Fraction Delivery Time Research Articles

Magnetic resonance image-guided adaptive radiotherapy enables safe CTV-to-PTV margin reduction in prostate cancer: a cine MRI motion study.

We aimed to establish if stereotactic body radiotherapy to the prostate can be delivered safely using reduced clinical target volume (CTV) to planning target volume (PTV) margins on the 1.5T MR-Linac (MRL) (Elekta, Stockholm, Sweden), in the absence of gating. Cine images taken in 3 orthogonal planes during the delivery of prostate SBRT with 36.25 Gray (Gy) in 5 fractions on the MRL were analysed. Using the data from 20 patients, the percentage of radiotherapy (RT) delivery time where the prostate position moved beyond 1, 2, 3, 4 and 5 mm in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) and any direction was calculated. The prostate moved less than 3 mm in any direction for 90% of the monitoring period in 95% of patients. On a per-fraction basis, 93% of fractions displayed motion in all directions within 3 mm for 90% of the fraction delivery time. Recurring motion patterns were observed showing that the prostate moved with shallow drift (most common), transient excursions and persistent excursions during treatment. A 3 mm CTV-PTV margin is safe to use for the treatment of 5 fraction prostate SBRT on the MRL, without gating. In the context of gating this work suggests that treatment time will not be extensively lengthened when an appropriate gating window is applied.

213 Radiotherapy fraction delivery time does not affect survival outcomes in patients with oropharynx cancer, unselected for chronotype

213 Radiotherapy fraction delivery time does not affect survival outcomes in patients with oropharynx cancer, unselected for chronotype

4D dosimetric-blood flow model: impact of prolonged fraction delivery times of IMRT on the dose to the circulating lymphocytes

To investigate the impact of prolonged fraction delivery of modern intensity-modulated radiotherapy (IMRT) on the accumulated dose to the circulating blood during the course of fractionated radiation therapy. We have developed a 4D dosimetric blood flow model (d-BFM) capable of continuously simulating the blood flow through the entire body of the cancer patient and scoring the accumulated dose to blood particles (BPs). We developed a semi-automatic approach that enables us to map the tortuous blood vessels of the surficial brain of individual patients directly from standard magnetic resonance imaging data of the patient. For the rest of the body, we developed a fully-fledged dynamic blood flow transfer model according to the International Commission on Radiological Protection human reference. We proposed a methodology enabling us to design a personalized d-BFM, such it can be tailored for individual patients by adopting intra- and inter-subject variations. The entire circulatory model tracks over 43 million BPs and has a time resolution of = 10−3 s. A dynamic dose delivery model was implemented to emulate the spatial and temporal time-varying pattern of the dose rate during the step-and-shoot mode of IMRT. We evaluated how different configurations of the dose rate delivery, and a time prolongation of fraction delivery may impact the dose received by the circulating blood (CB).Our calculations indicate that prolonging the fraction treatment time from 7 to 18 min will augment the blood volume receiving any dose from 36.1% to 81.5% during one single fraction. The results indicate that increasing the segment number has only a negligible effect on the irradiated blood volume, when the fraction time is kept identical. We developed a novel concept of customized 4D d-BFM that can be tailored to the hemodynamics of individual patients to quantify dose to the CB during fractionated radiotherapy. The prolonged fraction delivery and the variability of the instantaneous dose rate have a significant impact on the accumulated dose distribution during IMRT treatments. This impact should be considered during IMRT treatments design to reduce RT-induced immunosuppressive effects.

Total body irradiation using volumetric modulated arc therapy, experience of a cancer hospital in Pakistan

Abstract Introduction: To report the planning parameters, efficacy and toxicity of total body irradiation using volumetric modulated arc therapy (VMAT). Methods: From July 2019 till May 2021, nine patients treated with VMAT-based total body irradiation as a part of the myeloablative regimen for homologous stem cell transplant were evaluated. The CT acquisition, planning parameters, doses to target volume and critical structures were evaluated retrospectively. Results: Median age was 24 with median height 172 cm. Average Mean Lung dose was 9·5 Gy, mean dose to kidney was kidney dose 8·4 Gy, planning target volume (PTV) 95% was 98 % and mean heterogeneity index of PTV was 1·2 all patients. Total fraction delivery time including setup was 3·1 h while beam on time was 23 min. Main toxicity observed was mucositis and fatigue, while no Grade 3 or more acute radiation toxicity was observed. Conclusion: At our institution, high dose TBI performed with multi-isocentric VMAT is now a standard procedure. Though it is cumbersome and time-consuming process but VMAT offers an advantage of increased dose homogeneity in the target volume with reduction in doses to critical organs especially lungs and kidneys in comparison to standard source to skin distance technique, longer follow-up time is necessary to evaluate our method and long-term toxicity.

