Interstitial Irradiation Research Articles

OC-0039: Local recurrence after interstitial radiotherapy in bladder cancer

OC-0039: Local recurrence after interstitial radiotherapy in bladder cancer

Photoacoustic imaging driven by an interstitial irradiation source

Photoacoustic (PA) imaging has shown tremendous promise in providing valuable diagnostic and therapy-monitoring information in select clinical procedures. Many of these pursued applications, however, have been relatively superficial due to difficulties with delivering light deep into tissue. To address this limitation, this work investigates generating a PA image using an interstitial irradiation source with a clinical ultrasound (US) system, which was shown to yield improved PA signal quality at distances beyond 13mm and to provide improved spectral fidelity. Additionally, interstitially driven multi-wavelength PA imaging was able to provide accurate spectra of gold nanoshells and deoxyhemoglobin in excised prostate and liver tissue, respectively, and allowed for clear visualization of a wire at 7cm in excised liver. This work demonstrates the potential of using a local irradiation source to extend the depth capabilities of future PA imaging techniques for minimally invasive interventional radiology procedures.

Interstitial radiotherapy using phosphorus-32 for giant posterior fossa cystic craniopharyngiomas.

The treatment for giant posterior fossa cystic craniopharyngiomas remains an important challenge in neurosurgery. The authors evaluated the effects of treating 20 patients with giant posterior fossa cystic craniopharyngiomas using phosphorus-32 (P-32) interstitial radiotherapy at their hospital. The patients included 11 boys and 9 girls with an age range of 3 to 168 months. Before treatment, the tumor volumes ranged from 65 to 215 ml. The intracranial pressure was increased in 16 patients, and optic nerve damage had occurred in 18. The patients received P-32 interstitial radiotherapy following stereotactic cyst-fluid aspiration or drainage and were followed up for 7-138 months. The treatment immediately relieved the intracranial hypertension symptoms in all patients. At the end of follow-up, imaging examinations revealed that the cystic tumors had disappeared, but some residual calcification remained in 12 patients, and had decreased by more than 75% of the initial volume in 8 patients. The damaged optic nerve recovered in 3 cases, improved in 12 cases, remained unchanged in 1 case, and was aggravated in 2 cases. No other severe complications related to surgery or interstitial radiation occurred. During the follow-up period, 7 new cysts appeared in 5 patients who had received additional interstitial radiotherapies with a dose of P-32 that was calculated using the same formula as for the initial treatment. The new tumors then disappeared in 2 patients, significantly shrank in 2 patients, and progressed in 1 patient. For treating giant posterior fossa cystic craniopharyngiomas, P-32 interstitial radiation after stereotactic cyst-fluid aspiration or drainage can achieve a high tumor control rate and has relatively satisfactory clinical effects and quality of life outcomes with few complications.

Conditional Probability of Reclassification in an Active Surveillance Program for Prostate Cancer

We evaluated the risk of prostate cancer reclassification by time on active surveillance. From 1995 to 2014 we evaluated 557 and 251 men at very low and at low risk, respectively, who were on active surveillance and compliant with prostate biopsies. Our primary study outcome was reclassification to higher risk disease by grade or extent. Freedom from reclassification was estimated using the Kaplan-Meier approach with adjustment for covariates using the Cox proportional hazards model. Within the first 2 years of surveillance patient survival free of reclassification by grade (p = 0.20) and by any biopsy criteria (p = 0.25) was similar in men with very low and low risk disease. After 2 years men with low risk disease were 2.4 times more likely to be diagnosed with a Gleason score of greater than 6 than men with very low risk disease (p = 0.002, HR 2.4, 95% CI 1.9-3.5). Additionally, beyond 2 years on surveillance the risk of lifetime reclassification by grade and by any criteria decreased by 30% and 35% (each p <0.0001, HR 0.70, 95% CI 0.60-0.76 and HR 0.65, 95% CI 0.57-0.72, respectively) with each biopsy that showed no reclassification. The reclassification rate during surveillance is not equally distributed across time or risk groups. Due to misclassification at diagnosis the reclassification rate in very low and low risk groups is similar in the first 2 years but differs significantly beyond 2 years. The risk of reclassification decreases with time for each nonreclassifying biopsy beyond 2 years.

