Dose Of 2Gy Research Articles

Reporting Vaginal Dose Point in Cervical Cancer Patients of Asian Origin Treated With Combine 3D External Beam Radiotherapy and 3D Brachytherapy and Comparing It With a Caucasian Population - Is There a Difference?

Purpose: To investigate the clinical feasibility and treatment outcomes of image-based high dose rate (HDR) brachytherapy using an intracavitary multichannel vaginal cylinder for the definitive treatment of vaginal cancers Materials and Methods: Forty-one patients with vaginal cancer (24% primary vaginal, 76% recurrence from other gynecologic primaries) treated with definitive radiotherapy chemotherapy including imagebased HDR brachytherapy with a multichannel vaginal cylinder. Imagebased brachytherapy was completed using either CT-based (41%) or MR-based planning (59%) with each fraction. The high-risk clinical target volume (HR-CTV) was defined based on the preand post-external beam radiotherapy GTV (see Figure). Doses were converted to equivalent dose of 2Gy per fraction (EQD2Gy). Endpoints examined: dose-volume parameters and early clinical outcomes. Results: The median HR-CTV volume was 24.2cc [Interquartile range (IQR): 12.6], with a median dose to 90% (D90) of 77.1Gy (IQR: 3.4). The median dose to 2cc (D2cc) for the bladder, rectum, and sigmoid were 59.4Gy (IQR: 5.6), 58.2Gy (IQR: 4.1), and 52.3Gy (IQR: 5.5) respectively. After a median follow-up of 16 months (range: 3-35), complete clinical response was documented in 98% of patients. The 2year local control, regional control, distant control, disease free survival and overall survival were 93%, 100%, 81%, 78% and 88%. The 2-year actuarial rate of late $ grade 3 toxicity was 4% overall with 0% vaginal, 0% bladder, urethral 0%, and 4% gastrointestinal, respectively. Conclusions: Image-based HDR brachytherapy using an intracavitary multichannel cylinder appears feasible in definitive vaginal cancer treatment. The described clinical implementation of image-based multichannel cylinder brachytherapy, including concepts of HR-CTV delineation, patient selection, and dose-constraints show promising early clinical outcomes with high rates of local control and little toxicity which should be validated with extended follow-up.

Dependence of the safe rectum dose on the CTV–PTV margin size and treatment technique

BackgroundLate rectal injury is a common side effect of external beam radiotherapy for prostate cancer. AimThe aim of this study was to evaluate what total dose may be safely delivered for prostate patients for 3DCRT and IMRT techniques and the CTV–PTV margin. Materials and methods3DCRT and IMRT plans were prepared for 12 patients. For each patient PTV was defined with CTV–PTV margins of 0.4, 0.6, …, 1.0cm, and total doses of 70, 72, …, 80Gy, with 2Gy dose fraction. NTCP values for the rectum were calculated using the Lyman model. Both techniques were compared in terms of population mean DVH. ResultsSignificantly smaller NTCPs for IMRT were obtained. For both techniques diminishing the margin CTV–PTV of 2mm leads to decreasing the NTCP of about 0.03. For total dose of 80Gy the NTCP was smaller than 10% for the 4mm margin only. The QUANTEC dose volume constraints were more frequently fulfilled for the IMRT technique than for the 3DCRT technique. ConclusionsThe IMRT technique is safer for prostate patients than the 3DCRT. If very high total doses are applied the CTV–PTV margin of 0.4cm and the IMRT technique should be used. If the CTV–PTV margin of 0.6cm is applied, the NTCP is smaller than 10% for the 3DCRT and IMRT techniques for the total doses smaller than 74Gy and 78Gy, respectively.

Ionizing radiation affects protein composition of exosomes secreted in vitro from head and neck squamous cell carcinoma.

