Treatment outcomes of real-time intraoral sonography-guided implantation technique of 198Au grain brachytherapy for T1 and T2 tongue cancer.

It is often challenging to determine the accurate size and shape of oral lesions through computed tomography (CT) or magnetic resonance imaging (MRI) when they are very small or obscured by metallic artifacts, such as dental prostheses. Intraoral ultrasonography (IUS) has been shown to be beneficial in obtaining precise information about total tumor extension, as well as the exact location and guiding the insertion of catheters during interstitial brachytherapy. We evaluated the role of IUS in assessing the clinical outcomes of interstitial brachytherapy with 198Au grains in tongue cancer through a retrospective medical chart review. The data from 45 patients with T1 (n = 21) and T2 (n = 24) tongue cancer, who were mainly treated with 198Au grain implants between January 2005 and April 2019, were included in this study. 198Au grain implantations were carried out, and positioning of the implants was confirmed by IUS, to ensure that 198Au grains were appropriately placed for the deep border of the tongue lesion. The five-year local control rates of T1 and T2 tongue cancers were 95.2% and 95.5%, respectively. We propose that the use of IUS to identify the extent of lesions and the position of implanted grains is effective when performing brachytherapy with 198Au grains.

Dose characteristics of Au-198 eye brachytherapy applicator: A Monte Carlo study.

PURPOSE: The use of ocular plaques is a promising treatment option for eye melanoma brachytherapy. Although several studies have been done on various ocular plaques, little is known about the dose characterization of 198Au plaque. MATERIALS AND METHOD: The full mathematical model of the eye phantom, tumor, 106Ru/106Rh CCA, and 198Au plaque were simulated using the Monte Carlo MCNPX code. The dose distribution was measured in the plaque's central axis direction, and a dose profile was also measured at a distance of 2.5 mm from the plaque surface. RESULTS: The findings showed that 198Au plaque has superior dosimetric characteristics than CCA plaque for tumors with a thickness of greater than 3.5 mm, while CCA plaque is better for tumors with a thickness of less than 3.5 mm. The dose to the sclera and choroid is higher in the case of CCA plaque, while the dose to the organs at risk (lens and optic nerve) is greater in the case of 198Au applicator. In the case of 198Au plaque, however, the dose to sensitive organs was within their permissible dose range. CONCLUSION: In the treatment of medium and large tumors, 198Au plaque is more successful than CCA plaque. It can produce a much more homogeneous lateral dose profile in the target. In the treatment of dome-shaped tumors, 198Au plaque may be more successful than CCA plaque. As a result, the tumor's shape influences the plaque type selection.

Internalization capabilities of gold-198 nanoparticles: Comparative evaluation of effects of chitosan agent on cellular uptake into MCF-7.

In this study, internalization of positively charged chitosan-coated nanoparticles (198AuNPs@chitosan) on MCF-7 cells was investigated by γ-ray spectroscopy and then statistically compared to that of 198Au and negatively charged citrate-stabilized nanoparticles (198AuNPs). Sub-50 nm 198AuNPs@chitosan had a higher internalization compared to 198Au and 198AuNPs (p < 0.05). More cellular uptake of 198AuNP@chitosan means a higher dose of radioactivity to the tumor cells which, in turn, more effective treatment of the cancer.

Design of the spacer for brachytherapy using 198Au grain for carcinoma of the tongue as a tool of perioperative oral management.

PATIENTS: Seventy-one and 73 years-old males visited a perioperative oral care support center to receive perioperative oral management during tongue cancer (T1N0M0) treatment. To improve their quality of life (QOL) during brachytherapy while preventing radiation-related complications including osteoradionecrosis due to 198Au grain brachytherapy, spacers for their maxilla and mandible were designed with consideration of wearing condition at an isolation ward. The spacer was created with unilateral design and with consideration of the tongue mobility during day and night. Then, the spacer was thickened on the plaster model, demonstrating the cancer lesion in the tongue in order to secure the distances from the mandibular body, maxilla and sublingual gland to the radiation sources embedded in the tongue. DISCUSSION: Tongue impression made the spacers as small as possible by thickening just around the cancer lesions so that the patients could wear them comfortably, while keeping adequate distance between the radiation sources and peripheral normal tissues. Breakable hard materials were avoided so that the patients were able to utilize the spacers safely without accidentally swallowing a broken fragment. Additionally, considering the upward movement of the tongue in a sleeping posture, the upper spacers were also prepared to protect the maxillae. Computer simulation revealed that the design of our spacers had enough effect on a reduction in radiation to prevent osteoradionecrosis in the maxilla as well as mandibular body. CONCLUSIONS: This report demonstrated the importance of the spacers created with consideration of patients' wearing condition to improve their QOL during brachytherapy.

