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.

[Use of gold radionuclide markers implanted into the prostate for image-guided radiotherapy in prostate cancer: side effects caused by the marker implantation]. / A prosztatába ültetett aranymarkerek alkalmazásának bevezetése prosztatarákos betegek képvezérelt sugárkezeléséhez. A beültetés okozta mellékhatások ismertetése.

The purpose of the study was to introduce the use of the gold radiopaque markers implanted into the prostate for image-guided radiotherapy of prostate cancer patients and to present the side effects caused by the marker implantation. Between November 2011 and November 2013, three radiopaque, gold-plated markers (Best Medical International, Springfield, VA, USA, 1.0 mm x 3.0 mm) were implanted transperineally into the prostate of 60 patients under transrectal ultrasound guidance. Local anaesthesia was performed in all patients. A week after the procedure the patients filled in a questionnaire regarding the pain, dysuria, urinary frequency, nycturia, rectal bleeding, haematuria, haematospermia or fever symptoms caused by the implantation. The pain caused by the intervention was scored on a 1-10 scale, where 1 was a very weak and 10 was an unbearable pain. Ten days after the implantation a treatment planning CT was performed and subsequently patients started intensity-modulated radiation therapy (IMRT) within one week. During the treatments markers were used for daily verification and correction of patient's setup. No patients experienced fever or infection. Based on the questionnaires nobody experienced dysuria or rectal bleeding after implantation. Among the 60 patients studied, five (8 %) had haematospermia, nine (15 %) haematuria, which lasted in average of 3.4 and 1.8 days, respectively. The average pain score on 1-10 scale was 4.2 (range: 0-9). After the marker implantation 18 patients (30%) reported less, 10 patients (17%) more, and 27 patients (45%) equal amount of pain compared to biopsy. Five patients, who had a biopsy performed under general anaesthesia, did not answer this question. None of the patients needed analgesics after implantation. The gold marker implantation implemented for image-guided radiotherapy was well tolerated under a local anaesthesia. The complications were limited, rate and frequency of perioperative pain was comparable to the pain caused by biopsy. After implantation, the patients did not require analgesics. The method can be performed safely in clinical practice.

Repeat brachytherapy for patients with residual or recurrent tumors of oral cavity.

PURPOSE: To analyze data from patients receiving repeat brachytherapy (re-BT) for the treatment of residual or recurrent tumor in the oral cavity. METHODS AND MATERIALS: Between January 2003 and December 2007, 62 patients who had undergone definitive BT as an initial treatment of oral cancer subsequently underwent re-BT for the treatment of residual or recurrent tumors at the diagnostic radiology and oncology department (Tokyo Medical and Dental University Hospital). Re-BT was performed 0.9-73 months (median, 5.7) after the initial BT. Au-198 grains were used as the re-BT source in all 62 patients, and an area of 0.8-6.3 cm(2) (median, 3.1) was permanently irradiated with 60-110 Gy (median, 83) according to the system of Paterson-Parker. RESULTS: The 2-year local control and overall survival rate was 53% and 66%, respectively, and local control significantly affected overall survival. Both local control and overall survival were affected by the initial tumor characteristics and the macroscopic appearance of the residual or recurrent tumor. Grade 3 or 4 complications were seen in 5 patients. The incidence of mandibular and mucosal complications was significantly related to a biologic effective dose of α/ß of 3 Gy to the surface of the gingiva and mucosa, respectively. CONCLUSION: Re-BT using Au-198 grains for the treatment of residual or recurrent tumor after definitive BT in the oral cavity is effective and well tolerated.

[Dosimetric perturbation due to scattered rays released by a gold marker used for tumor tracking in external radiotherapy].

Image-guided radiation therapy using a gold marker-based tumor tracking technique provides precise patient setup and monitoring. However, the marker consists of high-Z material, and the resulting scattered rays tend to have adverse effects on the dose distribution of radiotherapy. The purpose of this study was to evaluate the dosimetric perturbation due to the use of a gold marker for radiotherapy in the lungs. The relative dose distributions were compared with film measurement, Monte Carlo simulation, and XiO calculation with the multi grid superposition algorithm using two types of virtual lung phantoms, which were composed of tough water phantoms, tough lung phantoms, cork boards, and a 2.0-mm-diameter gold ball. No dose increase and decrease in the vicinity of the gold ball was seen in the XiO calculations, although it was seen in the film measurements and the Monte Carlo simulation. The dose perturbation due to a gold marker cannot be evaluated using XiO calculation with the superposition algorithm when the tumor is near a gold marker (especially within 0.5 cm). To rule out the presence of such dose perturbations due to a gold marker, the distance between the gold marker and the tumor must therefore be greater than 0.5 cm.