Exosomes are membrane vesicles of endocytic origin that participate in inter-cellular communication. Environmental and physiological conditions affect composition of secreted exosomes, their abundance and potential influence on recipient cells. Here, we analyzed protein component of exosomes released in vitro from cells exposed to ionizing radiation (2Gy dose) and compared their content with composition of exosomes released from control not irradiated cells. Exosomes secreted from FaDu cells originating from human squamous head and neck cell carcinoma were analyzed using LC-MS/MS approach. We have found that exposure to ionizing radiation resulted in gross changes in exosomal cargo. There were 217 proteins identified in exosomes from control cells and 384 proteins identified in exosomes from irradiated cells, including 148 "common" proteins, 236 proteins detected specifically after irradiation and 69 proteins not detected after irradiation. Among proteins specifically overrepresented in exosomes from irradiated cells were those involved in transcription, translation, protein turnover, cell division and cell signaling. This indicated that exosomal cargo reflected radiation-induced changes in cellular processes like transient suppression of transcription and translation or stress-induced signaling.

Application of Volumetric Modulated Arc Therapy and Simultaneous Integrated Boost Techniques to Prepare "Safe Margin" in the Rabbit VX2 Limb Tumor Model.

BackgroundIn this study, we aimed to establish the rabbit VX2 limb tumor model, and then prepare a “necrotic zone” as a safe margin by volumetric modulated arc therapy and simultaneous integrated boost (VMAT-SIB) technique applied in the areas where the tumor is located adjacent to the bone (GTVboost area).Material/MethodsRabbits in the control group (n=10) were not treated, while those in the test group (n=10) were treated with the SIB schedule delivering a dose of 40Gy, 35Gy, 30Gy, and 25Gy to the GTVboost, GTV (gross tumor volume), CTV (clinical target volume), and PTV (planning target volume) in 10 fractions. Magnetic resonance diffusion-weighted imaging (MRDWI), 3-dimensional power Doppler angiography (3D-PDA), and histological changes were observed after radiotherapy.ResultsAfter radiotherapy, the two groups showed a significant difference in the GTVboost area. In the test group, the tumor necrosis showed a significantly low signal in DWI and high signal in apparent diffusion coefficient (ADC) maps. The 3D-PDA observation showed that tumor vascular structures decreased significantly. Histological analysis demonstrated that a necrotic zone could be generated in the GTVboost area, and microscopic examination observed cell necrosis and fibroplasia.ConclusionsThis studies demonstrated the feasibility of using VMAT-SIB technique in the rabbit VX2 limb tumor model. The formation of a necrotic zone can be effectively defined as safe margin in the GTVboost area. showing potential clinical applicability.

Dosimetric comparison of hybrid volumetric-modulated arc therapy, volumetric-modulated arc therapy, and intensity-modulated radiation therapy for left-sided early breast cancer

To compare the dosimetric performance of 3 different treatment techniques: hybrid volumetric-modulated arc therapy (hybrid-VMAT), pure-VMAT, and fixed-field intensity-modulated radiation therapy (F-IMRT) for whole-breast irradiation of left-sided early breast cancer. The hybrid-VMAT treatment technique and 2 other treatment techniques—pure-VMAT and F-IMRT—were compared retrospectively in 10 patients with left-sided early breast cancer. The treatment plans of these patients were replanned using the same contours based on the original computed tomography (CT) data sets. Dosimetric parameters were calculated to evaluate plan quality. Total monitor units (MUs) and delivery time were also recorded and evaluated. The hybrid-VMAT plan generated the best results in dose coverage of the target and the dose uniformity inside the target (p < 0.0001 for conformal index [CI]; p = 0.0002 for homogeneity index [HI] of planning target volume [PTV]50.4Gy and p < 0.0001 for HI of PTV62Gy). Volumes of ipsilateral lung irradiated to doses of 20Gy (V20Gy) and 5Gy (V5Gy) by the hybrid-VMAT plan were significantly less than those of the F-IMRT and the pure-VMAT plans. The volume of ipsilateral lung irradiated to a dose of 5Gy was significantly less using the hybrid-VMAT plan than that using the F-IMRT or the pure-VMAT plan. The total mean MUs for the hybrid-VMAT plan were significantly less than those for the F-IMRT or the pure-VMAT plan. The mean machine delivery time was 3.23 ± 0.29 minutes for the hybrid-VMAT plans, which is longer than that for the pure-VMAT plans but shorter than that for the F-IMRT plans. The hybrid-VMAT plan is feasible for whole-breast irradiation of left-sided early breast cancer.