P041 Five years results of interstitial radiation therapy in the treatment of prostate cancer: Toxicity and dosimetry analysis

P041 Five years results of interstitial radiation therapy in the treatment of prostate cancer: Toxicity and dosimetry analysis

Bi2S3-embedded mesoporous silica nanoparticles for efficient drug delivery and interstitial radiotherapy sensitization

A novel design of Bi2S3 nanoparticles with a coating of mesoporous silica (BMSN) is obtained by a surfactant induced condensation method. It was found that BMSNs exhibited a high doxorubicin (DOX) loading efficiency of 45 wt% and pH-responsive controlled drug release owing to the electrostatic interaction between silanol surface and DOX molecules. The cell viability results demonstrated the encapsulation of DOX into BMSNs could lead to significantly enhanced therapeutic effect against multidrug-resistance cancer cells compared to that of free DOX drug. Furthermore, the comparable study of tumor growth by different treatments demonstrated that the introduction of BMSNs in the X-ray therapy could lead to higher therapeutic effect, with just 2.10-fold increase in tumor volume through 24 days, in comparison to 4.40-fold increase for X-ray beams treatment alone. Meanwhile, the in vitro interstitial radiotherapy experiments demonstrated that the cell inhibiting effect of P-32 interstitial radiotherapy combined with BMSNs (50 μg/mL) was 1.55-fold higher than that of P-32 alone. Significantly, it is notable that the simultaneous chemo- and interstitial radiotherapy based on BMSNs could tremendously increase the therapeutic effect compared to those treatment alone. More importantly, the in vivo P-32 radiotherapy in conjunction with BMSNs was proved to present a significantly eradication of the tumor volumes by an average of 21% reduction to its initial values, in comparison to 2.01-fold increase in case of P-32 treatment alone. Thus, it is expected that the BMSNs could be applied as a highly efficient multifunctional nanosystem to realize the enhanced chemo- and radiotherapy in the further clinical applications.

New National Air-Kerma Standard for Low-Energy Electronic Brachytherapy Sources.

The new primary standard for low-energy electronic brachytherapy sources for the United States is described. These miniature x-ray tubes are inserted in catheters for interstitial radiation therapy and operate at tube potentials of up to about 50 kV. The standard is based on the realization of the air kerma produced by the x-ray beam at a reference distance in air of 50 cm.

Nomogram for predicting the risk of locoregional recurrence in patients treated with accelerated partial-breast irradiation.

59 Background: There are limited tools to guide clinicians regarding the risk of locoregional recurrence (LRR) in patients wishing to pursue APBI. The purpose of this study was to develop a nomogram taking into account clinicopathologic features to predict LRR in patients treated with APBI for early stage breast cancer. Methods: A total of 2,000 breasts (1,990 women) were treated with APBI at William Beaumont Hospital (N=551) or on the ASBrS MammoSite Registry Trial (N=1,449). Techniques included multiplanar interstitial catheters (N=98), balloon-based brachytherapy (N=1,689), and 3D conformal radiotherapy (N=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox Proportional Hazards Regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a C-index. Results: Median follow-up was 5.5 years (0.9 to 18.3). Of the 2,000 cases, 435 were excluded due to missing data. Univariate analysis found that age &lt;50, pre/perimenopausal status, close/positive margins, ER negativity, and high grade were associated with a higher frequency of LRR. These five independent covariates were used to create adjusted estimates, weighting each on a scale of 0 to 100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR with a C-index of 0.641. Conclusions: The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI.

