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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 -
Tidsskrift For Den Norske Laegeforening... Mar 2015Prostate cancer is a radiosensitive type of cancer for which radiotherapy is used for both curative and palliative purposes. Low-dose-rate brachytherapy is an internal... (Review)
Review
BACKGROUND
Prostate cancer is a radiosensitive type of cancer for which radiotherapy is used for both curative and palliative purposes. Low-dose-rate brachytherapy is an internal radiotherapy technique which allows high doses of radiation to be delivered to a tumour at short range and with a high degree of precision. We have conducted a systematic review of the evidence base for this treatment. The method is not established in Norway.
METHOD
This review is based on systematic review articles and publications on treatment, outcomes, adverse effects and health economics considerations found by searching the databases Cochrane Library, Current Controlled Trials, Medline, Embase and NICE (National Institute of Clinical Excellence).
RESULTS
Subsequent to long-term observations of the efficacy, adverse effects and costs presented in 43 selected studies, including one randomised, controlled trial, there is still uncertainty as to which of the three methods low-dose brachytherapy, external radiotherapy and radical prostatectomy is optimal. The reason for this is the methodological differences in patient selection and in endpoints such as biochemical disease-free interval and cause-specific survival. The evidence base appears to suggest that low-dose-rate brachytherapy causes more frequent grade 2 and 3 doctor-reported urogenital adverse effects than prostatectomy, but better patient-reported sexual functions and fewer patients with urinary incontinence than after surgery. Low-dose-rate brachytherapy appears to be socioeconomically cost-effective.
INTERPRETATION
The evidence base with respect to therapeutic effect and toxicity in men with low-risk prostate cancer treated with low-dose brachytherapy is regarded as solidly documented. However, there are no good prospective randomised multi-centre trials with overall survival as an endpoint.
Topics: Brachytherapy; Cost-Benefit Analysis; Disease-Free Survival; Erectile Dysfunction; Humans; Male; Prostatic Neoplasms; Treatment Outcome; Urinary Incontinence
PubMed: 25806763
DOI: 10.4045/tidsskr.13.1404 -
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 -
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 -
Cancer Science Nov 2023Rectal cancer is a common malignancy that requires multidisciplinary treatment. By utilizing the dose-response relationship in rectal cancer radiotherapy, increasing the... (Review)
Review
Rectal cancer is a common malignancy that requires multidisciplinary treatment. By utilizing the dose-response relationship in rectal cancer radiotherapy, increasing the radiotherapy dose can improve clinical complete remission rates. High-dose rate endorectal brachytherapy (HDREBT) is a novel technique that delivers high doses of radiotherapy directly to the tumor via an endorectal applicator, sparing the adjacent normal tissues from excessive radiation exposure. HDREBT includes contact X-ray brachytherapy and high-dose-rate intracavitary brachytherapy. We introduce the latest developments in applicators and imaging techniques for HDREBT in rectal cancer and summarize the current evidence on the efficacy, safety, and feasibility of HDREBT as a neoadjuvant, definitive, or palliative treatment option for all stages of rectal cancer patients. We also discuss the potential advantages and challenges of HDREBT in achieving organ preservation and improving the quality of life of rectal cancer patients. HDREBT has shown promising results in achieving high complete response rates, enabling nonoperative management, improving organ preservation rates, and providing effective palliation in rectal cancer patients. More studies are needed to optimize its dose and fractionation schemes in different clinical scenarios.
Topics: Humans; Brachytherapy; Quality of Life; Radiotherapy Dosage; Rectal Neoplasms; Rectum
PubMed: 37702196
DOI: 10.1111/cas.15959 -
Medical Physics Jun 2023Conformality has been a key requirement in radiation therapy for cancer to minimize normal tissue toxicity while maintaining tumor control. Since 2014, there has been... (Review)
Review
Conformality has been a key requirement in radiation therapy for cancer to minimize normal tissue toxicity while maintaining tumor control. Since 2014, there has been great interest in ultra-high dose rate (UHDR), "FLASH," radiation therapy to enhance this therapeutic window. In multiple pre-clinical studies, it was seen that normal tissue demonstrated less damage due to radiation of various modalities when the same dose was delivered at ultra-high mean dose rates exceeding ∼40 Gy/s while tumor control remained indifferent to changes in dose rate. The scientific community has large-scale interdisciplinary studies to investigate this potentially breakthrough technique to enhance treatment options for cancer. FLASH studies have been performed using a number of modalities and delivery techniques for many pre-clinical models. There have been several studies reporting evidence of the FLASH effect as well as technological developments relating to UHDR studies. There is sustained interest and motivation for this topic as well as many questions that are yet to be answered. We provide a short overview to highlight some of the major work and challenges to advance research in FLASH radiotherapy.
