Interstitial Irradiation Research Articles

Surgical management of hypothalamic hamartomas in patients with gelastic epilepsy

Gelastic epilepsy (GE) associated with hypothalamic hamartomas (HHs) is now a well-characterized clinical syndrome consisting of gelastic seizures starting in infancy, medically refractory seizures with or without the development of multiple seizure types, and behavioral and cognitive decline. It has been postulated that the development of the HH-GE syndrome is a result of a progressive epileptic encephalopathy or secondary epileptogenesis, which is potentially reversible with treatment of the HH. A variety of surgical options for the treatment of HHs exist, including open and endoscopic procedures, radiosurgery, interstitial radiotherapy, and stereotactic radiofrequency thermocoagulation. Surgical treatment can result in seizure freedom in up to 50% of patients and can be accompanied by significant improvements in behavior, cognition, and quality of life. Partial treatment of HHs may be sufficient to reduce seizure frequency and improve behavior and quality of life with less risk. A component of reversible cognitive dysfunction may be present in some patients with an HH-GE syndrome.

The Prostate cancer Intervention Versus Observation Trial:VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): Design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer

BackgroundProstate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death in men. Ninety percent of men with prostate cancer are over aged 60 years, diagnosed by early detection with the prostate specific antigen (PSA) blood test and have disease believed confined to the prostate gland (clinically localized). Common treatments for clinically localized prostate cancer include watchful waiting surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy and interstitial radiation therapy (brachytherapy) and androgen deprivation. Little is known about the relative effectiveness and harms of treatments due to the paucity of randomized controlled trials. The VA/NCI/AHRQ Cooperative Studies Program Study #407: Prostate cancer Intervention Versus Observation Trial (PIVOT), initiated in 1994, is a multicenter randomized controlled trial comparing radical prostatectomy to watchful waiting in men with clinically localized prostate cancer. MethodsWe describe the study rationale, design, recruitment methods and baseline characteristics of PIVOT enrollees. We provide comparisons with eligible men declining enrollment and men participating in another recently reported randomized trial of radical prostatectomy versus watchful waiting conducted in Scandinavia. ResultsWe screened 13,022 men with prostate cancer at 52 United States medical centers for potential enrollment. From these, 5023 met initial age, comorbidity and disease eligibility criteria and a total of 731 men agreed to participate and were randomized. The mean age of enrollees was 67 years. Nearly one-third were African-American. Approximately 85% reported they were fully active. The median prostate specific antigen (PSA) was 7.8 ng/mL (mean 10.2 ng/mL). In three-fourths of men the primary reason for biopsy leading to a diagnosis of prostate cancer was a PSA elevation or rise. Using previously developed tumor risk categorizations incorporating PSA levels, Gleason histologic grade and tumor stage, approximately 43% had low risk, 36% had medium risk and 20% had high-risk prostate cancer. Comparison to our national sample of eligible men declining PIVOT participation as well as to men enrolled in the Scandinavian trial indicated that PIVOT enrollees are representative of men being diagnosed and treated in the U.S. and quite different from men in the Scandinavian trial. ConclusionsPIVOT enrolled an ethnically diverse population representative of men diagnosed with prostate cancer in the United States. Results will yield important information regarding the relative effectiveness and harms of surgery compared to watchful waiting for men with predominately PSA detected clinically localized prostate cancer.

External Beam Radiation Therapy Followed by Interstitial Radiotherapy with Iridium-192 for Solitary Bladder Tumours: Results of 111 Treated Patients

