Local Resection and Brachytherapy for Primary Orbital Rhabdomyosarcoma: Outcome and Failure Pattern Analysis.

PURPOSE: Survival in patients with orbital rhabdomyosarcoma (RMS) is excellent. Therefore, new local treatment modalities, such as brachytherapy, have been developed to minimize adverse events. Since 1990, patients with orbital RMS and a residual tumor after induction chemotherapy were eligible for resection and brachytherapy. Otherwise patients received external beam radiotherapy. In this study, the authors describe the outcome for 20 patients with primary orbital RMS. The aim was to assess risk factors for treatment failure in this single center cohort. METHODS: In this retrospective cohort study, the authors reviewed imaging studies, surgery reports, histology reports, and radiotherapy plans in a multidisciplinary setting. The authors included 20 consecutive patients with orbital RMS, treated between 1990 and 2007, (median age: 7.4 years, range: 0.7-16.1; median follow up: 11.5 years). RESULTS: After induction chemotherapy, 12 patients were treated with surgery and brachytherapy, 2 with external beam radiotherapy, and in 5 patients who achieved complete remission, local treatment was withheld. In 1 patient, brachytherapy was incorrectly withheld after delayed surgery. Seven patients relapsed (no local treatment, N = 2; surgery and brachytherapy, N = 2; external beam radiotherapy, N = 2; surgery only, N = 1). The authors found no patient, tumor, or treatment characteristics that predisposed for treatment failure. Ten-year-overall survival and event-free survival were 89% and 65%, respectively. CONCLUSIONS: Overall survival in this cohort of orbital RMS patients was good, including surgery and brachytherapy as treatment modality for orbital RMS resulted in an effective local treatment approach with fewer adverse events than external beam radiotherapy. The authors could not identify factors predisposing for treatment failure.

Orbital Epithelioid Sarcoma: A Case Report.

Epithelioid sarcoma is a rare but often aggressive malignancy of soft tissue that usually occurs in young adults as a superficial lesion in the distal upper limbs. To date, there are only 4 case reports of epithelioid sarcoma primarily occurring in the orbit. Two of these patients were treated with primary exenteration only one of whom was alive 3 years after diagnosis. Radical surgical excision is thus the first treatment of choice for primary orbital epithelioid sarcoma. The authors present a patient with primary orbital epithelioid sarcoma who refused exenteration. Surgical debulking followed by local brachytherapy was performed. The patient remains tumor free 5 years after diagnosis. The literature remains limited regarding treatment options for primary orbital epithelioid sarcoma. However, based on reported cases and this case, the authors conclude that surgical excision combined with local iridium radiation therapy is an acceptable treatment when treating primary orbital epithelioid sarcoma.

Development of late toxicity and International Prostate Symptom Score resolution after external-beam radiotherapy combined with pulsed dose rate brachytherapy for prostate cancer.

PURPOSE: To investigate the development of gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, erectile dysfunction, and International Prostate Symptom Score (IPSS) resolution in a cohort of patients treated with external-beam radiotherapy (EBRT) followed by a brachytherapy pulsed dose rate (PDR) boost. METHODS AND MATERIALS: Between 2002 and 2008, 110 patients were treated with 46-Gy EBRT followed by PDR brachytherapy (24.96-28.80 Gy). The investigated outcome variables, GI toxicity, GU toxicity, erectile dysfunction, and IPSS were prospectively scored at several time points during follow-up. Association between time (as continuous and categorical variable) and the outcome variables was assessed using generalized linear models. RESULTS: No statistically significant association was found between time (continuous) and GI toxicity (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.89-1.06), GU toxicity (OR, 0.97; 95% CI, 0.91-1.03), erectile dysfunction (OR, 1.06; 95% CI, 0.99-1.11), and IPSS (-0.11; 95% CI, -0.41-0.20). Also, no statistically significant association was found between these variables and time as a categorical variable. GU toxicity was associated with IPSS resolution (OR, 1.16; 95% CI, 1.09-1.24). Posttreatment IPSS was associated with pretreatment IPSS (0.52; 95% CI, 0.25-0.79). CONCLUSIONS: No accumulation of high-grade toxicity over time could be established for a group of patients treated with EBRT and PDR brachytherapy for prostate cancer, probably because high-grade late toxicity resolves with time. Also, differences in IPSS values among patients are smaller after treatment than before treatment.

Treatment results of PDR brachytherapy combined with external beam radiotherapy in 106 patients with intermediate- to high-risk prostate cancer.