Topics: Humans; Neoplasms; Motivation; Radiotherapy Dosage
PubMed: 36758965
DOI: 10.1002/mp.16271 -
Medical Physics Jul 2022Higher dose rates, a trend for radiotherapy machines, can be beneficial in shortening treatment times for radiosurgery and mitigating the effects of motion. Recently,...
Higher dose rates, a trend for radiotherapy machines, can be beneficial in shortening treatment times for radiosurgery and mitigating the effects of motion. Recently, even higher doses (e.g., 100 times greater) have become targeted because of their potential to generate the FLASH effect (FE). We refer to these physical dose rates as ultra-high (UHDR). The complete relationship between UHDR and the FE is unknown. But UHDR systems are needed to explore the relationship further and to deliver clinical UHDR treatments, where indicated. Despite the challenging set of unknowns, the authors seek to make reasonable assumptions to probe how existing and developing technology can address the UHDR conditions needed to provide beam generation capable of producing the FE in preclinical and clinical applications. As a preface, this paper discusses the known and unknown relationships between UHDR and the FE. Based on these, different accelerator and ionizing radiation types are then discussed regarding the relevant UHDR needs. The details of UHDR beam production are discussed for existing and potential future systems such as linacs, cyclotrons, synchrotrons, synchrocyclotrons, and laser accelerators. In addition, various UHDR delivery mechanisms are discussed, along with required developments in beam diagnostics and dose control systems.
Topics: Cyclotrons; Particle Accelerators; Radiation Oncology; Radiosurgery; Radiotherapy Dosage; Synchrotrons
PubMed: 35403262
DOI: 10.1002/mp.15659 -
Journal of Cardiothoracic and Vascular... Sep 2022The clinical efficacy of corticosteroids remains unclear. The primary aim of this systematic review and meta-analysis was to evaluate the use of high-dose versus low-... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The clinical efficacy of corticosteroids remains unclear. The primary aim of this systematic review and meta-analysis was to evaluate the use of high-dose versus low- dose corticosteroids on the mortality rate of COVID-19 patients.
DESIGN
Systematic review and meta-analysis.
SETTING
Electronic search for randomized controlled trials and observational studies (MEDLINE, EMBASE, CENTRAL).
PARTICIPANTS
Hospitalized adults ≥ 18 years old who were SARS-CoV-2 PCR positive.
INTERVENTIONS
High-dose and low-dose corticosteroids.
MEASUREMENTS AND MAIN RESULTS
A total of twelve studies (n=2759 patients) were included in this review. The pooled analysis demonstrated no significant difference in mortality rate between the high-dose and low-dose corticosteroids groups (n=2632; OR: 1.07 [95%CI 0.67, 1.72], p=0.77, I=76%, trial sequential analysis=inconclusive). No significant differences were observed in the incidence of intensive care unit (ICU) admission rate (n=1544; OR: 0.77[95%CI 0.43, 1.37], p=0.37, I= 72%), duration of hospital stay (n=1615; MD: 0.53[95%CI -1.36, 2.41], p=0.58, I=87%), respiratory support (n=1694; OR: 1.51[95%CI 0.77, 2.96], p=0.23, I=84%), duration of mechanical ventilation (n=419; MD: -1.44[95%CI -4.27, 1.40], p=0.32, I=93%), incidence of hyperglycemia (n=516, OR: 0.91[95%CI 0.58, 1.43], p=0.68, I=0%) and infection rate (n=1485, OR: 0.86[95%CI 0.64, 1.16], p=0.33, I=29%).
CONCLUSION
The meta-analysis demonstrated high-dose corticosteroids did not reduce mortality rate. However, high-dose corticosteroids did not pose higher risk of hyperglycemia and infection rate for COVID-19 patients. Due to the inconclusive trial sequential analysis, substantial heterogeneity and low level of evidence, future large-scale randomized clinical trials are warranted to improve the certainty of evidence for the use of high-dose compared to low-dose corticosteroids in COVID-19 patients.
Topics: Adolescent; Adrenal Cortex Hormones; Adult; COVID-19; Humans; Hyperglycemia; Respiration, Artificial; SARS-CoV-2
PubMed: 35715291
DOI: 10.1053/j.jvca.2022.05.011 -
BMC Pregnancy and Childbirth Oct 2021Gonadotropin-releasing hormone antagonist(GnRH-ant) has been shown to have a negative effect on endometrial receptivity. Therefore, the use of lower doses of GnRH-ant...
