Interstitial hyperthermia of the prostate in combination with brachytherapy

Objective

A retrospective study to evaluate the feasibility and toxicity of interstitial hyperthermia (IHT) combined with high-dose-rate (HDR) brachytherapy as the initial treatment for low- and intermediate-risk prostate cancer, and as a salvage therapy in previously irradiated patients with local recurrence.

Patients and methods

Between 18 December 2008 and 5 September 2012, 73  prostate cancer patients were treated with interstitial HDR brachytherapy of the prostate combined with IHT. In 54 patients this was the initial therapy for prostate cancer, while the other 19 were treated for local recurrence after previously undergoing external beam radiotherapy (EBRT). Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 within 3 months after treatment.

Results

Median follow-up was 15 months (range 3–46). The combination of HDR brachytherapy and IHT was well tolerated. The toxicity profile was similar to that of HDR brachytherapy when not combined with hyperthermia. The most common minor complications were urinary frequency (grade 1: 37?%; grade 2: 22?%), nocturia (three times per night: 29?%; four- or more times per night: 20?%) and transient weakening of the urine stream (grade 1: 36?%; grade 2: 11?%). No early rectal complications were observed in the patient group and the severity of genitourinary toxicity was only grade 1–2.

Conclusion

Early tolerance of IHT in combination with HDR brachytherapy is good. Further prospective clinical studies should focus on the effects of combining IHT with HDR brachytherapy and the influence of this adjuvant therapy on biochemical disease-free survival, local control and overall survival.     

Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study

Objectives

To evaluate the clinical outcome of computed tomography (CT)-guided interstitial (IRT) high-dose-rate (HDR) brachytherapy (BRT) in the treatment of unresectable primary and secondary liver malignancies. This report updates and expands our previously described experience with this treatment technique.

Methods

Forty-one patients with 50 tumours adjacent to the liver hilum and bile duct bifurcation were treated in 59 interventions of CT-guided IRT HDR BRT. The tumours were larger than 4 cm with a median volume of 84 cm³ (38–1,348 cm³). The IRT HDR BRT delivered a median total physical dose of 20.0 Gy (7.0–32.0 Gy) in twice daily fractions of median 7.0 Gy (4.0–10.0 Gy) in 19 patients and in once daily fractions of median 8.0 Gy (7.0–14.0 Gy) in 22 patients.

Results

With a median follow-up of 12.4 months, the local control for metastatic hepatic tumours was 89 %, 73 % and 63 % at 6, 12 and 18 months respectively. The local control for primary hepatic tumours was 90 %, 81 % and 50 % at 6, 12 and 18 months respectively. Severe side effects occurred in 5.0 % of interventions with no treatment-related deaths.

Conclusions

CT-guided IRT HDR BRT is a promising procedure for the radiation treatment of centrally located liver malignancies.

Key points

? Interstitial high-dose-rate brachytherapy (IRT HDR BRT) is a promising treatment for central liver tumours ? CT-guided IRT HDR BRT is safe for treating extensive tumours ? CT-guided IRT HDR BRT could play a role in managing unresectable hepatic malignancies     

Evaluation of time,attendance of medical staff,and resources during interstitial brachytherapy for prostate cancer

Introduction

The German Society of Radiation Oncology initiated a multicenter trial to evaluate core processes and subprocesses of radiotherapy by prospective evaluation of all important procedures in the most frequent malignancies treated by radiation therapy. The aim of this analysis was to assess the required resources for interstitial high-dose-rate (HDR) and low-dose-rate (LDR) prostate brachytherapy (BRT) based on actual time measurements regarding allocation of personnel and room occupation needed for specific procedures.

Patients and methods

Two radiotherapy centers (community hospital of Offenbach am Main and community hospital of Eschweiler) participated in this prospective study. Working time of the different occupational groups and room occupancies for the workflow of prostate BRT were recorded and methodically assessed during a 3-month period.

Results

For HDR and LDR BRT, a total of 560 and 92 measurements, respectively, were documented. The time needed for treatment preplanning was median 24 min for HDR (n?=?112 measurements) and 6 min for LDR BRT (n?=?21). Catheter implantation with intraoperative HDR real-time planning (n?=?112), postimplantation HDR treatment planning (n?=?112), and remotely controlled HDR afterloading irradiation (n?=?112) required median 25, 39, and 50 min, respectively. For LDR real-time planning (n?=?39) and LDR treatment postplanning (n?=?32), the assessed median duration was 91 and 11 min, respectively. Room occupancy and overall mean medical staff times were 194 and 910 min respectively, for HDR, and 113 and 371 min, respectively, for LDR BRT.

