Advancements in brachytherapy

doi:10.1016/j.addr.2016.09.002

Advanced Drug Delivery Reviews

Volume 109, 15 January 2017, Pages 15-25

https://doi.org/10.1016/j.addr.2016.09.002 Get rights and content

Abstract

Brachytherapy is a radiotherapy modality associated with a highly focal dose distribution. Brachytherapy treats the cancer tissue from the inside, and the radiation does not travel through healthy tissue to reach the target as with external beam radiotherapy techniques. The nature of brachytherapy makes it attractive for boosting limited size target volumes to very high doses while sparing normal tissues. Significant developments over the last decades have increased the use of 3D image guided procedures with the utilization of CT, MRI, US and PET. This has taken brachytherapy to a new level in terms of controlling dose and demonstrating excellent clinical outcome. Interests in focal, hypofractionated and adaptive treatments are increasing, and brachytherapy has significant potential to develop further in these directions with current and new treatment indications.

Graphical abstract

Section snippets

Physical and radiobiological effects

Brachytherapy, also known as internal radiotherapy, is the delivery of radiotherapy with the use of sealed radioactive sources. Brachytherapy can be applied as mono-therapy or in combination with external beam radiotherapy (EBRT), surgery, and/or chemotherapy. Brachytherapy requires implantation of catheters and advances the radioactive source(s) into the patient through intracavitary, intraluminal or interstitial (needles) applicators. Brachytherapy sources can be permanently implanted or the

Advancements in planning and delivery technology — conventional and novel techniques

The integration of advanced volumetric (3D) imaging in brachytherapy has been a major progress in brachytherapy during the last decades. With focal irradiation, it has been logical to invest in improved precision of target definition and identification of organs at risk, as this defines the success to cover the disease appropriately and avoid high exposure of organs at risk. Investments in multimodality imaging and imaging with applicator in place, has played a major role [48] supported by

Future outlook

Future developments in brachytherapy will happen on multiple frontiers. This section focus on 7 items of importance for improved clinical outcome and improved utilization of brachytherapy.

1.
Further exploitation of individualized and risk adaptive treatment.
Response adaptive therapy was first applied in cervix cancer, but other sites with significant tumor response during treatment (radiotherapy, chemotherapy and other therapeutic strategies) have much potential for development of similar response

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Cited by (67)

