Anthony Goh

Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

Background The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. Methods Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). Results Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. Conclusions This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. Trial Registration ClinicalTrials.gov NCT00712790.

Radiation Dermatitis following Radioembolization for Hepatocellular Carcinoma: A Case for Prophylactic Embolization of a Patent Falciform Artery

The most common use of radioembolization is in the treatment of primary and secondary liver tumors, and the most common radioisotope used is yttrium-90. This form of therapy has been proven to be successful in achieving tumor reduction and prolonging survival. Adverse events, although uncommon and usually self-limiting, have been reported. The present report describes a case of radiation dermatitis caused by shunting of (90)Y microspheres to the anterior abdominal wall via a patent falciform artery. When identified, prophylactic embolization of this patent artery may prevent the potential adverse event of radiation-induced dermatitis after radioembolization.

[18F] FDG PET/CT in patients with fever of unknown origin: a local experience.

Objective2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F] FDG PET/CT) has become an established imaging tool in oncology and is now emerging in the field of infectious disease. The aim of this study is to assess the value of fluorine [18F] FDG PET/CT in the investigation of patients with fever of unknown origin (FUO). Methods[18F] FDG PET/CT scans and clinical data of 12 patients were reviewed. These patients met the revised definition criteria of FUO (febrile illness of greater than 3 weeks duration, temperature greater than 38.3°C and no diagnosis after at least 3 days of in-patient investigation or 2 weeks of outpatient investigation). A retrospective analysis of our local database was performed and evaluated for the diagnostic contribution of [18F] FDG PET/CT scans. ResultsAn infective cause of the FUO was found in four (33.3%) patients, a neoplasm in two (16.7%) patients, non-infectious inflammatory disease or autoimmune in one (8.3%) patient. A definitive causative agent could not be found in five (41.7%) patients despite extensive investigations.In all, five (41.6%) patients had a PET/CT scan that was abnormal and was deemed ‘helpful’ as part of the investigation that pointed to the final diagnosis. Two (16.7%) patients had abnormal scans, which were deemed ‘not-helpful’ for the final diagnosis. Conclusion[18F] FDG PET/CT can be helpful in some patients with FUO. This study adds value to the limited data published so far on this subject.

Underlying liver disease influences volumetric changes in the spared hemiliver after selective internal radiation therapy with 90Y in patients with hepatocellular carcinoma

Hypertrophy of the contralateral liver lobe after treatment with yttrium‐90 (90Y) microspheres has recently been reported. This study aimed to quantify left hepatic lobe hypertrophy after right‐sided radioembolization for hepatocellular carcinoma (HCC) and to identify pretreatment predictive factors of hypertrophy in an Asian population.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Dosimetric Considerations in Radioimmunotherapy and Systemic Radionuclide Therapies: A Review

Radiopharmaceutical therapy, once touted as the “magic bullet” in radiation oncology, is increasingly being used in the treatment of a variety of malignancies; albeit in later disease stages. With ever-increasing public and medical awareness of radiation effects, radiation dosimetry is becoming more important. Dosimetry allows administration of the maximum tolerated radiation dose to the tumor/organ to be treated but limiting radiation to critical organs. Traditional tumor dosimetry involved acquiring pretherapy planar scans and plasma estimates with a diagnostic dose of intended radiopharmaceuticals. New advancements in single photon emission computed tomography and positron emission tomography systems allow semi-quantitative measurements of radiation dosimetry thus allowing treatments tailored to each individual patient.

National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26th September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data.