Fully automated treatment planning for MLC-based robotic radiotherapy.

PurposeTo propose and validate a fully automated multicriterial treatment planning solution for a CyberKnife® equipped with an InCiseTM 2 multileaf collimator.MethodsThe AUTO BAO plans are generated using fully automated prioritized multicriterial optimization (AUTO MCO) of pencil‐beam fluence maps with integrated noncoplanar beam angle optimization (BAO), followed by MLC segment generation. Both the AUTO MCO and segmentation algorithms have been developed in‐house. AUTO MCO generates for each patient a single, high‐quality Pareto‐optimal IMRT plan. The segmentation algorithm then accurately mimics the AUTO MCO 3D dose distribution, while considering all candidate beams simultaneously, rather than replicating the fluence maps. Pencil‐beams, segment dose depositions, and final dose calculations are performed with a stand‐alone version of the clinical dose calculation engine. For validation, AUTO BAO plans were generated for 33 prostate SBRT patients and compared to reference plans (REF) that were manually generated with the commercial treatment planning system (TPS), in absence of time pressure. REF plans were also compared to AUTO RB plans, for which fluence map optimization was performed for the beam angle configuration used in the REF plan, and the segmentation could use all these beams or only a subset, depending on the dosimetry.ResultsAUTO BAO plans were clinically acceptable and dosimetrically similar to REF plans, but had on average reduced numbers of beams ((beams in AUTO BAO)/(beams in REF) (relative improvement): 24.7/48.3 (−49%)), segments (59.5/98.9 (−40%)), and delivery times (17.1/22.3 min. (−23%)). Dosimetry of AUTO RB and REF were also similar, but AUTO RB used on average fewer beams (38.0/48.3 (−21%)) and had on average shorter delivery times (18.6/22.3 min. (−17%)). Delivered Monitor Units (MU) were similar for all three planning approaches.ConclusionsA new, vendor‐independent optimization workflow for fully automated generation of deliverable high‐quality CyberKnife® plans was proposed, including BAO. Compared to manual planning with the commercial TPS, fraction delivery times were reduced by 5.3 min. (−23%) due to large reductions in beam and segment numbers.

134. DynaLog file-based Procedure for a daily monitoring of IMRT dose delivery

PurposeThanks to the intensity modulated radiation therapy (IMRT) it is possible to achieve highly conformal dose distribution with an important shield to the adjacent organs at risk. Nevertheless, the complex nature of such treatments requires a comprehensive Quality Assurance (QA). The last decade witnessed a proliferation of QA method based on machine log files (DynaLogs Files) since their several advantages [1,2]. In this study we propose a DynaLog file-based method to ensure a daily monitoring of the correct dose delivery. MethodsThe delivery of one prostate IMRT treatment has been daily monitored thanks to the DynaLogs Files. These files are generated for each field delivery and record many useful information [1,2]. Herein the DynaLogs information about planned and actual cumulative dose fraction is taken into account. The prostate IMRT plan consists of 5 fixed field arrangements using a dynamic delivery technique (sliding window). It was calculated using the Varian Eclipse TPS (version 13.6; Varian, Palo Alto) with the analytical anisotropic algorithm (AAA) and it was delivered on a Varian Clinac2100CD. Target dose prescription is 80 Gy in 40 fractions. ResultsThe deviation between planned and actual dose fraction was calculated, for each field, as a function of both fraction numbers and delivery time. The mean and maximum dose deviations were 0.1 and 0.3 Monitor Units, respectively. ConclusionsUsually the IMRT QA is performed before the treatment beginning and it is assumed that no further variations will occur. The proposed method allows to daily assess the correct dose delivery thanks to DynaLogs Files in a no time-consuming way.

Impact of Prolonged Fraction Delivery Time Modelling Stereotactic Body Radiation Therapy with High Dose Hypofractionation on the Killing of Cultured ACHN Renal Cell Carcinoma Cell Line.