Gene expression changes in residual advanced cervical cancer after radiotherapy: indicators of poor prognosis and radioresistance?

BackgroundDifferent sensitivity of advanced cervical cancer to irradiation can decrease effectiveness of radiotherapy in some cases. We attempted to identify the differentially expressed genes in residual cervical cancer after radiotherapy that might be associated with poor prognosis and radioresistance.Material/MethodsDifferential genes expression was identified by an oligonucleotide microarray in cervical cancer tissues before radiation and after a 50-Gy dose of radiation. The microarray results were validated by quantitative real-time PCR. CXCL12 was validated by immunohistochemistry in paraffin-embedded cervical cancer tissues before radiotherapy. The relationship between the differentiated gene and prognosis was validated by survival analysis.ResultsHierarchic cluster analysis identified 238 differentiated genes that exhibited ≥3.0-fold change and p<0.05. We found 111 genes that were in persistent up-regulation and 127 in persistent down-regulation after a 50-Gy dose of radiation when compared with the control group. These genes were involved in processes such as cell growth and death, cell-apoptosis, cell cycle regulation, cell signaling, DNA synthesis and repair, and cell adhesion. High differential expression of CXCL12, CD74, FGF7, COL14A1, PRC1, and RAD54L genes was validated by quantitative PCR before and after radiotherapy. Survival analysis results showed that the high expression of CXCL12 was closely related to poor prognosis.ConclusionsThe higher expression of CXCL12 might be informative regarding poor prognosis in patients undergoing radical radiotherapy. The differentially expressed genes identified in our study might provide a new method for diagnosis and treatment of radioresistance in cervical cancer.

Annexin V FITC conjugated as a radiation toxicity indicator in lymphocytes following radiation overexposure in radiotherapy programs.

Background:Following human radiation exposure in hospital or accidents, dose assessments are of prime importance in radiation accidents. These issues are of continuing importance with respect to socioeconomic policy relating to the industrial and medical uses of ionizing radiation, and also for risk assessment among people who are occupationally exposed to low and/or high linear energy transfer (LET) radiation, such as astronauts, pilots, stewardesses, nuclear power plant workers, and victims of radiation accidents.Materials and Methods:In this study, an assay for assessing radiation dose based on the induction of apoptosis in human T-lymphocytes was done to examine T-lymphocyte cells isolated from the fresh blood of 16volunteers, cultured and exposed to gamma rays. Radiation-induced apoptosis (RIA) was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation.Results:Dose-response experiments showed that at 2Gy dose level of radiotherapy programs, the RIA frequency was significantly above control. Apoptotic levels significantly depend on the dose of radiation rather than the donor.Conclusion:The results demonstrate the potential use of this assay as a biological indicator of radiation toxicity, optimizing patient dose in radiotherapy and biological dosimetry process.

4π Noncoplanar Stereotactic Body Radiation Therapy for Head-and-Neck Cancer: Potential to Improve Tumor Control and Late Toxicity

To evaluate the potential benefit of 4π radiation therapy in recurrent, locally advanced, or metastatic head-and-neck cancer treated with stereotactic body radiation therapy (SBRT). Twenty-seven patients with 29 tumors who were treated using SBRT were included. In recurrent disease (n=26), SBRT was delivered with a median 44 Gy (range, 35-44 Gy) in 5 fractions. Three patients with sinonasal mucosal melanoma, metastatic breast cancer, and primary undifferentiated carcinoma received 35 Gy, 22.5 Gy, and 40 Gy in 5 fractions, respectively. Novel 4π treatment plans were created for each patient to meet the objective that 95% of the planning target volume was covered by 100% of the prescription dose. Doses to organs at risk (OARs) and 50% dose spillage volumes were compared against the delivered clinical SBRT plans. Local control (LC), late toxicity, tumor control probability (TCP), and normal tissue complication probability were determined. Using 4π plans, mean/maximum doses to all OARs were reduced by 22% to 89%/10% to 86%. With 4π plans, the 50% dose spillage volume was decreased by 33%. Planning target volume prescription dose escalation by 10 Gy and 20 Gy were achieved while keeping doses to OARs significantly improved or unchanged from clinical plans, except for the carotid artery maximum dose at 20-Gy escalation. At a median follow-up of 10 months (range, 1-41 months), crude LC was 52%. The 2-year LC of 39.2% approximated the predicted mean TCP of 42.2%, which increased to 45.9% with 4π plans. For 10-Gy and 20-Gy dose escalation, 4π plans increased TCP from 80.1% and 88.1% to 85.5% and 91.4%, respectively. The 7.4% rate of grade ≥3 late toxicity was comparable to the predicted 5.6% mean normal tissue complication probability for OARs, which was significantly reduced by 4π planning at the prescribed and escalated doses. 4π plans may allow dose escalation with significant and consistent improvements in critical organ sparing, tumor control, and coverage.

