Concurrent carboplatin and iodine-125 brachytherapy for recurrent glioblastoma multiforme

Toxicity and safety study of concurrent carboplatin chemotherapy and iodine-125 (I-125) brachytherapy. I-125 brachy therapy has an established albeit limited role in surgically accessible recurrent gliomas. Carboplatin has anti-tumoral; activity against gliomas and demonstrated sensitization of tumor to radiotherapy. In 15 patients (age range 30-77 years; median 53) with recurrent glioblastoma multiforme, stereotactically placed catheters were afterloaded with I-125 sources. A median 50 Gy minimum treatment volume dose was delivered during a 100 h period in conjunction with continuous infusion carboplatin (100 mg/m(2)/20 h x 5). Tumor volumes ranged from 13 to 63 cm(3) (median, 32 cm(3)). Early complications included: headache (n=7), transient exacerbations of pre existing neurologic deficits (n=5), seizures (n=2), nausea/vomiting (n=2), myelosuppression (n=2) and a catheter site wound CSF leak (n=1). Late complications included: steroid dependency (n=10), carcinomatous meningitis in association with hydrocephalus (n=1) and radiation-induced necrosis requiring reoperation (n=6). All patients were evaluable with a median survival of 10 months. In 12 patients, best clinical and neuroradiographic response was stable disease all of whom died of recurrent tumor (local recurrence in 11; CSF dissemination in 1). In 3 patients best response was either complete (n=2) or partial (n=1) all of whom are alive with a median follow-up of 31 months. I-125 brachytherapy with concurrent carboplatin chemotherapy is associated with an acceptable level of toxicity, has anti-tumoral activity and warrants further investigation in carefully selected patients with recurrent gliomas.     

Intracranial arterial occlusion associated with high-activity iodine-125 brachytherapy for glioblastoma

Summary We describe two patients who developed devastating strokes due to intracranial arterial occlusion 15 weeks and 97 weeks following high dose stereotactic iodine-125 brachytherapy for glioblastoma multiforme. In both cases the occlusion was within the implant volume at points receiving 110–281 Gy and there was no other evidence of significant atherosclerosis in the patients. We therefore conclude that these complications were a direct result of the brachytherapy. The phenomenon of radiation-induced occlusion of large cerebral arteries is reviewed.     

Stereotactic iodine-125 brachytherapy for treatment of inoperable focal brainstem gliomas of WHO grades I and II: feasibility and long-term outcome

Microsurgical resection is the most frequently suggested treatment option for accessible focal brainstem gliomas (F-BSG) of World Health Organization (WHO) grades I and II. Because of their location in the highly eloquent brain, however, resection is associated with permanent postoperative morbidity, ranging from 12 to 33?%. Only a few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 seeds as a local treatment alternative. Between 1993 and 2010, 47 patients were treated with SBT (iodine-125 seeds; cumulative surface dose 50-65?Gy) for inoperable F-BSG, WHO grades I and II, in one of the largest reported patient series. We evaluated procedure-related complications, clinical outcome, and progression-free and overall survival (PFS, OS). Median follow-up was 81.6?months. Procedure-related mortality was zero. Within 30?days of seed implantation six patients (12.8?%) had transient neurological deficits. Two patients (4.3?%) deteriorated permanently. Space-occupying cysts occurred in six patients (12.8?%) after a median of 28.5?months, and required surgical intervention. Nine patients (19.1?%) presented with tumor relapse after a median of 56.6?months (range 7.9-118.0?months). For the remaining 38 patients complete response was observed for 23.4?%, partial response for 29.8?%, and stable disease for 27.7?%. Actuarial PFS was 97.7?±?2.2, 92.8?±?4.0, 81.2?±?6.5, and 62.0?±?10.4?% after 1, 2, 5, and 10?years, respectively. Corresponding OS was 100?±?0.0?% (1 and 2?years), 97.4?±?2.6?% (5?years), and 87.6?±?7.0?% (10?years). SBT is a comparatively safe, minimally invasive, and highly effective local treatment option for patients with inoperable F-BSG WHO grades I and II; it merits further evaluation in prospective randomized trials.     

Patterns of recurrence of malignant astrocytoma following stereotactic interstitial brachytherapy with iodine-125 implants.

