Placement Of Radioactive Sources Research Articles

Brachytherapy in Brain Metastasis Treatment: A Scoping Review of Advances in Techniques and Clinical Outcomes.

Brain metastases pose a significant therapeutic challenge in the field of oncology, necessitating treatments that effectively control disease progression while preserving neurological and cognitive functions. Among various interventions, brachytherapy, which involves the direct placement of radioactive sources into or near tumors or into the resected cavity, can play an important role in treatment. Current literature describes brachytherapy's capacity to deliver targeted, high-dose radiation while minimizing damage to adjacent healthy tissues-a crucial consideration in the choice of treatment modality. Furthermore, advancements in implantation techniques as well as in the development of different isotopes have expanded its efficacy and safety profile. This review delineates the contemporary applications of brachytherapy in managing brain metastases, examining its advantages, constraints, and associated clinical outcomes, and provides a comprehensive understanding of advances in the use of brachytherapy for brain metastasis treatment, with implications for improved patient outcomes and enhanced quality of life.

Brachytherapy: An overview for clinicians.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

MRI-driven design of customised 3D printed gynaecological brachytherapy applicators with curved needle channels

BackgroundBrachytherapy involves placement of radioactive sources inside or near the tumour. For gynaecological cancer, recent developments, including 3D imaging and image-guided adaptive brachytherapy, have improved treatment quality and outcomes. However, for large or complex tumours, target coverage and local control with commercially available applicators remain suboptimal. Moreover, side effects are frequent and impact on quality of life. This signifies that brachytherapy treatment conformity can improve. Therefore, the aim of this study is to develop 3D printed personalised brachytherapy applicators with a custom vaginal topography and guided needle source channels, based on the patients’ anatomy.MethodsCustomised applicators were derived from MRI data of two gynaecological cancer patients. Needle channels were planned by the Radiation Oncologist during image segmentation. Applicators contained multi-curved channels for 6F needles (ProGuide, Elekta) and were manufactured using a digital light processing-based 3D printer. Needle channel radius constraints were measured by analysing needle insertion forces in a 3D printed template, and imposed on the designs.ResultsTwo customised needle applicators are presented. Interstitial needle channels have tapered ends to increase needle protrusion angle accuracy. Additional structures were included to serve as anchor points in MR images for applicator and needle modelling and reconstruction during treatment planning. An insertion force analysis yielded a radius constraint of 35 mm to minimise the risk on needle jamming or buckling. For radii larger than 50 mm, no differences in insertion forces were found.ConclusionA novel method to design and produce vaginal topography-based 3D prints for personalised brachytherapy applicators, derived from patient MRI data, is presented. The applicators include curved needle channels that can be used for intracavitary and guided interstitial needle placement. Further spatial optimisation of brachytherapy source channels to the patient anatomy is expected to increase brachytherapy conformity and outcome.

Development of a quality assurance process for the SoLid experiment

The SoLid experiment has been designed to search for an oscillation pattern induced by a light sterile neutrino state, utilising the BR2 reactor of SCK⋅CEN, in Belgium. The detector leverages a new hybrid technology, utilising two distinct scintillators in a cubic array, creating a highly segmented detector volume. A combination of 5 cm cubic polyvinyltoluene cells, with 6LiF:ZnS(Ag) sheets on two faces of each cube, facilitate reconstruction of the neutrino signals. Whilst the high granularity provides a powerful toolset to discriminate backgrounds; by itself the segmentation also represents a challenge in terms of homogeneity and calibration, for a consistent detector response. The search for this light sterile neutrino implies a sensitivity to distortions of around \U0001d4aa(10)% in the energy spectrum of reactor ν̄e. Hence, a very good neutron detection efficiency, light yield and homogeneous detector response are critical for data validation. The minimal requirements for the SoLid physics program are a light yield and a neutron detection efficiency larger than 40 PA/MeV/cube and 50% respectively. In order to guarantee these minimal requirements, the collaboration developed a rigorous quality assurance process for all 12800 cubic cells of the detector. To carry out the quality assurance process, an automated calibration system called CALIPSO was designed and constructed. CALIPSO provides precise, automatic placement of radioactive sources in front of each cube of a given detector plane (16×16 cubes). A combination of 22Na, 252Cf and AmBe gamma and neutron sources were used by CALIPSO during the quality assurance process. Initially, the scanning identified defective components allowing for repair during initial construction of the SoLid detector. Secondly, a full analysis of the calibration data revealed initial estimations for the light yield of over 60 PA/MeV and neutron reconstruction efficiency of 68%, validating the SoLid physics requirements.