Bryostatin-1 causes radiosensitization of BMG-1 malignant glioma cells through differential activation of protein kinase-Cδ not evident in the non-malignant AA8 fibroblasts.

Bryostatin-1 (bryo-1), a non-phorbol ester, is known to sensitize mammalian cells against certain chemotherapeutic drugs. We assessed its ability to modify radiation response of mammalian cells using Chinese hamster fibroblasts AA8 cells and human malignant glioma BMG-1 cells. In the malignant glioma BMG-1 cell line, bryo-1 pre-treatment significantly enhanced radiation-induced growth inhibition and cytogenetic damage, and further reduced the clonogenic cell survival as compared to cells irradiated at the clinically relevant dose of 2Gy. PKCδ expression increased significantly when bryo-1 pre-treated BMG-1 glioma cells were irradiated at 2Gy and induced prolonged ERK-1/2 activation associated with p21 overexpression. Silencing PKCδ resulted in inhibition of bryo-1-induced radiosensitization. In contrast, bryo-1 failed to alter radiosensitivity (cell survival; growth inhibition; cytogenetic damage) or activate ERK1/2 pathway in the AA8 fibroblasts despite PKCδ phosphorylation at its regulatory (Y155) domain, indicating alternate mechanisms in these non-malignant cells as compared to the glioma cells. This study suggests that bryo-1 may effectively enhance the radiosensitivity of malignant cells and warrants further in-depth investigations to evaluate its radiosensitizing potential in various cell types.

ZnFe2O4 nanoparticles as radiosensitizers in radiotherapy of human prostate cancer cells.

Nanoparticles of high-Z elements exhibit stronger photoelectric effects than soft tissues under gamma irradiation. Hence, they can be used as effective radiosensitizers for increasing the efficiency of current radiotherapy. In this work, superparamagnetic zinc ferrite spinel (ZnFe2O4) nanoparticles were synthesized by a hydrothermal reaction method and used as radiosensitizers in cancer therapy. The magnetic nanoparticles showed fast separation from solutions (e.g., ~1 min for 2 mg mL(-1) of the nanoparticles in ethanol) by applying an external magnetic field (~1T). The ZnFe2O4 nanoparticles were applied in an in vitro radiotherapy of lymph node carcinoma of prostate cells (as high radioresistant cells) under gamma irradiation of (60)Co source. The nanoparticles exhibited no significant effects on the cancer cells up to the high concentration of 100 μg mL(-1), in the absence of gamma irradiation. The gamma irradiation alone (2Gy dose) also showed no significant effects on the cells. However, gamma irradiation in the presence of 100 μg mL(-1) ZnFe2O4 nanoparticles resulted in ~53% inactivation of the cells (~17 times higher than the inactivation that occurred under gamma irradiation alone) after 24h. The higher cell inactivation was assigned to interaction of gamma radiation with nanoparticles (photoelectric effect), resulting in a high level electron release in the media of the radioresistant cells. Our results indicated that ZnFe2O4 nanoparticles not only can be applied in increasing the efficiency of radiotherapy, but also can be easily separated from the cell environment by using an external magnetic field after the radiotherapy.

