David M. Liu

Hand-Held Thoracic Sonography for Detecting Post-Traumatic Pneumothoraces: The Extended Focused Assessment With Sonography For Trauma (EFAST)

BACKGROUND Thoracic ultrasound (EFAST) has shown promise in inferring the presence of post-traumatic pneumothoraces (PTXs) and may have a particular value in identifying occult pneumothoraces (OPTXs) missed by the AP supine chest radiograph (CXR). However, the diagnostic utility of hand-held US has not been previously evaluated in this role. METHODS Thoracic US examinations were performed during the initial resuscitation of injured patients at a provincial trauma referral center. A high frequency linear transducer and a 2.4 kg US attached to a video-recorder were used. Real-time EFAST examinations for PTXs were blindly compared with the subsequent results of CXRs, a composite standard (CXR, chest and abdominal CT scans, clinical course, and invasive interventions), and a CT gold standard (CT only). Charts were reviewed for in-hospital outcomes and follow-up. RESULTS There were 225 eligible patients (207 blunt, 18 penetrating); 17 were excluded from the US examination because of battery failure or a lost probe. Sixty-five (65) PTXs were detected in 52 patients (22% of patients), 41 (63%) being occult to CXR in 33 patients (14.2% whole population, 24.6% of those with a CT). The US and CXR agreed in 186 (89.4%) of patients, EFAST was better in 16 (7.7%), and CXR better in 6 (2.9%). Compared with the composite standard, the sensitivity of EFAST was 58.9% with a likelihood ratio of a positive test (LR+) of 69.7 and a specificity of 99.1%. Comparing EFAST directly to CXR, by looking at each of 266 lung fields with the benefit of the CT gold standard, the EFAST showed higher sensitivity over CXR (48.8% versus 20.9%). Both exams had a very high specificity (99.6% and 98.7%), and very predictive LR+ (46.7 and 36.3). CONCLUSION EFAST has comparable specificity to CXR but is more sensitive for the detection of OPTXs after trauma. Positive EFAST findings should be addressed either clinically or with CT depending on hemodynamic stability. CT should be used if detection of all PTXs is desired.

Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: Early results in 148 patients

Purpose:The use of 90Y-microspheres to treat unresectable liver metastases originating from a variety of neuroendocrine tumors was reviewed. Materials and Methods:This is a retrospective review from 10 institutions of patients given 90Y-microsphere therapy for neuroendocrine hepatic metastases. Physical, radiographic, biochemical, and clinical factors associated with treatment and response were examined. All patients were followed with laboratory and imaging studies at regular intervals until death, or censured whether other therapy was given after brachytherapy. Toxicities (acute and late) were recorded, and survival of the group determined. Results:A total of 148 patients were treated with 185 separate procedures. The median age was 58 years (26–95 years) at treatment with median performance status of Eastern Cooperative Oncology Group (0). The median activity delivered was 1.14 GBq (0.33–3.30 GBq) with a median of 99% of the planned activity able to be given (38.1%–147.4%). There were no acute or delayed toxicity of Common Terminology Criteria for Adverse Events v3.0 grade 3 in 67% of patients, with fatigue (6.5%) the most common side effect. Imaging response was stable in 22.7%, partial response in 60.5%, complete in 2.7% and progressive disease in 4.9%. No radiation liver failure occurred. The median survival is 70 months. Conclusion:Radioembolization with 90Y-microspheres to the whole liver, or lobe with single or multiple fractions are safe and produce high response rates, even with extensive tumor replacement of normal liver and/or heavy pretreatment. The acute and delayed toxicity was very low without a treatment related grade 4 acute event or radiation induced liver disease in this modest-sized cohort. The significant objective response suggests that further investigation of this approach is warranted.

Treatment Parameters and Outcome in 680 Treatments of Internal Radiation With Resin 90Y-Microspheres for Unresectable Hepatic Tumors

PURPOSE Radioembolization (RE) using (90)Y-microspheres is an effective and safe treatment for patients with unresectable liver malignancies. Radiation-induced liver disease (RILD) is rare after RE; however, greater understanding of radiation-related factors leading to serious liver toxicity is needed. METHODS AND MATERIALS Retrospective review of radiation parameters was performed. All data pertaining to demographics, tumor, radiation, and outcomes were analyzed for significance and dependencies to develop a predictive model for RILD. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria Adverse Events Version 3.0 scale. RESULTS A total of 515 patients (287 men; 228 women) from 14 US and 2 EU centers underwent 680 separate RE treatments with resin (90)Y-microspheres in 2003-2006. Multifactorial analyses identified factors related to toxicity, including activity (GBq) Selective Internal Radiation Therapy delivered (p < 0.0001), prescribed (GBq) activity (p < 0.0001), percentage of empiric activity (GBq) delivered (p < 0.0001), number of prior liver treatments (p < 0.0008), and medical center (p < 0.0001). The RILD was diagnosed in 28 of 680 treatments (4%), with 21 of 28 cases (75%) from one center, which used the empiric method. CONCLUSIONS There was an association between the empiric method, percentage of calculated activity delivered to the patient, and the most severe toxicity, RILD. A predictive model for RILD is not yet possible given the large variance in these data.

