Permanent I Interstitial Radiation Therapy in the Treatment of Non-GBM High-Grade Gliomas

This study evaluates prognostic factors influencing survival outcomes for 50 patients with permanent¹²⁵ iodine-125 implants in the primary treatment of non-GBM high-grade gliomas. Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/hour with ¹²⁵I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan–Meier method for unvariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 31 patients received external radiation therapy (5000 to 6000 cGy) before the implant; 10 patients were implanted without additional external beam radiation, and 9 patients underwent external radiation therapy before implant placement. With a mean follow-up of 40.76 months (range 3.47–87 months); 1–, 3–, and 5-year survival were 78.5% (± .05%), 58.7% (± .07%), and 56.2% (± .07%) respectively. Since 56.2% of the patients were alive at 5 years, median survival has not been reached yet. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%), and brain abcess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky, and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location, and preoperative Karnofsky greater than 70. Surgical treatment of patients with non-GBM high grade gliomas combined with external beam radiation and permanent ¹²⁵I implants represent a valuable alternative for the treatment of patients with malignant gliomas, allowing patients good quality of life and long survival.     

Permanent iodine-125 interstitial radiation therapy in the treatment of non-glioblastoma multiforme high-grade gliomas

BACKGROUND: This study evaluates prognostic factors influencing survival outcomes for 60 patients with permanent iodine-125 implants in the primary treatment of non-glioblastoma multiforme (GBM) high-grade gliomas. METHODS: Stereotactic treatment planning aimed to encompass the contrast-enhancing rim of the tumor visualized by CT, with an initial dose rate of 0.05 Gy/h with 125I, delivering 100 Gy at 1 year and 103.68 Gy at infinity. Survival was evaluated using the Kaplan-Meier method for univariate analysis and the Cox regressional method for multivariate analysis. In addition to the implant, 34 patients received external radiation therapy (5,000-6,000 cGy) before the implant; 13 patients were implanted without additional external beam radiation, and 13 patients underwent external radiation therapy before implant placement. RESULTS: With a mean follow-up of 77.6 months (range 3.5-164 months), 1-, 3-, 5- and 10-year survival were 86.7% (+/-0.05%), 60% (+/-0.07%), 50% (+/-0.07%) and 45.7% (+/-0.7%), respectively. The median survival time was 57 months. Second surgery was performed following the implant in 19 patients. Findings were tumor recurrence in 11 patients (22.5%), radiation necrosis in 7 patients (14.3%) and brain abscess in 1 patient (2%). Age, sex, tumor location, side of brain, tumor volume, Karnofsky score and neurological status were correlated with survival outcome. Favorable prognostic factors were age younger than 45 years, superficial tumor location and preoperative Karnofsky score greater than 70. RPA classification was used to define this group of patients. In RPA classes I and II (n = 43), 1-year survival was 93%, while 3-, 5- and 10-year survival was 67.4, 60.5 and 55.5%, respectively, and median survival time was 91 months. In RPA class III (n = 7), 1-year survival was 71.4%, while 3- and 5-year survival was 42.9 and 28.6%, respectively, and median survival time was 47 months. In RPA class IV (n = 10), 1-year survival was 60%, while 3-, 5- and 10-year survival was 50, 22.2 and 11.1%, respectively, and median survival time was 37 months. CONCLUSION: Brachytherapy with permanent implant of 125I appears promising in the treatment of primary non-GBM malignant gliomas. It improved survival time and reduced the incidence of complications and provided good quality of life. In order to further confirm these results, multicenter randomized prospective studies are needed. RPA analysis is a valid tool to define prognostically distinct survival groups. In this study, 2-year survival and median survival time were improved in all prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with 125I implants. Further randomized studies with effective stratification are needed.     