The pattern of tumor recurrence was studied in a series of 68 patients who were treated with interstitial brachytherapy for malignant astrocytoma. Thirty-six patients had newly diagnosed tumors and were treated following surgery and external beam therapy, while 32 were treated for recurrent tumors. Recurrence pattern was determined using computed tomography at the time of clinical deterioration. Thirty-eight percent of tumor recurrence occurred within the original tumor margin and 50% occurred at the original site but extended beyond the initial margin. In all, 88.0% recurred at the initial tumor site, 71.4% being confined to within 2 cm of the pretreatment tumor borders while 6.0% recurred intracranially outside of the initial tumor margin. One patient recurred with spinal metastasis while two patients developed systemic metastases. The significance of these findings is discussed.     

Stereotactic biopsy combined with stereotactic (125)iodine brachytherapy for diagnosis and treatment of locally recurrent single brain metastases

This paper reports on stereotactic biopsy combined with stereotactic ¹²⁵iodine brachytherapy (SBT) for locally recurrent, previously irradiated cerebral metastases, focusing on feasibility, complications, cerebral disease control, and survival. All patients with suspected locally recurrent metastases detected by MRI were selected for this combined procedure. After stereotactic biopsy, all patients with a verified vital tumor underwent SBT (50 Gy surface dose applied for 42 days) during the same surgical procedure. Histological results of biopsy, complications, treatment response, local and distant disease control, and survival were evaluated. Thirty patients underwent stereotactic biopsy, and 27 were treated with SBT for histologically proved tumor recurrence. There was no treatment-related mortality, and morbidity was transient and low (6.6%). Median survival was 14.8 months. After one year the actuarial incidence of local and distant relapse was 6.7 and 45.5%, respectively. There was no grade 3 or 4 CNS toxicity, even among the 18.5% of patients with tumors >30 mm. For these patients stereotactic biopsy seems to be a safe and valuable means of differentiating between radiation-induced tissue changes and tumor recurrence/progression. SBT is a safe, minimally invasive, and highly effective treatment option for cerebral disease control and survival. Furthermore, it can be performed during the same stereotactic operation.     

Biochemical control of prostate cancer with iodine-125 brachytherapy alone: experience from a single institution

Aim  

Brachytherapy is an adequate option as monotherapy for localised prostate cancer. The objective of this study was to evaluate and compare biochemical failure free survival (BFFS) after low-dose-rate brachytherapy (LDRB) alone for patients with prostate cancer using ASTRO and Phoenix criteria, and detect prognostic factors.     

Post-operative treatment of malignant salivary gland tumours of the palate with iodine-125 brachytherapy.

BACKGROUND AND PURPOSE: Malignant minor salivary gland tumours are usually small and clinically indistinguishable from benign lesions. Surgery is the treatment of choice with post-operative radiotherapy for involved margins or unfavourable histology. We assessed the results of a series of such patients treated with iodine-125 brachytherapy in the form of a temporary applicator or implant. PATIENTS AND METHODS: There were nine patients with T1/T2 tumours of the hard and/or soft palate that had been excised. All had close or involved margins. Six were treated with a dental applicator alone, two with an applicator and additional I-125 seeds in tubes and one with an implant alone. The applicator consists of two layers of plastic made from a dental impression enclosing a predetermined number of I-125 seeds, 9-39, glued to one surface and a layer of ash metal to protect the tongue. It was inserted 1-3 months post-operatively and delivered 35-62 Gy, median 56 Gy, at 5-7 mm depth over 58-156 h, median 120 h, at 0.26-0.67 Gy/h, median 0.45 Gy/h. RESULTS: The patients have been followed up for 32-158 months, median 50 months, and there were no recurrences. The applicator was well tolerated. A confluent mucositis developed which lasted 3-4 weeks. One patient developed a mucosal ulcer which healed spontaneously. CONCLUSIONS: Brachytherapy is an effective way of delivering post-operative radiotherapy to the hard and soft palate in patients with malignant salivary gland tumours that have been incompletely excised or have unfavourable histology. Local control is excellent, treatment time is short and morbidity is minimal.     

Three different intraoperative radiation modalities (electron beam, high-dose-rate brachytherapy, and iodine-125 brachytherapy) in the adjuvant treatment of patients with recurrent colorectal adenocarcinoma.