Radioluminescent gold nanocages with controlled radioactivity for real-time in vivo imaging.

Cerenkov luminescence imaging based on light emission from the decay of radionuclides has recently drawn great interest in molecular imaging. In this paper, we report for the first time the Cerenkov luminescence phenomenon of (198)Au isotope, as well as a facile route to the preparation of radioluminescent Au nanocages without additional radiolabeling or dye conjugation. The specific radioactivity of the Au nanocages could be easily and precisely controlled by varying the concentration of H(198)AuCl(4) precursor used for the galvanic replacement reaction. The direct incorporation of (198)Au atoms into the structure of Au nanocages enabled the ability of accurate analysis and real-time imaging in vivo. Furthermore, under biological conditions the radioactive Au nanocages were shown to emit light with wavelengths in the visible and near-infrared regions, enabling luminescence imaging of the whole mice in vivo, as well as the organs ex vivo. When combined with their favorable scattering and absorption properties in the near-infrared region, the radioactive Au nanocages can serve as a new platform for multimodality imaging and will have a significant impact on both small animal and clinical imaging.

A retrospective analysis of the use of brachytherapy in relation to early stage squamous cell carcinoma of the oropharynx and its relationship to second primary respiratory and upper digestive tract cancers.

The purpose of this study was to retrospectively evaluate brachytherapy for early stage squamous cell carcinoma of the oropharynx (SCO) in relation to second primary respiratory and upper digestive tract cancers (RUDT). Between 1976 and 2001, 111 previously untreated patients with stage I or II SCO were treated with Au-198 seed brachytherapy alone (36 cases) or Au-198 seed brachytherapy plus external irradiation (75 cases). Of the 111 patients, 28 patients had stage I disease and 83 patients had stage II disease. Each patient was evaluated for therapeutic efficacy, post-treatment quality of life (QOL) and a second cancer. The 5-year and 10-year cause-specific actuarial survival rates for stage I and II SCO were 87% and 86%, respectively. We found that the 5-year and 10-year survival rates for all SCOs combined with second primary RUDT cancers were 71% and 45%, respectively. 51 second primary RUDT cancers occurred successively in 41 patients following treatment for early stage oropharyngeal cancer and this was the sole prognostic factor by the multivariate analysis. Au-198 seed brachytherapy with or without ipsilateral external irradiation of up to 30 Gy was associated with fewer late complications in the oral cavity and salivary gland. We concluded that our treatment policy of brachytherapy with or without external irradiation for patients with early stage SCO was effective and acceptable from the standpoint of tumour control and post-treatment QOL.

Clinical feasibility study for the use of implanted gold seeds in the prostate as reliable positioning markers during megavoltage irradiation.

BACKGROUND AND PURPOSE: The aim of this study was to assess the feasibility of using gold seed implants in the prostate for position verification, using an a-Si flat panel imager as a detector during megavoltage irradiation of prostate carcinoma. This is a study to guarantee positioning accuracy in intensity-modulated radiotherapy. METHODS AND MATERIALS: Ten patients with localized prostate carcinoma (T2-3) received between one and three fiducial gold markers in the prostate. All patients were treated with 3-D conformal radiotherapy with an anterior-posterior (AP) and two lateral wedge fields. The acute gastrointestinal (GI) and genitourinary (GU) toxicities were scored using common toxicity criteria scales (CTC). Using three consecutive CT scans and portal images obtained during the treatment we have studied the occurrence of any change in prostate shape (deformation), seed migration and the magnitude of translations and rotations of the prostate. RESULTS: We observed no acute major complications for prostate irradiation regarding the seed implantation. The maximum acute GU toxicity grade 2 (dysuria and frequency) was observed in seven patients during the treatment. The maximum grade 2 (diarrhoea) was scored in two patients regarding the acute GI toxicities. No significant prostate deformation could be detected in the consecutive CT scans. It appeared that the distances between the markers only slightly changed during treatment (S.D. 0.5 mm). Random prostate translations were (1 S.D.) 2.1, 3.2 and 2.2 mm in the lateral (LR), AP and cranial-caudal (CC) directions, respectively, whereas systematic translations were 3.3, 4.8 and 3.5 mm in the LR, AP and CC directions, respectively. Random prostate rotations were (1 S.D.) 3.6, 1.7 and 1.9 degrees around the LR, AP and CC axis, respectively, whereas systematic rotations were 4.7, 2.0 and 2.7 degrees around the LR, AP and CC axis, respectively. CONCLUSIONS: We found that the fiducial gold seeds are a safe and appropriate device to verify and correct the position of prostate during megavoltage irradiation. The amount of seed migration and prostate deformation is far below our present tumour delineation accuracy.