Stereotactic body radiotherapy delivers hypofractionated irradiation with high dose per fraction through complex treatment techniques. The increased complexity leads to longer dose delivery times for each fraction. The purpose of this study is to investigate the impact of prolonged fraction delivery time with high-dose hypofractionation on the killing of cultured ACHN cells. The radiobiological characteristics and repair half-time of human ACHN renal cell carcinoma cell line were studied with clonogenic assays. A total dose of 20 Gy was administered in 1, 2 or 3 fractions over 15, 30 or 45 min to investigate the biological effectiveness of radiation delivery time and hypofractionation. Cell cycle and apoptosis analysis was performed after 3-fraction irradiation over 30 and 45 min. The α/β and repair half-time were 5.2 Gy and 19 min, respectively. The surviving fractions increased with increase in the fraction delivery time and decreased more pronouncedly with increase in the fraction number over a treatment period of 30 to 45 min. With increase in the total radiation time to 30 and 45 min, it was found that with the same total dose, 2- and 3-fraction irradiation led to more cell killing than 1-fraction irradiation. 3-fraction radiation induced G2/M arrest, and the percentage of apoptotic cells decreased when the fraction delivery time increased from 30 min to 45 min. Our findings revealed that sublethal damage repair and redistribution of the cell cycle were predominant factors affecting cell response in the prolonged and hypofractionated irradiation regimes, respectively.

The application of the linear quadratic model to compensate the effects of prolonged fraction delivery time on a Balb/C breast adenocarcinoma tumor: An in vivo study

Purpose To investigate the effect of increasing the overall treatment time as well as delivering the compensating doses on the Balb/c breast adenocarcinoma (4T1) tumor.Materials and methods A total of 72 mice were divided into two aliquots (classes A and B) based on the initial size of their induced tumor. Each class was divided into a control and several treatment groups. Among the treatment groups, group 1 was continuously exposed to 2 Gy irradiation, and groups 2 and 3 received two subfractions of 1 Gy over the total treatment times of 30 and 60 min, respectively. To investigate the effect of compensating doses, calculated based on the developed linear quadratic model (LQ) model, the remaining two groups (groups 4 and 5) received two subfractions of 1.16 and 1.24 Gy over the total treatment times of 30 and 60 min, respectively. The growing curves, Tumor Growth Time (TGT), Tumor Growth Delay Time (TGDT) and the survival of the animals were studied.Results For class A (tumor size ≤ 30 mm3), the average tumor size in the irradiated groups 1–5 was considerably different compared to the control group as one unit (day) change in time, by amount of −160.8, −158.9, +39.4 and +44.0, respectively. While these amounts were +22.0, +17.9, −21.7 and −0.1 for class B (tumor size ≥ 400 mm3). For the class A of animals, the TGT and TGDT parameters were significantly lower (0 ≤ 0.05) for the groups 2 and 3, compared to group 1. There was no significant difference (p > 0.05) between groups 1, 4 and 5 in this class. There was no significant difference (p > 0.05) between all the treated groups in class B.Conclusions Increasing total treatment time affects the radiobiological efficiency of treatment especially in small-sized tumor. The compensating doses derived from the LQ model can be used to compensate the effects of prolonged treatment times at in vivo condition.

Will intrafraction repair have negative consequences on extreme hypofractionation in prostate radiation therapy?

The aim of the present study was to investigate the impact of increasing fraction delivery time on the outcome of hypofractionated radiation therapy for prostate cancer. Monoexponential and biexponential repair models have been used for patients with prostate cancer to study the loss of biochemical control at 5 years for several clinically relevant irradiation times. The theoretical predictions were compared with newly reported clinical results from 4607 patients undergoing conventionally fractionated and hypofractionated prostate radiation therapy. Time-demanding irradiation techniques appear to lead to biochemical control rates that sometimes are about 10-20 percentage points below predictions that neglect intrafraction repair. This difference appears to be of the same order of magnitude as that predicted by moderately slow to slow repair taking place during the irradiation time. The impact is largest for the patient risk groups receiving doses corresponding to the steepest part of the dose-response curve. By contrast, for treatment techniques requiring irradiation times shorter than about 20 min, the impact of intrafraction repair appears to be much smaller and probably difficult to be observed in the light of other sources of uncertainty in clinical data. Neglecting intrafraction repair might overestimate the effectiveness of some treatment schedules and could also influence any subsequent estimations of fractionation sensitivity for prostate tumours. The effect of intrafraction repair for prostate cancer should be taken into account for long irradiation sessions as might be expected from scanned beams and/or from multiple intrafraction imaging sessions to check the positioning of the patient.