Salvage therapy for recurrent glioblastoma multiforme: a multimodal approach combining fluorescence-guided resurgery, interstitial irradiation, and chemotherapy

Objectives:Several studies have revealed that different salvage treatments in glioblastoma multiforme patients presenting a recurrence have limited palliative treatment options. The aim of this study was to evaluate the utility and limitations of multimodal salvage treatments in recurrent glioblastoma multiforme patients combining 5-aminolevulinic acid (5-ALA) fluorescence-guided resurgery, interstitial irradiation, and dense dose temozolomide chemotherapy (ddTMZ).Methods:Seventeen consecutive patients with recurrent globlastoma multiforme underwent a combined scheme of salvage treatments including fluorescence-guided reoperation, high dose rate (HDR) brachytherapy, and ddTMZ chemotherapy and were included in this prospective study. This multimodal treatment group was compared with a 1∶1 matched historical control group of 17 patients who have been treated with intensive temozolomide chemotherapy as the only treatment modality. All patients were previously treated with surgery of the primary pathology, concomitant, and adjuvant radiochemotherapy with temozolomide.Results:Median follow-up was 32 months (range: 28–36 months). Median survival was 9 months for the entire cohort after salvage treatment and can be translated into a 3-month improvement in survival compared to the control group of patients with glioblastoma recurrence treated with temozolomide alone (P = 0·043). Complications rates of multimodal salvage treatment were comparable with the temozolomide control group.Discussion:Our experience suggests that a combined salvage treatment plan have the advantages of all three methods and, thus, provide additional survival benefit and can be considered in selected patients affected by recurrent high grade gliomas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal treatment.

Implementation and early clinical results utilizing Cs-131 permanent interstitial implants for gynecologic malignancies

ObjectivePermanent interstitial brachytherapy is an ideal yet underutilized treatment modality for accessible, small volume gynecological malignancies. We present early clinical results utilizing a new permanent isotope, Cs-131. MethodsA retrospective review was performed evaluating patients treated with Cs-131 permanent interstitial radiation at our institution from July 2011 through June 2013. Doses were most commonly prescribed and calculated to a depth of 5mm using Paterson-Parker planar implant rules for Au-198. This activity was converted to air-kerma strength (U). A conversion factor of 1.1 was applied based on RBE calculations, clinical observation and experience. Results14 patients were identified among whom 17 Cs-131 implants were performed. Seven patients were implanted as sole therapy, and a median dose of 50Gy was delivered. Ten implants were performed as boost within a more extensive radiation treatment plan. In these patients, a median implant dose of 27.5Gy was used and the median total dose delivered in combination was 78.25Gy. After a median follow up of 12months, the actuarial local control rate was 84.4%. A very low level of grade 1–3 reactions was observed with no fistula formations or other severe side effects. ConclusionsPermanent interstitial brachytherapy with Cs-131 was well tolerated with favorable early results compared to other series. Cs-131 has multiple favorable properties, including minimal radiation exposure to treating staff, and should be considered as a therapeutic option in appropriately selected patients. A methodology for dose prescription, calculation of radioactivity required and distribution of the isotope is also presented.

Comprehensive visualization of paresthesia in breast cancer survivors

As breast cancer survivors are benefiting increasingly from advanced forms of therapy, the side effects of locoregional treatment in the adjuvant setting are becoming more and more important. This article presents a new method of assessing the spatial distribution of paresthesia in breast cancer survivors after different locoregional treatments. A structured questionnaire assessing paresthesia, with body pictograms for marking paresthesia areas, was completed by 343 breast cancer survivors. The image information was digitized, generating gray-scale summation images with numbers from 0, indicating black (100 % of the patients had paresthesia), to 255, indicating white (none had paresthesia). The resulting map visualization showed the locations of paresthesia on body pictograms. The group included patients who had undergone breast-conserving surgery (BCS) and mastectomy, and also patients who had received percutaneous and interstitial radiation. A total of 56.5 % of the patients stated that they had paresthesia. The paresthesia areas were distributed within the range suggested by clinical experience. Most patients stated that they had paresthesia in the upper outer quadrant and axilla. Patients who had undergone mastectomy or percutaneous radiotherapy appeared to have more paresthesia on some areas of the body surface. Patients who had undergone mastectomy indicated larger areas of paresthesia than those with BCS-4,066 pixels (px) vs. 2,275 px. Radiotherapy did not appear to influence the spatial distribution of paresthesia. Paresthesia is a common symptom after breast cancer treatment. This paper describes a new method of assessing this side effect to improve and individualize treatment for it in the future.

