Dose Rate Technique Research Articles

Simulation-guided development of an optical calorimeter for high dose rate dosimetry.

Optical Calorimetry (OC) is based on interferometry and provides a direct measurement of spatially resolved absorbed dose to water by measuring refractive index changes induced by radiation. The purpose of this work was to optimize and characterize in software an OC system tailored for ultra-high dose rate applications and to build and test a prototype in a clinical environment.A radiation dosimeter using the principles of OC was designed in optical modelling software. Traditional image quality instruments, fencepost and contrast phantoms, were utilized both in software and experimentally in a lab environment to investigate noise reduction techniques and to test the spatial and dose resolution of the system. Absolute dose uncertainty was assessed by measurements in a clinical 6 MV Flattening Filter Free (FFF) photon beam with dose rates in the range 0.2-6Gy/s achieved via changing the distance from the source.Design improvements included: equalizing the pathlengths of the interferometer, isolating the system from external vibrations and controlling the system's internal temperature as well as application of mathematical noise reduction techniques. Simulations showed that these improvements should increase the spatial resolution from 22 to 35 lp/mm and achieve a minimum detectable dose of 0.2Gy, which was confirmed experimentally. In the FFF beam, the absolute dose uncertainty was dose rate dependent and decreased from 2.5 ± 0.8 to 2.5 ± 0.2Gy for dose rates of 0.2 and 6Gy/s, respectively.A radiation dosimeter utilizing the principles of OC was developed and constructed. Optical modelling software and image quality phantoms allowed for iterative testing and refinement. The refined OC system proved capable of measuring absorbed dose to water in a linac generated photon beam. Reduced uncertainty at higher dose rates indicates the potential for OC as a dosimetry system for high dose rate techniques such as microbeam and ultra-high dose-rate radiotherapy.

Idiopathic Pneumonitis Syndrome After Total Body Irradiation in Pediatric Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplantation: A PENTEC Comprehensive Review

Pulmonary complications, especially idiopathic pneumonitis syndrome (IPS), are potentially life altering or fatal sequelae of hematopoietic cell transplantation (HCT). Total body irradiation (TBI) as part of the conditioning regimen has been implicated in IPS. A comprehensive PENTEC (Pediatric Normal Tissues in the Clinic) review was performed to increase our understanding of the role of TBI in the development of acute, noninfectious IPS. A systematic literature search was conducted using the MEDLINE, PubMed, and Cochrane library databases for articles describing pulmonary toxicity in children treated with HCT. Data pertaining to TBI and pulmonary endpoints were extracted. Risk of IPS was analyzed in relation to patient age, TBI dose, fractionation, dose rate, lung shielding, timing, and type of transplant, with the goal to better understand factors associated with this complication in children undergoing HCT. A logistic regression model was developed using a subset of studies with comparable transplant regimens and sufficient TBI data. Six studies met criteria for modeling of the correlation of TBI parameters with IPS; all consisted of pediatric patients undergoing allogeneic HCT with a cyclophosphamide-based chemotherapy regimen. IPS was variably defined, but all studies that reported IPS were included in this analysis. The mean incidence of post-HCT IPS was 16% (range, 4%-41%). Mortality from IPS, when it occurred, was high (median, 50%; range, 45%-100%). Fractionated TBI prescription doses encompassed a narrow range of 9 to 14 Gy. Many differing TBI methods were reported, and there was an absence of 3-dimensional dose analysis of lung blocking techniques. Thus, a univariate correlation between IPS and total TBI dose, dose fractionation, dose rate, or TBI technique could not be made. However, a model, built from these studies based on prescribed dose using a normalized dose parameter of equivalent dose in 2-Gy fractions (EQD2), adjusted for dose rate, suggested correlation with the development of IPS (P = .0004). The model-predicted odds ratio for IPS was 24.3 Gy-1 (95% confidence interval, 7.0-84.3). Use of TBI lung dose metrics (eg, midlung point dose) could not be successfully modeled, potentially because of dosimetric uncertainties in the actual delivered volumetric lung dose and imperfections in our modeling process. This PENTEC report is a comprehensive review of IPS in pediatric patients receiving fractionated TBI regimens for allogenic HCT. IPS was not clearly associated with 1 single TBI factor. Modeling using dose-rate adjusted EQD2 showed a response with IPS for allogeneic HCT using a cyclophosphamide-based chemotherapy regimen. Therefore, this model suggests IPS mitigation strategies can focus on not just the dose and dose per fraction but also the dose rate used in TBI. More data are needed to confirm this model and to determine the influence of chemotherapy regimens and contribution from graft-versus-host disease. The presence of confounding variables (eg, systemic chemotherapies) that affect risk, the narrow range of fractionated TBI doses found in the literature, and limitations of other reported data (eg, lung point dose) may have prevented a more straightforward link between IPS and total dose from being observed.