Brachytherapy is an effective and safe salvage option for re-irradiation in recurrent glioblastoma (rGBM): A systematic review
2024, Radiotherapy and Oncology
To evaluate the clinical efficacy and toxicity of brachytherapy as a salvage therapy for patients with recurrent glioblastoma (rGBM).
We searched the PubMed, Embase, and Cochrane libraries from its inception to June 2023, for eligible studies in which patients underwent brachytherapy for rGBM. Outcomes of interest were mOS, mPFS, OS, PFS, and adverse events (AEs). For individual clinical survival outcomes and common AEs, weighted-mean descriptive statistics were calculated as a summary measure using study sample size as the weight. The calculation formula is as follows: weighted-mean = Σwx/Σw (w is the sample size and x is the outcome).
This review included 29 studies with a total of 1202 rGBM patients, including 22 retrospective and 7 prospective studies. The results showed that from the time of brachytherapy, the mOS and mPFS were 6.8 to 24.4 months and 3.7 to 11.7 months. The OS of 6 months, 1 year, 18 months, 2 years, and 3 years after brachytherapy were 58.3 % to 85.2 % (weighted-mean 76.2 %), 26 % to 66 % (weighted-mean 41.9 %), 20 % to 37 % (weighted-mean 27.6 %), 11 % to 23 % (weighted-mean 14.8 %), and 8 % to 15 % (weighted-mean 12.1 %), respectively. The PFS of 6 months and 1 year after brachytherapy were 26.7 % to 86 % (weighted-mean 53.4 %) and 14 % to 81 % (weighted-mean 24.1 %). Most patients with rGBM will experience treatment failure again during the follow-up period, mainly local (10.7 % to 79.4 %) or marginal(3.6 % to 22.2 %) recurrence, followed by distant failure (6.7 % to 57.7 %). Although therapeutic AEs had not been uniformly reported, the overall toxicity rate was considered to be low. The common AEs reported included progressive neurologic deterioration, seizures, CSF leak, brain necrosis, hemorrhage, and infection/meningitis, with a weighted-mean incidence of 1.9 %, 2.4 %, 4.1 %, 5.4 %, 2.1 %, and 3.8 %, respectively.
The evidence summarized above, albeit mostly level III, suggests that brachytherapy has acceptable safety and good post-treatment clinical efficacy for selected patients with rGBM. Well-designed, high-quality, large-sample randomized controlled and prospective studies are needed to further validate these findings.
Iodine-125 seed implantation in the treatment of malignant tumors
2023, Journal of Interventional Medicine
Malignant tumors are major causes of morbidity and mortality in China. Despite advances in surgical, radiological, chemotherapeutic, molecular targeting, and immunotherapeutic treatments, patients with malignant tumors still have poor prognoses. Low-dose-rate brachytherapy, specifically ¹²⁵I seed implantation, is beneficial because of its high local delivery dose and minimal damage to surrounding tissues. Consequently, it has gained increasing acceptance as a treatment modality for various malignant tumors. In this study, we explored the fundamental principles, clinical applications, and new technologies associated with ¹²⁵I radioactive seed implantation.
Self-assembled short peptides: Recent advances and strategies for potential pharmaceutical applications
2023, Materials Today Bio
Self-assembled short peptides have intrigued scientists due to the convenience of synthesis, good biocompatibility, low toxicity, inherent biodegradability and fast response to change in the physiological environment. Therefore, it is necessary to present a comprehensive summary of the recent advances in the last decade regarding the construction, route of administration and application of self-assembled short peptides based on the knowledge on their unique and specific ability of self-assembly. Herein, we firstly explored the molecular mechanisms of self-assembly of short peptides, such as non-modified amino acids, as well as Fmoc-modified, N-functionalized, and C-functionalized peptides. Next, cell penetration, fusion, and peptide targeting in peptide-based drug delivery were characterized. Then, the common administration routes and the potential pharmaceutical applications (drug delivery, antibacterial activity, stabilizers, imaging agents, and applications in bioengineering) of peptide drugs were respectively summarized. Last but not least, some general conclusions and future perspectives in the relevant fields were briefly listed. Although with certain challenges, great opportunities are offered by self-assembled short peptides to the fascinating area of drug development.
Intracoronary Brachytherapy for Drug-Eluting Stent Restenosis: Outcomes and Clinical Correlates
2023, Journal of the Society for Cardiovascular Angiography and Interventions
This study aimed to report outcomes of intracoronary brachytherapy (ICBT) in treating drug-eluting stent (DES) in-stent restenosis (ISR) and identify correlated factors.
Patients who underwent ICBT for DES ISR from 2010 to 2021 were included in this single-institution retrospective PCI registry. Patients were treated with balloon angioplasty, laser atherectomy, and/or rotational atherectomy, followed by ICBT at a dose of 18.4-25 Gy delivered at the site of ISR with dose determined by the reference vessel size. The primary outcome was 3-year target lesion failure rate (TLF). Secondary end points were 1-year TLF, target lesion revascularization (TLR), all-cause mortality, and cardiac mortality.
In total, 330 consecutive patients presented with 345 treated lesions; 70% were male, age was 66 ± 11 years, 55% were diabetic patients, 62% underwent previous bypass surgery, and 89% were placed with at least 2 stent layers at the treated site. The rate of TLF was 18% at 1 year and 46% at 3 years. All-cause mortality and cardiac mortality rates were 19.8% and 12.3% at 3 years. The number of stent layers was associated with 3-year TLF (1 layer, 33.3%; 2 layers, 47.0%, >3 layers, 60.2%; P = .045). Diabetes, repeat ICBT, final percent stenosis, lesion length, and intravascular imaging use were not correlated with the primary outcome. Lower ICBT dose (P = .035) and restenosis <1 year from previous percutaneous coronary intervention (P = .044) were correlated with early (1-year) TLF.
ICBT for recurrent DES ISR provided low recurrence rates at 1 year, which increased substantially by 3 years. Outcomes were most closely correlated with the number of stent layers, but early restenosis and lower ICBT dose adversely affected early TLF.
Performance evaluation of a homemade extrapolation chamber in low energy radiation field
2022, Vacuum
Extrapolation chambers are widely used to detect the weakly-penetrating types of radiation beams. Normally, the sensitive volume of them is limited, only a few cubic centimeters. Their collecting electrodes use sheet structure, which lead to more backscattering photons. In this work, a large volume extrapolation chamber with (235–1413) cm³ was designed for the absolute measurement of air kerma strength of ¹²⁵I brachytherapy seeds. The developed chamber has the following innovation: large sensitive volume and the Aluminized Polyethylene terephthalate (PET) collecting electrode foil. In order to give a more comprehensive performance evaluation for the designed chamber, a series of experiments were conducted. Evaluation parameters include leakage current, saturation curve, polarity effect, ion collecting efficiency, linearity of response, collecting area and zero point. Those tests were measured in the standard X-ray radiation field. A comparative experiment with the primary standard free air chamber (FAC) was performed. Moreover, extrapolation curve was measured in ¹²⁵I radiation field. Evaluation results show a good behavior of the extrapolation chamber. The Al-coated PET collecting electrode influence the response of the chamber to 0.07% with the simulation of MCNP5 Monte Carlo. All the results indicate the usefulness of the extrapolation chamber for the absolute measurement for ¹²⁵I seeds.
Knowledge-based three-dimensional dose prediction for tandem-and-ovoid brachytherapy
2022, Brachytherapy
The purpose of this work was to develop a knowledge-based dose prediction system using a convolution neural network (CNN) for cervical brachytherapy treatments with a tandem-and-ovoid applicator.
A 3D U-NET CNN was utilized to make voxel-wise dose predictions based on organ-at-risk (OAR), high-risk clinical target volume (HRCTV), and possible source location geometry. The model comprised 395 previously treated cases: training (273), validation (61), test (61). To assess voxel prediction accuracy, we evaluated dose differences in all cohorts across the dose range of 20−130% of prescription, mean (SD) and standard deviation ( $σ)$ , as well as isodose dice similarity coefficients for clinical and/or predicted dose distributions. We examined discrete Dose-Volume Histogram (DVH) metrics utilized for brachytherapy plan quality assessment (HRCTV D90%; bladder, rectum, and sigmoid D2cc) with $Δ D_{x} = D_{x, a c t u a l} - D_{x, p r e d i c t e d}$ mean, standard deviation, and Pearson correlation coefficient further quantifying model performance.
Ranges of voxel-wise dose difference accuracy ( $\bar{δ D} \pm σ)$ for 20−130% dose interval in training (test) sets ranged from [-0.5% ± 2.0% to +2.0% ± 14.0%] ([-0.1% ± 4.0% to +4.0% ± 26.0%]) in all voxels, [-1.7% ± 5.1% to -3.5% ± 12.8%] ([-2.9% ± 4.8% to -2.6% ± 18.9%]) in HRCTV, [-0.02% ± 2.40% to +3.2% ± 12.0%] ([-2.5% ± 3.6% to +0.8% ± 12.7%]) in bladder, [-0.7% ± 2.4% to +15.5% ± 11.0%] ([-0.9% ± 3.2% to +27.8% ± 11.6%]) in rectum, and [-0.7% ± 2.3% to +10.7% ± 15.0%] ([-0.4% ± 3.0% to +18.4% ± 11.4%]) in sigmoid. Isodose dice similarity coefficients ranged from [0.96,0.91] for training and [0.94,0.87] for test cohorts. Relative DVH metric prediction in the training (test) set were HRCTV ${\bar{Δ D}}_{90} \pm σ_{Δ D}$ = -0.19 ± 0.55Gy (-0.09 ± 0.67 Gy), bladder ${\bar{Δ D}}_{2 c c} \pm σ_{Δ D}$ = -0.06 ± 0.54Gy (-0.17 ± 0.67 Gy), rectum ${\bar{Δ D}}_{2 c c} \pm σ_{Δ D}$ = -0.03 ± 0.36Gy (-0.04 ± 0.46 Gy), and sigmoid ${\bar{Δ D}}_{2 c c} \pm σ_{Δ D}$ = -0.01 ± 0.34Gy (0.00 ± 0.44 Gy).
A 3D knowledge-based dose predictions provide voxel-level and DVH metric estimates that could be used for treatment plan quality control and data-driven plan guidance.