Effects of age and comorbidity on treatment and survival of patients with muscle‐invasive bladder cancer

Our study assessed whether rising age, socioeconomic status (SES) and the presence of serious comorbidity affected treatment choice and survival in a population-based series of patients with muscle-invasive bladder cancer (MIBC) in The Netherlands. Therefore, a consecutive series was studied, including all patients diagnosed with MIBC between 1995 and 2009 in the Eindhoven Cancer Registry, preceding centralization of cystectomy. The independent effects of age, SES and serious comorbidity on therapy choice and their effects on overall survival were estimated by multivariate logistic regression and multivariate Cox proportional hazard analyses, respectively. Out of the 2,445 patients, 38% were aged ≥ 75 years at diagnosis and 63% had at least one serious comorbid condition. Higher age and serious comorbidity were independent predictors for abstaining from cystectomy, where SES was not (61-74 vs. ≤ 60: odds ratio [OR], 0.8; 95% confidence interval [CI], 0.6-1.0; ≥ 75 vs. ≤ 60: OR, 0.1; 95% CI,0.1-0.2; one comorbid condition vs. none: OR, 0.7; 95% CI, 0.5-0.9; two vs. none: OR, 0.6; 95% CI, 0.5-0.8). Patients undergoing cystectomy, external beam radiotherapy or interstitial radiotherapy survived longer independent of age, SES and serious comorbidity (hazard ratio [HR]: 0.4; 95% CI: 0.4-0.5; HR: 0.8; 95% CI: 0.7-0.9; HR: 0.4; 95% CI: 0.3-0.5, respectively). Consequently, preceding centralization of cystectomy, higher age and serious comorbidity were independent predictors for abstaining from cystectomy owing to an expected high rate of short-term medical problems. As cystectomy is associated with a better survival, independently of age, SES and serious comorbidity, it can be questioned whether cystectomy has been underutilised in elderly and in patients with serious comorbidity. Centralization might be a solution for this suggested underutilisation.

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Bladder Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surgery in Bladder Cancer Patients: Long-term Results

Bladder Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surgery in Bladder Cancer Patients: Long-term Results

Permanent Interstitial Radiation With Cs-131 Implants for Gynecologic Malignancies: Analysis and Results of an Initial 13 Applications

Interstitial brachytherapy is an ideal, yet underutilized, treatment modality for small volume gynecological malignancies, especially in circumstances where higher doses of radiation are needed while respecting normal tissue toxicity. Our institution has extensive experience using Au-198 radioactive sources for interstitial brachytherapy. We recently performed the first interstitial implant for a gynecologic malignancy using a newer isotope, Cs-131, which has a more favorable dosimetric profile.

Low-Dose-Rate (LDR) Interstitial Radiation for Gynecologic Malignancies: A Single Institution Experience

Low-Dose-Rate (LDR) Interstitial Radiation for Gynecologic Malignancies: A Single Institution Experience

Treatment Outcome of High-dose-rate Interstitial Radiation Therapy for Patients with Stage I and II Mobile Tongue Cancer

The aim of the study was to investigate the outcomes of high-dose-rate interstitial radiation therapy for patients with Stage I and II mobile tongue cancer retrospectively. Sixty-seven patients with Stage I and II mobile tongue cancer were treated with high-dose-rate interstitial radiation therapy, with or without external beam radiation therapy, between 1997 and 2007. The median dose of interstitial radiation therapy was 50 Gy in 10 fractions over 6 days. Thirty-five patients received external beam radiation therapy before interstitial radiation therapy. The median dose of external beam radiation therapy was 20 Gy delivered with single-lateral or bilateral fields, including the primary tumor site and upper jugular lymph nodes. Thirty-seven patients received concurrent chemotherapy, including carboplatin, cisplatin, fluorouracil or tegafur, gimeracil and oteracil (TS-1) systemically or with intra-arterial injection. Thirty-three patients received intratumoral injection of bleomycin before catheter insertion. The median follow-up time was 58.6 months (range 15.1-102.4 months). The 5-year overall, cause-specific, progression-free survival rate and local control rate were 88.7, 92.1, 76.0 and 94.0%, respectively. Fourteen patients developed cervical lymph node recurrence, 11 of which were distributed within the external beam radiation therapy field. We found local failures in four cases within 2 years after the treatment and in three cases after >7 years, even though the latter were difficult to distinguish from second primary cancers. The treatment results of our institutions were equivalent to previous reports. Most cervical lymph node metastases occurred within the external beam radiation therapy field, which implied that the external beam radiation therapy dose of 20-30 Gy was insufficient to prevent late cervical lymph node metastases.