PURPOSE: To evaluate treatment outcome of pulsed dose-rate brachytherapy (PDR) combined with external-beam radiotherapy (EBRT) for the treatment of prostate cancer. METHODS AND MATERIALS: Between 2002 and 2007, 106 patients were treated by EBRT combined with PDR and followed prospectively. Two, 38, and 66 patients were classified as low-, intermediate-, and high-risk disease respectively according to the National Comprehensive Cancer Network criteria. EBRT dose was 46 Gy in 2.0-Gy fractions. PDR dose was increased stepwise from 24.96 to 28.80 Gy. Biochemical disease free survival and overall survival were determined by the Kaplan-Meier method. Cumulative incidence of late gastrointestinal (GI) and genitourinary (GU) toxicity were scored, according to the Common Terminology Criteria for Adverse Events. RESULTS: The 3- and 5-year biochemical nonevidence of disease (bNED) were 92.8% (95% confidence interval [CI], 87.1-98.5) and 89.5% (95% CI, 85.2-93.8), respectively. Overall survival at 3 and 5 years was 99% (95% CI, 96-100) and 96% (95% CI, 90-100), respectively. The 3- and 5-year Grade 2 GI toxicity was 5.3% (95% CI, 0-10.6) and 12.0% (95% CI, 1.4-22.6), respectively. No Grade 3 or higher GI toxicity was observed. The 3- and 5-year Grade 2 or higher GU toxicity was 18.7% (95% CI, 10.3-27.1) and 26.9% (95% CI, 15.1-38.7), respectively. CONCLUSION: Results on tumor control and late toxicity of EBRT combined with PDR are good and comparable to results obtained with EBRT combined with high-dose-rate brachytherapy for the treatment of prostate cancer.

Brachytherapy as part of the multidisciplinary treatment of childhood rhabdomyosarcomas of the orbit.

INTRODUCTION: Rhabdomyosarcomas in the orbit form a major challenge in terms of cure without severe side effects in childhood cancer. Our specifically developed approach consists of applying brachytherapy to the tumor area using a mold. Analysis of its results for 20 patients was performed. METHODS AND MATERIALS: Thirteen patients were referred for brachytherapy if complete remission was not reached after chemotherapy (Group I) and 7 in case of relapse (Group II). In total, 20 patients were treated between 1991 and 2007. Four were female and 16 male; their ages varied from 1.1 to 16.5 years, with an average of 8.5 years. After macroscopically radical tumor resection, molds with holes drilled to hold flexible catheters were placed into the orbit. The dose to the clinical target volume was 40-50 Gy. RESULTS: Three patients of Group I and 1 patient of Group II developed local recurrence and underwent exenteration. The progression-free survival in Group I is 71.9% (95% CI 0.44-1.0), in Group II 85.7% (95% CI 0.60-1.0), the overall 5-year survival rate of the entire group is 92% (95% CI 0.76-1.0). During treatment, no serious side effects were observed. The late complications encountered in this series were cataract in 2 patients, 1 of whom also developed mild retinopathy. Two patients with ptosis needed surgical correction. No facial asymmetries or bone growth anomalies were observed. CONCLUSIONS: This entire procedure of brachytherapy with a mold offers a tailor-made treatment for orbital rhabdomyosarcomas with only few signs of late toxicity.

The AMORE protocol for advanced-stage and recurrent nonorbital rhabdomyosarcoma in the head-and-neck region of children: a radiation oncology view.

PURPOSE: A multidisciplinary approach, consisting of consecutive Ablative Surgery, MOld technique with afterloading brachytherapy and immediate surgical REconstruction (AMORE) applied after chemotherapy, was designed for children with rhabdomyosarcoma in the head-and-neck region. Analysis of the first 42 patients was performed. METHODS AND MATERIALS: After macroscopically radical tumor resection, molds were constructed for each individual to fit into the surgical defect. The molds, made of 5-mm-thick layers of thermoplastic rubber, consisted of different parts. Flexible catheters were positioned between layers. After brachytherapy, the molds were removed. Surgical reconstruction was performed during the same procedure. RESULTS: Dose to the clinical target volume varied from 40 to 50 Gy for the primary treatment (31 patients) and salvage treatment groups (11 patients). There were 18 females and 24 males treated from 1993 until 2007. Twenty-nine tumors were located in the parameningeal region, and 13 were located in the nonparameningeal region. Patient age at the time of AMORE was 1.2-16.9 years (average, 6.5 years). Follow-up was 0.2-14.5 years (average, >5.5 years). Eleven patients died, 3 with local recurrence only, 6 with local and distant disease, 1 died of distant metastases only, and 1 patient died of a second primary tumor. Overall 5-year survival rates were 70% for the primary treatment group and 82% for the salvage group. Treatment was well tolerated, and acute and late toxicity were mild. CONCLUSIONS: The AMORE protocol yields good local control and overall survival rates, and side effects are acceptable.