Late-responding normal tissue cells benefit from high-precision radiotherapy with prolonged fraction delivery times via enhanced autophagy.

High-precision radiotherapy (HPR) has established its important role in the treatment of tumors due to its precise dose distribution. Given its more complicated delivery process, HPR commonly requires more fraction delivery time (FDT). However, it is unknown whether it has an identical response of prolonged FDT on different normal tissues. Our results showed that fractionated irradiation with prolonged FDTs (15, 36, and 50 minutes) enhanced cell surviving fractions for normal tissue cells compared with irradiation with an FDT of 2 minutes. However, the late-responding normal cell line HEI-OC1 was more responsive to prolonged FDTs and demonstrated higher surviving fractions and significantly decreased apoptosis and DNA damage compared to the acute-responding normal cell line HaCaT. Increased autophagy mediated via the ATM-AMPK pathway was observed in HEI-OC1 cells compared with HaCaT cells when irradiated with prolonged FDTs. Furthermore, treatment with the autophagy inhibitor 3-MA or ATM inhibitor KU55933 resulted in enhanced ROS accumulation and attenuation of the effect of prolonged FDT-mediated protection on irradiated HEI-OC1 cells. Our results indicated that late-responding normal tissue cells benefitted more from prolonged FDTs compared with acute-responding tissue cells, which was mainly attributed to enhanced cytoprotective autophagy mediated via the ATM/AMPK signaling pathway.

SU‐E‐T‐674: Parameter Sensitivity Analysis of VMAT Planning for Spine SBRT

Purpose: To analyze the sensitivity of VMAT plan quality to various delivery parameters for spine SBRT. Methods: Ten spine patients, previously treated to 18 Gy in 1 fraction with 11 field IMRT plans generated using a Multi‐Criteria Optimization approach in Raystation (RaySearch Laboratories, Stockholm, Sweden) were selected for this study. Optimal VMAT plans, of comparable quality were generated using dual partial arcs and defined as baseline plans. The sensitivity of plan quality on dose rate level (variable dose rates (VDR), discrete dose rates (DDR)), leaf speed constraints (0.1, 0.2, 0.4, 0.6, 0.8 cm/degree and no constraint), was tested. The effect of maximum dose rate, maximum delivery time, and fraction size (18Gy*1, 9Gy*2 and 2Gy*9) was also tested. The resulting VMAT plan quality was analyzed by comparing PTV homogeneity index and conformity number, and D1 of spinal cord. Results: A leaf speed constraint of less than 0.2 cm/degree will degrade PTV conformity and spinal cord sparing, and plan quality of leaf speed more than 0.6 cm/degree is close to that without any leaf speed constraint. The proper selection of VMAT delivery parameters allows VMAT plan quality to match IMRT. In addition, VMAT plan quality of VDR is superior to that of DDR when either maximum delivery time or maximum dose rate is increased. Conclusion: VMAT plan quality for spine SBRT depends on the combination of delivery time, fraction size, and leaf speed. The sensitivity of plan quality depends on dose per fraction and maximum delivery time. Funding support: NCI Federal Share Proton Beam Program Income Grant.Conflict of Interest:none.

Establishing the Use of [11C]Choline PET-CT as an Image-based Biomarker in Prostate Cancer: Evaluation of [11 C]Choline Parameters Following Neoadjuvant Androgen Deprivation and Radical Radiation Therapy

more events. EPIC domain summary scores before and after radiation therapy is reported in the Table. Conclusions: VMAT with a gentle concomitant integrated boost of 2.3 Gy per fraction to the prostate was well tolerated in this study with only up to 3% grade 2 toxicity and no grade 3 or more toxicity. Three months to 1year post-radiation, the domains of urinary incontinence, irritation, and bowel scores maintained excellent function compared to pre-radiation scores. Furthermore, reduced dose to organs at risk (reported separately), reduction of treatment planning time and both individual fraction and overall treatment delivery time inherent in this approach, offer significant advantages for both providers and patients. Author Disclosure: Z. Symon: None. L. Tsvang: None. S. Dubinski: None. I. Weiss: None. M. Pfeffer: None. Y.R. Lawrence: None.

