Long-Term Outcome After Liver Transplantation for Hepatocellular Carcinoma Following Yttrium-90 Radioembolization Bridging Treatment.

BACKGROUND Bridging treatments are employed in liver transplant waitlist patients with hepatocellular carcinoma (HCC) because of the risk of tumor progression during the waiting time. Radioembolization is mostly employed in the control of large or multifocal HCCs when other locoregional treatment modalities cannot be applied because of the number or size of lesions. The purpose of this study was to evaluate our experience with the use of radioembolization as a bridge to transplantation and its effect on tumor recurrence and survival after liver transplantation. MATERIAL AND METHODS A retrospective review of 40 consecutive patients with HCC who underwent liver transplantation after radioembolization bridging treatment between January 2007 and December 2015 at the University Hospital Essen, Germany, was performed. Patients' characteristics, alpha-fetoprotein (AFP) levels, pathologic tumor response, tumor recurrence rate, and survival rates were examined through chart review. RESULTS Histopathological examination of the explanted liver specimen revealed complete tumor necrosis in 17 specimens, partial necrosis in 18 specimens, and no significant necrosis in five specimens. Median overall survival was 46 months. Nine patients developed recurrent HCC. Median time from liver transplantation to diagnosis of tumor recurrence was 15 months. There was a trend towards a lower risk of tumor recurrence for patients with complete necrosis on explant specimens. Patients with tumor recurrence demonstrated statistically significantly higher pre- and post-treatment AFP levels (p=0.0234 and p=0.0236) and statistically significantly more frequently microvascular invasion (p=0.0163). CONCLUSIONS Histopathological assessment of explanted livers revealed at least partial necrosis in 87.5% of patients. Patients with successful bridging treatment, i.e. complete necrosis of explant specimens, demonstrate a trend towards a lower risk of tumor recurrence.

Effect of voxel size and computation method on Tc-99m MAA SPECT/CT-based dose estimation for Y-90 microsphere therapy.

The use of selective internal radiation therapy for treatment of hepatocellular carcinoma and liver metastases using Y-90 labeled microspheres has become an effective and widely used treatment regimen. However, dosimetric evaluations of this treatment are still primitive as uniform distribution models based only on injected activity are often used. This investigation attempts to quantify the effectiveness of several sophisticated patient-specific techniques which utilize the source distribution of Tc-99m MAA simulation studies to perform voxelized dosimetric computations. Among these techniques are complete Monte-Carlo radiation transport computation in patient-specific CT-based voxel phantoms, local energy deposition in patient specific phantoms and kernel transport techniques in water. Each technique was evaluated using three different phantom voxel dimensions and SPECT reconstruction matrix sizes. Dose evaluation results using all methods were compared to the exact solution, obtained using fully 3-D Monte-Carlo simulations with source distribution based not on SPECT data, but on the injected activity and exact boundaries of the anthropomorphic phantom used in the study. The results of this study show that at large voxel sizes and using SPECT reconstructions with a small matrix size (64 x 64), Monte-Carlo and local deposition methods are nearly equivalent. However, using a large SPECT reconstruction matrix (256 x 256) the local deposition method is significantly more accurate than full 3-D Monte-Carlo transport, and with a negligible computational burden.

Biologic and immunologic therapies for ovarian cancer.

Biologic therapy of ovarian cancer has been conducted using nonspecific biologic response modifiers, cytokines, monoclonal antibodies (MAbs), vaccines, and gene therapy. Antibodies directed toward her2/neu have also been studied. Phase I and II gene therapy trials using adenoviral vectors containing a wild-type or modified p53 have shown that the treatment is well tolerated. Phase II and III trials are ongoing with MAbs directed against CA-125 (MAb B43.13) and an antibody directed against HMFG1 (anti-HMFG1-yttrium-90-labeled antibody). The trials have shown that these agents are well tolerated and that immunologic responses occur, although the ultimate clinical value of these agents remains to be determined. Prolonged survival after MAb B43.13 treatment has been correlated with changes in several immune parameters, including human antimurine antibody, Ab2, anti-CA-125 antibody development, and induced T-cell immunity. Clinical trials using a MAb directed toward the encoded products of her2/neu have shown minimal activity against ovarian cancer in a phase I and II trial conducted by the Gynecologic Oncology Group. Cytokine therapies have been administered systemically and intraperitoneally. Intracavitary interferon alfa, interferon gamma, and interleukin-2 alone or in combination with cytotoxic therapy in phase I and II trials demonstrated intraperitoneal lymphoid cell stimulation and produced antitumor responses. A randomized trial of chemotherapy with or without interferon gamma in primary treatment produced a response and a progression-free survival advantage in the arm that incorporated the interferon gamma, without a statistically significant benefit in overall survival. A phase III study of interferon gamma in combination with first-line chemotherapy is currently ongoing.

Comparative dosimetry of copper-64 and yttrium-90-labeled somatostatin analogs in a tumor-bearing rat model.