Risk Stratification of Patients with Extraprostatic Extension and Negative Lymph Nodes at Radical Prostatectomy: Identifying Optimal Candidates for Adjuvant Therapy

Randomized trials demonstrate a benefit to adjuvant radiation therapy after radical prostatectomy in patients with pathologically locally advanced tumors. However, limited data exist on natural history, specifically in men with extraprostatic extension, and wide variability in outcomes has been reported. We evaluated long-term outcomes in patients with pT3aN0 disease and determined predictors of recurrence in these men. We evaluated 20,744 patients who underwent radical prostatectomy at our clinic between 1987 and 2011. Of these men 1,073 with pT3aN0 disease were identified who did not receive neoadjuvant or adjuvant therapy. Biochemical recurrence-free survival was estimated using the Kaplan-Meier method. Multivariate stepwise selection was used to develop a prognostic model for biochemical recurrence. Median followup after radical prostatectomy was 10.9 years, during which 449 patients experienced biochemical recurrence. On stepwise selection preoperative prostate specific antigen (HR 1.3, p=0.0003), clinical tumor stage (HR 1.2, p=0.001), pathological Gleason score (HR 1.9, p<0.0001), surgical margin status (HR 1.6, p<0.0001) and detectable first postoperative prostate specific antigen (HR 2.2, p<0.0001) were significantly associated with biochemical recurrence. Cumulative weighted scores of these variables were used to stratify patients into quintiles according to biochemical recurrence risk. The 15-year biochemical recurrence-free survival rate in the lowest to the highest risk group was 70%, 56%, 44%, 34% and 25%, respectively (p<0.0001). The c-index for this model was 0.69. We present a model to individualize the estimation of biochemical recurrence in men with pT3aN0 disease at radical prostatectomy. These data may be used for patient counseling, specifically in regard to risk stratification when discussing secondary therapy.

Interstitial brachytherapy with iodine-125 seeds for low grade brain stem gliomas in adults: Diagnostic and therapeutic intervention in a one-step procedure

To report on iodine-125 (I125) interstitial irradiation in the treatment of low grade brain stem gliomas in adults. Ten patients with well-circumscribed lesions of the brainstem and histological confirmation of low grade glioma treated with stereotactically implanted I-125 seed in our department between 1995 and 2012 were retrospectively analyzed. In 9 patients the lesion was treated with one I-125 seed and in one patient, 2 spatial separated lesions were implanted, therefore a total of 11 I-125 seeds were implanted. The mean volume of the 11 lesions was 2.76 ml (range: 0.5-7.2 ml), mean activity of the seeds was 6.23 mCi (range: 1.5-11.1 mCi), mean duration of irradiation was 28.5 days (range: 21-41 days) and mean effective dose rate was 9.16 cGy/h (range: 6.2-12 cGy/h). The 30 days perioperative morbidity and mortality rate was 0%. Median follow up was 72.5 month (range 5-168 months). Six of ten patients were free of progression until last follow up. In our experience at the University Clinic in Freiburg Germany, interstitial radiosurgery based on MRI is a safe and effective method to diagnose and treat low grade gliomas of the brain stem. Furthermore randomized studies are needed to confirm the therapeutic impact of this method in comparison to external beam radiation of brain stem gliomas.

OC-0235: APBI with interstitial brachytherapy vs whole breast irradiation: 1-year toxicity of the GEC-ESTRO Phase III Trial

OC-0235: APBI with interstitial brachytherapy vs whole breast irradiation: 1-year toxicity of the GEC-ESTRO Phase III Trial