Dose and dose rate objectives in Bragg peak and shoot-through beam orientation optimization for FLASH proton therapy.

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. 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 10mm region of interest (ROI) surrounding the clinical target volume (CTV). 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 40Gy/s ( was 51.0%, 91.4%, 95.5%, and 92.1% on average. 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.

A Systematic Comparison of Dose Distributions Delivered in 125I Plaque Brachytherapy and Proton Radiation Therapy for Ocular Melanoma

To characterize dose distributions with 125I plaque brachytherapy compared with proton radiation therapy for ocular melanoma for relevant clinical scenarios, based on tumor base diameter (d), apical height (h), and location. Plaque and proton treatment plans were created for 4 groups of cases: (1) REF: 39 instances of reference midsize circular-base tumor (d=12 mm, h=5 mm), in locations varying by retinal clock hours and distance to fovea, optic disc, and corneal limbus; (2) SUP: 25 superiorly located; (3) TEMP: 25 temporal; and (4) NAS: 25 nasally located tumors that were a fixed distance from the fovea but varying in d (6-18 mm) and h (3-11 mm). For both modalities, 111 unique scenarios were characterized in terms of the distance to points of interest, doses delivered to fovea, optic disc, optic nerve at 3 mm posterior to the disc (ON@3mm), lens, and retina. Comparative statistical evaluation was performed with the Mann-Whitney U test. Superior dose distributions favored plaque for sparing of (1) fovea in large (d+h ≥ 21 mm) NAS tumors; (2) ON@3mm in REF cases located ≤4 disc diameters from disc, and in NAS overall. Protons achieved superior dose sparing of (1) fovea and optic disc in REF, SUP, and TEMP; (2) ON@3mm in REF >4 disc diameters from disc, and in SUP and TEMP; and (3) the lens center overall and lens periphery in REF ≤6 mm from the corneal limbus, and in TEMP with h = 3 mm. Although protons could completely spare sections of the retina, plaque dose was more target conformal in the high-dose range (50% and 90% of prescription dose). Although comparison between plaque and proton therapy is not straightforward because of the disparity in dose rate, prescriptions, applicators, and delivery techniques, it is possible to identify distinctions between dose distributions, which could help inform decisions by providers and patients.

Hydrogel spacers and prostate brachytherapy

The use of brachytherapy for the definitive treatment of localized prostate cancer has been established for over four decades (1). Therapy may be delivered using either permanent seed low dose rate (LDR) or high dose rate (HDR) technique. Both techniques are recommended in the ASCO/CCO joint guidelines (2), and data suggests comparable oncologic outcomes. Brachytherapy may be used as monotherapy for low risk and selected intermediate risk patients or in conjunction with external beam radiation therapy (EBRT) for unfavorable intermediate and high risk patients.

High Dose Rate Brachytherapy in High-Risk Localised Disease – Why Do Anything Else?

The management of high-risk prostate cancer is challenging, as patients have a high risk of both local and distant relapse. Although adjuvant systemic treatment remains an important component of management, for those receiving radiotherapy, optimal local treatment should include a brachytherapy boost. This may be given by low dose rate (LDR) or high dose rate (HDR) techniques, but HDR has several advantages over LDR by virtue of more consistent dose optimisation, ability to treat outside the prostate and lower toxicity. A significant body of evidence now supports the use of HDR brachytherapy in addition to supplementary pelvic external beam radiotherapy for men with high-risk disease. Consistent evidence has emerged from randomised clinical trials, meta-analyses, and from institutional and multicentre cohort studies. It has been shown to improve local disease control and possibly reduce metastases and improve cancer-specific survival compared with external beam radiotherapy alone. It should be considered as standard treatment.