90Y-DOTA-tyrosine3-octreotide (90Y-DOTA-Y3-OC) is currently being evaluated as a radiotherapy agent for trials in patients with somatostatin-receptor positive cancer. In this study, we compared the estimated absorbed doses to human organs, as well as to a CA20948 rat tumor, of 90Y- and 64Cu-labeled DOTA-Y3-OC and DOTA-Y3-octreotate (DOTA-Y3-TATE). Assuming that the radiopharmaceutical biodistributions are the same in rodents and humans, human absorbed dose estimates were obtained from rat biodistribution data. The absorbed doses of 90Y-DOTA-Y3-TATE were determined from the biodistribution of the 88Y-labeled peptide, with and without co-injection of a therapeutic amount of the 90Y-labeled peptide. Additionally, the absorbed doses of 90Y-DOTA-Y3-TATE were determined from data using two different biodistribution endpoints, 48 h and 168 h. Human absorbed dose estimates were calculated using MIRD methodology assuming that rats and humans have the same biodistribution. The biodistribution of the radiolabeled somatostatin analogs was dependent on the peptide and the radiometal. For 90Y-DOTA-Y3-TATE, the tumor dose was dependent on both the administration of therapeutic 90Y-peptide and the biodistribution endpoint. Our data suggested that, for both radionuclides, the TATE derivatives imparted a higher absorbed dose to the tumor than the OC analogs. 90Y-DOTA-Y3-OC and 64Cu-DOTA-Y3-OC were comparable with respect to their tumor-to-normal tissue dose ratios, while 90Y-DOTA-Y3-TATE appeared to have distinct advantages over 64Cu-DOTA-Y3-TATE.

Yttrium 90 in persistent synovitis of the knee - a single centre comparison. The retention and extra-articular spread of four 90-U radiocolloids.

The characteristics of three colloidal preparations of 90-Y currently used for the irradiation of chronic synovitis of the knee have been studied. One, 99-Y silicate, showed less leakage away from the joint than the other two preparations, 90-Y ferric hydroxide and 90-Y citrate. Comparable amounts of 90-Y were taken up regional lymph nodes when the silicate and ferric hydroxide forms were used; the greatest irradiation of regional lymph-nodes occured using the citrate form. In this respect all three preparations are inferior to the previously used preparation 90-Y resin colloid which is no longer manufactured.

Treatment of multiple superficial papillary tumors of the bladder by intracavitary yttrium-90.

Intravesical Y-90 was used in 38 patients with multiple papillary T1 tumors considered beyond control by cystodiathermy. Of the 32 patients available for 3-year observation 19 (60 per cent) were alive after 3 years, 6 had died of progression of the tumor and 7 had died of other causes. Prolonged imporvement was noted in 23 patients (72 per cent). The complication rate was moderate and only 2 patients required cystectomy for symptoms caused by radiation damage alone.

A controlled trial of intra-articular radiocolloids versus surgical synovectomy in persistent synovitis.

The results of a randomised trial of irradiation of the knee (synoviorthése), by intra-articular injection of yttrium-90, and surgical synovectomy have been compared in twenty knees in seventeen patients. The mean length of follow-up was 2 years. Relapse occurred in three out of ten irradiated knees, and in 2 out of 10 operated knees. Fewer irradiated knees were involved when generalised exacerbations of polyarthritis occurred. Irradiation carries a lower risk of complications than does synovectomy, it is more acceptable to patients, requires fewer days in hospital, and is cheaper; it would seem to be the treatment of choice in the older patient.

The effect of yttrium-90 implantation on endocrine function and visual fields in patients with "functionless" pituitary tumors, with biopsy and radiological findings.

Thirty patients with symptoms from "functionless" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of "functionless" pituitary tumour. The "supressive" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.

Gel filtration of human urinary immunoreactive luteinizing hormone.

In human urinary concentrates and also in a urinary gonadotrophin standard (2nd IRP-HMG), gel-filtration analysis revealed three main peaks of immunoassayable luteinizing hormone (LH). A similar analysis of LH extracted from human pituitaries showed most of the activity in a peak of larger molecular weight, and only minor fractions in the positions of the urinary peaks. In an extract of normal human serum, analyss showed only one similar peak of large molecular weight, which also emerged before the urinary peaks. During an i.v. infusion of pituitary LH into normal men, the urinary LH activity increased but was still found only in the same three peaks on gel filtration, and all were of a molecular weight smaller than that of the infused material; but a higher proportion of the urinary LH was found in the earliest of these peaks compared with that found before infusion. Conversely, 20-35 h after the i.v. infusion, there was a slightly higher proportion of LH activity in the third peak of smallest molecular weight. These findings suggest that the urinary immunoassayable LH, which is found in three peaks of different molecular weights, is derived from the pituitary or serum LH of higher molecular weight. The changes in the proportions of larger or smaller molecular weight fractions in the urine during and after LH infusion suggest that the earliest peak may be disaggregated serum LH, while the last or smallest molecular weight peak may comprise metabolites of LH.

Dosimetry of spherical Sr-90-Y-90 beta ray eye applicators.

A modification of the conventional extrapolation chamber to perform absolute dose measurements from surfaces of spherical beta applicators (type SIA.I, SIA.3, SIA.6) is described. A stack of Ilford N 550 films has been used in a spherical geometry to obtain the variation of surface dose, the depth dose data and the isodose curves. The results obtained are compared with data available in the literature.