Migration of intraprostatic fiducial markers and its influence on the matching quality in external beam radiation therapy for prostate cancer.

PURPOSE: To assess the influence of fiducial marker (FM) migration on the matching quality in external beam radiation therapy (EBRT) for prostate cancer. MATERIALS AND METHODS: The position of FMs were identified using on-board kV imaging (OBI) and their 3-D position established using an in-house reconstruction algorithm for 31 patients with prostate adenocarcinoma. To carry out the match, the positions were overlaid on the digitally reconstructed radiographs (DRR) generated from the planning CT. The distance between each FM was calculated for seven treatments throughout the EBRT course. Four radiotherapy technologists were asked to independently perform and rate the match from OBI to DRR which was then correlated to the extent of FM migration. RESULTS: All the matches were rated by at least three radiotherapy technologists as "very easy" ("easy" subgroup) for 24 patients (77%), while the other seven patients had their match rated less than "very easy" and considered the "not easy" subgroup. The average daily FM migration was 0.93+/-0.34 mm for the "easy" subgroup vs. 1.82+/-0.75 mm for the latter. An average migration >2 mm was seen in five/seven patients in the "not easy" subgroup as compared to none in the "easy" subgroup. There was a trend towards less FM migration and better matching if the planning CT was done later than the day of the FM implant (p=0.093). CONCLUSIONS: FM migration >2 mm predicts for a more difficult matching process; PTV margins might have to be adjusted or the planning CT repeated.

Long-term experience with transrectal and transperineal implantations of fiducial gold markers in the prostate for position verification in external beam radiotherapy; feasibility, toxicity and quality of life.

BACKGROUND AND PURPOSE: This study presents an overview of the experience with transrectal and transperineal implantations of fiducial markers for position verification in prostate radiotherapy, regarding the practical feasibility, procedure-related toxicity and influence on quality of life (QoL). MATERIAL AND METHODS: Since 2001, 914 patients scheduled for intensity-modulated radiotherapy (IMRT) have received gold markers in the prostate. The incidence of severe toxicity, defined by the CTCAE v3.0, was evaluated retrospectively. The influence on QoL was measured prospectively in 36 patients using a combination of three validated questionnaires: the Rand-36, the EORTC QLQ-C30(+3) and the prostate cancer-specific EORTC QLQ-PR25. Next, the incidence of marker migration was assessed. RESULTS: From 2001 to 2005, 402 patients received markers via the transrectal route. Two of these patients developed urosepsis (grade 3 toxicity). Since 2005, 512 patients received markers via the transperineal route. No grade 3 or 4 toxicity occurred in this group. No significant and clinically relevant differences were found in QoL between pre- and post-implant measures. In 5 patients marker migration led to discontinuation of the marker-based IMRT. CONCLUSIONS: Clinical use of transperineal-implanted fiducial gold markers for position verification in external beam radiotherapy for prostate cancer is a feasible and safe procedure without influencing patients' QoL.

Corneoscleral necrosis after episcleral Au-198 brachytherapy of uveal melanoma.

PURPOSE: To describe the risk factors for the development of corneoscleral necrosis (CSN) and its management in patients with primary choroidal or ciliochoroidal melanoma who underwent episcleral Au-198 brachytherapy. METHODS: Clinical records of patients with symptoms of dry eye, foreign body sensation, pain, and evidence of CSN after Au-198 brachytherapy for uveal melanoma treated over a 22-year period were reviewed retrospectively. Risk factors for the development of CSN were identified and various methods of management were evaluated. The data were analyzed using multivariant analysis. A P < 0.05 was taken as a level of statistical significance. RESULTS: Of the 202 eyes of 202 patients treated with Au-198 radioactive plaque, 15 (7.4%) patients with symptomatic complaints of dry eye and pain showed evidence of CSN. First signs were noted as early as 1 month to as late as 5 years (median time 5 months) after the treatment. Risk factors for the development of CSN included tumor thickness greater than 6 mm and ciliary body involvement (P < 0.05). Associated risk factor included intraocular pressure greater than 21 mmHg. Four patients required conservative management, 11 patients required scleral patch and/or conjunctival flaps, and 6 eyes eventually required enucleation. Eyes which developed CSN were more likely to undergo enucleation compared with eyes having no evidence of CSN (P < 0.05). None of the eyes with CSN, which required enucleation because of the failed treatment, had histopathologic evidence of recurrent tumor or tumor invading sclera. CONCLUSION: Corneoscleral necrosis may occur soon or several years after Au-198 brachytherapy for uveal melanoma. Risk factors for CSN include tumor thickness greater than 6 mm, ciliary body involvement, and intraocular pressure >21 mmHg. Closer follow-up, early recognition, and timely intervention may avert serious consequences.