Salvage Re-irradiation With Single-modality Interstitial Brachytherapy for the Treatment of Recurrent Gynaecological Tumours in the Pelvis: A Multi-institutional Study

AimsRecurrent gynaecological tumours can cause significant morbidity with limited salvage options. This study investigates the strategy of salvage single-modality interstitial brachytherapy (SM-ISBT) for recurrent gynaecological pelvic cancer at two specialised ISBT centres. Materials and methodsPatients who had received salvage SM-ISBT for pelvic recurrence of gynaecological cancers from September 2008 to January 2017 were included. None had distant metastasis at the time of recurrence. Local control, progression-free and overall survival and long-term toxicities were evaluated. ResultsTwenty-six patients with a median follow-up of 24 months (range 2.5–106.3 months) after SM-ISBT were included. Primary cancer sites were endometrium (20), cervix (4), vulva (1) and vagina (1). All patients had prior whole-pelvic external beam irradiation and 16 had prior brachytherapy. The median disease-free survival prior to SM-ISBT was 20.3 months (interquartile range 9.9–30.5). SM-ISBT was delivered with high dose rate technique over three to six fractions. The median high-risk clinical target volume was 34.6 cm3, with a median D90 of 29.1 Gy (range 16.1–64.6). The median bladder, rectum and sigmoid D2cm3 were 15.5, 18.7 and 3.7 Gy, respectively. After SM-ISBT, complete and partial responses were achieved in 17 (64%) and 5 (19%) patients, respectively. Two (7.4%) patients had grade 3 toxicities (both vaginal stenosis), with no grade 4 complications. Eighteen patients (69%) recurred, including local, regional and metastatic in 14 (54%), 8 (30%) and 5 (19%) patients, respectively. Two-year local control, progression-free survival and overall survival were 50, 38 and 78%, respectively. In follow-up, 12 patients (46%) remained in local control. ConclusionsSalvage SM-ISBT re-irradiation for pelvic recurrence of gynaecological malignancies was feasible and safe. With limited salvage options, the local control obtained in more than a quarter of patients seems reasonable. Further efforts are needed to establish a consensus about the optimal patient selection, dose fractionation, implant technique and combination with systemic therapies.

Correlation Between High Dose Rate Irradiation and Low Dose Rate Irradiation for Switched Dose Rate Technique

Based on gated lateral p-n-p (GLp-n-p) transistors, the correlation between the high dose rate (HDR) and low dose rate (LDR) irradiations during the switched dose rate experiments is investigated. Experimental results show that a significant deviation of the current gain degradation caused by switching dose rate irradiations from that by individual LDR ones is found. It is also observed that, after the switching of dose rate from HDR to LDR, the positive oxide-trapped charges induced by the HDR irradiations would influence the recombination of interface traps produced by the LDR irradiations, leading to an abnormal evolution of the excess base current and excess collector current for the GLp-n-p transistors. The decrease in the positive oxide-trapped charges from HDR to LDR is not caused by an annealing effect. The evolution of positive oxide-trapped charges could influence the formation of interface traps during switched dose rate experiments. All the experimental results indicate that the degradations in the GLp-n-p caused by the HDR and LDR irradiations are not two independent processes for the switched dose rate technique.

Safety of high dose rate prostate brachytherapy in patients with high baseline international prostate symptom scores.