In vitro and in vivo studies on radiobiological effects of prolonged fraction delivery time in A549 cells

Intensity-modulated radiation therapy, when used in the clinic, prolongs fraction delivery time. Here we investigated both the in vivoand in vitroradiobiological effects on the A549 cell line, including the effect of different delivery times with the same dose on A549 tumor growth in nude mice. The in vitroeffects were studied with clonogenic assays, using linear-quadratic and incomplete repair models to fit the dose-survival curves. Fractionated irradiation of different doses was given at one fraction per day, simulating a clinical dose-time-fractionation pattern. The longer the interval between the exposures, the more cells survived. To investigate the in vivoeffect, we used sixty-four nude mice implanted with A549 cells in the back legs, randomly assigned into eight groups. A 15 Gy radiation dose was divided into different subfractions. The maximum and minimum tumor diameters were recorded to determine tumor growth. Tumor growth was delayed for groups with prolonged delivery time (40 min) compared to the group receiving a single dose of 15 Gy (P< 0.05), and tumors with a 20 min delivery time had delayed growth compared to those with a 40 min delivery time [20′ (7.5 Gy × 2 F) vs 40′ (7.5 Gy × 2 F), P= 0.035; 20′ (3 Gy × 5 F) vs 40′ (3 Gy × 5 F); P= 0.054; 20′ (1.67 Gy × 9 F) vs 40′ (1.67 Gy × 9 F), P= 0.028]. A prolonged delivery time decreased the radiobiological effects, so we strongly recommend keeping the delivery time as short as possible.

An Estimation of Radiobiological Parameters for Head-and-Neck Cancer Cells and the Clinical Implications.

In vitro survival measurements using two human head-and-neck cancer (HNC) cell lines were performed. The specially designed split-dose surviving fraction was obtained and fitted to the linear-quadratic formalism. The repair halftime (Tr), the potential doubling time (Td), α/β and radiosensitivity α, were estimated. Other radiobiological models: EUD, BED, TCP, etc., were used to examine the potential treatment effectiveness of different IMRT techniques. Our data indicated the repair halftime of ~17 min based on two HNC cell lines. The combined α/β, α and Td are α/β = 8.1 ± 4.1 Gy, α = 0.22 ± 0.08 Gy−1, Td = 4.0 ± 1.8 day, respectively. The prolonged IMRT dose delivery for entire HNC treatment course could possibly result in the loss of biological effectiveness, i.e., the target EUDs decreased by 11% with fraction dose delivery time varying from 5 to 30 min. We determined the sublethal damage repair halftime and other radiobiological parameters for HNC cells, and to evaluate treatment effectiveness of the prolonged dose delivery times associated with different IMRT techniques. The estimated repair halftime for HNC is relatively short and may be comparable to the step-and-shoot IMRT fraction dose delivery time. The effectiveness of IMRT treatment may be improved by reducing the fraction delivery time for HNC treatment.

SU-E-T-599: Pelvic Volumetric Modulated Arc Therapy with Hypofractionated Concomitant Integrated Prostate Boost: An Isoeffective Dose Comparison.