BACKGROUND: Intraoperative electron beam radiation therapy (IOERT) has been used in the treatment of patients with recurrent colorectal adenocarcinoma for the last 2 decades. Other intraoperative radiation modalities, such as intraoperative high-dose-rate brachytherapy (IOHDR) and intraoperative iodine-125 (125I) brachytherapy, present theoretic advantages for selected patients with recurrent colorectal adenocarcinoma. The experience of a single-institution series in which these three intraoperative radiation modalities were used in a nonrandomized manner is discussed in this report. METHODS: Between September 1989 and January 1997, 80 patients with colorectal adenocarcinoma recurrent in the pelvis or in the paraaortic lymph nodes were treated with IOERT (28 patients), IOHDR (23 patients), or 125I brachytherapy (29 patients). RESULTS: The overall 5-year local control rate was 26% (median = 12 months; 95% confidence interval [95%CI], 6-17). Tumors in paraaortic sites had significantly better local control than those in the pelvis (P = 0.03). The 5-year overall survival rate was 4% (median = 20 months; 95% CI, 17-23). Patients with microscopic residual disease (P = 0.02) and those treated with postoperative external beam irradiation (EBRT) (P = 0.0007) had statistically significant longer survival. Forty-one percent of the treated patients experienced complications: These were severe (Radiation Therapy Oncology Group Grade 4-5) in 19% of patients. CONCLUSIONS: Intraoperative radiation can locally control recurrent colorectal adenocarcinoma in a select group of patients. Patients with localized relapses, microscopic residual tumor, and no distant metastases and those receiving additional EBRT are most likely to benefit from intraoperative irradiation. The authors now routinely recommend EBRT to all patients for whom it is suitable (including those who have had prior EBRT) and consider the combination of the intraoperative modalities whenever feasible.     

Phase I trial of gross total resection, permanent iodine-125 brachytherapy, and hyperfractionated radiotherapy for newly diagnosed glioblastoma multiforme

PURPOSE: To evaluate the feasibility of gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy for patients with newly diagnosed glioblastoma. METHODS AND MATERIALS: From April 1999 to May 2002, 21 patients with glioblastoma multiforme were enrolled on a Phase I protocol investigating planned gross total resection and immediate placement of permanent I-125 seeds, followed by postoperative hyperfractionated radiotherapy to a dose of 60 Gy at 100 cGy b.i.d., 5 days per week. Median age and Karnofsky performance status were 50 years (range, 32-65 years) and 90 (range, 70-100), respectively. Toxicity was assessed according to Radiation Therapy Oncology Group criteria. RESULTS: Eighteen patients completed treatment according to protocol. The median preoperative tumor volume on magnetic resonance imaging was 18.6 cm(3) (range, 4.4-41.2 cm(3)). The median brachytherapy dose measured 5 mm radially outward from the resection cavity was 400 Gy (range, 200-600 Gy). Ten patients underwent 12 reoperations, with 11 of 12 reoperations demonstrating necrosis without evidence of tumor. Because of high toxicity, the study was terminated early. Median progression-free survival and overall survival were 57 and 114 weeks, respectively, but not significantly improved compared with historical patients treated at University of California, San Francisco, with gross total resection and radiotherapy without brachytherapy. CONCLUSIONS: Treatment with gross total resection and permanent I-125 brachytherapy followed by hyperfractionated radiotherapy as performed in this study results in high toxicity and reoperation rates, without demonstrated improvement in survival.     

Results of stereotactic brachytherapy used in the initial management of patients with glioblastoma

Recent studies have shown a survival benefit for patients with recurrent glioblastomas treated with stereotactic brachytherapy. On the basis of these encouraging results, we began a prospective study in 1987 to evaluate the use of brachytherapy in patients with newly diagnosed glioblastoma. Patients were considered eligible for this study if they met the following criteria: Karnofsky performance status 70% or greater; tumor size not greater than 5 cm in any dimension; a radiographically well delineated, supratentorial lesion not involving the ependymal surfaces; and pathologically confirmed glioblastoma. We treated 35 such patients between 1987 and 1990 with stereotactic brachytherapy as part of their initial therapy. The treatment protocol involved surgery, partial brain external-beam radiotherapy (59.4 Gy in 33 fractions), and stereotactic brachytherapy with temporary high-activity iodine 125 sources giving an additional 50 Gy to the tumor bed. Chemotherapy was not used in the initial management of these 35 patients. To compare our results with those obtained in a matched control group, we identified 40 patients with glioblastoma treated with surgery and external radiotherapy, with or without chemotherapy, between 1977 and 1986 at our institution. These patients had clinical and radiographic characteristics that would have made them eligible for the brachytherapy protocol. Survival rates at 1 and 2 years after diagnosis were 87% and 57%, respectively, for patients receiving brachytherapy versus 40% and 12.5%, respectively, for the controls (P less than .001). We conclude that stereotactic brachytherapy improves the survival of patients with glioblastoma when it can be incorporated into the initial treatment approach. Unfortunately, only about one in four patients with glioblastoma are suitable candidates for brachytherapy at the time of initial presentation.     