25 Background: Though a high baseline international prostate symptom score (IPSS) is considered a relative contraindication for low dose rate (LDR) brachytherapy, use of high dose rate (HDR) technique has several theoretical advantages including increased ability to sculpt dose and spare normal tissue via post-implant dosimetry. We report our institutional QOL data for those undergoing HDR with an IPSS score ≥15 compared to those with an IPSS score <15. Methods: The charts of 95 patients with localized adenocarcinoma of the prostate treated with HDR as monotherapy or as a boost after external beam radiation (EBRT) at a single institution between 2012 and 2015 were reviewed. All patients completed the IPSS and Expanded Prostate Index for Prostate Cancer–Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and at least one follow-up survey. Linear mixed models were performed to test for significant changes and differences in each outcome over time. Results: Median follow-up in the IPSS <15 group (n=79) was 23 months and 16 months in the IPSS ≥15 group (n=16). Median IPSS score was 6 (range 0-14) and 19 (range 15-30), respectively. A majority of patients in both groups were diagnosed with National Comprehensive Cancer Network (NCCN) intermediate risk disease. Median prostate volume was 45.4cc in the IPSS ≥15 group and 46.3cc in the IPSS <15 group (p=0.901). IPSS, incontinence, and urinary irritation/obstruction scores were significantly higher in the IPSS ≥15 group compared to the IPSS <15 group at baseline (all p≤0.05). By the >24 months time point, these scores had decreased below baseline and were not significantly different from those with a baseline IPSS score <15 (all p>0.1). 12.5% in the IPSS ≥15 group developed a new grade 2 GU toxicity requiring an alpha-blocker compared to 26.5% in the IPSS <15 group (p=0.34). No patients required emergency placement of a foley catheter within 30 days of treatment. Conclusions: Given the low rates of GU toxicity, including a low risk of urinary obstruction requiring catheterization after HDR brachytherapy for those with a baseline IPSS score ≥15, this technique appears appropriate even for those with high baseline urinary symptoms.

Curiethérapie des cancers de la tête et du cou : synthèse des recommandations européennes et principales indications

The main indications of the brachytherapy of head and neck cancers are the limited tumours of the lip, the nose, the oral cavity and the oropharynx. Nasopharynx tumours are nowadays treated by intensity-modulated radiotherapy. This technique can be exclusive, associated with external radiotherapy or postoperative. It can also be a salvage treatment for the second primaries in previously irradiated areas. If the low dose rate brachytherapy rules remain the reference, the pulse dose rate technique allows the prescription of the dose rate and the optimisation of the dose distribution. Results of high dose rate brachytherapy are now published. This paper reports the recommendations of the Gec-ESTRO, published in 2017, and takes into account the data of the historical low dose rate series, and is upgraded with the pulsed-dose rate and high dose rate series.

(OA16) Repeat Whole Brain Radiation Therapy Using a Pulsed Reduced Dose Rate Technique

Limited salvage options exist for patients with multiple recurrent brain metastases previously treated with whole brain radiation therapy (WBRT). Pulsed reduced dose rate radiation therapy (PRDR) is a biologically-unique irradiation strategy that lowers the effective dose rate, potentially decreasing toxicity to normal tissue by allowing for sublethal damage repair. PRDR has been shown to be safe and effective in patients with gliomas receiving partial brain re-irradiation. To our knowledge, this technique has not been reported before in patients with brain metastases who have received repeat WBRT with PRDR. We report our early outcomes using repeat WBRT with PRDR. We conducted a retrospective review of all brain tumor patients treated with PRDR at our institution. We further analyzed patients with brain metastases previously treated with WBRT who received repeat WBRT with PRDR at the time of clinical and/or radiographic progression. PRDR treatments were delivered with a series of 0.20 Gy pulses given over a 3-minute period, resulting in an apparent dose rate of 0.0667 Gy/min. Patients were treated with parallel-opposed whole brain lateral fields with dose prescribed to isocenter. We identified 26 patients who received WBRT with PRDR from 2012 to 2017 . We excluded 4 patients from further analysis as 2 patients had not received prior WBRT and 2 patient expired during treatment course due to extracranial disease. Primary histology included breast cancer (n=8), melanoma (n=5), NSCLC (n=6), non-seminomatous testicular cancer (n=1), SCLC (n=1) and sarcoma (n=1). Initial WBRT dose regimens included 30 Gy in 10 fractions (n=14), 37.5 Gy in 15 fractions (n=7), and 39.6 Gy in 18 fractions (n=1). KPS was 70-100 for all patients at time of first WBRT. Median time to progression after first WBRT was 7.7 months (range 1.3 - 54.8 months) at which time patients underwent repeat WBRT with PRDR. Patients received daily fractions of 2 – 3 Gy (median = 2 Gy) to a total dose of 20 Gy - 30 Gy (median = 24 Gy). KPS at repeat irradiation was 70-100 and age ranged from 28.3 yrs to 77.0 yrs (mean = 55.38 yrs). With a mean follow-up of 7.1 months (range 0.63 – 33.4 months), mean time to intracranial progression after repeat WBRT with PRDR was 4.7 months (range 0.53 – 15.5 months). Four patients had intracranial disease control after repeat WBRT with PRDR for > 6 months and 1 patient is still alive at the time of this review. No acute grade 3 toxicities were seen as a result of reirradiation based on CTCAE v4.03. Grade 1/2 toxicities included fatigue, anorexia, and alopecia. To our knowledge, this is the first report of repeat WBRT with PRDR. This technique appears to be a safe and feasible option for patients with multiple brain metastases who previously received WBRT. Future prospective studies using this technique are being considered.