Radioembolization with 90Y Microspheres: Angiographic and Technical Considerations

The anatomy of the mesenteric system and the hepatic arterial bed has been demonstrated to have a high degree of variation. This is important when considering pre-surgical planning, catheterization, and trans-arterial hepatic therapies. Although anatomical variants have been well described, the characterization and understanding of regional hepatic perfusion in the context of radioembolization have not been studied with great depth. The purpose of this review is to provide a thorough discussion and detailed presentation of the angiographic and technical aspects of radioembolization. Normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors are discussed. Furthermore, the principles described here apply to all liver-directed transarterial therapies.

Angiographic Considerations in Patients Undergoing Liver-directed Therapy

The rapid evolution and increasing complexity of liver-directed therapies has forced the medical community to further advance its understanding of hepatic arterial anatomy. The anatomy of the mesenteric system, and particularly the hepatic arterial bed, has been demonstrated to have a high degree of variation. This is important when considering presurgical planning, catheterization, and transarterial hepatic therapies. Although anatomic variants have been well described, the characterization and understanding of regional hepatic perfusion is also required to optimize endovascular therapy and intervention. Although this is true for patients undergoing bland embolization or chemoembolization, drug delivery, and hepatic infusional pump therapy, it is particularly true for intraarterial brachytherapy. The purpose of this review is to provide historical perspective in angiographic aspects of liver-directed therapy, as well as a discussion of normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors. Methods of optimizing the safety and efficacy of liver-directed therapies with use of percutaneous techniques will be discussed. This review is based on the experience gained in treating more than 500 patients with transarterial liver-directed therapies. Although the principles described in this article apply to all liver-directed therapies such as chemoembolization and administration of drug-coated microspheres, they apply particularly to intraarterial brachytherapy.

90Y radioembolization for metastatic neuroendocrine liver tumors: Preliminary results from a multi-institutional experience

Purpose:Minimally invasive therapies such as transarterial chemoembolization and radiofrequency ablation are used for hepatic metastatic neuroendocrine tumor (NET) therapy. Results from another minimally invasive therapy, radioembolization, remain unknown. The purpose of this multicenter open label phase II study was to assess the efficacy and safety of yttrium-90 (90Y) radioembolization for treating hepatic metastatic NET using a primary outcome of tumor response and secondary outcomes of serologic toxicities and survival. Material/Methods:In this multicenter study, all patients underwent lobar radioembolization using glass or resin 90Y radioembolic agents. Patients were assessed serologically and radiographically at 2 to 4 weeks and then at 1 to 3 month intervals after treatment. We 1) compared liver volumes, radiation doses, and serologic liver function tests (unpaired t test, P = 0.05) and 2) assessed tumor response, serologic toxicity, and median survival from first 90Y therapy. The clinicaltrials.gov identifier was NCT00532740. Results:Forty-two patients underwent radioembolization using glass (mean age 58 ± 12 years) or resin (mean age 61 ± 11 years) microspheres. A statistically significant greater median radiation dose was delivered to each lobe using glass (right lobe 117 Gy; left lobe 108 Gy) than using resin (right 50.8 Gy; left 44.5 Gy) (P < 0.01). Using Response Criteria in Solid Tumors, 92% of glass and 94% of resin patients were classified as partial response or stable disease at 6 months after treatment. Six patients experienced grade 3/4 toxicities during the follow-up period. Median survival was 22 months (glass) and 28 months (resin) (P = 0.82). Conclusion:90Y radioembolization of metastatic NET is a viable therapy with acceptable toxicity. Further investigation is warranted.