Results of ovary tumor treatment with abdominally administered (198)Au evaluated on the basis of long term follow up.

In the period between 1959 and 1980 165 patients previously operated with ovarian tumor were treated by intraperitoneally administered (198)Au in the Oncoradiological Centre of the Uzsoki Hospital. The stage distribution of the 158 patients with common epithelial histology was as it follows: Stage I/A 31; Stage I/B 9; Stage I/C 59; Stage II/A 19; Stage II/B 11; Stage II/C 7, Stage III/A 22. The five year survival result is the next: Stage I/A 90%; Stage I/B 78%; Stage I/C 58%; Stage II/A 26%; Stage II/B 27%; Stage II/C 14%; Stage III/A 18%. From the other 7 patients six had sex cord tumor and one lipid cell tumor. The number of the side effects is in good agreement with the data in literature. The use of (198)Au for intraperitoneal treatment of ovary tumors is not contemporary today because of gamma radiation of radiogold, but intraperitoneal radiation treatment should not be forgotten.

Synoviorthesis with radioactive gold in haemophilia.

According to the experiences of the Malmö Haemophilia Centre, the best way to avoid recurrent joint bleedings and synovitis in haemophilic patients and to prevent progressive joint disease is prophylactic factor treatment. If prophylaxis is impracticable and also in patients with factor inhibitors, radioactive synoviorthesis seems to be a good treatment option if started early.

On the safety of synoviorthesis in haemophilia.

One of the best procedures to prevent haem-arthrosis has been radioactive synovectomy (synoviorthesis). Since the first report of radioactive synovectomy in haemophilia of Ahlberg in 1971 [1], many centres adopted this procedure as the one of choice, through fibrosing the synovial membrane, prevent further haemarthrosis. Since 1976 we have performed 104 such radioactive synoviorthesis in 97 patients, age ranging from 6 to 40 years with a mean of 10 years. Sixty-five of these patients were under 12 years of age. The knees were injected in 61 cases, elbow in 26 cases, ankles in 14 cases and shoulders in three cases. The clinical results of this procedure show 80% of excellent results with no further bleeding. In case of failure, a new injection can be given in the same joint at a 6-month interval, or an injection for the same purpose in other joint. One of the criticisms against this method is the possible chromosomal damage induced by the radioactive material. In our centre, four studies have been carried out in order to see whether these changes, when they occur, are everlasting; all have demonstrated that chromosomal changes are reversible. The radioactive material used in the two first studies was Gold-189 (189Au). In 1978, 354 metaphases were studied with 61 ruptures, 17.23% (nonpremalign) and six structural changes, considered premalign (1.69%). Any number below 2% is considered not to be dangerous. A further study was done in 1982, in the same group of patients with a result of 21 ruptures (3.34%) and no structural changes. This demonstrated that the possible premalign changes disappeared with time. A third study was performed in a series of 13 patients that sustained radioactive synoviorthesis with Rhenium-186 (186Re) in November 1991. For comparison, we carried out a chromosomal study just before and 6 months after the radioactive material injection. The results confirmed that changes that could be linked to the radiation, appeared equally in nonirradiated patients, and those changes due to the radiation disappear with time, never reaching the dangerous zone of 2%. In the group treated with 186Re we studied an additional number of 130 metaphases with identical results and no structural changes. In a study on patients where 90Y was the radiocolloid, no premalign change was found before or after the synoviorthesis. It seems, in view of these results, that radioactive synovectomy is safe and gives great benefits to the haemophilic patients.

Intraoperative gold grain implants for pelvic wall recurrences of various malignancies: toxicity, results, and failure analysis in 37 patients.