Brachytherapy for intracranial meningioma using a permanently implanted iodine-125 seed

PURPOSE: To investigate the response and complications of iodine-125 brachytherapy for the treatment of recurrent and newly diagnosed meningiomas. Clinical cases of 2 patients treated with this method are presented. MATERIALS AND METHODS: Thirteen patients with primary and recurrent intracranial meningioma were treated by frameless stereotactic implantation of iodine-125 seeds from January 1996 to June 1998. The total dose to decay ranged from 7,000 to 17,000 cGy, with a dose rate of 5-10 cGy/h. RESULTS: All 11 evaluable patients had a decrease or stabilization in the size of their lesions as detected by MRI during follow-up. There were no acute complications. All patients who received a total dose greater than 10,000 cGy had postoperative radiation necrosis and/or vasogenic edema while only 20% of the patients who received doses of 10,000 cGy or less had radiation changes (p = 0.002). CONCLUSIONS: MRI-guided stereotactically assisted permanent implantation of iodine-125 seeds seems to be a safe, effective and noncomplicated method for the treatment of primary and recurrent meningiomas for selected patients, when doses are limited to 10,000 cGy.     

Interstitial brachytherapy for low-grade cerebral gliomas: Analysis of results in a series of 36 cases

Summary The results obtained with interstitial brachytherapy in thirty-six low-grade cerebral gliomas (2 pilocytic astrocytomas, 23 astrocytomas and 11 oligodendrogliomas) are reported (mean follow-up: 75 months, range 37–159). All tumours were situated in locations which did not call for surgical removal as the treatment of choice. Their volume ranged from 4 to 82 cc (m=32); the Karnofsky performance status (KPS) of the treated patients lay between 0.60 and 0.90.The sources utilized (Iridium-192 in 32 cases and Iodine-125 in 4) were implanted permanently in 22 patients and temporarily in 14, using the Talairach stereotactic apparatus. The mean peripheral dose was 89.7 Gy for the permanent implants and and 42.8 Gy with a rate of 32.05 cGy/h for the temporary implants. External beam irradiation was added for tumour volumes greater than 35 cc (19 cases) on a second target volume extending 2 cm beyond the tumoural borders treated with interstitial irradiation.The survival estimates for the entire group showed a probability of 82.9% at 60 months, of 56.8% at 96, 39.4% at 120 (m.s.t.: 112 months). The quality of life in the treated patients was satisfactory, KPS never falling below a mean score of 0.70. The extent of the target volume turned out to be the most significant factor influencing survival at the multivariate analysis. Severe neurological impairment due to radionecrosis occurred in 4 patients (11%), three of them requiring surgical decompression. Target volume and radiation dose showed a direct correlation with the risk of radionecrosis at the regression analysis, the critical values being 35 cc and 100 Gy (permanent implants) or 50 Gy (42 cGy/h, temporary implants) respectively. The analysis of the results indicates that, even though many questions still remain open, brachytherapy can represent a valid alternative to surgery for tumours not suitable for surgical removal.Study partially supported by a grant from the Italian Ministry of University and of Scientific and Technological Research.     

An assessment of quality of life following radical prostatectomy, high dose external beam radiation therapy and brachytherapy iodine implantation as monotherapies for localized prostate cancer

PURPOSE: Monotherapy with radical prostatectomy, high dose external beam radiotherapy or a (125)I implant is reported to produce equivalent outcomes. We assessed the health related quality of life associated with these 3 treatment approaches. MATERIALS AND METHODS: Extended Prostate Index Composite surveys were mailed to all 960 patients treated with a (125)I implant, high dose external beam radiotherapy or radical prostatectomy with or without hormonal therapy at our institution from 1998 to 2000. A total of 625 patients (65%) completed the surveys. Nerve sparing radical prostatectomy was performed when appropriate. The (125)I implant consisted of 145 Gy and high dose external beam radiotherapy consisted of 78 Gy. For urinary, rectal and sexual domains mean scores were calculated, compared by treatment modality and compared to normative values. RESULTS: A total of 234 patients with radical prostatectomy, 135 with external beam radiotherapy and 74 with a (125)I implant were treated with a monotherapy approach. Median age was 61 years in the radical prostatectomy group, 68 years in the high dose external beam radiotherapy group and 64 years in the (125)I implant group (p <0.001). Of the patients 97% [corrected] had cT1-2 disease and Gleason score 7 or less [corrected] Median time from treatment was 4.0 years for radical prostatectomy, 4.7 years for high dose external beam radiotherapy and 3.5 years for (125)I implantation. Radiation caused significantly worse bowel bother and bowel function than radical prostatectomy (p < or =0.018). Patients with high dose external beam radiotherapy had significantly better urinary function than patients with radical prostatectomy (p <0.001). While patients with radical prostatectomy had significantly worse urinary incontinence than those with a (125)I implant or high dose external beam radiotherapy (p <0.0001), patients with a (125)I implant had more urinary irritation than those with high dose external beam radiotherapy and radical prostatectomy (p <0.01 and <0.0001, respectively). Patients with a (125)I implant had significantly better sexual function than those with high dose external beam radiotherapy and radical prostatectomy (p = 0.01 and 0.0003, respectively). CONCLUSIONS: Of patients with prostate cancer treated with a monotherapy approach we noted better urinary continence in those who underwent radiation based therapies, and better bowel function and less urinary irritation in those who underwent surgery. Sexual function was impaired across all monotherapies but higher scores were seen in men who selected brachytherapy.     