BackgroundEvaluation of bladder-preserving treatment protocol. ObjectiveTo evaluate the long-term results of iridium-192 brachytherapy-based bladder-sparing treatment strategy in patients with solitary invasive bladder tumours. Design, setting, and participantsWe performed a retrospective analysis of 111 patients with solitary T1G3–T2Gall bladder tumours (≤5cm), who were treated with iridium-afterloading brachytherapy between February 1988 and May 2007. InterventionAfter transurethral tumour resection, external beam radiotherapy (28Gy; 12 fractions) was given, followed by brachytherapy (Iridium-192; 40Gy). Partial cystectomy was part of the treatment strategy in nine patients. In five of those patients a T3 tumour was found, and they were included in the analysis. MeasurementsThe 5-, 10- and 15-yr overall survival rate (OS); disease-specific survival rate (DSS); and disease-free survival rate (DFS) estimates were determined using the Kaplan-Meier method. Results and limitationsMean follow-up period was 6.2 yr (range: 0.2–16.3 yr). At the last follow-up 75 patients were alive without evidence of disease, whereas 17 patients had died without evidence of disease. Nineteen patients died of bladder cancer after a mean follow-up period of 2.9 yr (range: 0.5–9.0). OS rates at 5 yr, 10 yr, and 15 yr were 70%, 55%, and 51%, respectively. DSS rates at 5 yr, 10 yr, and 15 yr were 82%, 73% and 73%, respectively. DFS rates at 5 yr, 10 yr, and 15 yr were 60%, 47%, and 23%, respectively. Higher tumour stage (T3 vs T1) was negatively associated with DSS (hazard ratio [HR]:19.8; p=0.01) and DFS (HR: 4.67; p=0.02). No prognostic factor was found for OS. Local recurrence occurred in 27% of patients and salvage cystectomy was performed in 9% of patients. Bladder function was able to be preserved in 99 of 111 patients (89%). ConclusionsIn patients with solitary stage T1–T2 bladder cancer (≤5cm) who refuse radical cystectomy or who are poor candidates for major surgical procedures, this modality is a valuable treatment alternative.

Editorial Comment on: External Beam Radiation Therapy Followed by Interstitial Radiotherapy with Iridium-192 for Solitary Bladder Tumours: Results of 111 Treated Patients

Editorial Comment on: External Beam Radiation Therapy Followed by Interstitial Radiotherapy with Iridium-192 for Solitary Bladder Tumours: Results of 111 Treated Patients

Editorial Comment on: External Beam Radiation Therapy Followed by Interstitial Radiotherapy with Iridium-192 for Solitary Bladder Tumours: Results of 111 Treated Patients

Editorial Comment on: External Beam Radiation Therapy Followed by Interstitial Radiotherapy with Iridium-192 for Solitary Bladder Tumours: Results of 111 Treated Patients

Basal Cell Carcinoma Arising 57 Years after Interstitial Radiotherapy of a Nasal Hemangioma

WEISS, ELLIOT MD*; SUKAL, SEAN A. MD, PHD†; ZIMBLER, MARC S. MD, FACS‡; GERONEMUS, ROY G. MD†,§ Author Information

Prediction of volumetric change in the "triple ring" caused by glioma I-125 brachytherapy.

The aim of this study was to reveal the volumetric changes in tumor necrosis, reactive zone, and edema referred to as the "triple ring" appearing after low-dose-rate iodine-125 (I-125) interstitial irradiation of 20 inoperable low-grade gliomas. To enable prediction of these volumetric changes, we provide mathematical expressions that describe the dynamics of the triple ring. Volumes of the three regions on image-fused control CT/MR images were measured for a 24-month period. The delivered dose on the tumor surface was 50-60 Gy. Dose planning and image fusion were performed with Brain-Lab Target 1.19 software; mathematical and statistical computations were carried out with Matlab numeric computation and visualization software. To determine the volumes, control images with the triple rings were fused with the planning images. Relative volumes normalized with respect to the volume of reference dose were calculated and plotted in the time domain. First, the mean values of volumes were determined from the patients' measured data; then, polynomials were fitted to the mean values using the polynomial curve-fitting method. The accuracy of our results was verified by correlating the predicted data with the measured ones. The polynomial prediction approach proposed here reveals the dynamics of the triple ring. These polynomials will assist with (1) designing the best treatment, (2) following the patient's condition, and (3) planning reirradiation if necessary.

Basal Cell Carcinoma Arising 57 Years after Interstitial Radiotherapy of a Nasal Hemangioma

Cutaneous hemangiomas are benign vascular tumors that represent the most common benign tumor of infancy. These tumors characteristically have an early phase of rapid proliferation followed by a slower regression phase; over 90% of cutaneous hemangiomas will regress completely by age 10. Irradiation of infantile hemangiomas was commonly performed in the 1950s and 1960s, but this treatment was largely abandoned after the long-term risks of radiotherapy and the benign nature of most hemangiomas were appreciated.

