Radioembolisation in patients with hepatocellular carcinoma that have previously received liver-directed therapies.

PURPOSE: Radioembolisation is part of the multimodal treatment of hepatocellular carcinoma (HCC) at specialist liver centres. This study analysed the impact of prior treatment on tolerability and survival following radioembolisation. METHODS: This was a retrospective analysis of 325 consecutive patients with a confirmed diagnosis of HCC, who received radioembolisation with yttrium-90 resin microspheres at eight European centres between September 2003 and December 2009. The decision to treat was based on the clinical judgement of multidisciplinary teams. Patients were followed from the date of radioembolisation to last contact or death and the nature and severity of all adverse events (AEs) recorded from medical records. RESULTS: Most radioembolisation candidates were Child-Pugh class A (82.5%) with multinodular HCC (75.9%) invading both lobes (53.1%); 56.3% were advanced stage. Radioembolisation was used first-line in 57.5% of patients and second-line in 34.2%. Common prior procedures were transarterial (chemo)embolisation therapies (27.1%), surgical resection/transplantation (17.2%) and ablation (8.6%). There was no difference in AE incidence and severity between prior treatment subgroups. Median (95% confidence interval [CI]) survival following radioembolisation was similar between procedure-naive and prior treatment groups for Barcelona Clinic Liver Cancer (BCLC) stage A: 22.1 months (15.1-45.9) versus 30.9 months (19.6-46.8); p = 0.243); stage B: 18.4 months (11.2-19.4) versus 22.8 months (10.9-34.2); p = 0.815; and stage C: 8.8 months (7.1-10.8) versus 10.8 months (7.7-12.6); p = 0.976. CONCLUSIONS: Radioembolisation is a valuable treatment option for patients who relapse following surgical, ablative or vascular procedures and remain suitable candidates for this treatment.

Molecular response assessed by (68)Ga-DOTANOC and survival after (90)Y microsphere therapy in patients with liver metastases from neuroendocrine tumours.

PURPOSE: We investigated the prognostic role of (68)Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing (90)Y radioembolization ((90)Y-RE). METHODS: A group of 15 consecutive patients with unresectable NET liver metastases underwent (68)Ga-DOTANOC PET at baseline and 6 weeks after (90)Y-RE. Molecular response was defined as a reduction of >50% in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50% and nonresponders with ΔT/S <50%) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following (90)Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). RESULTS: A decrease in T/S ratio was seen in all patients on (68)Ga-DOTANOC PET scans performed after (90)Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. CONCLUSION: Molecular response assessed with (68)Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with (90)Y-RE.

Plerixafor and autologous stem cell transplantation: impressive result in a chemoresistant testicular cancer patient treated with high-dose chemotherapy.

Plerixafor, a CXCR4 antagonist, induces the rapid release of hematopoietic progenitor stem cells from the bone marrow into peripheral blood; it is approved for autologous hematopoietic progenitor stem cell mobilization in multiple myeloma and non-Hodgkin's lymphoma patients. We report the case of a 34-year-old patient with metastatic testicular embryonal carcinoma who was extensively and in vain pretreated with chemotherapy and failed to mobilize an adequate number of hematopoietic progenitor stem cells following high-dose chemotherapy, with the support of granulocyte colony-stimulating factors. After a cycle of high-dose cyclophosphamide associated with granulocyte colony-stimulating factors, plerixafor was administered to the patient, with the clinical evidence of an increase in hematopoietic progenitor stem cells in the peripheral blood. The patient achieved a complete engraftment following two cycles of high-dose chemotherapy (paclitaxel, ifosfamide, carboplatin, etoposide), with the support of hematopoietic progenitor stem cells; the patient showed discrete tolerability to the treatment. At biochemical control, the ß-human chorionic gonadotropin value decreased from 86 to less than 1.2 mUI/ml and total body PET-CT scan showed a complete response to chemotherapy. According to this experience, we believe that in patients with advanced germ cell cancer, it is essential to explore the possibility of the use of high-dose chemotherapy to induce a stable and permanent response; in this context, plerixafor, with the support of granulocyte colony-stimulating factors, may be an innovative option for satisfactory mobilization during high-dose chemotherapy protocols.

Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.

UNLABELLED: A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. CONCLUSION: This analysis provides robust evidence of the survival achieved with radioembolization, including those with advanced disease and few treatment options.

A case report of thyroid carcinoma confined to ovary and concurrently occult in the thyroid: is conservative treatment always advised?