New perspectives in brachycurietherapy of malignant brain tumors. Preliminary report

Between 1980 and 1988, 16 patients (9 females, 7 males) with malignant neuroepithelial tumors of the brain were treated by brachycurietherapy (BCT) and external radiation therapy (ERT) in a phase II nonrandomized study. There were 13 grade III and 3 grade IV tumors according to the WHO classification. Five patients in the grade III group who showed anaplastic foci in a generally grade II background were separately examined. Six patients received only BCT whereas 10 patients were treated by a combination of BCT and ERT, according to the tumor volume. We utilized as radioactive sources 192Ir in 14 cases and 125I in 2. Thirteen patients underwent permanent implant, 3 others received temporary irradiation with removable afterloaded catheters. The target volume was less than 50 cc in 8 cases, between 50 and 100 cc in 7, and larger than 100 cc in 1 patient. The total dose at the periphery of these volume ranged between 70 and 144 Gy. The result were analyzed referring to the following aspects: performance status, survival, side effects, grading. The impact of BCT was analyzed especially in a grade III with anaplastic foci group which showed a median survival of 6 years compared with only 2 years median survival of the pure grade III group.     

Incidence of late radiation necrosis with transient mass effect after interstitial low dose rate radiotherapy for cerebral gliomas

Late radiation necroses constitute a hazard in low dose rate interstitial irradiation for inoperable gliomas. An incidence of 40% (8/20 patients) was found after permanent implantation of Iodine-125 seeds. This finding may even underestimate the real frequency, because follow-up of unaffected patients was shorter than in patients with radiation necrosis. The necrotic reactions caused a transient mass effect, which lead to a significant deterioration of performance scores. Further manifestations of late delayed radiation damage were observed in two patients. The occurrence of radiation necrosis was correlated with total radiation dose, amount of implanted radioactivity, and with velocity of tumour shrinkage. A mechanism underlying the development of radiation necrosis is proposed: A rapid shrinkage of tumour after interstitial Iodine-125 implantation may cause a significant irradiation of surrounding brain tissue, which was initially lying outside the target volume. Since most patients affected by radiation necrosis were children or adolescents, the risk of radiation damage should be minimized. This could probably be achieved either by reduction of irradiation dose, or by using temporary implants of Iodine-125.     

Permanent Iodine-125 Implants in the Treatment of Low-Grade Gliomas

We report a retrospective study on the use of the permanent iodine-125 (¹²⁵I) implants in the management of low-grade gliomas. From July 1988 to July 1997, 16 patients with low-grade gliomas underwent permanent ¹²⁵I implants in the management of their lesions. There were 7 males and 9 females ranging in age from 4 to 48 years (mean 19). The location was in the cerebral hemisphere in 7 patients, brainstem in 5 patients and thalamus/basal ganglia in 4 patients. Prior to brachytherapy, 9 patients underwent surgical resection and 7 patients underwent stereotactic biopsy procedures. Fourteen patients were treated as part of the initial management and 2 were recurrent. The histological diagnosis was: 9 WHO grade II astrocytomas, 3 oligodendrogliomas, 2 gemistocytic astrocytomas, 1 pilocytic astrocytoma, and 1 ependymoma. The tumor volume ranged from 0.7 to 33.4 cc (mean 8.4). Stereotactic treatment planning was used to encompass the contrast-enhancing rim of the tumor visualized by computerized tomography with an initial dose rate of 0.05 Gy/hour with ¹²⁵I. The total activity ranged from 0.8 to 20.5 mCi. With a median follow-up period of 35 months (range, 4–105 months), the 2- and 5-year survival rates were 93.7% and 87.5%, respectively. Three patients underwent reoperation after implants, two of three had recurrent disease, and one had radiation necrosis. Permanent ¹²⁵I implants appear to be safe and effective as a part of the multimodality management of low-grade gliomas.     