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^☆: This review is part of the Advanced Drug Delivery Reviews theme issue on “Radiotherapy for Cancer: Present and Future”.

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Advancements in brachytherapy☆

Abstract

Graphical abstract

Section snippets

Physical and radiobiological effects

Advancements in planning and delivery technology — conventional and novel techniques

Future outlook

Radiother. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Int. J. Radiat. Oncol. Biol. Phys.

Brachytherapy

Lancet (London, England)

Int. J. Radiat. Oncol. Biol. Phys.

Clin. Oncol. (R. Coll. Radiol)

Radiother. Oncol.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Brachytherapy

Semin. Radiat. Oncol.

Int. J. Radiat. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol.

Brachytherapy

Int. J. Radiat. Oncol.

Int. J. Radiat. Oncol.

Int. J. Radiat. Oncol.

Radiother. Oncol.

Lancet Oncol.

Cancer Radiother.

Int. J. Radiat. Oncol. Biol. Phys.

Semin. Radiat. Oncol.

J. Urol.

Radiother. Oncol.

Int. J. Radiat. Oncol.

Radiother. Oncol.

Radiother. Oncol.

Brachytherapy

Radiother. Oncol.

Radiother. Oncol.

Brachytherapy

Int. J. Radiat. Oncol. Biol. Phys.

Brachytherapy

Brachytherapy

Radiother. Oncol.

Int. J. Radiat. Oncol. Biol. Phys.