Abstract P2-11-19: Safety and efficacy of re-irradiation for locoregional breast cancer recurrences using pulsed reduced dose rate technique and concurrent capecitabine

Abstract Purpose: Locoregionally recurrent breast cancer presents a tremendous therapeutic challenge, but successful treatment can provide a durable cure. Re-irradiation has been performed infrequently in the recurrent setting due to concern for toxicity. Pulsed reduced dose rate radiation is a technique that can decrease the toxicity of re-irradiation by increasing normal tissue repair. Here, we update our previously published results of chest wall re-irradiation with an additional 16 patients and a focus on outcomes and long term toxicities. Methods: Patients treated from 11/09/2000 to 04/21/2016 with pulsed reduced dose rate radiation therapy at the University of Wisconsin were identified by query of Aria radiation oncology record software. Patients were retreated to a median dose of 54 Gy (range 37.5-66 Gy) using pulsed reduced does rate technique, delivering radiation at an apparent dose rate of 0.067 Gy/min to allow for normal tissue repair. The median cumulative dose was 109.8 Gy (range 75 to 236 Gy). Eleven patients underwent comprehensive re-irradiation to the chest wall and locoregional lymphatics, while the remainder underwent re-treatment limited to the site of recurrence. Concurrent capecitabine was given to 15 patients, most frequently at 500mg BID (range 1000 mg to 1500mg daily). The Kaplan-Meier method was used for survival analysis. Results: Thirty-three patients were identified who were treated with pulsed reduced dose rate radiation therapy for locoregionally recurrent invasive breast cancer with a median follow-up of 19.8 months (range 6.8-133.8 months). Sixteen patients were treated with curative intent and 17 patients were treated with palliative intent. Twenty-two patients had gross disease present at the time of treatment, 6 patients had microscopically positive surgical margins, and 5 patients were treated who had negative margins. The 2 year locoregional recurrence free survival was 70.5% by the Kaplan-Meier method for all patients and 81.5% for patients treated with curative intent. Two year overall survival was 43.6% for all patients and 72.2% in patients treated with curative intent. The rate of acute grade 3 skin toxicity was 21.2%. No other acute grade three toxicities occurred. A total of 9 patients (27.2%) developed late grade 3 or greater toxicities, including 4 patients who developed lymphedema, 4 patients who developed non-healing wounds, and one patient who developed both lymphedema and a non-healing wound. Conclusion: Pulsed reduced dose rate radiation therapy with capecitabine is an effective method for treating patients with recurrent breast cancer. The moderate risk of toxicity is warranted in a subset of patients with high risk of disease recurrence or morbidity from disease progression. Further work, including prospective studies, is needed to determine the patients who who will benefit most from this technique. Citation Format: Burr A, Howard S. Safety and efficacy of re-irradiation for locoregional breast cancer recurrences using pulsed reduced dose rate technique and concurrent capecitabine [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-19.

Brachytherapy for Buccal Cancer: From Conventional Low Dose Rate (LDR) or Mold Technique to High Dose Rate Interstitial Brachytherapy (HDR-ISBT).