Stereotactic interstitial radiotherapy for brain tumors

The narrow margin between tumor sensitivity and healthy brain sensitivity to radiation considerably limits conventional radiation therapy (teletherapy). Interstitial radiotherapy (brachytherapy) with iodine-125 permanent implants is effective for local tumor control. So far, interstitial radiotherapy using low activity permanent or temporary implants has been carried out in 179 patients with differentiated gliomas (132 cases) and other tumors-anaplastic gliomas and glioblastomas (16 cases), ependymomas and papillomas (4 cases) and a variety of other mostly extracerebral tumors (27 cases)-in functionally critical cortical or deep-seated location. Brachytherapy with I-125 implants is recommended for slowly proliferating, differentiated non-resectable tumors in functionally critical areas. It enables the surgeon to achieve a radiosurgical tumor removal while carefully avoiding radiation and operative damage to healthy brain. Experimental and clinical data make an individualized treatment for each patient desirable.     

Breast-conserving therapy with adjuvant paclitaxel and radiation therapy: feasibility of concurrent treatment

As commonly used, adjuvant paclitaxel after doxorubicin in high-risk breast cancer patients results in a prolonged delay of the onset of radiation therapy after breast-conserving surgery. Concurrent delivery of breast irradiation with paclitaxel would allow for earlier initiation of radiation. We report on the toxicity of concurrent paclitaxel and breast irradiation after doxorubicin and cyclophosphamide. Twenty-four patients were treated with concurrent breast radiation and paclitaxel. All patients received four cycles of doxorubicin and cyclophosphamide followed by four cycles of paclitaxel, 175 mg/m2 every 3 weeks. The radiation therapy started after the first cycle in 3 patients, after the second cycle in 16, and after the third in 5. The breast received 4680-5040 cGy external beam irradiation, followed by a boost of 1000-2000 cGy. Fifteen patients received supraclavicular irradiation, and a posterior axillary supplement was used in five patients. Median follow-up after completion of irradiation was 11.5 months (range 2-29 months) with 21 patients followed >or=6 months, 12 followed >or=12 months, and 7 followed >or=18 months. Using Radiation Therapy Oncology Group (RTOG) acute toxicity scoring criteria, 7 patients experienced grade 1 skin and/or soft tissue reactions and 17 patients had grade 2 reactions. The average total duration of radiation treatment was 49 days (range 41-57 days). Only eight patients had radiation therapy interruptions for a median of 3.5 days (range 2-8 days): two more than 5 days. None had a chemotherapy dose reduction. One patient discontinued paclitaxel after the third cycle due to bilateral upper extremity neuropathy. No cases of pneumonitis or brachial plexopathy were seen. Concurrent treatment with every 3-week paclitaxel and breast irradiation was well tolerated. Additional study is needed to determine optimal timing, long-term toxicity, and potential benefits of concurrent radiation therapy and paclitaxel.     

Brachytherapie des lokalen Prostatakarzinoms

Brachytherapy of prostate cancer has become attractive in recent years in Germany. There are several radioactive sources available, which are physically different. Some of them are used as permanent or temporary implants. The permanent sources most frequently used are iodine 125, palladium 103, and gold 198. Iridium is a temporary implant. The techniques used in Germany are low-dose rate (LDR) and high-dose rate brachytherapy, which differ in dose distribution and patient population. The success of prostate cancer brachytherapy depends on patient selection and choosing the right source for the technique used. Best suited for LDR monotherapy is the low-risk patient with a prostate-specific antigen (PSA) level below 10 ng/ml, maximal tumor stage T2b, and a Gleason score of less than 7.     