99Tcm-polyclonal IgG and 99Tcm nanocolloid scans in orthopaedics: a comparison with conventional bone scan

The bone scan is sensitive in detection of active bone/joint lesions. A normal bone scan virtually excludes the presence of an inflammatory process with high precision, but the poor specificity of bone scans is well known. In recent years, various new agents including 99Tcm-hexamethylpropylene amine oxime (HMPAO)-labelled white blood cells, nanocolloid, polyclonal IgG, anti-granulocyte antibody, 111In-labelled IgG, leucocytes, chemotactic peptides etc. have been widely evaluated in inflammatory imaging, especially in the orthopaedic context. This study was undertaken to compare the usefulness of 99Tcm-nanocolloid and 99Tcm-polyclonal IgG in the detection of focal bone/joint inflammation. Twenty-seven patients with a common presentation of bone/joint pain resulting from various pathologies were included in the study. A total of 47 lesions were imaged. The overall sensitivity and specificity of both nanocolloid scan and IgG scan were identical with 95% sensitivity and 100% specificity, in detecting inflammatory foci. However, specificity dropped to 18% with nanocolloid scans and 16% with IgG scans when an attempt was made to distinguish noninfective from infective inflammatory processes; thus neither type of scan permits differentiation between septic and nonseptic inflammatory processes with sufficient accuracy. As both nanocolloid and IgG scans are equally sensitive and specific in detecting inflammation, the choice of type of scan will depend on cost, imaging time and availability of the radiopharmaceutical.

Radioembolization with Infusion of Yttrium-90 Microspheres into a Right Inferior Phrenic Artery with Hepatic Tumor Supply Is Feasible and Safe

PURPOSE To evaluate the feasibility and safety of yttrium-90 ((90)Y) radioembolization through the inferior phrenic arteries (IPAs). MATERIALS AND METHODS Retrospective analysis of 108 patients referred for radioembolization to treat primary (n = 103) or secondary (n = 5) liver malignancy was performed. Five patients had malignant hepatic tumors supplied by the IPA and met criteria for infusion of (90)Y spheres into the IPA. Digital subtraction angiography (DSA), catheter-directed computed tomographic (CT) angiography, and technetium-99m ((99m)Tc) macroaggregated albumin (MAA) single photon emission CT (SPECT)/CT were used to plan treatment. Bremsstrahlung SPECT/CT was performed 1 day after radioembolization. Follow-up included clinical and biochemical tests and cross-sectional CT or magnetic resonance imaging. RESULTS Parasitized extrahepatic arteries were detected in 37% of patients (n = 40). Of these, 62.5% (n = 25) had tumor supply through an IPA. Of the patients with IPA supply, 20% (n = 5) underwent infusion of (90)Y into the right IPA. Reasons for disqualifying patients from infusion into the IPA were less than 10% tumor supply (n = 11), failed catheterization of IPA (n = 3), arterioportovenous shunt (n = 2), failed identification of IPA on pretreatment angiography (n = 1), and gastric or esophageal enhancement on catheter-directed CT angiography (n = 3). In all five patients, technical success was demonstrated on (90)Y imaging, with no significant extrahepatic radionuclide activity. No adverse events related to IPA radioembolization occurred at mean follow-up of 4.5 months (range, 2.2-10.1 mo). CONCLUSIONS Delivery of (90)Y microspheres through the right IPA is feasible and safe with the use of catheter-directed CT angiography in addition to DSA and (99m)Tc MAA SPECT/CT in patients with tumors with greater than 10% IPA supply.

Hepatic falciform ligament Tc-99m-macroaggregated albumin activity on SPECT/CT prior to Yttrium-90 microsphere radioembolization: prophylactic measures to prevent non-target microsphere localization via patent hepatic falciform arteries

Yttrium-90 (Y-90) selective internal radiation therapy (SIRT) is increasingly used to treat inoperable hepatocellular carcinoma. We describe two patients where hepatic falciform ligament Technetium-99m-macroaggregated albumin (Tc-99m-MAA) activity was identified on single photon emission computed tomography with integrated low-dose CT (SPECT/CT) scan during pre-therapy planning, and the steps taken to prevent radiation dermatitis. The first patient underwent prophylactic coil embolization of the patent hepatic falciform artery; the second patient underwent super-selective infusion of Y-90 resin microspheres to avoid the patent hepatic falciform artery. The incidence of falciform ligament Tc-99m-MAA activity detected on SPECT/CT at our institution is 10%. Tc-99m-MAA SPECT/CT scan provides valuable diagnostic information for treatment planning prior to Y-90 SIRT.