Conclusion

In this prospective analysis, the resource requirements for the application of HDR and LDR BRT of prostate cancer were assessed methodically and are presented for first time.     

Anmerkungen zum Problem der Dosierung in der HDR-Brachytherapie

Background

In HDR brachytherapy activity distributions can be achieved which were unknown in LDR brachytherapy. For this reason the classical dosage systems can only be used with caution in HDR brachytherapy.

Methods

Different simple applications are used to investigate the effect of various activity distributions on dose and integrated reference air kerma.

Results

Within the classical LDR dosage systems dose and integrated reference air kerma were equivalent. Due to the possibility to “opotimize” the activity distribution in HDR brachytherapy this is not longer the case. Different optimization algorithms and different optimization goals may lead to quite different activity distributions and different integrated reference air kerma values even if the source positions are the same. For target volume oriented optimization schemes a dosage system is described which is based on dose-volume-histograms.

Conclusions

A widely accepted dosage system in HDR brachytherapy is missing. The dosage system described in this paper may be useful in solving this problem.     

Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

Purpose

The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy.

Patients and methods

Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83?%). The aim of the hyperthermia treatment was to heat the prostate to 41–43?°C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir +?2 ng/ml).

Results

The median age was 71 years (range 62–83 years), the median initial PSA level was 16.3 ng/ml (range 6.37–64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044–25.346 ng/ml). The median follow-up was 13 months (range 4–48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan–Meier estimate of biochemical control after salvage treatment was 74?%. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir <?0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients.

Conclusion

IHT in combination with salvage HDR brachytherapy is a well tolerated and effective treatment.     

Salvagebehandlung fortgeschrittener Plattenepithelkarzinome der Mundhöhle und des Oropharynx

Purpose

The clinical effect of high-dose-rate (HDR) interstitial brachytherapy combined with tumor resection was investigated in this retrospective study on patients with recurrent oral and oropharyngeal squamous cell carcinoma.

Patients and Methods

Oral and oropharyngeal squamous cell carcinoma in 38 patients were treated over a period of 7 years (1988–1994) by HDR interstitial brachytherapy using Gammamed 12i^® equipment. Pretreatment of patients in terms of irradiation and surgery differed (33 irradiated with a total dose between 60.0 and 75.6 Gy, including 8 patients with additional surgery; 1 patient with surgery alone, and 4 patients without any pretreatment). Indications for interstitial brachytherapy differed according to individual responses to treatment and medical histories.

Results

Interstitial brachytherapy was successful in the majority of patients, i. e. complete remission: 12, partial remission: 19, no change: 2, progression: 5. Local control and overall survival including patients with surgical treatment was 59% and 81% at 6 months and 47% and 49% after 12 months, respectively.

Conclusion

Interstitial HDR brachytherapy with Iridium 192 is recommended in patients with local recurrences or second primary carcinomas after previous external radiotherapy in the head and neck region. Combination of interstitial brachytherapy and surgery is preferable for these patients.     

Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy

Purpose

To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM).

Materials and methods

From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5–82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified.

Results

The median biological equivalent dose (BED) was 37.4?Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both.

Conclusion

Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

     

125I brachytherapy alone for recurrent or locally advanced adenoid cystic carcinoma of the oral and maxillofacial region

Background and purpose

This retrospective study was to evaluate the local control and survival of ¹²⁵I brachytherapy for recurrent and/or locally advanced adenoid cystic carcinoma (ACC) of the oral and maxillofacial region.

Patients and methods

A total of 38 patients with recurrent and/or locally advanced ACC of the oral and maxillofacial region received ¹²⁵I brachytherapy alone from 2001–2010. Twenty-nine were recurrent cases following previous surgery and radiation therapy. The other 9 cases involved primary tumors. Overall, 12 tumors were located in the major salivary glands, 12 in the minor salivary glands, and 14 in the paranasal region, the nasal cavity or the skull base. The prescribed dose was 100–160 Gy.

Results

Patients were followed for 12–122 months (median 51 months). The 2-, 5-, and 10-year local tumor control rates were 86.3, 59, and 31.5?%, respectively. The 2-, 5-, and 10-year overall survival rates were 92.1, 65 and 34.1?%, respectively. Tumors >?6 cm had significantly lower local control and survival rates. No severe complications were observed during follow-up.