PURPOSE: We conducted this study to determine the complications and long-term results of intraoperative gold-grain implants as therapy for pelvic wall recurrences of various malignancies. MATERIALS AND METHODS: We retrospectively analyzed complications and long-term results of intraoperative radioactive 198Au gold grain implants of 4-mc radon equivalent in 37 patients with pelvic wall recurrences of various malignancies treated at the University of Texas M. D. Anderson Cancer Center. The estimated dose was 30-100 Gy, which was increased to 100-120 Gy plus external-beam irradiation if the dose to the tumor volume was too low. All patients had follow-up of 4 months to 12 years. Of the 37 patients, 34 had lower leg edema, 22 had lower limb pain, and 22 had ureteral obstruction. RESULTS: Six of 34 patients with lower limb pain had partial relief and nine had complete relief. Of 22 patients with ureteral obstruction, ten had complete resolution and four had partial relief. Lower limb edema was improved in 16 of 22 patients. Of the 37 patients studied, 14 are alive and 23 have died. CONCLUSION: In selected patients, gold grain implantation to a dose of 70-100 Gy relieved some symptoms of unresectable pelvic wall recurrences of various malignancies. We believe that intraoperative gold grain implants appear to be the only useful treatment for patients with recurrent malignancies fixed to the pelvic wall and provide these patients with better and longer palliation and a good quality of life.

Brachytherapy of a choroidal melanoma using radioactive gold grains: a long-term follow-up study.

PURPOSE: We used radioactive gold grains to treat a patient with choroidal malignant melanoma. Radioactive sources were placed into surgically constructed scleral pockets. The patient was followed up for six years after therapy to assess changes in the tumor, recurrence, and side effects. METHODS AND MATERIALS: A male patient presented with malignant melanoma arising from the choroidal membrane of the posterior pole of the left eyeball. We placed radioactive gold grains into surgically constructed scleral pockets adjacent to the tumor, arranged in a plane based on the Manchester's method. The patient was followed up for six years after treatment. RESULTS: The radiation dose was 120 Gy at the apex of the tumor, which slowly became smaller and completely disappeared at one year and 10 months after treatment. Tumor recurrence was not observed. Radiation dose at the ipsilateral lens was 280 cGy. Side effects associated with therapy were a decrease in visual acuity secondary to retinal degeneration and atrophy, but his vision was correctable with suitable glasses. In addition, the visual field of the left eye was also restricted. Mild cataracts also developed in the ipsilateral eye after treatment. CONCLUSION: Although this therapeutic method is technically difficult compared with other methods, it permits the tumor to be treated without loss of the eye. This may significantly improve the patient's quality of life.

The Baylor College of Medicine experience with gold seed implantation.

Advances in imaging technology and implant technique have led to the resurgent interest and practice of brachytherapy for the treatment of prostate cancer. Brachytherapy is a form of radiation treatment in which radioactive sources are placed directly into the tumor; it offers the advantage of maximizing the radiation dose delivered to the tumor while sparing the adjacent normal tissue. Permanent implants have become an important component of radiation delivery. Interstitial gold radioisotope (Au-198) implants for prostate cancer were introduced at Baylor College of Medicine in 1965. The rationale for using Au-198, instead of the two most commonly used radioisotopes, Palladium-103 (Pd-103) and Iodine-125 (I-125), is discussed, and the Baylor implant technique is compared to that used in other centers. Retrospective review divides the patient population into pre-ultrasound versus post-ultrasound eras. Dosimetric calculation and disease control with the Au-198 seed implant for prostatic cancer are reviewed for the two different eras; toxicity is evaluated in the post-ultrasound era only. In the pre-ultrasound era, 510 patients were treated with pelvic lymph node sampling and gold seed insertion of the prostate followed by external beam radiation. In the post-ultrasound era, 54 patients were treated definitively with ultrasound-guided transperineal Au-198 implant followed by external beam irradiation. A small group of 30 patients in the post-ultrasound era were evaluated for the efficacy of Au-198 re-implantation for locally recurrent disease.

Gold seed implantation in prostate brachytherapy.

Interstitial brachytherapy for treatment of prostate cancer with radioactive gold--initially with liquid gold and later with seed technique--is based on an experience of more than four decades. With biopsy results approaching a 80% negative rate, and, at 5 years, a cancer specific survival of 100% for Stages A and B1, 90% for Stage B2, and 76% for Stage C, this form of treatment offers an effective and well-tolerated alternative mode of therapy for patients with localized prostate cancer.

Radioactive synoviorthesis in patients with hemophilia with factor inhibitor.

In nine patients with hemophilia and factor inhibitor (six with hemophilia A; three with hemophilia B), 19 joints were treated with radioactive synoviorthesis using Au-198. Ages ranged from 3 to 40 years. Synoviorthesis was performed when the antibody titer was low (< 10 Bethesda units), thus making hemostasis possible by factor administration for 2 to 4 days. On five occasions, radioactive synoviorthesis was performed simultaneously with tolerance induction according to the Malmö protocol. A bleeding free interval of more than 6 months was obtained in 11 joints, six of which remained bleeding free for more than a year. At long term followup (range, 18-182 months) five joints were rated good, one joint was fair, and 11 joints were poor. Although the results are inferior to those for patients with hemophilia without inhibitor, radioactive synoviorthesis should be considered because of its ease of performance and the definite decrease in joint bleeding frequency that it brings about. This is of particular interest in patients with hemophilia caused by factor inhibitor who otherwise are difficult to treat.

