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Radiotherapy and Oncology : Journal of... Feb 2022This is an evidence-based guideline for prostate brachytherapy. Throughout levels of evidence quoted are those from the Oxford Centre for Evidence based Medicine...
This is an evidence-based guideline for prostate brachytherapy. Throughout levels of evidence quoted are those from the Oxford Centre for Evidence based Medicine (https://www.cebm.ox.ac.uk/resources/levels-of-evidence/oxford-centre-for-evidence-based-medicine-levels-of-evidence-march-2009). Prostate interstitial brachytherapy using either permanent or temporary implantation is an established and evolving treatment technique for non-metastatic prostate cancer. Permanent brachytherapy uses Low Dose Rate (LDR) sources, most commonly I-125, emitting photon radiation over months. Temporary brachytherapy involves first placing catheters within the prostate and, on confirmation of accurate positioning, temporarily introducing the radioactive source, generally High Dose Rate (HDR) radioactive sources of Ir-192 or less commonly Co-60. Pulsed dose rate (PDR) brachytherapy has also been used for prostate cancer [1] but few centres have adopted this approach. Previous GEC ESTRO recommendations have considered LDR and HDR separately [2-4] but as there is considerable overlap, this paper provides updated guidance for both treatment techniques. Prostate brachytherapy allows safe radiation dose escalation beyond that achieved using external beam radiotherapy alone as it has greater conformity around the prostate, sparing surrounding rectum, bladder, and penile bulb. In addition there are fewer issues with changes in prostate position during treatment delivery. Systematic review and randomised trials using both techniques as boost treatments demonstrate improved PSA control when compared to external beam radiotherapy alone [5-7].
Topics: Brachytherapy; Humans; Iodine Radioisotopes; Male; Prostate; Prostatic Neoplasms; Radiotherapy Dosage
PubMed: 34999134
DOI: 10.1016/j.radonc.2021.12.047 -
Radiation and Environmental Biophysics Nov 2022Despite decades of research to understand the biological effects of ionising radiation, there is still much uncertainty over the role of dose rate. Motivated by a... (Review)
Review
Despite decades of research to understand the biological effects of ionising radiation, there is still much uncertainty over the role of dose rate. Motivated by a virtual workshop on the "Effects of spatial and temporal variation in dose delivery" organised in November 2020 by the Multidisciplinary Low Dose Initiative (MELODI), here, we review studies to date exploring dose rate effects, highlighting significant findings, recent advances and to provide perspective and recommendations for requirements and direction of future work. A comprehensive range of studies is considered, including molecular, cellular, animal, and human studies, with a focus on low linear-energy-transfer radiation exposure. Limits and advantages of each type of study are discussed, and a focus is made on future research needs.
Topics: Animals; Humans; Radiation Protection; Radiation Dosage; Radiation Injuries; Radiation Exposure; Radiation, Ionizing; Radiobiology
PubMed: 36241855
DOI: 10.1007/s00411-022-00996-0 -
Frontiers in Oncology 2022To evaluate the plan quality and robustness of both dose and dose rate of proton pencil beam scanning (PBS) transmission FLASH delivery in lung cancer treatment.
PURPOSES
To evaluate the plan quality and robustness of both dose and dose rate of proton pencil beam scanning (PBS) transmission FLASH delivery in lung cancer treatment.
METHODS AND MATERIALS
An in-house FLASH planning platform was used to optimize 10 lung cancer patients previously consecutively treated with proton stereotactic body radiation therapy (SBRT) to receive 3 and 5 transmission beams (Trx-3fds and Trx-5fds, respectively) to 34 Gy in a single fraction. Perturbation scenarios (n=12) for setup and range uncertainties (5 mm and 3.5%) were introduced, and dose-volume histogram and dose-rate-volume histogram bands were generated. Conventional proton SBRT clinical plans were used as a reference. RTOG 0915 dose metrics and 40 Gy/s dose rate coverage (V) were used to assess the dose and dose rate robustness.