Low dose rate prostate brachytherapy.

Low dose rate (LDR) prostate brachytherapy is an evidence based radiation technique with excellent oncologic outcomes. By utilizing direct image guidance for radioactive source placement, LDR brachytherapy provides superior radiation dose escalation and conformality compared to external beam radiation therapy (EBRT). With this level of precision, late grade 3 or 4 genitourinary or gastrointestinal toxicity rates are typically between 1% and 4%. Furthermore, when performed as a same day surgical procedure, this technique provides a cost effective and convenient strategy. A large body of literature with robust follow-up has led multiple expert consensus groups to endorse the use of LDR brachytherapy as an appropriate management option for all risk groups of non-metastatic prostate cancer. LDR brachytherapy is often effective when delivered as a monotherapy, although for some patients with intermediate or high-risk disease, optimal outcome are achieved in combination with supplemental EBRT and/or androgen deprivation therapy (ADT). In addition to reviewing technical aspects and reported clinical outcomes of LDR prostate brachytherapy, this article will focus on the considerations related to appropriate patient selection and other aspects of its use in the treatment of prostate cancer.

Non-rigid MRI/CT registration for effective planning of prostate brachytherapy.

Prostate brachytherapy is an intraoperative radiotherapy technique for irradiating prostate tumors by placing radioactive sources inside the prostate. CT image is used to calculate a personalized dose distribution (PDD) while the MRI is used to visualize the tumor and the organs at risk. Therefore, a registration of preoperative MRI and CT is essential since it could improve the overall precision of the treatment planning, the placement of radioactive sources inside the prostate as well as the visualization of the dose distribution with respect to the tumor. This registration should compensate for prostate deformations due to changes in size and form between the acquisitions of each modality. In this paper, we present an intensity-based non-rigid registration method that does not require any manual segmentation or visual identification of landmarks. This method is based on the maximization of the mutual information in combination with a deformation field parameterized by cubic B-Spline. The method was validated on clinical patient datasets; the preliminary evaluation shows encouraging results that satisfy the desired clinical accuracy.

Does prior transurethral resection of prostate compromise brachytherapy quality: A dosimetric analysis

To evaluate, in a retrospective review, prostate brachytherapy dosimetry outcomes relative to the transurethral resection of the prostate (TURP) cavity size to address the theoretical concern that an intraprostatic cavity may hinder adequate radioactive source placement. A total of 73 patients who underwent prostate brachytherapy as part of their treatment of localized prostate cancer had a history of a prior TURP. Of these 73 patients, 37 underwent (125)I implantation, 19 (103)Pd implantation, and 17 partial (103)Pd implantation. The dose was calculated using the dose to 90% of the prostate gland (D(90)) from the 1-month post-implant dosimetric analysis. The doses were normalized relative to 100% of the prescription dose. Archived transrectal ultrasound images were used to determine the maximal length and width of the visible residual TURP cavities. The prolate spheroid or symmetric egg shape was used to calculate each residual cavity volume. The derived volume of the TURP cavity was divided by the measured ultrasound volume of the prostate at brachytherapy, creating a percentage of volume measurement for each prostate. All p values, unless otherwise specified, were generated by comparing patients without a visible TURP defect with the subgroups of patients with a visible defect using the Student t test. A visible residual TURP defect was noted on the operative transrectal ultrasound images of 55 (75%) of the 73 patients with a history of TURP before brachytherapy. The 18 patients without a visible TURP defect had a median D(90) of 96% and were used for subsequent statistical comparison. Thirty-six patients with a TURP defect <10% of the entire prostate volume had a median D(90) of 109% (p = 0.02). Thirteen patients with a TURP defect between 10% and 20% of the prostate volume had a median D(90) of 112% (p = 0.03). Six patients with a TURP defect >20% of the prostate volume had a D(90) of 89% (p = 0.43). A visible residual TURP cavity that is assumed to have a prolate spheroid shape and occupy >/=10% of a prostate volume did not appear to be a statistically significant hindrance to proper dosimetric outcome.