MRI findings of radiation-induced myocardial damage in patients with oesophageal cancer

To evaluate radiation-induced myocardial damage after mediastinal radiotherapy using MRI. Between May 2010 and April 2011, delayed contrast-enhanced MRI was performed for patients who had maintained a complete response to curative radiotherapy for oesophageal cancer for more than 6 months. The patients received radiotherapy with a median total dose of 66Gy (60-70Gy) for the primary tumour and metastatic lymph nodes. Images of MRI were analysed by a 17-segment method recommended by the American Heart Association. A segment included mainly in the 40Gy dose line was defined as Segment 40Gy, a segment included mainly in the 60Gy dose line as Segment 60Gy, and a segment out of the radiation fields as Segment OUT. The percentage of late gadolinium enhancement (LGE) was examined in those categories. The layer in which LGE was predominantly distributed was evaluated for each patient. Four hundred and eight segments in 24 patients were analysed. The median interval from completion of radiotherapy to MRI was 23.5 months (range 6-88 months). LGE was detected in 12 of the 24 patients. LGE was detected in 15.38% of Segment 40Gy cases, 21.21% of Segment 60Gy cases, and 0% of Segment OUT cases. LGE in mid-myocardial and subendocardial layers was detected in 11 patients and one patient, respectively. LGE suggesting radiation induced myocardial fibrosis was observed by performing delayed contrast-enhanced MRI. Care should be taken when planning radiotherapy to avoid late cardiac damage.

Hybrid Modulated Arc Therapy (HMAT) on an Artiste Linac

Purpose/Objective(s): Pulsed low dose rate radiation therapy (PLDR) has been investigated in a number of clinical trials for the management of recurrent cancers and radiation resistant malignancies based on the in vitro and in vivo experimental findings indicating that many tumor cell lines exhibited hyper radio-sensitivities (HRS) at small doses and enhanced normal tissue repair at low dose rates. This retrospective study aimed to develop treatment planning strategies for PLDR treatment of recurrent cancers utilizing advanced delivery techniques including IMRT and VMAT. Materials/Methods: The current PLDR treatment protocol requires that the daily 2Gy dose be delivered in 10 x 0.2Gy sub-fractions (pulses) with a 3min interval. To take advantage of low-dose HRS the mean dose to the target volume is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. The 3min interval is selected for clinical practicality; PLDR is primarily for palliative treatment, which should be delivered within a reasonable time for recurrent patients. Sixty patients were randomly selected from our patient database for the following body sites: head and neck, breast, thorax, abdomen and pelvis. Practical planning strategies/ guidelines were developed for IMRT and VMAT delivery techniques: (1) use 10 beam angles for IMRT and 10 arcs for VMAT (2-arc plan to be delivered 5 times) with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no hard constraints to the OAR); (3) select optimal beam/arc angles to avoid OARs; and (4) add reference structures in or around target/ OARs to reduce maximum dose to the target and OARs. IMRT, VMAT and 3DCRT plans were generated for these patients and compared. Results: Target dose heterogeneity is intrinsic for PLDR with 3DCRT when each pulse is delivered using one single field due to difference in beam attenuation and scattering. Further dose variation is introduced with IMRT due to lateral intensity modulation. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Following the planning guidelines developed in this work, all PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol. The mean dose was 0.20Gy 0.01Gy and the maximum dose was <0.3Gy for 75% of fields/arcs, <0.35Gy for 98% of fields/arcs and all < 0.4Gy. In comparison with 3DCRT, IMRT, and VMAT exhibited significantly improved target dose conformity and OAR dose sparing. Conclusions: Both IMRT and VMAT can be used for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol. Author Disclosure: C. Ma: None. M. Lin: None. K. Wei: None. J. Li: None. P. Wang: None. J. Lang: None.