Long-Term Follow-Up of Brachytherapy in Untreated Malignant Glioma

Objective: Long-term follow-up of patients with malignant glioma randomized to treatment with and without brachytherapy. Methods: Twenty-six patients were randomized to brachytherapy and external radiation, and 23 to external radiation alone. There were 19 and 17 glioblastomas, and 3 and 8 anaplastic astrocytomas, in the nonimplant and implant groups, respectively, and 1 malignant oligodendroglioma in each group. For brachytherapy, iodine- 125 seeds were implanted to deliver a homogeneous dose of 40 cGy/hr for a maximum of 6000 cGy to the enhancing tumor margin. All patients received external radiation for a total of 6020 cGy delivered to the tumor plus 3 cm margin over 7 weeks, followed by BCNU chemotherapy. Conclusions: The median survival was 78 and 66 weeks in the implant and nonimplant groups respectively, and their survival curves were not different (log rank, p=0.394). A significant multivariate relationship did exist between survival and age (p=0.0092), tumor grade (p=0.0001), and Karnofsky (p=0.021). Treatment with brachytherapy is subject to selection bias, which does exclude a large proportion of patients.     

Stereotactic management of midline brain lesions.

Eighty-seven patients, aged 10 months to 92 years, with midline brain lesions were treated using stereotactic techniques at our institution between January 1987 and June 1990. A total of 119 stereotactic procedures were performed with no operative mortality. Procedures included 53 biopsies only, 22 endoscopic laser decompressions, 8 stereotactic microsurgical resections, 9 permanent implants of 125I, 12 temporary implants of 125I, 11 cyst aspirations, 2 cystoperitoneal shunts and 2 intracavitary 32P. The morbidity rate was 4.21%. Local anesthesia was used in 106 of the procedures (89%). Accurate diagnosis was achieved in all cases. Image guidance and stereotactic techniques open new frontiers in the diagnostic and therapeutic management of deep-seated midline intraparenchymal lesions.     

Interstitial stereotactic radiosurgery of pilocytic astrocytomas in paediatric patients

Summary Objective. To evaluate the clinical presentation, tumour response, clinical improvement and complications in 12 children and young people with a pilocytic astrocytoma, WHO I grade 1, who were treated with interstitial radiosurgery using Iodine-125 seed implants. Patients and Methods. Retrospective analysis of 12 patients aged under 18 years (mean 8.4 years, ranging from 8 months to 17 years of age) with a pilocytic astrocytoma treated between 1993 and 2006. Iodine-125 seeds were used as temporary implants with low-dose rate (≤10 cGy/h) and a calculated reference dose of 60 and 100 Gy to the outer ring of the tumour. Results. There was no perioperative mortality. Two patients worsened transiently, but thereafter each patient improved clinically. Eleven out of 12 tumours shrank after the treatment. The mean volume of the tumours before implantation was 17.9 cm³. and was reduced to 60% of this volume at 6 months, to 26.5% at 12 months, to 8% at 24 months, and was less than 1% at 30–36 months One patient underwent a reimplantation to treat a recurrence 3 years after the initial treatment. Ten patients were alive 2 years after the first intervention. In the longest surving patient, there was no evidence of progression after 13.4 years of follow up.     

Interstitial radiation implantation for unresectable nonoat cell carcinoma of the lung. Techniques and preliminary results

The majority of lung cancers are unresectable at diagnosis. The radiation tolerance of the surrounding spinal cord and heart limits the external radiation therapy dose. Interstitial radiation implantation was utilized to deliver higher radiation dose, sparing the surrounding normal tissues in patients with unresectable nonoat cell cancers of the lung less than 8 cm in diameter localized to the thorax with no associated pleural effusion. The methods of implantation included permanent interstitial iodine-125 implantation of the gross disease in the lung and/or lymph nodes delivering about 120 Gy (12,000 rads) in 1 year and removable iridium-192 interstitial implantation of residual disease in the mediastinum, chest wall, or margin or resection in the lung, delivering about 30 Gy (3000 rads) in three days. Supplementary external radiation therapy of 40 Gy (4000 rads) in 4 weeks is delivered 4-6 weeks after implantation. The interstitial implant procedure adds only about 45 minutes to 1 hour to the operating time, and converts a palliative procedure into a potentially curative treatment. This article presents our experience with 11 cases, with early short-term follow-up results, and is designed to stimulate others to evaluate a similar approach to improve local control and survival in unresectable lung cancers.     