INTRODUCTION: Struma ovarii is an ovarian teratoma, represented in more than 50% by thyroid tissue. Five percent of struma ovarii cases have been proven to be malignant and, as in the thyroid gland, papillary thyroid carcinoma is the most common histotype arising in struma ovarii. Because of the unusual occurrence of this tumor, its management and follow-up after pelvic surgery is still controversial. Usually, total thyroidectomy followed by radioiodine treatment is the choice treatment in metastatic malignant struma ovarii, while these procedures are still controversial in non-metastatic thyroid cancer arising in struma ovarii. CASE PRESENTATION: We report a female with follicular variant of papillary thyroid carcinoma arising in struma ovarii. After pelvic surgery, thyroid morphofunctional examinations were performed and a single nodular lesion in the left lobe was discovered. The patient underwent total thyroidectomy and histological examination showed a papillary carcinoma. Radioiodine-ablation of residual thyroid tissue was performed and levothyroxine mildly-suppressive treatment was started. CONCLUSIONS: A more aggressive treatment should not be denied for malignant struma ovarii without any evidence, even when apparently confined into the ovary. However, in selected cases, aggressive treatment may be advisable to decrease the risk of recurrence and to allow an accurate follow-up.

Usefulness of dual-time point imaging after carbonated water for the fluorodeoxyglucose positron emission imaging of peritoneal carcinomatosis in colon cancer.

BACKGROUND: Fluorodeoxygluose (FDG) positron emission/computed tomography (PET/CT) is emerging as a useful tool for the diagnosis of peritoneal carcinomatosis (PC). In this study, we assessed whether dual-time point imaging can improve the accuracy of FDG PET/CT for the diagnosis of PC after colon rectal cancer (CRC). METHODS: Thirty-nine patients with past history of CRC were evaluated. Whole-Body PET/CT scan was acquired 1 hour after tracer injection. If one or more focal areas of increased FDG uptake (standardized uptake value, SUV max>2.5) were found in the abdomen, 1 L of carbonated water was orally administered to patients and a delayed scan of the abdominal region was acquired at 2 hours. The SUV max and the mean Delta (Δ) SUV were calculated. The scintigraphic results were compared with the results of colonoscopy and histology and with the clinical follow-up. RESULTS: Thirteen out of the 39 patients did not show any significant area of FDG uptake at the whole-body scan. The remaining 26 patients showed an overall number of 27 sites of focal increased uptake, showing a mean SUV max of 6.5+3.3. Late scan of the abdomen showed vanishing spots in 11 cases. Focal and increasing FDG uptake was found in 15 subjects (for an overall number of 16 sites) with SUV max of 15.6+4 and mean Δ SUV of +26.3%±7.5%. In these cases, final diagnosis was PC in 10 patients (according to cytology or histology) and dysplastic polyp in 5 cases. No significant difference in Δ SUV was found between patients with PC and those with polypoid formations. CONCLUSIONS: According to our results, dual-time point imaging after carbonated water may increase the accuracy of FDG PET/CT for the imaging of PC in patients affected by CRC.

Absorbed dose to lesion and clinical outcome after liver radioembolization with 90Y microspheres: a case report of PET-based dosimetry.

A 54-year-old woman with metastatic colorectal carcinoma underwent liver radioembolization with (90)Y resin microspheres. Microsphere biodistribution was assessed 2 h after the treatment through a 20-min long (90)Y PET scan. Isodose map and lesion dose-volume histogram (DVH) were then evaluated using a MATLAB-based code. Response to therapy was assessed performing a (18)F-FDG PET 6 months after the treatment. At (90)Y PET the patient showed a well-defined horseshoe-shaped hepatic lesion with hot margins and a cold core. The lesion presented a heterogeneous DVH with a hot margin receiving an average radiation dose as high as 287 Gy and a cold area receiving an average radiation dose of 70 Gy approximately. Six months after the treatment the patient reported a complete remission of tumour areas which received a high radiation dose, while progression of metastases was observed in the area that presented scarce microsphere localization at (90)Y PET. According to our experience, the use of (90)Y PET voxel dosimetry may provide a useful tool to assess possible correlations between microsphere biodistribution and clinical outcome of the treatment. In agreement with current literature findings, an average radiation dose greater than approximately 100 Gy may be required to sterilize liver metastases.

90Y-PET for the assessment of microsphere biodistribution after selective internal radiotherapy.