Stereotactic iodine-125 brachytherapy for the treatment of WHO grades II and III gliomas located in the central sulcus region

Background

Resection of gliomas located in eloquent brain areas remains a neurosurgical challenge. The reported incidence of transient or permanent neurological deficits after microsurgery in eloquent brain ranges 20%–100%, or 0%–47% among contemporary neurosurgical series. The aim of this study was to assess the feasibility of stereotactic brachytherapy (SBT) as a local treatment alternative to microsurgical resection for patients with gliomas in highly eloquent areas, located in the central sulcus region (CSR).

Method

Between 1997 and 2010, 60 patients with World Health Organization (WHO) grades II and III gliomas located in the CSR were treated with SBT (iodine-125 seeds; cumulative therapeutic dose, 50–65 Gy). Following SBT, WHO grade III glioma patients additionally received percutaneous radiotherapy (median boost dose, 25.2 Gy). We evaluated procedure-related complications, clinical outcome, and progression-free survival.

Results

Procedure-related mortality was zero. Within 30 days of SBT, 3 patients (5%) had transient neurological deficits, and 8 patients (13%) had temporarily increased seizure activity. One patient (1.6%) deteriorated permanently. Space-occupying cysts (6 patients) and radiation necrosis (1 patient) developed after a median of 38 months and required surgical intervention. Seizure activity, rated 12 months following SBT, decreased in 82% of patients (Engel classes I–III). Median progression-free survivals were 62.2 ± 19.7 months (grade II gliomas) and 26.1 ± 17.9 months (grade III gliomas).

Conclusions

Compared with microsurgical resection, SBT harbors a low risk of procedural complications, is minimally invasive, and seems to be an effective local treatment option for patients with inoperable, eloquent WHO grade II and III gliomas in the CSR. However, the value of SBT for treating gliomas still needs to be determined in prospective, randomized studies.     

High-dose rate brachytherapy (HDRB) for primary or recurrent cancer in the vagina

A 45-year-old white male presented to our department with postoperative recurrence of gastrointestinal poorly differentiated neuroendocrine carcinoma manifesting as lymph node dissemination and a solitary implantation metastasis in the rectovesical pouch. Following disease progression on chemotherapy, the patient was treated with radiotherapy using either a conventional daily treatment or an accelerated hyperfractionated protocol to separate sites of disease progression. Using serial CT scan assessment, changes in cross-sectional area of the separately treated metastatic lesions were evaluated for determination of therapy response. The accelerated hyperfractionated radiotherapy appeared to limit the rate of tumor growth to a greater degree than the conventional fractionation schedule. Of uttermost importance, in this palliative setting, the patient completed the intensified radiotherapy regimens with acceptable acute toxicity. Given the proliferative capacity of poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract, radiotherapy may be a therapeutic supplement to chemotherapy, which represents the main treatment option in this tumor entity. Importantly, tumors with a capacity for rapid proliferation and regeneration may be particularly sensitive to the use of intensified fractionation protocols in clinical radiotherapy.     

Intensity-modulated stereotactic radiotherapy for the treatment of medically inoperable patients with NSCLC stage I

The standard treatment for stage I non-small cell lung cancer (NSCLC) is lobectomy. However, a considerable number of patients are not eligible for standard lung surgery due to poor pulmonary function or comorbidities. We evaluated the efficacy and tolerability of intensity-modulated stereotactic radiotherapy (IMSRT) with moderate hypofractionation for these patients. Twelve patients were selected for IMSRT. 4D-CT planning was performed by gating CT-scanning positioning. The applied doses ranged between 10x4.5?Gy (80% ID) (N=1), 12x4.5?Gy (95% ID) (N=1) and 10x5.5?Gy (95% ID) (N=10). Long-term follow-up was performed including spirometry and CT for evaluation of local, locoregional and distant control. Even in patients with poor pulmonary function IMRST was safe and well tolerated. No severe acute adverse effects were observed. Estimated local control at 2?years was 90%. Moreover, IMSRT does not induce a significant deterioration of pulmonary function. IMRST is safe and feasible even for patients with very poor pulmonary function. The applied dose provides a high local control rate, although the biological equivalent dose (BED) is lower compared to the average of other SRT regimens. Therefore, IMRST may be an efficient alternative for all NSCLC stage I patients with contraindications to standard lobectomy especially in patients with small tumors in high-risk localisations.     