To examine the effectiveness of newly-installed high-dose-rate interstitial brachytherapy (HDR-ISBT) for buccal cancer. We retrospectively reviewed 36 patients (25 men and 11 women) with buccal cancer treated with curative brachytherapy with or without external radiotherapy with a median follow-up of 99 months. A total of 15 HDR-ISBT (median 48 Gy/ 8 fractions, range=24-60 Gy) patients were compared to conventional 15 cases LDR-ISBT (70 Gy, range=42.8-110 Gy) and 7 molds techniques (15 Gy, range=9-74 Gy). A total of 31 patients also underwent external radiotherapy (30 Gy, range=24-48 Gy). They comprised of 3T1, 23 T2, 8 T3, 3 T4 including 11 node positive cases. HDR-ISBT provided 82% of local control rate at 5 years, whereas conventional brachytherapy showed 72% [p=0.44; LDR-ISBT (65%), mold therapy (85.7%)]. Patients with early lesions (T1-2 or stage I-II) showed better local control rates than those with advanced lesions (T3-4 or stage III-IV). Severe late grade 3 complications developed in two patients treated with LDR-ISBT and EBRT. There is no significant difference in toxicity grade ≤2 between conventional brachytherapy (5/15=33%) and HDR-ISBT (7/32=32%, p=0.92). HDR-ISBT achieved good and comparable local control rates to conventional brachytherapy without elevating the toxicity.

10. SFPM workgroup report: “New techniques and quality assurance in brachytherapy”

Introduction Brachytherapy is a well-known treatment technique which delivers a high dose to a tumorous volume yet reducing irradiation for healthy surrounding tissue. Recent developments regarding the use of imaging highlighted the necessity to update and to complete the SFPM n°11 report of 1995 which used to be only about Iridium 192 high dose rate technique. This new report deals with techniques associated to a source projector for any dose rate (high dose rate HDR or pulsed PDR) and permanent Iodine 125 implants. Methods Propositions are based on tests proposed by the SFPM, IAEA, GEC-ESTRO, AAPM, constructor guidelines, a recent bibliographic study and French users experience. Results The report deals with: • Source calibration presenting iridium 192 (most commonly used), Iodine 125 (non-available in French primary laboratory), Cobalt 60 ( still in development) • Different kinds of imaging used for implantation or planning: ultrasound (US), scan (CT), MRI. More particularly, specific tests concerning US are presented due to their use for needles, applicators or sources implantation. • Treatment planning: proposed tests concern mainly algorithms based on TG43 formalism but also new algorithms. Tests are divided into three groups: generic tests common to all techniques, specific tests dealing with treatments delivered by source projectors (HDR or PDR), specific tests concerning permanent implants. • Quality assurance of the source projector is detailed according to HDR/PDR specificities for any radioelement used. Conclusions These guidelines allow defining necessary tests from the implementation of a new technique to the current use. Each test is associated to a frequency and a level of action yet remaining suitable as a matter of clinical routine.

Dose Rate Switching Technique onELDRS-Free Bipolar Devices

The Switched Dose Rate technique is investigated when devices do not exhibit ELDRS. Experimental data and modeling results are presented and discussed in terms of hardness assurance. It is shown, for devices that do not show ELDRS, that a time is required before the switched devices reach the LDR curve. As a solution, it is proposed to apply an annealing between the HDR and the LDR irradiation.

Repeat Whole-Brain Radiation Therapy Using a Pulsed Reduced Dose Rate Technique

Repeat Whole-Brain Radiation Therapy Using a Pulsed Reduced Dose Rate Technique

Pulsed Low-Dose-Rate External Beam Radiation Therapy: An in-vivo Study on Prostate Cancer

Although hyper radio-sensitivity has been demonstrated at low doses below 0.4 Gy for various tumor cell lines in vitro, there was no report on in vivo studies for human prostate cancer cell lines. In our previous in vivo studies, we performed total body irradiation of nude mice with both pulsed low dose rate (PLDR) and conventional radiation therapy (CRT) techniques. The PLDR treated animal group showed significantly lower level of radiation toxicity to normal tissues than CRT, which leads to much longer survival of the irradiated animals.