Safety aspects of pulsed dose rate brachytherapy: analysis of errors in 1,300 treatment sessions.

PURPOSE: To determine the safety of pulsed-dose-rate (PDR) brachytherapy by analyzing errors and technical failures during treatment. METHODS AND MATERIALS: More than 1,300 patients underwent treatment with PDR brachytherapy, using five PDR remote afterloaders. Most patients were treated with consecutive pulse schemes, also outside regular office hours. Tumors were located in the breast, esophagus, prostate, bladder, gynecology, anus/rectum, orbit, head/neck, with a miscellaneous group of small numbers, such as the lip, nose, and bile duct. Errors and technical failures were analyzed for 1,300 treatment sessions, for which nearly 20,000 pulses were delivered. For each tumor localization, the number and type of occurring errors were determined, as were which localizations were more error prone than others. RESULTS: By routinely using the built-in dummy check source, only 0.2% of all pulses showed an error during the phase of the pulse when the active source was outside the afterloader. Localizations treated using flexible catheters had greater error frequencies than those treated with straight needles or rigid applicators. Disturbed pulse frequencies were in the range of 0.6% for the anus/rectum on a classic version 1 afterloader to 14.9% for orbital tumors using a version 2 afterloader. Exceeding the planned overall treatment time by >10% was observed in only 1% of all treatments. Patients received their dose as originally planned in 98% of all treatments. CONCLUSIONS: According to the experience in our institute with 1,300 PDR treatments, we found that PDR is a safe brachytherapy treatment modality, both during and outside of office hours.

The influence of previous orbital irradiation on the outcome of rehabilitative decompression surgery in graves orbitopathy.

PURPOSE: To investigate whether orbital irradiation influences the outcome of decompression surgery in Graves orbitopathy. DESIGN: Retrospective, comparative case series. METHODS: The medical records of all the patients with Graves orbitopathy treated with a three-wall orbital decompression through a coronal approach at our institution between January 1, 1990 and December 31, 2000 were reviewed. Only patients who underwent bilateral surgery for aesthetic rehabilitation, without preoperative diplopia, and who, in the active phase of the disease, had received orbital radiotherapy alone (20 Grays (Gy) in 10 daily fractions of two Gy over a period of two weeks; group R), systemic glucocorticoids alone (daily administration for more than three months independently from the dosage; group G), or both radiotherapy and glucocorticoids (group RG) were selected. Groups were compared for demographics, smoking habits, preoperative characteristics, and surgical outcome (mean reduction of exophthalmos, reduction of lid retraction, persistence of periorbital swelling requiring cosmetic eyelid surgery, onset of diplopia within 20 degrees of the central position of gaze, and variations in the peripheral field of diplopia). RESULTS: Sixty-one of 376 patients were selected for this study. There were no differences between group R (n=29), group G (n=15), and group RG (n=17) with respect to demographics or predecompression characteristics, whereas the number of smokers was significantly greater in group RG (P=.019). We could not find differences in surgical outcome by comparing the three groups. CONCLUSIONS: The total radiation dose, fraction size, and irradiated volume commonly used to treat active Graves orbitopathy do not adversely interfere with the outcome of rehabilitative decompression surgery.

Results of bladder-conserving treatment, consisting of brachytherapy combined with limited surgery and external beam radiotherapy, for patients with solitary T1-T3 bladder tumors less than 5 cm in diameter.

PURPOSE: To evaluate the long-term, local relapse-free, distant metastasis-free, and overall survival rates in patients with a solitary bladder tumor <5 cm in diameter who were treated with external beam radiotherapy, limited surgery, and brachytherapy. METHODS AND MATERIALS: The results of 122 patients after bladder-saving treatment were analyzed. After EBRT, the patients underwent cystotomy, and catheters were implanted. Of the 122 patients, 99 were treated with a continuous low-dose-rate technique and 23 patients with a pulsed-dose-rate technique. The median follow-up period was 5 years. RESULTS: The 5-year local and distant relapse-free survival rate was 76% and 83%, respectively. The 5 and 10-year relapse-free survival rate was 69% and 66%, respectively. For overall survival, the corresponding rates were 73% and 49%. Toxicity was low. No differences were found between the continuous low-dose-rate and pulsed-dose-rate groups. CONCLUSION: The results of our study have shown that external beam radiotherapy followed by brachytherapy as a bladder-saving treatment for a selected group of patients with bladder cancer yields excellent local tumor control and low toxicity.

Minimal displacement of novel self-anchoring catheters suitable for temporary prostate implants.