Pulsed Low-Dose-Rate Radiation Therapy (PLDR) for Recurrent Cancers: Treatment Planning Strategies for IMRT and VMAT

Purpose/Objective(s): Pulsed low dose rate radiation therapy (PLDR) has been investigated in a number of clinical trials for the management of recurrent cancers and radiation resistant malignancies based on the in vitro and in vivo experimental findings indicating that many tumor cell lines exhibited hyper radio-sensitivities (HRS) at small doses and enhanced normal tissue repair at low dose rates. This retrospective study aimed to develop treatment planning strategies for PLDR treatment of recurrent cancers utilizing advanced delivery techniques including IMRT and VMAT. Materials/Methods: The current PLDR treatment protocol requires that the daily 2Gy dose be delivered in 10 x 0.2Gy sub-fractions (pulses) with a 3min interval. To take advantage of low-dose HRS the mean dose to the target volume is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. The 3min interval is selected for clinical practicality; PLDR is primarily for palliative treatment, which should be delivered within a reasonable time for recurrent patients. Sixty patients were randomly selected from our patient database for the following body sites: head and neck, breast, thorax, abdomen and pelvis. Practical planning strategies/ guidelines were developed for IMRT and VMAT delivery techniques: (1) use 10 beam angles for IMRT and 10 arcs for VMAT (2-arc plan to be delivered 5 times) with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no hard constraints to the OAR); (3) select optimal beam/arc angles to avoid OARs; and (4) add reference structures in or around target/ OARs to reduce maximum dose to the target and OARs. IMRT, VMAT and 3DCRT plans were generated for these patients and compared. Results: Target dose heterogeneity is intrinsic for PLDR with 3DCRT when each pulse is delivered using one single field due to difference in beam attenuation and scattering. Further dose variation is introduced with IMRT due to lateral intensity modulation. A single arc can minimize the difference in the target dose due to multi-angle incidence although the delivery time is longer than 3DCRT and IMRT. Following the planning guidelines developed in this work, all PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol. The mean dose was 0.20Gy 0.01Gy and the maximum dose was <0.3Gy for 75% of fields/arcs, <0.35Gy for 98% of fields/arcs and all < 0.4Gy. In comparison with 3DCRT, IMRT, and VMAT exhibited significantly improved target dose conformity and OAR dose sparing. Conclusions: Both IMRT and VMAT can be used for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol. Author Disclosure: C. Ma: None. M. Lin: None. K. Wei: None. J. Li: None. P. Wang: None. J. Lang: None.

Immunostimulatory activities of Haberlea rhodopensis leaf extract on the specific antibody response: protective effects against γ-radiation-induced immunosuppression

Immunomodulatory and radioprotective properties of Haberlea rhodopensis extract (HRE) in relation to the primary and secondary specific antibody production were evaluated in New Zealand white rabbits. Rabbits were immunised with keyhole limpet hemocyanin (KLH) and were treated with HRE before irradiation with single dose of 2Gy. Control group without irradiation were also treated with HRE. Rabbits were reimmunised and treated again with HRE on Day 36. KLH-specific total IgM, G, A and KLH-specific IgG antibody production were determined during primary and secondary antibody response by enzyme-linked immunosorbent assay (ELISA). We observed a well-defined γ-radiation-induced immunosuppression on the total primary antibody production. Application of HRE restored primary total KLH-specific antibody as well as significantly increased primary KLH-specific IgG antibody response. We also established that HRE strongly enhanced KLH-specific antibody production after reimmunisation. We concluded that HRE exhibits immunostimulatory properties and could play protective role against γ-irradiation damage of immune response.

143 Carotid Intraplaque Neovascularization is Increased in Patients with Prior Ipsilateral Neck Irradiation - A Contrast Enhanced Ultrasound Study

BackgroundIrradiation of the carotid artery during radiotherapy (RT) for head/neck cancer (HNC) increases intima-media thickness, plaque formation and risk of stroke. However, the effects of RT on plaque composition are...