Stereotactic radiosurgery versus gold grain implantation in salvaging local failures of nasopharyngeal carcinoma.

BACKGROUND: Limited local failure of nasopharyngeal carcinoma (NPC) can often be salvaged by reirradiation using different techniques. Both gold grain implantation (GGI) and stereotactic radiosurgery (SRS) have been used as salvage treatment of NPC but the relative efficacy of these two treatments is not known. METHODS AND MATERIALS: A total of 74 patients with local NPC failure were included in this retrospective analysis. Of these patients, 37 underwent SRS (median dose, 12.5 Gy) and 37 split-palatal GGI at a dose of 60 Gy. The two groups were individually matched for prognostic factors, except for tumor volume. The median follow-up was 42 months. RESULTS: Local control was better in the GGI group. The 3-year local failure-free rate was 77.9% for the GGI group compared with 68.3% for the SRS group. However, the difference was not statistically significant (p = 0.098). In the subgroup with a tumor volume of

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.

Late normal tissue injury from permanent interstitial implants.

PURPOSE: To develop a simple method of calculating biologically effective doses in high-dose regions of permanent interstitial implants. METHODS AND MATERIALS: The incomplete repair model is used to clarify the relationship between dose, D, and biologically effective dose (BED), for permanent interstitial implants. The relationship is used to ascertain the BED at high-dose regions that may occur in (125)I, (103)Pd, and (198)Au prostate implants. RESULTS: The relationship between D and BED is nonlinear and is given by BED(D) = D + D(2)/D(lambda), where D(lambda) = [(t(lambda)/t(mu)) + 1](alpha/beta), t(lambda) and t(mu) are the half-lives of the isotope and of sublethal damage repair respectively, and alpha/beta is the alpha:beta ratio. Idealized geometrically identical (125)I, (103)Pd, and (198)Au prostate implants with minimum target dose (MTD) of 160 Gy, 120 Gy, and 64 Gy, respectively, are considered. The BED for (103)Pd and (198)Au will be less than the BED for (125)I, for doses up to about 2.5 times the MTD. For higher doses, the BED for (103)Pd may be significantly higher than for (125)I. CONCLUSION: Permanent interstitial implants using short-lived isotopes may have regions with very high biologically effective doses.

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.

Radiation keratosis associated with exposure to a gold ring.

A radiation keratosis occurred in a woman who wore a radioactive gold ring forty-three years ago. Clinicians should be aware that not all "warty lesions" on the hands are actinic keratosis, seborrheic keratosis, or warts. Radioactive gold rings still exist. Diagnosis requires a high index of suspicion, since patients may no longer be wearing the offending ring.

Post-irradiation vasculopathy of intracranial major arteries in children--report of two cases.

We report two rare cases of post-irradiation vasculopathy of intracranial major arteries in children. A 13-year-old girl suffered from transient right hemiparesis 1 year after irradiation for suprasellar germinoma. Left carotid angiograms revealed marked stenoses of the intracranial internal carotid, middle cerebral, and anterior cerebral arteries, which were previously normal, and moyamoya vessels. A 2.5-year-old girl underwent internal irradiation with 198Au colloid for cystic craniopharyngioma. At the age of 10 years, she suddenly became unconscious after vomiting. Computed tomographic scans showed a right frontal intracerebral hematoma. Right carotid angiograms disclosed complete obstruction of the intracranial internal carotid, middle cerebral, and anterior cerebral arteries and moyamoya vessels, previously not present. The danger of radiation therapy causing occlusive vasculopathy in small and major cerebral arteries in children is emphasized. To prevent permanent ischemic neurological deficits, vasculopathy should be treated either medically or surgically as early as possible.