Catheters were developed that can be fixed in the prostate gland by self-expanding parts for use in PDR brachytherapy. Daily CT-scans were made to investigate the magnitude of catheter displacement. The mean absolute displacement during the 3 day treatment was 1.2 mm. The resulting minor alterations in dose-volume parameters were of no clinical importance.

AMORE protocol in pediatric head and neck rhabdomyosarcoma: descriptive analysis of failure patterns.

BACKGROUND: The AMORE protocol is a local treatment for patients with nonorbital pediatric head and neck rhabdomyosarcoma (HNRMS). The objectives of this study were: (1) to assess the adequacy of the concept, and (2) to identify factors associated with relapse. METHODS: We performed a retrospective multidisciplinary review of 22 children primarily treated according to the AMORE protocol, excluding two children with inadequate imaging data. RESULTS: Seven patients had a local relapse, six within and one outside the residual tumor area. Five of the six patients with relapse in the residual area had gross total or debulking (incomplete) surgery, suboptimal position of the mold for brachytherapy, or both. In the 15 nonrecurrent cases, four patients had either incomplete surgery or suboptimal mold position. Both surgical and brachytherapeutic factors seem to be associated with relapse. CONCLUSIONS: AMORE is an adequate concept. More rigid preoperative imaging and intraoperative verification of the brachytherapy mold position might lead to a reduction in the number of local failures.

Orbital irradiation for Graves' ophthalmopathy: Is it safe? A long-term follow-up study.

PURPOSE: We evaluated the frequency of long-term complications of orbital irradiation (radiation-induced tumors, cataract, and retinopathy) in comparison with glucocorticoids. DESIGN: We conducted a follow-up study in a cohort of 245 Graves' ophthalmopathy patients who had been treated with retrobulbar irradiation (20 Gy in 2 weeks) and/or oral glucocorticoids between 1982 and 1993 in our institution. Irradiated patients were compared with nonirradiated patients. METHODS: Data on mortality and cause of death were obtained. Living patients were invited to participate in a follow-up study. Possible retinopathy was assessed in a masked fashion and defined as the presence of > or =1 hemorrhages and/or microaneurysms on red-free retina photographs. If >5 lesions were present, patients were categorized as suffering from definite retinopathy. Cataract was assessed using the Lens Opacity Classification System II score. MAIN OUTCOME MEASURES: Mortality, prevalence of retinopathy, prevalence of cataract, and type of cataract. RESULTS: Thirty-seven of the 245 patients had died, none of them from an intracranial tumor. Mortality was similar in the irradiated (27/159 [17%]) and nonirradiated patients (10/86 [12%]; P = 0.264). One hundred fifty-seven of the 208 living patients (75%) consented to participate in a follow-up ophthalmologic investigation; the mean follow-up time (+/- standard deviation) was 11+/-3 years. Possible retinopathy was present in 15% of patients, 22 of the irradiated and 1 of the nonirradiated patients (P = 0.002). In 5 patients (all had been irradiated), definite retinopathy (i.e., >5 retinal lesions) was present. Of these, 3 had diabetes mellitus, and 1 had hypertension. Diabetes was associated with both possible (P = 0.029) and definite (P = 0.005) retinopathy, with a relative risk of 21 (95% confidence interval, 3-179). The prevalence and severity of cataract were similar in the radiotherapy group (29%) and the glucocorticoid group (34%); it should be noted that 88 of 104 of the irradiated patients were also treated with oral glucocorticoids. CONCLUSION: The data suggest that orbital irradiation for Graves' ophthalmopathy is a safe treatment modality, except possibly for diabetic patients.

Late toxicity following conventional radiotherapy for prostate cancer: analysis of the EORTC trial 22863.

Late toxicity and other serious adverse events (SAE) were analysed in the European Organisation for Research and Treatment of Cancer (EORTC) trial 22863. The study evaluated the value of adjuvant endocrine treatment for locally advanced prostate cancer treated with radiotherapy. From 1987 to 1995, 415 patients were randomised. There was long-term toxicity information for 377 patients (91%). Median age was 70 years (range 50-80 years). Median follow-up for late toxicity was 42 months (range 3-136 months). Toxicity was graded according to a modified Radiotherapy and Oncology Group (RTOG) scale. Other late SAE, that was not classified as severe treatment toxicity, but were still life-threatening, were also assessed. There were 72 patients with grade 2, 10 patients with grade 3 and 4 patients with grade 4 toxicity. There were 20 patients with other late SAE, who were grouped according to their relationship to treatment; likely related (n = 1), unrelated (n = 7) and not assessable (n = 12). Although four treatment-related deaths (1%) occurred, grade 3 or 4 late complications were less than 5%.