Ultrasound-guided transperineal interstitial HDR radiation therapy in recurrent uterine cancer

Purpose: The prognosis of postoperative and/or postradiation local recurrence of the uterine cancer remains dismal. We have treated these patients with transrectal ultrasound (TRUS)-guided high-dose-rate interstitial radiation (HDR-ISRT). The local control and morbidities of the HDR-ISRT were analyzed retrospectively.

Perioperative interstitial irradiation as a boost in breast conserving therapy

Perioperative interstitial irradiation as a boost in breast conserving therapy

Management of Complications of Prostate Cancer Treatment

Prostate cancer is the most commonly diagnosed noncutaneous cancer in men in the United States. Treatment of men with prostate cancer commonly involves surgical, radiation, or hormone therapy. Most men with prostate cancer live for many years after diagnosis and may never suffer morbidity or mortality attributable to prostate cancer. The short-term and long-term adverse consequences of therapy are, therefore, of great importance. Adverse effects of radical prostatectomy include immediate postoperative complications and long-term urinary and sexual complications. External beam or interstitial radiation therapy in men with localized prostate cancer may lead to urinary, gastrointestinal, and sexual complications. Improvements in surgical and radiation techniques have reduced the incidence of many of these complications. Hormone treatment typically consists of androgen deprivation therapy, and consequences of such therapy may include vasomotor flushing, anemia, and bone density loss. Numerous clinical trials have studied the role of bone antiresorptive therapy for prevention of bone density loss and fractures. Other long-term consequences of androgen deprivation therapy may include adverse body composition changes and increased risk of insulin resistance, diabetes, and cardiovascular disease. Ongoing and planned clinical trials will continue to address strategies to prevent treatment-related side effects and improve quality of life for men with prostate cancer.

Initial CT findings in early tongue and oral floor cancer as predictors of late neck metastasis

Detecting the risk factors for late neck metastasis (LNM) in early tongue and oral floor cancer is important for establishing an accurate prognosis, as well as for increasing survival rates. Patients with either stage I or II tongue and oral floor cancer underwent either a resection of the primary tumor or interstitial radiotherapy without neck dissection. We measured the short- and long-axis diameters of lymph nodes on initial CT images. Of the 38 patients, 20 had LNM and 18 did not. CT images showed a total of 161 lymph nodes. Twenty-five "occult lymph nodes" developed into LNM, whereas the remaining 136 "reactive lymph nodes" did not. Comparison between "occult" and "reactive" lymph nodes revealed significant differences in the short-axis diameters (p=0.01). The measure of short-axis diameters of neck lymph nodes on initial CT images is a useful predictor of LNM in patients with early tongue and oral floor cancer.

Prostate Cancer Volume at Biopsy Predicts Clinically Significant Upgrading

A significant proportion of patients with prostate cancer with Gleason score 6 disease at biopsy is upgraded to Gleason score 7 or higher after radical prostatectomy, increasing the risk of adverse outcome. We identified clinical and pathological parameters that predict pathological upgrading in this population. A total of 268 patients with biopsy Gleason score 6 prostate cancer who underwent biopsy and radical prostatectomy between October 1999 and January 2007 were included in the study. Pretreatment characteristics were used to identify predictors of pathological upgrading. Upgrading significance was established by comparing radical prostatectomy pathology between cases that were and were not upgraded. A total of 134 patients (50%) were upgraded postoperatively to Gleason score 7 or higher. Preoperative prostate specific antigen greater than 5.0 ng/ml (p = 0.036), prostate weight 60 gm or less (p = 0.004) and more cancer volume at biopsy, defined by cancer involving greater than 5% of the biopsy tissue (p = 0.002), greater than 1 biopsy core (p <0.001) or greater than 10% of any core (p = 0.014), were associated with pathological upgrading. Upgraded patients were more likely to have extraprostatic extension and positive surgical margins at radical prostatectomy (p <0.001 and 0.001, respectively). Prostate specific antigen, prostate volume and biopsy cancer volume predict clinically significant upgrading in patients diagnosed with Gleason score 6 disease. These parameters may be valuable in the pretreatment risk assessment of this patient population.