Conclusion

¹²⁵I brachytherapy is a feasible and effective modality for the treatment of locally advanced unresectable or recurrent ACC.     

CT-guided interstitial HDR-brachytherapy for recurrent glioblastoma multiforme: a 20-year single-institute experience

Purpose

To report our results of computed tomography-guided interstitial high-dose-rate (HDR) brachytherapy (BRT) in the treatment of patients with recurrent inoperable glioblastoma multiforme (GBM).

Patients and methods

Between 1995 and 2014, 135 patients were treated with interstitial HDR BRT for inoperable recurrent GBM located within previously irradiated volumes. Patient’s median age was 57.1 years (14–82 years). All patients were pretreated with surgery, postoperative external beam radiation therapy (EBRT) and systemic chemotherapy (ChT). The median recurrent tumor volume was 42?cm³ (2–207?cm³). The prescribed HDR dose was median 40?Gy (30–50?Gy) delivered in twice-daily fractions of 5.0?Gy over consecutive days. No repeat surgery or ChT was administered in conjunction with BRT. Survival from BRT, progression-free survival (PFS), toxicity as well as the impact of several prognostic factors were evaluated.

Results

At a median follow-up of 9.2 months, the median overall survival following BRT and the median PFS were 9.2 and 4.6 months, respectively. Of the prognostic variables evaluated in univariate analysis, extent of surgery at initial diagnosis, tumor volume at recurrence, as well as time from EBRT to BRT reached statistical significance, retained also in multivariate analysis. Eight patients (5.9%) developed treatment-associated complications including intracerebral bleeding in 4 patients (2.9%), symptomatic focal radionecrosis in 3 patients (2.2%), and severe convulsion in 1 patient (0.7%).

Conclusions

For patients with recurrent GBM, interstitial HDR BRT is an effective re-irradiation method for even larger tumors providing palliation without excessive toxicity.

     

125I Seed implant brachytherapy for the treatment of parotid gland cancers in children and adolescents

Background and purpose

There is a lack of optimal treatment strategies for managing salivary gland cancers in children and adolescents. This study is aimed at assessing the effect of ¹²⁵I seed implantation for the treatment of parotid cancers in children and adolescents.

Patients and methods

A total of 12 patients younger than 16 years with parotid gland malignant tumors underwent ¹²⁵I seed implant brachytherapy between October 2003 and November 2008. All patients were assessed after treatment and at the local tumor control appointments. Facial nerve function, maxillofacial development, and radioactive side-effects were assessed.

Results

The follow-up period ranged from 41–104 months. One patient with T4b died of pulmonary metastasis. The other patients were alive during the follow-up period. There were no serious radiation-related complications. The treatment did not affect facial nerve function and dentofacial growth in any of the children.

Conclusion

For parotid gland cancers in children, ¹²⁵I seed implant brachytherapy may be an acceptable treatment without serious complications and with satisfactory short-term effects.     

Clinical role of guidance by C-arm CT for <Superscript>125</Superscript>I brachytherapy on pulmonary tumors

Purpose

To evaluate the clinical value of C-arm CT (CACT)-guided interstitial iodine-125 (¹²⁵I) brachytherapy on pulmonary tumors.

Materials and methods

30 patients with 40 solid pulmonary tumors were enrolled to undergo CACT-guided interstitial ¹²⁵I brachytherapy between November 2011 and November 2014. The needle path was planned on a CACT virtual navigation and real-time fluoroscopy system. Technical success, puncture score, procedure time, local control rate (LCR), radiation exposure, complications and survival were investigated.

Results

The technical success of interstitial ¹²⁵I brachytherapy under CACT guidance was 40/40 (100%). The performance score was 4.7 ± 0.5 with a mean total procedure time of 17.7 ± 5.6 min. LCR in small (≤2.0 cm), intermediate (2.1–4.9 cm) and large (≥5.0 cm) pulmonary tumors was 100, 89.5 and 72.7% at the 4-month follow-up, respectively. The mean effective dose was 10.1 ± 2.8 mSv. Major complications occurred in four patients (13.3%). The mean survival time was 28.4 ± 2.3 months.

Conclusion

CACT can provide virtual navigation and real-time fluoroscopy synchronously for interstitial ¹²⁵I seed implantation on pulmonary tumors.

     

Dosimetric investigation of LDR brachytherapy 192Ir wires by Monte Carlo and TPS calculations

Purpose

The aim of this study was to investigate the dose rate distribution around ¹⁹²Ir wires used as radioactive sources in low-dose-rate brachytherapy applications.

