very early and early stage HCC or as a palliative option for local disease control in unresectable and advanced stage HCC. In advanced stage HCC, SIRT did not demonstrate superiority in comparison to systemic treatment options in several recent large prospective trials, though for carefully selected patients, may confer improved tolerability with similar disease control rates. The latest embolotherapeutic techniques and literature as they pertain to the management of HCC, as well as future directions, are reviewed in this article.

Purpose To compare the performance of 4 metrics of metabolic response on FDG-PET/CT against RECIST 1.0 for determining response and predicting overall survival (OS) following 90Y resin microspheres radioembolization of colorectal liver metastases (CLM). Methods We conducted an IRB-waived retrospective review of our radioembolization database to identify patients with unresectable CLM treated between December 2009 and December 2013. We included patients who had both PET/CT and contrast enhanced CT (CECT) available at baseline and on the first follow-up post-radioembolization. On baseline CECT up to five target tumors were chosen per patient according to RECIST 1.0. Four metrics of FDG-avidity (SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)) on PET/CT were measured for the same target tumors. Using RECIST 1.0, patients were classified as no progression (partial response or stable disease) and progression. For each PET metric, a cut-off point of ≥30% decrease was chosen to define response. OS was calculated from the time of radioembolization using Kaplan-Meier methodology. The log-rank test was used for univariate analysis to identify predictors of OS. Results The study enrolled 49 patients with 119 target tumors; a median of 2 (range: 1–5) tumors were selected per patient. Median OS was 12.7 months (95%CI: 7.2–16.7). Response by MTV (P=0.035) and TLG (P=0.044) reached statistical significance in predicting OS. Response by SUVmax (P=0.21), SUVpeak (P=0.20) or no progression by RECIST1.0 (P=0.44) did not predict OS. Conclusion Metabolic response based on changes in MTV and TLG can predict OS post-radioembolization of CLM.

Cancer-associated venous thromboembolism (CAT) is a well-described complication of cancer and a leading cause of death in cancer patients. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clonal hematopoiesis. We analyzed deep-coverage targeted DNA-sequencing data of >14,000 solid tumor samples using the MSK-IMPACT™ platform to identify somatic alterations associated with VTE. Endpoint was defined as the first instance of cancer-associated pulmonary embolism and/or proximal/distal lower extremity deep vein thrombosis. Cause-specific Cox proportional hazards regression was used, adjusting for pertinent clinical covariates. Of 11,695 evaluable individuals, 72% had metastatic disease at time of IMPACT. Tumor-specific mutations in KRAS (HR=1.34 [1.09-1.64]; adjusted p=0.08), STK11 (HR=2.12 [1.55-2.89]; adjusted p<0.001), KEAP1 (HR=1.84 [1.21-2.79]; adjusted p=0.07), CTNNB1 (HR=1.73 [1.15-2.60]; adjusted p=0.09), CDKN2B (HR= 1.45 [1.13-1.85], adjusted p=0.07) and MET (HR=1.83 [1.15-2.92]; adjusted p=0.09) were associated with a significantly increased risk of CAT independent of tumor type. Mutations in SETD2 were associated with a decreased risk of CAT (HR=0.35 [0.16-0.79], adjusted p=0.09). The presence of clonal hematopoiesis was not associated with an increased VTE rate. This is the first large-scale analysis to elucidate tumor-specific genomic events associated with CAT. Somatic tumor mutations of STK11, KRAS, CTNNB1, KEAP1, CDKN2B and MET were associated with an increased risk of VTE in solid tumor patients. Further analysis is needed to validate these findings and identify additional molecular signatures unique to individual tumor types.

Loss of Discslarge (Dlg) in early

The aim was to analyze Tp53 and HDM2 in T1G3 bladder tumors and to determine the prognostic value of their alterations. Experimental Design: Tumors (n = 119) were extracted from a prospective study of 1,356 bladder cancers. Tp53 mutations (exons 4-9) were assessed by sequencing of PCR products. HDM2 dose was assessed by quantitative PCR. p53, HDM2, and the products of p53 target genes were analyzed by immunohistochemistry. Cases were distributed in three categories. The association with prognosis was determined using Kaplan-Meier and Cox analyses. Results: Eighty-five percent of tumors harbored alterations in Tp53 or HDM2 . In group 1 (n = 77), 69 tumors had inactivating Tp53 mutations (58%), and 8 had HDM2 gains (7%). Group 2 (n = 24) comprised tumors overexpressing p53 in the absence of mutations (20%). Group 3 tumors (n = 18) had no alterations. HDM2 gains were associated to HDM2 overexpression and to wild-typeTp53. Expression of type 1 insulin-like growth factor receptor, 14-3-3 j, and cyclooxygenase-2 was similar in groups 1 and 2 and significantly different from group 3. Survivin was expressed in the majority of tumors regardless of p53 pathway status.Taking group 3 as reference, the hazard ratios (HR) for recurrence, progression, and death were not significantly different in the other patient groups. HRs for recurrence were 1.13 for group 1 [95% confidence interval (95% CI), 0.25-5.03] and 1.40 for group 2 (95% CI, 0.27-7.20). HRs for progression were 0.50 for group 1 (95% CI, 0.18-1.40) and 0.25 for group 2 (95% CI, 0.05-1.29). Conclusions: The p53 pathway is inactivated in most T1G3 bladder tumors. These genetic alterations do not independently predict patient's prognosis.

While traditionally reserved for patients with unresectable HCC and stage B disease, there is an important role for embolization therapies in earlier stage patients as an adjunct to ablation, bridging, or downstaging therapy, as a means to improve safety of resection, and potentially as an arterial ablative option in the case of radioembolization. Newer applications of radioembolization such as radiation segmentectomy have the potential to provide cure in localized unifocal disease, and transarterial chemoembolization-portal vein embolization and radiation lobectomy may provide a combination of treatment and future liver remnant hypertrophy for planned hepatic resection. There is also an increasing role for embolization in the treatment of stage C disease, and recent data suggest it can be used in combination with sorafenib with the potential for survival benefit over sorafenib alone, even in the case of portal vein tumor thrombus. Embolization therapies play an increasingly important role in patients with BCLC stage A-C hepatocellular carcinoma. While different therapies may be offered on a patient-specific basis, there are limited prospective RCT data to support superiority of one technique over another.