TH‐A‐BRD‐01: Radiation Biology for Radiation Therapy Physicists

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear‐quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented.The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed.Biologically‐guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient‐specific information about tumor and normal tissue biology. Treatment individualization based on patient‐specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose‐based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how they might be used to address clinically relevant problems. Underlying assumptions and limitations of existing models and their proper application will be discussed.This multidisciplinary educational session combines the fundamentals of radiobiology for radiation therapy and radiation protection with the practical application of biophysical models for treatment planning and evaluation.Learning Objectives: To understand fractionation in teletherapy and dose rate techniques in brachytherapy. To understand how the linear‐quadratic models the effect of radiobiological parameters for radiotherapy. To understand the radiobiological basis of radiation protection standards applied to radiotherapy. To distinguish between stochastic effects and tissue reactions. To learn how to apply concepts of biological effective dose and RBE‐weighted dose and to incorporate biological factors that alter radiation response. To discuss clinical strategies to increase therapeutic ratio, i.e., maximize local control while minimizing the risk of acute and late normal tissue effects.

TU‐C‐WAB‐01: Accuracy Requirements and Uncertainty Considerations in Radiation Therapy

Recent years have seen major advances in the technology of radiation oncology allowing for a transition from 2‐D radiation therapy (RT) to 3‐D conformal RT, intensity modulated RT (IMRT), image‐guided RT (IGRT), adaptive RT (ART), and 4‐D imaging and motion management in RT. Brachytherapy procedures have evolved both for high dose rate (HDR) techniques as well as permanent implants, and image‐guided brachytherapy is the modern standard. While a number of publications have defined accuracy needs in radiation oncology, most of these reports were developed in an era with different radiation technologies and date back to the 1980s and 90s. In view of modern treatment procedures, improvements in dosimetry methodologies, and new clinical dose‐volume data, the AAPM 2011 summer school dealt with uncertainties in external beam radiation therapy and the International Atomic Energy Agency (IAEA) is completing a new guidance document on “Accuracy Requirements and Uncertainties in Radiation Therapy”. This symposium will review the latest information on accuracy requirements and uncertainty considerations in radiation therapy in terms of radiobiological rationale, clinical needs and a practical reality check.Learning Objectives:1. To review historical and current data related to accuracy and uncertainties in the overall radiation treatment process.2. To provide a radiobiological rationale for accuracy considerations in RT.3. To provide a clinical rationale for accuracy considerations in RT.4. To review recent data demonstrating realistically achievable accuracy levels in RT.

Brachytherapy: Current Status and Future Strategies — Can High Dose Rate Replace Low Dose Rate and External Beam Radiotherapy?

Brachytherapy delivers the most conformal high dose radiotherapy possible to the prostate, using either a low dose rate (LDR) or high dose rate (HDR) technique. It may be used either alone as monotherapy or in combination with external beam radiotherapy (EBRT) as a local boost. Comparative efficacy studies, including one randomised controlled trial, consistently show higher cancer control rates when brachytherapy is used compared with EBRT alone, with even some evidence of improvement in survival. There are now extensive mature data supporting the use of LDR as monotherapy for patients with low-risk and selected intermediate-risk disease, with most series reporting long-term disease control rates of over 90% after high-quality implants. HDR is most commonly combined with EBRT to treat intermediate- and high-risk disease, with disease control rates of over 90% reported. The low alpha/beta ratio of prostate cancer combined and the ability to optimally sculpt dose distribution provides the biological and dosimetric rationale for HDR. HDR enables more consistent implant quality than LDR, with evidence of lower acute and late toxicity. Many dose and fractionation schedules of HDR in combination with EBRT have been investigated, but a single fraction of 10–15 Gy is commonly combined with EBRT to a dose of 40–50 Gy to treat intermediate- and high-risk disease. High disease control rates are also reported with HDR as monotherapy, particularly in patients with low- and intermediate-risk disease. Although older series have delivered four to six fractions of HDR, there is growing evidence to support the delivery of HDR in three or even two fractions. Single-fraction HDR monotherapy is now being investigated and if early data are confirmed with longer follow-up, may well become the treatment of choice for many men with localised prostate cancer.