Materials and methods

Monte Carlo modeling of a 0.3-mm diameter source and its surrounding water medium was performed for five different wire lengths (1–5 cm) using the MCNP software package.

Results

The computed dose rates per unit of air kerma at distances from 0.1 up to 10 cm away from the source were first verified with literature data sets. Then, the simulation results were compared with the calculations from the XiO CMS commercial treatment planning system.

Conclusion

The study results were found to be in concordance with the treatment planning system calculations except for the shorter wires at close distances.     

Computed Tomography-Guided Interstitial HDR Brachytherapy (CT-HDRBT) of the Liver in Patients with Irresectable Intrahepatic Cholangiocarcinoma

Purpose

This study was designed to investigate the clinical outcome of patients with irresectable, intrahepatic cholangiocarcinoma (IHC) treated with computed tomography (CT)-guided HDR-brachytherapy (CT-HDRBT) for local tumor ablation.

Method

Fifteen consecutive patients with histologically proven cholangiocarcinoma were selected for this retrospective study. Patients were treated by high-dose-rate internal brachytherapy (HDRBT) using an Iridium-192 source in afterloading technique through CT-guided percutaneous placed catheters. A total of 27 brachytherapy treatments were performed in these patients between 2006 and 2009. Median tumor enclosing target dose was 20?Gy, and mean target volume of the radiated tumors was 131 (±?90) ml (range, 10?C257?ml). Follow-up consisted of clinical visits and magnetic resonance imaging of the liver every third month. Statistical evaluation included survival analysis using the Kaplan?CMeier method.

Results

After a median follow-up of 18 (range, 1?C27) months after local ablation, 6 of the 15 patients are still alive; 4 of them did not get further chemotherapy and are regarded as disease-free. The reached median local tumor control was 10?months; median local tumor control, including repetitive local ablation, was 11?months. Median survival after local ablation was 14?months and after primary diagnosis 21?months.

Conclusion

In view of current clinical data on the clinical outcome of cholangiocarcinoma, locally ablative treatment with CT-HDRBT represents a promising and safe technique for patients who are not eligible for tumor resection.     

In vivo dosimetry with semiconductors in medium dose rate (MDR) brachytherapy for cervical cancer

Purpose

This study was performed to evaluate the role of in vivo dosimetry with semiconductor detectors in gynaecological medium dose rate brachytherapy, and to compare the actual doses delivered to organs at risk (as measured using in vivo dosimetry) with those calculated during treatment planning.

Materials and methods

Doses to the rectum and bladder were measured in a group of patients with cervical carcinoma using semiconductor detectors and compared to the doses calculated using a treatment planning system. 36 applications of brachytherapy at dose rates of 1.8–2.3 Gy/h were performed in the patients.

Results

The mean differences between the measured and calculated doses were 3 % for the rectum and 11 % for the bladder.

Conclusions

The main reason for the differences between the measured and calculated doses was patient movement. To reduce the risk of large errors in the dose delivered, in vivo dosimetry should be performed in addition to treatment planning system computations.     

MR-guided liver tumor ablation employing open high-field 1.0T MRI for image-guided brachytherapy

Objective

To determine the feasibility and safety of image-guided brachytherapy employing a modified open high-field MR system.

Methods

This is a follow-up study of a development project enabling technologies for interventional use of 1.0T open MRI. Modifications included coils and in-bore visualization, fluoroscopic sequences and user interfaces. We recruited 104 patients with 224 liver malignancies to receive MR-guided brachytherapy. Interventions were performed >20 min after Gd-EOB-DTPA. We recorded interventional parameters including the intervention time (from acquisition of the first scout until the final sequence for brachytherapy treatment planning). Two reviewers assessed MR-fluoroscopic images in comparison to plain CT as used in CT intervention, applying a rating scale of 1–10. Statistical analysis included Friedman and Kendall’s W tests.

Results

We employed freehand puncture with interactive dynamic imaging for navigation. Technical success rate was 218 complete ablations in 224 tumours (97%). The median intervention time was 61 min. We recorded no adverse events related to the use of MRI. No major complications occurred. The rate of minor complications was 4%. Local control at 3 months was 96%. Superiority of MR-fluoroscopic, Gd-EOB-DTPA-enhanced images over plain CT was highly significant (P?<?0.001).

Conclusion

MR-guided brachytherapy employing open high-field MRI is feasible and safe.     