RESULTS
Trx-5fds yields a comparable iCTV D of 105.3%, whereas Trx-3fds resulted in inferior D of 111.9% to the clinical SBRT plans with D of 105.6% (p<0.05). Both Trx-5fds and Trx-3fds plans had slightly worse dose metrics to organs at risk than SBRT plans. Trx-5fds achieved superior dosimetry robustness for iCTV, esophagus, and spinal cord doses than both Trx-3fds and conventional SBRT plans. There was no significant difference in dose rate robustness for V coverage between Trx-3fds and Trx-5fds. Dose rate distribution has similar distributions to the dose when perturbation exists.
CONCLUSION
Transmission plans yield overall modestly inferior plan quality compared to the conventional proton SBRT plans but provide improved robustness and the potential for a toxicity-sparing FLASH effect. By using more beams (5- versus 3-field), both dose and dose rate robustness for transmission plans can be achieved.
PubMed: 36059710
DOI: 10.3389/fonc.2022.970602 -
Scientific Reports Apr 2022Reproductive sterility is the basis of the sterile insect technique (SIT) and essential for its success in the field. Numerous factors that influence dose-response in...
Reproductive sterility is the basis of the sterile insect technique (SIT) and essential for its success in the field. Numerous factors that influence dose-response in insects have been identified. However, historically the radiation dose administered has been considered a constant. Efforts aiming to standardize protocols for mosquito irradiation found that, despite carefully controlling many variable factors, there was still an unknown element responsible for differences in expected sterility levels of insects irradiated with the same dose and handling protocols. Thus, together with previous inconclusive investigations, the question arose whether dose really equals dose in terms of biological response, no matter the rate at which the dose is administered. Interestingly, the dose rate effects studied in human nuclear medicine indicated that dose rate could alter dose-response in mammalian cells. Here, we conducted experiments to better understand the interaction of dose and dose rate to assess the effects in irradiated mosquitoes. Our findings suggest that not only does dose rate alter irradiation-induced effects, but that the interaction is not linear and may change with dose. We speculate that the recombination of reactive oxygen species (ROS) in treatments with moderate to high dose rates might minimize indirect radiation-induced effects in mosquitoes and decrease sterility levels, unless dose along with its direct effects is increased. Together with further studies to identify an optimum match of dose and dose rate, these results could assist in the development of improved methods for the production of high-quality sterile mosquitoes to enhance the efficiency of SIT programs.
Topics: Animals; Humans; Infertility; Insecta; Mammals; Pupa; Radiation Dosage
PubMed: 35422488
DOI: 10.1038/s41598-022-10027-z -
Cancer Reports (Hoboken, N.J.) Jan 2022High-dose-rate brachytherapy (HDR BRT) has been enjoying rapid acceptance as a treatment modality offered to selected prostate cancer patients devoid of risk group,... (Review)
Review
BACKGROUND
High-dose-rate brachytherapy (HDR BRT) has been enjoying rapid acceptance as a treatment modality offered to selected prostate cancer patients devoid of risk group, employed either in monotherapy setting or combined with external beam radiation therapy (EBRT) and is currently one of the most active clinical research areas.
RECENT FINDINGS
This review encompasses all the current evidence to support the use of HDR BRT in various clinical scenario and shines light to the HDR BRT rationale, as an ultimately conformal dose delivery method enabling safe dose escalation to the prostate.
CONCLUSION
Valid long-term data, both in regard to the oncologic outcomes and toxicity profile, support the current clinical indication spectrum of HDR BRT. At the same time, this serves as solid, rigid ground for emerging therapeutic applications, allowing the technique to remain in the spotlight alongside stereotactic radiosurgery.
Topics: Brachytherapy; Dose Fractionation, Radiation; Humans; Male; Prostatic Neoplasms
PubMed: 34164950
DOI: 10.1002/cnr2.1450 -
Chemico-biological Interactions Mar 2019The goal of this manuscript is to define the role of dose rate and dose protraction on the induction of biological changes at all levels of biological organization. Both... (Review)
Review
The goal of this manuscript is to define the role of dose rate and dose protraction on the induction of biological changes at all levels of biological organization. Both total dose and the time frame over which it is delivered are important as the body has great capacity to repair all types of biological damage. The importance of dose rate has been recognized almost from the time that radiation was discovered and has been included in radiation standards as a Dose, Dose Rate, Effectiveness Factor (DDREF) and a Dose Rate Effectiveness Factor (DREF). This manuscript will evaluate the role of dose rate at the molecular, cellular, tissue, experimental animals and humans to demonstrate that dose rate is an important variable in estimating radiation cancer risk and other biological effects. The impact of low-dose rates on the Linear-No-Threshold Hypothesis (LNTH) will be reviewed since if the LNTH is not valid it is not possible to calculate a single value for a DDREF or DREF. Finally, extensive human experience is briefly reviewed to show that the radiation risks are not underestimated and that radiation at environmental levels has limited impact on total human cancer risk.