Brachytherapy of brain tumors.

Temporary implants of high-activity 125iodine sources have been used in the treatment of brain tumors since December 1979 at the University of California, San Francisco. For previously untreated patients who underwent external beam radiation therapy followed by implant boost, median survival from the date of diagnosis was 88 weeks for 34 patients with glioblastoma multiforme (GM) and 157 weeks for 29 patients with nonglioblastoma gliomas (NGM). For recurrent tumors treated with brachytherapy only, median survival from the date of the implant was 54 weeks for 45 patients with GM and 81 weeks for 50 patients with NGM. Finally, in 48 patients with recurrent tumors treated with combined hyperthermia and brachytherapy, median survival from the date of the implant was 46 weeks for 25 patients with GM and 44 weeks for 7 patients with metastases; 18-month survival was 65% for 16 patients with NGM. Brachytherapy appears to be a useful technique for the treatment of selected recurrent brain tumors and selected primary glioblastomas.     

Conformal prostate brachytherapy guided by realtime dynamic dose calculations using permanent 125iodine implants: technical description and preliminary experience

OBJECTIVE: Low dose rate (LDR) prostate brachytherapy (permanent 125I or 103Pd seeds) is an accepted treatment option for low risk prostate cancer patients. However, differences in prostate spatial location, volume and gland deformation between the images obtained during pre-planning and later on during the implant procedure prevent the pre-planned intended dose to be accurately delivered. We are reporting on a new technique based on interactive real-time dynamic intra-operative dose calculation with avoidance of postimplant CT for final dosimetry. The reasons leading us to implementing this new technique are discussed and preliminary results reported. 47-78 years). For the real time intra-operative dosimetric analysis the following values were obtained: a median of 98% (90%-100%) for V90, of 60% (22%-76%) for V150 and 24% (9%-34%) for V200. The median intro-operative D90 obtained was 16,817 cGy with a range of 13,743 to 19,553 cGy. The median dose point calculation to the rectum maximum was 12,936 cGy and for the maximum in urethra was 21,880 cGy. For the real-time dynamic planning, the acute GU grade 1&2 toxicity was reduced from 28% and 2 1% to 16% and 6% respectively. Acute urinary retention was seen in 2/63 or 3% requiring a temporary post-implant bladder catheter. In addition, a decrease in chronic GU grade 1-2 toxicity was also seen from 16% and 17% to 1 1% and 2% respectively. No change in GI toxicity pattern was noted. No severe grade 3-4 intra-operative complications were noted. CONCLUSION: Real-time intra-operative planning was successfully implemented in our center. It avoids the possible implant quality and dose delivery disadvantages of the standard post-implant CT-based dosimetry by improving the accuracy of seed placement on real time, which was translated in lower rates of acute and chronic GU morbidity. In addition, avoids the unnecessary time, effort and cost of post-implant CT-based dosimetry.     

Brachytherapy: a viable alternative in the management of basal meningiomas

Thirteen patients with intracranial meningiomas of the skull base were treated with one or more high-activity iodine-125 seeds. In 11 patients, the seeds were implanted stereotactically under local anesthesia. A minimum dose of 100 to 500 Gy was delivered to the tumor at a dose rate of 5 to 25 cGy/h. Indications for this procedure included recurrence after initial surgery or as the primary modality of treatment in patients who were not candidates for surgery. All 13 patients are alive at a median follow-up of 15 months. Nine of 11 patients (82%) without calcification in their meningiomas achieved complete response. The remaining 4 patients-2 with calcification and 2 without--achieved partial response. No early or late complications were observed. We conclude from our experience that both recurrent and primary meningiomas of the skull base can be treated effectively with permanent iodine-125 brachytherapy.