OBJECTIVES: To demonstrate the feasibility of 90Y-PET imaging for biodistribution assessment after selective internal radiotherapy treatments with 90Y-microspheres, comparing the results with 99mTc-macroaggregated albumin (MAA) images obtained with single-photon emission computed tomography. METHODS: Preliminary studies were performed with the aim of evaluating the imaging system spatial resolution and scanner sensitivity for detecting annihilation photons. Subsequently, microsphere distribution was evaluated in 10 patients who underwent liver selective internal radiotherapy treatment. 99mTc-MAA and 90Y-microsphere were simultaneously injected for immediate monitoring after treatment. For each patient, the metastases detected with 90Y-PET and 99mTc-MAA were assessed and compared with 18F-fluorodeoxyglucose-PET (18F-FDG-PET) obtained before treatment and used as an imaging benchmark procedure. The correlation between these techniques was thus investigated in terms of matching lesions. Lesions were considered true positive in the case of matching with 18F-FDG-PET. The sensitivity of both techniques was evaluated as the true-positive fraction of detected spots in the treated liver sectors. RESULTS: With our experimental setup, a maximum scanner sensitivity of 0.577 and 0.077 cps/MBq was obtained for three-dimensional and two-dimensional acquisitions, respectively. A good correlation was obtained between images obtained before and after treatment, with 90Y-PET being by far the most accurate technique in detecting microsphere distribution and tumor nonhomogeneity areas. A sensitivity as high as 0.91 was obtained with 90Y-PET, whereas 99mTc-MAA imaging showed a SE of 0.75. CONCLUSION: 90Y-PET is a promising and reliable technique for microsphere biodistribution evaluation after liver selective internal radiotherapy treatment. Because of the better resolution and the possibility to perform computed tomography fusion, 90Y-PET images are more accurate than 99mTc-MAA single-photon emission computed tomography, which is now considered the gold standard for biodistribution assessment.

90Y PET-based dosimetry after selective internal radiotherapy treatments.

OBJECTIVES: The decay of 90Y has a minor branch to the O+ first excited state of 89Zr, the de-excitation of which to the fundamental state is followed by a ß+­ß- emission that has been used recently for biodistribution assessment after selective internal radiotherapy (SIRT) treatments. The purpose of the present study is to demonstrate the feasibility of 90Y PET imaging for dose assessment after radioembolization with 90Y microspheres. METHODS: Activity quantification was validated through preliminary phantom studies using a cylindrical body phantom composed of six inserts of different volumes filled with a calibrated amount of 90Y microspheres. A GE Discovery ST PET/CT scanner provided with bismuth germinate (BGO) crystals was used for image acquisition. Images were reconstructed with an ordered subset expectation­maximization method. The effect of object size and the effect of the number of iterations on dose evaluation and volume recovery were investigated. Microsphere dose distribution was then evaluated on one patient (one lesion) who underwent liver SIRT treatment. Dose calculations were made with a MATLAB-based code developed in our department. Dedicated Monte Carlo calculations were executed to evaluate dose S-values for the 90Y source. The activity distribution derived from 90Y PET acquisitions was convolved with the voxel S-values to obtain a three-dimensional absorbed dose distribution and dose­volume histograms. RESULTS: Dosimetry studies carried out on the body phantom with ordered subset expectation­maximization algorithm, three iterations, provided an accuracy of 7.62% in determining the absorbed dose in the largest insert. The dose difference increases as the insert size reduces. Preliminary results on a patient provided a high-resolution absorbed dose distribution map. An average dose of 139.3 Gy was evaluated for the tumor area, with a maximum dose as high as 237.9 Gy. The absorbed dose to the healthy liver was below the tolerance dose of 35 Gy (33.8 Gy). A clear correlation between absorbed dose and tumor response was observed at 18F-fluorodeoxyglucose PET acquired 6 months after treatment. CONCLUSION: According to our experience, 90Y PET is a promising and reliable technique for microsphere dose assessment and might pave the way for a patient-specific PET-based dosimetry after liver SIRT treatments.

Selective internal radiation therapy with SIR-spheres for the treatment of unresectable colorectal hepatic metastases.

The purpose of this study was to evaluate the effectiveness of colorectal cancer (CRC) liver metastasis radioembolization with yttrium-90 (Y90), assessing toxicity and survival rates in patients with no response to chemotherapy through our 3-year experience. From February 2005 to January 2008, we treated 41 patients affected by CRC from a cohort of selective internal radiation therapy patients treated at our institution. All patients examined showed disease progression and arrived for our observation with an abdominal CT, a body PET, and a hepatic angiography followed by gastroduodenal artery coiling previously performed by us. We excluded patients with a bilirubin level>1.8 mg/dl and pulmonary shunt>20% but not patients with minor extrahepatic metastases. On treatment day, under fluoroscopic guidance, we implanted a dose of Y90 microspheres calculated on the basis of liver tumoral involvement and the body surface area formula. All patients were discharged the day after treatment. We obtained, according to Response Evaluation Criteria on Solid Tumors, a complete response in 2 patients, a partial response in 17 patients, stable disease in 14 patients, and progressive disease in 8 patients. In all cases, we obtained a carcinoembryonic antigen level decrease, especially in the week 8 evaluation. Technical success rate was 98% and technical effectiveness estimated at 3 months after treatment was 80.5%. Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, two grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated by Kaplan-Meier analysis were 354 and 279 days, respectively. In conclusion, according to our 3-year experience, Y90 SIR-Spheres radioembolization is a feasible and safe method to treat CRC liver metastases, with an acceptable level of complications and a good response rate.