WE‐E‐BRE‐07: High‐Throughput Mapping of Proton Biologic Effect

Purpose:To systematically relate the relative biological effectives (RBE) of proton therapy to beam linear energy transfer (LET) and dose.Methods:Using a custom irradiation apparatus previously characterized by our group, H460 NSCLCs were irradiated using a clinical 80MeV spot scanning proton beam. Utilizing this system allowed for high‐throughput clonogenic assays performed in 96‐well tissue culture plates as opposed to the traditional 6‐well technique. Each column in the 96‐well plate received a set LET‐dose combination. By altering the total number of dose repaintings, numerous dose‐LET configurations were examined to effectively generate surviving fraction (SF) data over the entire Bragg peak. The clonogenic assay was performed post‐irradiation using an INCell Analyzer for colony quantification. SF data were fit to the linear‐quadratic model for analysis.Results:Irradiation with increasing LETs resulted in decreased cell survival largely independent of dose. A significant correlation between LET and SF was identified by two‐way ANOVA and the extra sum‐of‐squares F test. This trend was obscured at the lower LET values in the plateau region of the Bragg peak; however, it was clear for LET values at and beyond the Bragg peak. Data fits revealed the SF at a dose of 2Gy (SF2) to be 0.48 for the lowest tested LET (1.55keV/um), 0.47 at the end of the plateau region (4.74keV/um) and 0.33 for protons at the Bragg peak (10.35keV/um). Beyond the Bragg peak we measured SF2s of 0.16 for 15.01keV/um, 0.02 for 16.79keV/um, and 0.004 for 18.06keV/um.Conclusion:We have shown that our methodology enables high‐content automated screening for proton irradiations over a range of LETs. The observed decrease in cellular SF in high LET regions confirms an increased RBE of the radiation and suggests further evaluation of proton RBE values is necessary to optimize clinical outcomes.Rosalie B. Hite Graduate Fellowship in Cancer Research, NIH Program Project Grant P01CA021239

SU‐E‐T‐34: An in Vivo Study On Pulsed Low Dose‐Rate Radiotherapy for Prostate Cancer

Purpose:Re‐irradiation with conventional radiotherapy techniques (CRT) may pose significant risks due to high accumulative radiation doses. Pulsed low dose‐rate radiotherapy (PLDR) has been used in clinical trials for recurrent cancer treatment. In our previous studies, PLDR irradiation showed significantly lower toxicity than CRT, resulting in much longer survival of mice after PLDR total body irradiation (TBI) than conventional TBI. The purpose of this study was to investigate tumor control efficacy of PLDR treatment for prostate cancer with an animal model of prostate cancer LNCaP.Methods:We used an orthotopic murine model of LNCaP cell line for this study. LNCaP cells were implanted into immune‐suppressed male nude mice via surgery. We monitored the tumor growth with MRI. The tumor‐bearing mice were allocated into a PLDR(n=9), CRT(n=7), and control group(n=7) randomly. The mice in the PLDR and CRT groups were irradiated with 2Gy dose for one time. For the CRT treatment, the mice received 2Gy at a dose‐rate of 300 MU/minute. For the PLDR treatment, the 2Gy dose was further divided into ten pulses of 0.2Gy at the same dose‐rate with an interval of 3 minutes between the pulses.Results:Sizable tumor growth delays were observed for the PLDR and CRT groups through weekly MRI scans. The mean values of the normalized tumor volumes (± standard deviation of the mean) were 1.53±0.07, 1.53±0.14, and 1.81±0.09 at one week after treatment, 2.28±0.13, 2.19±0.16, and 3.04±0.25 at two weeks after treatment, and 3.31±0.23, 3.14±0.24 and 4.62±0.49 at three weeks after treatment, for the PLDR, CRT, and control groups, respectively.Conclusion:The PLDR and CRT treatments showed comparable tumor control rates in this study. Our in vivo results indicate that PLDR may be a viable option for treating recurrent prostate cancer due to its equivalent tumor control but low normal tissue toxocities.