Hemophilic synovitis of the knee and the elbow.

A prospective study from 1974 to 1996 was done to determine optimal treatment for chronic hemophilic synovitis of the knee and synovitis of the elbow. Sixty-five patients with synovitis affecting 65 knee joints and 40 patients who had synovitis of the elbow (44 elbows), despite a 3-month trial of prophylactic substitution therapy, were treated by synovectomy. Radiation synovectomies (Au-198 synoviorthesis) were done on 38 knees, open surgical synovectomy on 18, and nine had an arthroscopic procedure. Radioactive gold synoviorthesis was performed on 29 elbows, and 15 had a resection of the radial head and partial open synovectomy. Synovectomy (by any method) significantly reduced bleeding episodes, but did not halt the radiographic deterioration of the joints. It is thought that radiation synovectomy is the best choice for patients with persistent synovitis of the knee and synovitis of the elbow unresponsive to a 3-month trial of prophylactic factor replacement. If two to three consecutive synoviortheses with 3 to 6 months intervals had been ineffective, or when the radiographic score is more than two points, an open synovectomy is indicated.

Application of 198Au grains for carcinoma of oral cavity.

PURPOSE: The purpose of this study is to analyze the results of the treatment using gold grain implants over the past 9 years and to evaluate the usefulness of this treatment method. PATIENTS AND METHODS: From January 1985 through April 1993, a total of 45 patients with squamous cell carcinomas of the oral cavity and the oropharynx were treated with 198Au grain (gold grain) at the Department of Radiology, Osaka University Medical School. The initial activity of the grains supplied weekly by the Japan Radioisotope Association was usually 5 mCi (185 MBq), and single implants were usual. In case of combined external irradiation, telecobalt gamma-rays or 4 MV X-rays were used for treatment before implant. RESULTS: The local control rate for patients with T1 stages was 80% (20/25) and with T2 stages, 59% (10/17). The local control rate was 71% (10/14) for gold grain alone and 72% (13/18) for external irradiation combined with gold grain implants (combined therapy). In combined therapy, the median of the interval between external irradiation and gold grain implants was 21 days. The treatment interval for patients with recurrent diseases was 22 days, 22, 27, 39 and 46, respectively. The progression rate showed a tendency to increase in the patients with longer interval (more than 21 days), and with partial regression after external irradiation (p = 0.0085). CONCLUSION: Our findings show that the time interval between external irradiation and gold grain implantation is an important factor in combined therapy. Therefore, we emphasize that the time interval should be shorter than 3 weeks.

Three-dimensional viewing of and dosimetric calculations in Au-198 implants of the prostate.

A three-dimensional system for dosimetric calculation of radiation from interstitial brachytherapeutic implants was developed and was compared with conventional dosimetry performed with a commercial two-dimensional system. Software programs written for this study enabled the authors to place radioactive sources in the correct reconstructed anatomic locations, compute the isodose distribution around these sources, and display the isodose curves in their correct relationship to anatomic structures. Eight radiation oncologists evaluated the usefulness of both systems. Verification studies in phantoms and in 20 patients with gold-198 implants in the prostate gland showed that the experimental system was very accurate in volume reconstruction, seed localization, isodose distribution, point-dose calculation, and computation of dose-volume histograms. Although the dose depictions in the two systems matched almost exactly, statistically significant differences existed in interpretation of the dosimetric data generated by both systems. For example, the oncologists consistently believed that the dose to the prostate was lower when the three-dimensional system was used (P less than or equal to .0001).

Synoviorthesis in young patients with hemophilia and inhibitory antibodies.

In five patients under the age of 15 with hemophilia and inhibitors, due to frequent joint bleedings, 13 joints were treated with synoviorthesis (intra-articular injection of radioactive gold). The patients received high doses of factor VIII/IX for 2-4 days or were treated simultaneously with tolerance induction according to the Malmö protocol. Of the 13 joints treated, a bleeding-free interval of more than 6 months was obtained in nine of which six remained free from bleedings for more than a year. Ease of performance, the limited requirements of pre- and postoperative care, and a definite decrease in the joint bleeding frequency render synoviorthesis well suited for use in hemophiliacs with inhibitors who are otherwise difficult to treat.