Topics: Animals; Dose-Response Relationship, Radiation; Humans; Linear Models; Models, Statistical; Neoplasms, Radiation-Induced; Radiation Dosage; Risk Assessment
PubMed: 30763551
DOI: 10.1016/j.cbi.2018.12.007 -
Medical Physics Mar 2022Compared to CONV-RT (with conventional dose rate), FLASH-RT (with ultra-high dose rate) can provide biological dose sparing for organs-at-risk (OARs) via the so-called...
PURPOSE
Compared to CONV-RT (with conventional dose rate), FLASH-RT (with ultra-high dose rate) can provide biological dose sparing for organs-at-risk (OARs) via the so-called FLASH effect, in addition to physical dose sparing. However, the FLASH effect only occurs, when both dose and dose rate meet certain minimum thresholds. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method accounting for both FLASH dose and dose rate constraints during treatment planning for pencil-beam-scanning proton therapy.
METHODS
SDDRO optimizes the FLASH effect (specific to FLASH-RT) as well as the dose distribution (similar to CONV-RT). The nonlinear dose rate constraint is linearized, and the reformulated optimization problem is efficiently solved via iterative convex relaxation powered by alternating direction method of multipliers. To resolve and quantify the generic tradeoff of FLASH-RT between FLASH and dose optimization, we propose the use of FLASH effective dose based on dose modifying factor (DMF) owing to the FLASH effect.
RESULTS
FLASH-RT via transmission beams (TB) (IMPT-TB or SDDRO) and CONV-RT via Bragg peaks (BP) (IMPT-BP) were evaluated for clinical prostate, lung, head-and-neck (HN), and brain cases. Despite the use of TB, which is generally suboptimal to BP for normal tissue sparing, FLASH-RT via SDDRO considerably reduced FLASH effective dose for high-dose OAR adjacent to the target. For example, in the lung SBRT case, the max esophageal dose constraint 27 Gy was only met by SDDRO (24.8 Gy), compared to IMPT-BP (35.3 Gy) or IMPT-TB (36.6 Gy); in the brain SRS case, the brain constraint V12Gy≤15cc was also only met by SDDRO (13.7cc), compared to IMPT-BP (43.9cc) or IMPT-TB (18.4cc). In addition, SDDRO substantially improved the FLASH coverage from IMPT-TB, e.g., an increase from 37.2% to 67.1% for lung, from 39.1% to 58.3% for prostate, from 65.4% to 82.1% for HN, from 50.8% to 73.3% for the brain.
CONCLUSIONS
Both FLASH dose and dose rate constraints are incorporated into SDDRO for FLASH-RT that jointly optimizes the FLASH effect and physical dose distribution. FLASH effective dose via FLASH DMF is introduced to reconcile the tradeoff between physical dose sparing and FLASH sparing, and quantify the net effective gain from CONV-RT to FLASH-RT.
Topics: Humans; Male; Organs at Risk; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 34800301
DOI: 10.1002/mp.15356 -
Journal of Contemporary Brachytherapy Oct 2014High-dose-rate brachytherapy (HDR) is a method of conformal dose escalation to the prostate. It can be used as a local boost in combination with external beam... (Review)
Review
High-dose-rate brachytherapy (HDR) is a method of conformal dose escalation to the prostate. It can be used as a local boost in combination with external beam radiotherapy, with a high degree of efficacy and low rate of long term toxicity. Data consistently reports relapse free survival rates of greater than 90% for intermediate risk patients and greater than 80% for high risk. Results are superior to those achieved with external beam radiotherapy alone. A wide range of dose and fractionation is reported, however, we have found that a single 15 Gy HDR combined with hypofractionated radiotherapy to a dose of 37.5 Gy in 15 fractions is well tolerated and is associated with a long term relapse-free survival of over 90%. Either CT-based or trans-rectal ultrasound-based planning may be used. The latter enables treatment delivery without having to move the patient with risk of catheter displacement. We have found it to be an efficient and quick method of treatment, allowing catheter insertion, planning, and treatment delivery to be completed in less than 90 minutes. High-dose-rate boost should be considered the treatment of choice for many men with high and intermediate risk prostate cancer.