TH‐C‐12A‐07: Implementation of a Pulsed Low Dose Date Radiotherapy (PLRT) Protocol for Recurrent Cancers Using Advanced Beam Delivery

Purpose:Recent in vitro and in vivo experimental findings provided strong evidence that pulsed low‐dose‐rate radiotherapy (PLDR) produced equivalent tumor control as conventional radiotherapy with significantly reduced normal tissue toxicities. This work aimed to implement a PLDR clinical protocol for the management of recurrent cancers utilizing IMRT and VMAT.Methods:Our PLDR protocol requires that the daily 2Gy dose be delivered in 0.2Gy×10 pulses with a 3min interval between the pulses. To take advantage of low‐dose hyper‐radiosensitivity the mean dose to the target is set at 0.2Gy and the maximum dose is limited to 0.4Gy per pulse. Practical planning strategies were developed for IMRT and VMAT: (1) set 10 ports for IMRT and 10 arcs for VMAT with each angle/arc as a pulse; (2) set the mean dose (0.2Gy) and maximum dose (0.4Gy) to the target per pulse as hard constraints (no constraints to OARs); (3) select optimal port/arc angles to avoid OARs; and (4) use reference structures in or around target/OARs to reduce maximum dose to the target/OARs. IMRT, VMAT and 3DCRT plans were generated for 60 H&amp;N, breast, lung, pancreas and prostate patients and compared.Results:All PLDR treatment plans using IMRT and VMAT met the dosimetry requirements of the PLDR protocol (mean target dose: 0.20Gy±0.01Gy; maximum target dose &lt; 0.4Gy). In comparison with 3DCRT, IMRT and VMAT exhibited improved target dose conformity and OAR dose sparing. A single arc can minimize the difference in the target dose due to multi‐angle incidence although the delivery time is longer than 3DCRT and IMRT.Conclusion:IMRT and VMAT are better modalities for PLDR treatment of recurrent cancers with superior target dose conformity and critical structure sparing. The planning strategies/guidelines developed in this work are practical for IMRT/VMAT treatment planning to meet the dosimetry requirements of the PLDR protocol.

SU‐E‐T‐480: Radiobiological Dose Comparison of Single Fraction SRS, Multi‐Fraction SRT and Multi‐Stage SRS of Large Target Volumes Using the Linear‐Quadratic Formula

Purpose:To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi‐fractionated SRT, and multi‐staged SRS treatment.Methods:An anthropomorphic head phantom with a centrally located large volume target (18.2 cm3) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue.Results:Singe fraction SRS, multi‐stage plan and multi‐fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively.Conclusion:The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi‐stage treatment provided for a more potent biologically effect on target compared to the multi‐fraction SRT treatments with less biological normal tissue than single‐fraction SRS treatment.

SU-E-T-189: First Experimental Verification of the Accuracy of Absolute Dose Reconstruction From PET-CT Imaging of Yttrium 90 Microspheres

Purpose: In the past few years there have been numerous proposals for 3D dose reconstruction from the PET-CT imaging of patients undergoing radioembolization treatment of the liver with yttrium-90 microspheres. One of the most promising techniques uses convolution of the measured PET activity distribution with a pre-calculated Monte Carlo dose deposition kernel. The goal of the present study is to experimentally verify the accuracy of this method and to analyze the significance of various error sources. Methods: Optically stimulated luminescence detectors (OSLD) were used (NanoDot, Landauer) in this experiment. Two detectors were mounted on the central axis of a cylinder filled with water solution of yttrium-90 chloride. The total initial activity was 90mCi. The cylinder was inserted in a larger water phantom and scanned on a Siemens Biograph 16 Truepoint PET-CT scanner. Scans were performed daily over a period of 20 days to build a calibration curve for the measured absolute activity spanning 7 yttrium-90 half-lives. The OSLDs were mounted in the phantom for a predetermined period of time in order to record 2Gy dose. The measured dose was then compared to the dose reconstructed from the activity density at the location of each dosimeter. Results: Thorough error analysis of the dose reconstruction algorithm takes into account the uncertainties in the absolute PET activity, branching ratios, and nonlinearity of the calibration curve. The measured dose for 105-minute exposure on day 10 of the experiment was 219(11)cGy, while the reconstructed dose at the location of the detector was 215(47)cGy. Conclusion: We present the first experimental verification of the accuracy of the convolution algorithm for absolute dose reconstruction of yttrium-90 microspheres. The excellent agreement between the measured and calculated point doses will encourage the broad clinical adoption of the convolution-based dose reconstruction algorithm, making future quantitative dose/outcome studies possible.