Intracavitary brachytherapy for carcinoma of the uterine cervix—Comparison of HDR (Ir-192) and MDR (Cs-137)—

Purpose

To compare the results of high dose rate (HDR) (Ir-192) and medium dose rate (MDR) (Cs-137) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix.

Materials and Methods

Between May 1991 and March 2001, a total of 206 patients with Stage I-IVA previously untreated cervical cancer were treated with ICRT combined with external beam radiotherapy (EBRT). HDR was administered to a total of 135 patients: 22 patients in Stage I, 49 in Stage II, 56 in Stage III, and eight in Stage IVA. MDR was administered to a total of 71 patients: six patients in Stage I, 27 in Stage II, 33 in Stage III, and five in Stage IVA. The MDR at point A was 30 Gy/hour for HDR and 1.7 Gy/hour for MDR treatment, and the corresponding median follow-up periods for survivors were 55 and 68 months.

Results

For the HDR group, 5-year cause-specific survival rates were 90%, 78%, 53% and 33% for Stages I, II, III, and IVA, respectively. For the MDR group, the corresponding rates were 100%, 76%, 51%, and 40%. In the HDR group, 19 patients (14%) developed Grade 2 or higher late complications, and, in the MDR group, four patients (6%) did.

Conclusions

There was no statistically significant difference in cause-specific survivals between the results of HDR and MDR brachytherapy for cervical cancer. The incidence of late complications tended to be higher for the HDR group than for the MDR group, but did not show a statistically significant difference (p=0.07).     

Spectral CT evaluation of interstitial brachytherapy in pancreatic carcinoma xenografts: preliminary animal experience

Objectives

We sought to evaluate the capability of spectral CT to detect the therapeutic response to ¹²⁵I interstitial brachytherapy in a pancreatic carcinoma xenograft nude mouse model.

Methods

Twenty mice bearing SWl990 human pancreatic cancer cell xenografts were randomly separated into two groups: experimental (n?=?10; 1.0 mCi) and control (n?=?10; 0 mCi). After a two-week treatment, spectral CT was performed. Contrast-to-noise ratio (CNR) and iodine concentration (IC) in the lesions were measured and normalized to the muscle tissue, and nIC CD31 immunohistochemistry was used to measure microvessel density (MVD). The relationships between the nIC and MVD of the tumours were analysed.

Results

The nIC of the experimental group was significantly lower than that of the control group during the multiphase examination. A significant difference in the MVD was observed between the two groups (P <0.001). The nIC values of the three-phase scans have a certain positive correlation with MVD (r?=?0.57, p?Conclusions Spectral CT can be a useful non-invasive imaging modality in evaluating the therapeutic effect of ¹²⁵I interstitial brachytherapy to a pancreatic carcinoma.

Key Points

? Spectral CT offers opportunities to assess therapeutic response in pancreatic cancer cases. ? Spectral CT findings correlated with vascular changes associated with ¹²⁵I seed implantation. ? Spectral CT with monochromatic imaging removed most ¹²⁵I seed artefacts.     

Percutaneous Image-Guided Cryoablation in Inoperable Extra-abdominal Desmoid Tumors: A Study of Tolerability and Efficacy

Objective

To determine the tolerability, effectiveness and outcomes of percutaneous image-guided cryoablation on inoperable extra-abdominal desmoid tumors.

Methods

Between 2011 and 2012, 13 patients (mean age 39.3 years, range 15–74) with inoperable extra-abdominal desmoid tumors were consecutively treated with cryoablation (17 tumors treated in 17 procedures), including two patients with Gardner syndrome and nine recurrences after surgery. Disease-free survival (DFS) and local control based on RECIST criteria were calculated on prospective clinical and imaging follow-up until 2013.

Results

Cryoablation was performed under ultrasound (n = 8), computed tomography (n = 1), or combined (n = 8) guidance, and under general (n = 15) or local (n = 2) anesthesia. A major complication was observed in one session (5.8 %). Mean follow-up was 11.3 months (6–27 months). Among all the patients treated, eight patients (47 %) presented residual tumors on the first magnetic resonance follow-up, which were asymptomatic. The DFS rate was stable at 82.3 % (95 % confidence interval 0.55–0.94) at 6, 12, and 24 months. The local tumor progression rate was 0 % at 6, 12, and 24 months. Two patients (12 %) presented an in situ recurrence.

Conclusions

Despite high rates of partial ablation, percutaneous image-guided cryoablation appears to be safe and effective for local control for patients with inoperable extra-abdominal desmoid tumors.