Treatment of Unresectable Primary and Metastatic Liver Cancer with Yttrium-90 Microspheres (TheraSphere®): Assessment of Hepatic Arterial Embolization

In Canada and Europe, yttrium-90 microspheres (TheraSphere®; MDS Nordion, Ottawa, Canada) are a primary treatment option for primary and secondary hepatic malignancies. We present data from 30 patients with hepatocellular carcinoma (HCC) and metastatic liver disease treated with TheraSphere from a single academic institution to evaluate the angiographically evident embolization that follows treatment. Seven interventional radiologists from one treatment center compared pretreatment and posttreatment angiograms. The reviewers were blinded to the timing of the studies. The incidence of postembolization syndrome (PES) was determined as well as objective tumor response rates by the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), and European Association for the Study of the Liver (EASL) criteria. There were 420 independent angiographic observations that were assessed using the chi-squared statistic. The pretreatment and posttreatment angiograms could not be correctly identified on average more than 43% of the time (p = 0.0004). The postprocedure arterial patency rate was 100%. The objective tumor response rates for all patients were 24%, 31%, and 72% for WHO, RECIST, and EASL criteria, respectively. All of the patients tolerated the procedure without complications and were treated on an outpatient basis, and four patients had evidence of PES. This treatment method does not result in macroscopic embolization of the hepatic arteries, thereby maintaining hepatic tissue perfusion. These data support the principle that the favorable response rates reported with TheraSphere are likely due to radiation and microscopic embolization rather than flow-related macroscopic embolization and ischemia.

Research Reporting Standards for Radioembolization of Hepatic Malignancies

Primary Liver Tumors Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver; its incidence is increasing worldwide. It ranks as the sixth most common tumor and third most common cause of cancer-related mortality (1,2). Primary liver tumors include HCC and intrahepatic cholangiocarcinoma. Surgical resection is preferred over transplantation and is considered potentially curative in patients with resectable HCC and normal liver function (3). Transplantation is considered the gold standard for patients with unresectable HCC and whose disease is within the Milan criteria (4). Resection and transplantation have limited roles, given advanced disease (chronic liver disease and/or tumor extent) at presentation and limited organ availability (5–7). Chemoembolization and radiofrequency ablation represent standard therapies in treating patients and serve as a bridge to transplantation in selected patients (8,9). Radioembolization has an emerging role in “bridging” patients within criteria by delaying tumor progression. It has also been shown to downstage disease beyond the Milan, to within, transplant criteria (10–12). A recent study has demonstrated that radioembolization leads to longer time-to-progression and better toxicity profile when compared with chemoembolization (13). Patients with macrovascular tumor involvement have also exhibited evidence of clinical benefit after radioembolization (14).

Incidence of radiation pneumonitis after hepatic intra-arterial radiotherapy with yttrium-90 microspheres assuming uniform lung distribution.

Objective:To assess the incidence of clinical and imaging radiation pneumonitis (RP) in a cohort of patients treated with >30 Gy cumulative lung dose (CLD) using Y90 microspheres. Materials and Methods:Four hundred three patients were treated with Y90 microspheres during a 4-year period. Of these, 58 patients received >30 Gy CLD. Patients were followed for toxicities suggestive of imaging or clinical RP. Toxicities were graded using the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. Patients were also followed for survival from time of first treatment. Results:There were 44 men and 14 women. Forty-three patients had hepatocellular carcinoma (HCC), whereas 15 had liver metastases. Mean and median follow-up were 7.3 and 6.0 months, respectively. Mean lung shunt fraction was slightly greater in the patients with HCC versus metastases (20% vs. 16.7%, P = 0.2308). The lifetime CLD for metastases and HCC groups were not statistically different (54.04 Gy vs. 48.44 Gy, P = 0.4303). Forty-three of 53 patients demonstrated no lung imaging findings suggestive of pneumonitis. Imaging findings in 10 patients included pleural effusions, atelectasis, and ground glass attenuation. There were no cases of clinical or imaging RP. Survival varied depending on stage as well as single and CLD. None of the patient deaths were attributed to respiratory compromise. Conclusion:RP was not predicted using the currently used Y90 dosimetry models that assume uniform distribution in the lungs. Further investigation and dose escalation studies are required to more precisely define the radiation tolerance of lung parenchyma using this mode of therapy.

Percutaneous Ablation of Hepatocellular Carcinoma: Current Status

Hepatocellular carcinoma (HCC) is an increasingly common disease with dismal long-term survival. Percutaneous ablation has gained popularity as a minimally invasive, potentially curative therapy for HCC in nonoperative candidates. The seminal technique of percutaneous ethanol injection has been largely supplanted by newer modalities, including radiofrequency ablation, microwave ablation, cryoablation, and high-intensity focused ultrasound ablation. A review of these modalities, including technical success, survival rates, and complications, will be presented, as well as considerations for treatment planning and follow-up.