PubMed: 25337138
DOI: 10.5114/jcb.2014.45759 -
World Journal of Plastic Surgery Jan 2021Radiotherapy as an adjuvant therapy to surgical resection has shown variable rates of recurrence treating earlobe keloids. The purpose of this study was to describe our...
BACKGROUND
Radiotherapy as an adjuvant therapy to surgical resection has shown variable rates of recurrence treating earlobe keloids. The purpose of this study was to describe our experience with surgical excision followed by high-dose-rate brachytherapy and present our outcomes after 24 months of follow-up.
METHODS
Retrospective chart of 14 patients with 14 earlobe keloids treated with surgical excision followed by high-dose-rate brachytherapy, between January 2015 and May 2016 were enrolled. Database included demographics, Fitzpatrick skin type, laterality, lesion size, and follow-up visits information. Outcomes were assessed in terms of keloid recurrence rates, complications, and patient subjective aesthetical result satisfaction after 24 months of follow-up.
RESULTS
All procedures were completed without complications. Three patients experienced keloid recurrence after 6 (14.28%) and 12 months (7.14%). Three patients experienced mild signs of self-limited post-radiation dermatitis. Self-assessment of aesthetical result was considered "very good" in 71.43% of patients.
CONCLUSION
Surgical excision followed by high-dose-rate brachytherapy is secure and effective to treat earlobe keloids, and can be considered a first line combined treatment. Larger clinical trials comparing different irradiation protocols are still needed.
PubMed: 33833958
DOI: 10.29252/wjps.10.1.78 -
Medical Physics Dec 2022The combined use of Bragg peak (BP) and shoot-through (ST) beams has previously been shown to increase the normal tissue volume receiving FLASH dose rates while...
PURPOSE
The combined use of Bragg peak (BP) and shoot-through (ST) beams has previously been shown to increase the normal tissue volume receiving FLASH dose rates while maintaining dose conformality compared to conventional intensity-modulated proton therapy (IMPT) methods. However, the fixed beam optimization method has not considered the effects of beam orientation on the dose and dose rates. To maximize the proton FLASH effect, here, we incorporate dose rate objectives into our beam orientation optimization framework.
METHODS
From our previously developed group-sparsity dose objectives, we add upper and lower dose rate terms using a surrogate dose-averaged dose rate definition and solve using the fast-iterative shrinking threshold algorithm. We compare the dosimetry for three head-and-neck cases between four techniques: (1) spread-out BP IMPT (BP), (2) dose rate optimization using BP beams only (BP-DR), (3) dose rate optimization using ST beams only (ST-DR), and (4) dose rate optimization using combined BP and ST (BPST-DR), with the goal of sparing organs at risk without loss of tumor coverage and maintaining high dose rate within a 10 mm region of interest (ROI) surrounding the clinical target volume (CTV).
RESULTS
For BP, BP-DR, ST-DR, and BPST-DR, CTV homogeneity index and Dmax were found to be on average 0.886, 0.867, 0.687, and 0.936 and 107%, 109%, 135%, and 101% of prescription, respectively. Although ST-DR plans were not able to meet dosimetric standards, BPST-DR was able to match or improve either maximum or mean dose in the right submandibular gland, left and right parotids, constrictors, larynx, and spinal cord compared to BP plans. Volume of ROIs receiving greater than 40 Gy/s ( was 51.0%, 91.4%, 95.5%, and 92.1% on average.
CONCLUSIONS
The dose rate techniques, particularly BPST-DR, were able to significantly increase dose rate without compromising physical dose compared with BP. Our algorithm efficiently selects beams that are optimal for both dose and dose rate.
Topics: Humans; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Neoplasms; Protons; Radiotherapy, Intensity-Modulated; Organs at Risk
PubMed: 36222217
DOI: 10.1002/mp.16009