Median Effective Local Anesthetic Doses of Plain Bupivacaine and Ropivacaine for Spinal Anesthesia Administered Via a Spinal Catheter for Brachytherapy of the Lower Abdomen

Continuous spinal anesthesia via a spinal catheter allows adjusting the duration and extent of anesthesia to surgical needs, maintenance of hemodynamic stability, and good postoperative analgesia. This study was designed to determine the median effective local anesthetic dose of plain ropivacaine and bupivacaine administered intrathecally for interstitial brachytherapy of the lower abdomen using the Dixon up-and-down method. Forty patients were randomly allocated to receive either intrathecal bupivacaine 5 mg per mL or ropivacaine 10 mg per mL via a 24-gauge spinal catheter at the L3-4 interspace. The initial dose was 10 mg of bupivacaine or 20 mg of ropivacaine; the dosing intervals were 1 mg and 2 mg, respectively. Doses for subsequent patients were determined by the response of the previous patient in that group. Successful anesthesia was defined as a loss of sensation to a cold stimulus at the T6 level and full motor blockade within 20 minutes after administration of the local anesthetic. The median effective local anesthetic dose for intrathecal bupivacaine was 11.2 mg (95% confidence interval [CI], 10.3-12.1) and 22.6 mg for ropivacaine (95% CI, 20.5-24.6). A relative analgesic potency ratio of 0.50 (95% CI, 0.44-0.56) was calculated between the median effective local anesthetic dose of intrathecal bupivacaine and ropivacaine. Bupivacaine and ropivacaine are appropriate for continuous spinal anesthesia for interstitial radiation therapy procedures of the lower abdomen. In the dose-ranges investigated, intrathecal ropivacaine is approximately half as potent as bupivacaine.

Association of Polymorphisms in TGFB1 and Prostate Cancer Prognosis

Because of the role of TGFB1 in prostate cancer and progression, we hypothesized that polymorphisms of TGFB1 at C-509T may be associated with prostate cancer risk and/or more aggressive tumors. This is a case-control study. Controls consisted of male volunteers 40 years old or older with a normal digital rectal examination and prostate specific antigen 2.5 ng/ml or less. Cases consisted of men with biopsy proven prostate cancer. High grade prostate cancer included all cancers of Gleason sum 7 or greater. Poor prognosis in cases was defined as any stage with Gleason sum 8-10, pT3A (if Gleason sum was greater than 7), pT3B or higher (all Gleason sums), any N1 or higher, any M1 or higher, or any documented PSA recurrence (biochemical failure). Single nucleotide polymorphisms were genotyped using allelic discrimination assays. Logistic regression models were used to estimate the OR with the corresponding 95% CI for individual racial/ethnic groups. Allelic frequency across ethnic/racial groups was compared using Pearson's chi-square test. A total of 653 cases and 1,476 controls were genotyped at C-509T. The TT genotype showed a significant protective effect against high grade prostate cancer (OR 0.482, 95% CI 0.274-0.849). In addition, the TT genotype was associated with a decreased risk of poor prognosis prostate cancer (OR 0.488, 95% CI 0.236-1.009). Limiting analysis to nonHispanic white men showed that the TT genotype had an even more pronounced protective effect for poor prognosis prostate cancer (OR 0.297, 95% CI 0.100-0.887). Finally, there was a significant difference in the distribution of allelic frequency across racial/ethnic groups (p <0.0001). We observed an association between single nucleotide polymorphisms of TGFB1 at C-509T and a decreased risk of aggressive prostate cancer. The TT genotype of TGFB1 at C-509T demonstrates a protective effect against high grade prostate cancer and cases with poor prognosis.

Study on treating glioblastoma with 125I seed implantation during operations

Objective To evaluate the therapeutic efficacy of treating glioblastoma with interstitial irradiation using radioactive seeds.