BACKGROUND
Gonadotropin-releasing hormone antagonist(GnRH-ant) has been shown to have a negative effect on endometrial receptivity. Therefore, the use of lower doses of GnRH-ant during controlled ovarian stimulation (COS) may improve endometrial receptivity and clinical pregnancy rate. However, the GnRH-ant dose is relatively flexible and there is no fixed requirement for guidance. In this retrospective study, we determined the effects of half-dose and full-dose GnRH-ant on IVF-ET outcomes.
METHODS
Of the 316 cycles in the 314 patients analyzed in this study, 149 received GnRH-ant half-dose (Group1), while 167 received GnRH-ant full-dose (Group2). The groups were further classified based on age and BMI. Age subgroups, were divided as age ≤ 35(subgroup A) and age > 35(subgroup B): 180 cycles in subgroup A (107 cycles in subgroup A1,73 cycles in subgroup A2), 136 cycles in subgroup B (42 cycles in subgroup B1,94 cycles in subgroupB2). The subgroups based on BMI were divided as BMI < 25 (subgroup C)and BMI ≥ 25 (subgroup D):208 cycles in subgroup C (94 cycles in subgroup C1,114 cycles in subgroup C2), 108 cycles in subgroup D (55 cycles in subgroup D1,53 cycles in subgroup D2).
RESULTS
The number of fertilized oocytes, superior-quality embryos, clinical pregnancy rate, and live birth rate differed significantly between the two groups. However, the number of retrieved oocytes and available embryos were significantly higher in Group 1 than Group 2 (8.17 ± 4.10 vs. 7.07 ± 4.05, 2.96 ± 2.03 vs. 2.52 ± 1.62, respectively,p<0.05). Differences between the age subgroups were not statistically significant. However, in the subgroups based on BMI, the fertilized oocytes, available embryos, the number of superior-quality embryos, and the live birth rate differed significantly between the four subgroups. The number of retrieved oocytes was higher in subgroup C1 than in subgroup C2 (8.24 ± 4.04 vs. 6.83 ± 3.92,p < 0.05), In addition, the clinical pregnancy rate was slightly higher in subgroup D1 than in subgroup D2(45.45 vs. 24.53%, P < 0.05).
CONCLUSIONS
The results showed that half-dose GnRH-ant was as effective as full-dose GnRH-ant for most patients. Moreover, half-dose GnRH-ant may be more suitable in patients with BMI greater than or equal to 25. The findings of this study need to be validated in a large sample RCT.
TRIAL REGISTRATION
Retrospectively registered.
Topics: Adult; Age Distribution; Birth Rate; Body Mass Index; China; Embryo Transfer; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Live Birth; Oocyte Retrieval; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies
PubMed: 34706665
DOI: 10.1186/s12884-021-04176-8 -
Translational Andrology and Urology Jun 2018High dose-rate (HDR) brachytherapy involves delivery of a high dose of radiation to the cancer with great sparing of surrounding organs at risk. Prostate cancer is... (Review)
Review
High dose-rate (HDR) brachytherapy involves delivery of a high dose of radiation to the cancer with great sparing of surrounding organs at risk. Prostate cancer is thought to be particularly sensitive to radiation delivered at high dose-rate or at high dose per fraction. The rapid delivery and high conformality of dose results in lower toxicity than that seen with low dose-rate (LDR) implants. HDR combined with external beam radiotherapy results in higher cancer control rate than external beam only, and should be offered to eligible high and intermediate risk patients. While a variety of dose and fractionations have been used, a single 15 Gy HDR combined with 40-50 Gy external beam radiotherapy results in a disease-free survival of over 90% for intermediate risk and 80% for high risk. HDR monotherapy in two or more fractions (e.g., 27 Gy in 2 fractions or 34.5 Gy in 3) is emerging as a viable alternative to LDR brachytherapy for low and low-intermediate risk patients, and has less toxicity. The role of single fraction monotherapy to a dose of 19-20 Gy is evolving, with some conflicting data to date. HDR should also be considered as a salvage approach for recurrent disease following previous external beam radiotherapy. A particular advantage of HDR in this setting is the ease of delivering focal treatments, which combined with modern imaging allows focal dose escalation with minimal toxicity. Trans-rectal ultrasound (TRUS) based planning is replacing CT-based planning as the technique of choice as it minimizes or eliminates the need to move the patient between insertion, planning and treatment delivery, thus ensuring high accuracy and reproducibility of treatment.
PubMed: 30050796
DOI: 10.21037/tau.2017.12.08