Mixed Integer Programming Approaches to Treatment Planning for Brachytherapy – Application to Permanent Prostate Implants

Mixed integer programming models and computational strategies developed for treatment planning optimization in brachytherapy are described. The problem involves the designation of optimal placement of radioactive sources (seeds) inside a tumor site. Two MIP models are described. The resulting MIP instances are difficult to solve, due in large part to dense constraint matrices with large disparities in the magnitudes of the nonzero entries. A matrix reduction and approximation scheme is presented as a computational strategy for dealing with the dense matrices. Penalty-based primal heuristic and branching strategies to assist in the solution process are also described. Numerical results are presented for 20 MIP instances associated with prostate cancer cases. Compared to currently used computer-aided planning methods, plans derived via the MIP approach use fewer seeds (20–30 fewer) and needles, and provide better coverage and conformity – measures commonly used to assess the quality of treatment plans. Good treatment plans are returned in 15 CPU minutes, suggesting that incorporation of this MIP-based optimization module into a real-time comprehensive treatment planning system is feasible.

Transperineal interstitial permanent prostate brachytherapy for carcinoma of the prostate

Prostate cancer is the second most frequently diagnosed cancer of men of all ages, in 1997 approximately 18 300 new cases were registered in England and Wales. The ageing of the population means that the number of men with prostate cancer can be expected to increase over the next 10 years. With the increasing use of PSA screening the number of patients diagnosed with organ confined disease has increased significantly. Brachytherapy is the placement of radioactive sources in close proximity to any tumour. It takes advantage of the physical properties of radiation, allowing high radiation dose to tumours with rapid dose decay in normal tissues. It has been an established treatment modality for many tumour sites for a number of years. Like many apparently new developments prostate brachytherapy was first attempted many years ago by Pasteau and Degrais [1], who inserted radium 226 sources using a silver tube through the urethra. Barringer [2], in 1917 reported on the first transperineal application using radium 226. In the early 1970s the technique of open retropubic Iodine-125 seed implantation was developed at the Memorial Hospital, New York, by Whitmore and colleagues [3]. The technique had serious limitations due to inability to accurately place the sources. The poor dose distribution and the inclusion of patient’s with extra capsular disease led to reports of poor outcomes and unacceptable long-term morbidity and the technique was understandably abandoned [4]. The modern era of prostate brachytherapy began in 1983 when Holm et al. [5], described the technique of transrectal ultrasound with template guidance that allowed accurate positioning of needles within the prostate. Blasko and colleagues in Seattle [6] developed and improved the technique with reduced complications and improved outcomes. In North America there has been a dramatic rise in the number of patients undergoing transperineal interstitial permanent prostate brachytherapy (TIPPB) in the last 5 years and a similar expansion is expected in Europe.

Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer

Purpose: Prostate brachytherapy (PB) entails the placement of radioactive sources throughout the entire prostate gland to treat localized cancer. Typically, the target volume in PB encompasses the entire prostate gland because of the inability to localize the cancer and the multifocal nature of this malignancy. However, because of the unique biochemical nature of the prostate gland, recent advances in magnetic resonance spectroscopic imaging (MRSI) of the prostate have allowed precise delineation of the cancer location within the prostate gland. This report reveals our initial experience of MRSI-guided PB. Methods: An MRSI study was obtained in 15 favorable-risk (prostate-specific antigen level ≤10 ng/mL, Gleason score ≤6, and clinical Stage ≤T2a) patients before their scheduled PB. The results of this study were used to internally map 7 × 7 × 9-mm volumes of prostate tissue to assign cancerous areas a higher dose of radiation. Such tumor-bearing areas had a low citrate/(choline+creatine) ratio consistent with cancer. On the basis of the anatomic MRI and MRSI correlation, three-dimensional coordinates were assigned to the locations of MRSI-defined cancer. The entire target volume was treated to 145 Gy using 125I. Abnormal citrate regions, termed the biologic tumor volume, were prescribed a dose of 130% of the target volume dose (188 Gy) to dose escalate in the abnormal citrate regions while respecting the normal radiation tolerances of the surrounding areas. Three-dimensional treatment planning was used to perform the implant. Results: Of the 15 prostate cancer patients evaluated, all had successful three-dimensional MRSI acquisition before their scheduled PB procedure. In 14 of the 15 patients planned with MRSI, the data were successfully incorporated into their treatment planning and were used to increase the radiation dose prescription to 130% in the MRSI-defined volumes. In 1 patient, MRSI revealed significant multifocal disease that made focal boosts impractical. Postimplant dosimetry confirmed a median V100 of 95% (range 89–98%) in the 15 evaluated patients for the prescription dose of 145 Gy to the target volume. Furthermore, the median BTV100 for the abnormal citrate region was 90% (range 80–100%) as determined by postimplant dosimetry. Urethral and rectal dose-volume histograms were within normal limits. Morbidity was comparable with that for conventionally treated patients. Conclusion: MRSI offers a promising new approach for the delivery of ionizing radiation in PB. Although this series was small and with a short follow-up, MRSI-guided implants are feasible and warrant further investigation as a means of improving the therapeutic ratio in PB.

A practical method to achieve prostate gland immobilization and target verification for daily treatment

Purpose: A practical method to achieve prostate immobilization and daily target localization for external beam radiation treatment is described. Methods and Materials: Ten patients who underwent prostate brachytherapy using permanent radioactive source placement were selected for study. To quantify prostate motion both with and without the presence of a specially designed inflatable intrarectal balloon, the computerized tomography–based coordinates of all intraprostatic radioactive sources were compared over 3 consecutive measurements at 1-min intervals. Results: The placement and inflation of the intrarectal balloon were well tolerated by all patients. The mean (range) displacement of the prostate gland when the intrarectal balloon was present vs. absent was 1.3 (0–2.2) mm vs. 1.8 (0–9.1) mm ( p = 0.03) at 2 min respectively. The maximum displacement in any direction (anterior–posterior, superior–inferior, or right–left) when the intrarectal balloon was inflated vs. absent was reduced to ≤1 mm from 4 mm. Conclusions: Both prostate gland immobilization and target verification are possible using a specially designed inflatable intrarectal balloon. Using this device, the posterior margin necessary on the lateral fields to ensure dosimetric coverage of the entire prostate gland could be safely reduced to 5 mm and treatment could be set up and verified using a lateral portal image.