Factors associated with a higher rate of distant failure after primary treatment for glioblastoma

Our purpose was to analyze the pattern of failure in glioblastoma (GBM) patients at first recurrence after radiotherapy and temozolomide and its relationship with different factors. From 77 consecutive GBM patients treated at our institution with fluorescence guided surgery and standard radiochemotherapy, 58 first recurrences were identified and included in a retrospective review. Clinical data including age, Karnofsky performance score, preoperative tumor volume and location, extend of resection, MGMT promoter methylation status, time to progression (PFS), overall survival (OS) and adjuvant therapies were reviewed for every patient. Recurrent tumor location respect the original lesion was the end point of the study. The recurrence pattern was local only in 65.5 % of patients and non-local in 34.5 %. The univariate and multivariate analysis showed that greater preoperative tumor volume in T1 gadolinium enhanced sequences, was the only variable with statistical signification (p < 0.001) for increased rate of non-local recurrences, although patients with MGMT methylation and complete resection of enhancing tumor presented non-local recurrences more frequently. PFS was longer in patients with non-local recurrences (13.8 vs. 6.4 months; p = 0.019, log-rank). However, OS was not significantly different in both groups (24.0 non-local vs. 19.3 local; p = 0.9). Rate of non-local recurrences in our series of patients treated with fluorescence guided surgery and standard radiochemotherapy was higher than previously published in GBM, especially in patients with longer PFS. Greater preoperative enhancing tumor volume was associated with increased rate of non-local recurrences.     

Conservative treatment of choroidal melanoma using iodine-125 brachytherapy, technique and preliminary analysis of 78 patients]

PURPOSE: Iodine 125 curietherapy is one of the conservative treatments of uveal melanoma. The technique used to achieve these results was simplified through the physical characteristics of the radioelement and the optimized-dosimetry program employed. PATIENTS AND METHODS: 78 patients with choroidal melanoma were treated with iodine 125. About 100 Gy were delivered to the superior pole of the tumour. The minimal length of follow-up was 17 months and the average, 67 months. RESULTS: There was 88% local control, leading to lowered visual acuity in 76% of the cases. Radiation retinopathy, directly related to proximity to the macula, is the principle etiology. Seven patients died of hepatic metastasis, five patients were enucleated. Four patients were further treated with protontherapy to make up for noncontrol locally. CONCLUSION: One dose of 100 Gy to the superior pole of the tumor seemed to lead to good local control, with the exception of complications related to proximity to the macula and the optic nerve. In this attempt to optimize irradiation, the time lapse between any benefit in local control derived from irradiation and posttherapeutic complications observed remains insufficient to evaluate any relationship.     

Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma

PURPOSE: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy (RT) alone. The goal of this study was to update our experience of high-dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT), for such patients. METHODS AND MATERIALS: Between 1984 and 2003, 38 patients with Stage I and Stage II adenocarcinoma of the endometrium considered high operative risk received RT as the primary treatment. The median age was 74.1 years. Before 1996, the local extent of the disease was assessed by an examination under anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter. Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy, typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was 42 Gy. RESULTS: At a median follow-up of 57.5 months for patients at risk, 11 patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%) distantly, and 1 patient (3%) locally and distantly. Local failure was established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and higher grade were both associated with increased failure rate. The 15-year disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42% for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade II and III combined (p = 0.0254). Patients with Stage I disease established by MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of 100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3 Grade III or IV. CONCLUSION: Medically inoperable Stage I endometrial carcinoma may be safely and effectively treated with HDRB as the primary therapy. In selected Stage I patients, our results are equivalent to that of surgery. We believe that the alternative option of HDRB as the primary therapy for selected Stage I endometrial carcinoma, even in patients with low operative risks, needs further evaluation.