Validity of the CAPRA Score to Predict Biochemical Recurrence-Free Survival After Radical Prostatectomy. Results From a European Multicenter Survey of 1,296 Patients

The CAPRA (Cancer of the Prostate Risk Assessment) score from the University of California, San Francisco provides a new statistical model to predict recurrence-free survival and pathological tumor stage after radical prostatectomy. It was originally developed using data from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. To calculate the score, which ranges from 0 to 10, 5 clinical variables are needed, ie prostate specific antigen, Gleason sum, clinical tumor grade, percentage of positive biopsies and patient age. To date, the only external validation of the CAPRA score has been conducted using the SEARCH (Shared Equal Access Regional Cancer Hospital) database. The present study uses a German database to contribute to existing validation work and to test transferability of the CAPRA score to a sample that differs fundamentally from the SEARCH sample in terms of clinical features. Data from 1,296 German patients after radical prostatectomy were used for validation. Mean followup was 56.5 (+/-35.4) months. Accuracy of prediction of recurrence-free survival and pathological tumor stage with the CAPRA score was analyzed using Kaplan-Meier analysis, proportional hazards regression, logistic regression and graphic representation. For the external validation of the CAPRA score, the underlying clinical variables of our study group were unfavorable compared to the original cohort from the CaPSURE data set. The recurrence-free survival rate decreased after 3 and 5 years from 100% to 97%, respectively, in the CAPRA score 0 to 1 group, and from 44% to 31%, respectively, in the CAPRA score of 7 or higher group. The hazard ratios of a biochemical recurrence per 1-group increase were 1.50 (95% CI 1.43-1.56) for the CAPRA sum score, 1.62 (95% CI 1.53-1.71) for the 7-group CAPRA score and 3.52 (95% CI 3.00-4.12) for the 3-group CAPRA score. Concordance indices between 0.78 and 0.81 suggested good predictive accuracy. Of the 5 CAPRA constituents 4 independently predicted recurrence-free survival, ie prostate specific antigen, Gleason sum, cT stage and percent of positive biopsies. Positive margins occurred in 13.1% of patients with a CAPRA score of 0 to 1 vs 62% of patients with a score of 7 to 10 (p <0.001). Organ confined tumors were present in 97.7% of patients with a CAPRA score of 0 to 1 vs 19.3% of those with a score of 7 to 10 (p <0.001). Despite different clinical features in the present patient cohort and the CaPSURE data set, the accuracy of the CAPRA nomogram in predicting recurrence-free survival was high. These results underscore the effectiveness and the clinical applicability of the CAPRA score which, in addition to patient counseling, may also be used for risk stratification in clinical studies.

Erectile function outcome reporting after clinically localized prostate cancer treatment: Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D’Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus S, Liebert M, Moul JW, Tangen C, Thrasher JB, Thompson I, AUA Prostate Cancer Guideline Update Panel

In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. Based on inclusion criteria 436 articles were selected. Of these articles, database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology, and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function, and intact erectile function that were 26% to 100%, 16% to 48%, and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47%, and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Accelerated partial breast irradiation

Breast-conserving surgery followed by whole-breast radiotherapy (WBRT) has become the standard treatment for the majority of patients with early breast cancer. Whereas the indications for systemic adjuvant treatment have continuously expanded, there is a tendency to restrict postoperative radiotherapy to accelerated partial breast irradiation (APBI) instead of WBRT. The different techniques of APBI are described and their respective advantages or potential drawbacks outlined. Moreover, the results described in the literature are briefly reviewed as a basis for the consensus statements and recommendations of the German Society of Radiation Oncology, the German Society of Senology, and the Working Group for Gynecological Oncology of the German Cancer Society. The methods mainly used for APBI are: interstitial radiotherapy with multicatheter technique, intraoperative radiotherapy (IORT) using either electrons produced by linear accelerators or 50 kV x-rays (Intrabeam), the balloon-catheter technique (MammoSite), or 3D conformal external beam radiotherapy. These techniques have marked differences in dose distribution and homogeneity. The published range of local recurrence rates varies between 0% to 37%, the median follow-up from 8 to 72 months. To date, follow-up times mostly do not yet permit a definite judgment concerning the long-term effectiveness and side effects of APBI. The relevant societies in Germany support randomized clinical studies comparing APBI with WBRT in a well-defined subset of low-risk patients. However, the authors expressly discourage the routine use of APBI outside clinical trials. Until definite results show that APBI neither impairs therapeutic outcome nor cosmetic results, WBRT remains the gold standard in the treatment of early breast cancer.

Erectile Function Outcome Reporting After Clinically Localized Prostate Cancer Treatment

In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.