A modified technique for RF-LCF interstitial hyperthermia

To provide uniform heating of a tumour, it is necessary to establish sufficient volumetric control of power deposition. The interstitial Radio-Frequency Localized Current Field (RF-LCF) technique may provide such control when segmented electrodes are used. The length of segments is equal to 1-1.5cm. Each segment is connected to a separate power source. However, this technique requires an additional implant for interstitial radiotherapy, because the lumen of segmented electrodes is filled with wires necessary to connect each segment to a separate power source. In this work, a modified method of implant that allows delivery of sequential and concomitant controlled thermoradiotherapy was investigated. In this method, each segmented electrode is surrounded by four continuous electrodes. Continuous electrodes pass through vertices of 1.5x1.5cm square and a segmented electrode passes through the centre of the square. The distance between segmented and continuous electrodes is 1.06cm. The electric field induced between an electrically interacting segment and continuous electrodes is concentrated primarily between this segment and its projection on continuous electrodes. Therefore, control of temperature distribution achieved with a modified implant is similar to that achieved with an implant containing only segmented electrodes. For temperature control during treatment, plastic catheters are inserted at a 0.5cm distance from each segmented electrode. Temperature is monitored using multisensor temperature probes. The continuous electrodes are also used for placement of radioactive sources. The lateral distance between radioactive sources is equal to 1.5cm. Besides allowing a sequential and concomitant thermoradiotherapy, the modified method is simpler to implement because it uses several fold less amount of segmented electrodes and power sources.

Physical and biological approaches to the improvement of dosimetry and delivery of brachytherapy treatments

The linear quadratic model has been successfully used to describe the biological effects of radiation on normal tissue and tumors. In the first part of this study a generalized extrapolated response dose equation has been developed based on the linear quadratic model to account for the variation of dose rate, including incomplete repair of sublethal damage during and between fractions of irradiation. In addition, this equation can deal with treatment times that are not identical for different fractions. This equation has been applied to pulsed brachytherapytreatments. The therapeutic advantage over low dose rate brachytherapy has been studied. It is seen that a therapeutic advantage of greater than unity is possible. This equation has also been used to suggest pulsing schemes that would maximize the therapeutic advantage while complying with the requirement of the Nuclear Regulatory Commission without increasing hospital personnel hours. The second aspect studied relates to permanent implantation of the prostate. The ultrasound guided technique of implantation has improved the ease of effective radioactive source placement. The prostate base dose coverage, the issue of differences in prostate volume as imaged using ultrasound and CT, techniques to perform CT-based post-implant dosimetry, and finally various treatment strategies have been proposed, evaluated, and discussed.

The fallacy of the localized supratentorial malignant glioma.

Supratentorial glioblastoma multiforme (GBM) is a lethal malignancy. Subtotal surgical resection and post operative external beam radiotherapy palliate symptoms and prolong survival, but very few patients survive more than 3 years following diagnosis.‘,3,20*32,43,46,48*5’*58,66 Whereas the probability of survival of supratentorial anaplastic astrocytoma (AA) is slightly better, most patients will still succumb to the tumor.58-60*66 The resistance of these neoplasms to conventional therapies has prompted many physicians to undertake new clinical and laboratory investigations. These have included the use of chemotherapy,44 immunotherapy,40 multiple-fraction-perday radiotherapy,2’,34,49 radiotherapy with chemical radiosensitizers,6’ and neutron radiotherapy.45 As interest in the biology and treatment of malignant gliomas has increased, many conceptual verities have been proposed to guide therapeutic investigations, These include the significance of the cellular heterogeneity of AA and GBM,‘2,24 the presence of the blood-brain-barrier (BBB) as a functional obstruction to chemotherapy, and the local nature of these tumors. In this editorial, we focus on the last of these premises. We have selected this issue because of its major implications for any treatment that is directed at a specific portion of the brain rather than the whole brain: BBB disruption, intracarotid drug administration, and brain brachytherapy. Interstitial brachytherapy is used for primary and recurrent GBM and AA. The technique consists of the stereotactic computed tomography (CT) or magnetic resonance imaging (MRI) guided placement of coaxial catheters within and around the tumor. Radioactive sources are after-loaded into the catheters to deliver continuous low-dose rate irradiation. After a specified dose is delivered, the system is removed.22~27~28~39~45 Interstitial hyperthermia generated by implanted microwave antennae may be administered in conjunction with the radiation.52 One of the justifications invoked for brachytherapy is the concept of malignant gliomas as localizedlesions. Allusions to this concept abound in the literature. “Most malignant gliomas are localized to a single area of the brain, central nervous system (CNS) metastases from these tumors are uncommon and systemic metastases are rare.“29 “Since an astrocytoma is almost invariably a nonmetastatizing single mass, ideally it should lend itself best to regional treatment.“** “Because a primary brain tumor is most often a localized disease, hyperthermia, intratumoral chemotherapy, and interstitial irradiation, the stereotactic placement of radioactive sources directly into brain tumors, have been suggested as possible local treatments for brain tumors.“*’