Aneurysm, arachnoiditis and intrathecal Au (gold).

This report is a 20-year follow-up of 14 patients treated with external beam craniospinal irradiation and intrathecal gold (10-45 mCi) for medulloblastoma. Six of the patients died within 2 years of treatment from persistent disease. No patients are alive without complications. Six of eight surviving patients developed arachnoiditis and cauda equina syndrome within 5 to 10 years of treatment. Seven of eight survivors developed aneurysms and/or cerebrovascular accidents 9 to 20 years after treatment. Four of the cerebrovascular events were fatal. Intrathecal gold pools in the basal cisterns and cauda equina delivering an extremely inhomogeneous dose throughout the neuroaxis. Its use is discouraged.

Palliation of bronchogenic carcinoma with 198Au implantation using the fiberoptic bronchoscope.

The majority of cases of bronchogenic carcinoma remain incurable, and many of these patients require palliation of the effects of the tumor on the airway. We have developed a technique for implanting radioactive (198Au) seeds via the fiberoptic bronchoscope. We now retrospectively review the results obtained in 111 procedures in 54 patients. Response was assessed by improvement in symptoms, chest roentgenogram, or bronchoscopic appearance. Nineteen of 29 (66 percent) patients with occluding endobronchial lesions benefitted. Twenty of 22 (91 percent) with hemoptysis improved. All six patients with tracheal lesions benefitted. Two of six (33 percent) patients with nonoccluding endobronchial lesions responded. Complications directly related to the procedure were rarely of major consequence, although a single patient had an exsanguinating hemoptysis four days following the last of multiple implantations. The simplicity, relative safety, and potential wide availability coupled with low equipment costs would suggest an increasing role for this technique in the palliation of endobronchial neoplasms.

Severe rectal injury following radiation for prostatic cancer.

Between 1970 and 1981, 348 patients underwent definitive irradiation. Of these patients 6 (1.7 per cent) sustained severe rectal injury as manifest by major rectal bleeding, rectal stricture, rectal mucosal slough and rectal ulceration. Severe rectal injury was observed in 0 of 13 patients (0 per cent) treated with 125iodine, 3 of 329 (1 per cent) treated with 6,400 to 6,800 rad external irradiation, 2 of 39 (5 per cent) treated with 7,000 to 7,300 rad external irradiation, and 1 of 7 (14 per cent) treated with 198gold and external irradiation. The impact of radiation dose, radiation therapy technique and surgical trauma was assessed. Rectal injury was managed by supportive measures in 2 patients and by diverting colostomy in 3 with benefit. One patient underwent abdominoperineal resection. A small bowel fistula and an intra-abdominal abscess developed, and the patient died.

Radioisotopes in the treatment of ovarian cancer.

Ovarian cancer, currently, is the leading cause of death from malignancies arising in the female genital tract. Investigators and collaborative groups are focusing on this problem in an attempt to improve patient survival. The material reviewed has attempted to gather the data that relate to the use of radioisotopes in the treatment of ovarian cancer. The conclusions reached from this review are: Dose. The initial therapeutic dose of 198Au was empirically determined by Muller. This empirically determined dose was then used to estimate a dose of 32P, based on certain assumptions about these radiocolloids that have been shown to be erroneous. It would appear that the administered dose of 100-150 mCi of 198Au yields a significantly greater tissue dose than 10-15 mCi of 32P. Complications. Complications associated with 198Au are a result of a possibly excessive dose, delivered over a shorter period of time, with a significant gamma component. It is clear that in greater than 99 per cent of disintegrations each beta particle is associated with a gamma component. Distribution, dose distribution, and dose rate. These three critical factors have recently been evaluated for intraperitoneal 32P. It would appear that distribution is non-uniform, and thus dose distribution is not homogeneous, and that dose rate is low and may be ineffective in controlling ovarian cancer. Results of treatment. It would appear from a review of the literature that no prospective randomized well-controlled study as indicated the effectiveness of 32P over other treatment modalities. There is only circumstantial evidence for its effectiveness. The clinical applicability of 32P in the treatment of Stage I ovarian cancer, as part of a treatment protocol, awaits the results of well controlled prospective clinical trials.