125I Interstitial brachytherapy for primary malignant brain tumors: Technical aspects of treatment planning and implantation methods

Use of interstitial radiation holds promise in the treatment of primary malignant brain tumors, but optimal technical factors have yet to be determined. We have developed a method of precise CT directed stereotactic placement of radioactive sources in a predetermined target volume. We use low activity (1–2 millicurie/seed) sources of 125I loaded in silastic catheters, which are positioned in a parallel array in the target. Positioning of such multiple sources toward the periphery of the volume enhances achievable dose homogeneity. Seeds of various activities can be differentially loaded into each catheter and the catheters can be positioned at various radii from the central target so that the treated volume corresponds to the identified (often irregular) target volume. Although the implant is designed to be permanent, the sources can be removed easily in a second procedure.

Computer Simulation for the Stereotactic Placement of Interstitial Radionuclide Sources into Computed Tomography-defined Tumor Volumes

Abstract This report describes a method for the preoperative determination of radioactive interstitial source placement within computed tomography (CT)-defined tumor boundaries. The method utilizes CT data obtained under stereotactic conditions. Tumor boundaries are digitized from CT slices and are retained in a three-dimensional computer matrix. A solid tumor volume is created by an interpolation program and may be sliced orthogonal to any specific stereotactic surgical view line. The surgeon may simulate radioactive source placement within the slices and view the resultant isodose configuration against tumor contours on successive slices. Once the best source placement has been determined, the computer outputs the mechanical adjustments that will be necessary on a stereotactic frame located in the operating room for the stereotactic placement of each source and gives the length of each source. Sources are stereotactically implanted utilizing a double-catheter afterloading technique.

Computer simulation for the stereotactic placement of interstitial radionuclide sources into computed tomography-defined tumor volumes.

This report describes a method for the preoperative determination of radioactive interstitial source placement within computed tomography (CT)-defined tumor boundaries. The method utilizes CT data obtained under stereotactic conditions. Tumor boundaries are digitized from CT slices and are retained in a three-dimensional computer matrix. A solid tumor volume is created by an interpolation program and may be sliced orthogonal to any specific stereotactic surgical view line. The surgeon may simulate radioactive source placement within the slices and view the resultant isodose configuration against tumor contours on successive slices. Once the best source placement has been determined, the computer outputs the mechanical adjustments that will be necessary on a stereotactic frame located in the operating room for the stereotactic placement of each source and gives the length of each source. Sources are stereotactically implanted utilizing a double-catheter afterloading technique.

Transnasal permanent interstitial implantation for carcinoma of the nasopharynx

A technique for transnasal permanent interstitial implantation of the nasopharynx with 125I seeds is described. This technique allows the precise placement of radioactive sources into mucosal and submucosal tumors, without the need for palatal fenestration. Preliminary results in 10 patients treated by this technique for recurrent nasopharyngeal carcinoma are presented. In the future we also hope to employ this technique for delivering “boost” irradiation to the primary site, in the initial definitive management of carcinoma of the nasopharynx.

A coaxial catheter system for afterloading radioactive sources for the interstitial irradiation of brain tumors. Technical note.

✓ A coaxial two-catheter system that facilitates accurate stereotaxic placement of radioactive sources for the interstitial irradiation of brain tumors is described.