Pelvic irradiation is controversial in prostate cancer and has been associated with significant late toxicity, but may be beneficial in patients with high risk disease. To evaluate dose reduction to organs at risk (OAR), we compared volumetric intensity modulated arc therapy with hypofractionated concomitant integrated prostate boost (VMAT) to sequential 3-D conformal 4 field pelvis plan and prostate IMRT boost (Sequential IMRT). The planning CT's of 20 consecutive high risk prostate cancer patients were utilized for this study. Dose planning using triple A algorithm (Varian Eclipse). CTV included prostate and proximal seminal vesicles. These were expanded by 6 mm for the PTV1 . Pelvic LN were delineated and expanded by 3 mm for the PTV2. Volume based equivalent dose at 2Gy/fx (EQD2) doses were calculated using alpha/beta ratios of 1.5 Gy for the prostate and 3 Gy for normal tissues. VMAT prescription was 73.6 Gy (EQD2-80 Gy) to PTV1 and 54.4 Gy to PTV2 (EQD2-50 Gy) in 32 fractions of 2.3 Gy and 1.7 Gy, respectively. Sequential prescription was 46 Gy to the pelvis and 34 Gy for IMRT boost to a total of 80 Gy in 40 fractions of 2 Gy each. A significant reduction in mean dose was observed for rectum, bladder, bowel, femur head, and penile bulb for VMAT vs. Sequential IMRT (p<0.001) (table 1). Rectal V75 and V70 was 6.2% and 11.2% for VMAT and 13.6% and 19% for Sequential IMRT (p<0.001). Bowel V50 was 0.35 cm3 vs. 24.1 cm3 (p<0.001), respectively. The 98% isodose conformity index for the PTV was 1.44 for VMAT vs. 1.69 for Sequential IMRT (p<0.001). VMAT with concomitant boost significantly reduced dose to OAR compared to Sequential IMRT, potentially leading to less late toxicity, while providing excellent target coverage and conformity. Furthermore, reduction of treatment planning time and both individual fraction and overall treatment delivery time inherent in this approach, offer significant advantages for both providers and patients.

SU‐E‐T‐650: Impact of Machine Output Rate on Effective Dose Rate and Biologically Equivalent Fraction Size in Total Body Irradiation (TBI)

Purpose: Examine the feasibility and biological significance of increasing machine output rates in extended‐distance Total Body Irradiation (TBI). Methods: Biologically equivalent doses for TBI are derived from the LQ cell survival model. Effective dose rates and corrected fraction size for a mini‐TBI (i.e., 1 fraction × 2 Gy to patient mid‐line) delivered using 4 and 8 beams are computed as a function of machine output rate. The number of beams used for a TBI tends to increase with increasing patient size because of the clinical constraint of no more than 1000 MU per beam. All of the reported results include a 1 minute gap between beams and a (conservative) 5 minute gap for patient repositioning. Results: For a 4 beam treatment, increasing the machine output rate from 200 to 400 MU/minute reduced the fraction delivery time by 36% (28 to 18 minutes), and only increased the effective dose rate from 7 to 11 cGy/minute. For 8 beams, the fraction delivery times for 200 and 400 MU/min are 52 minutes (3.85 cGy/min) to 20 minutes (6.16 cGy/min), respectively. Increasing the machine output rate from 200 to 400 MU/min is unlikely to require more than 2–5% reduction in fraction size (alpha/beta = 1 Gy). The size of the required correction decreases as alpha/beta increases. Conclusions: Patient‐specific planning to correct for differences in beam number (patient size) are unlikely to alter the determination of biologically equivalent fraction sizes by more than 5%, which is well within the +/− 10% uniformity specified in many TBI protocols. A clinical trial to evaluate patient safety and treatment efficacy for machine output rates as high as 600–700 MU per minute are reasonable. Such a trial has the potential to substantially to increase patient comfort and reduce facility and labor costs without jeopardizing treatment effectiveness or safety.

The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

BackgroundHigh-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo.Methods1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed.ResultsThe tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P < 0.05). The tumor grow delay of groups with prolonged delivery time 30 min was longer than that of groups with prolonged delivery time 60 min P < 0.05). There was no significant difference between groups with same delivery time (P > 0.05). Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min.ConclusionsThe prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

Impact of Prolonged Fraction Delivery Times Simulating IMRT on Cultured Nasopharyngeal Carcinoma Cell Killing

To determine the impact of prolonged fraction delivery times (FDTs) simulating intensity-modulated radiotherapy (IMRT) on cultured nasopharyngeal carcinoma (NPC) cell killing. Cultured NPC cell lines CNE1 and CNE2 were used in this study. The biological effectiveness of fractionated irradiation protocols simulating conventional external beam radiotherapy and IMRT (FDT of 15, 36, and 50 minutes) was estimated with standard colony assay, and the differences in cell surviving fractions after irradiation with different protocols were tested by use of the paired t test. The impact degree of prolonged FDTs (from 8 to 50 minutes) on cell killing was also assessed by the dose-modifying factors, which were estimated by comparing the effectiveness of intermittently delivered 2 Gy with that of continuously delivered 1.5 to 2 Gy. The cell surviving fractions of both CNE1 and CNE2 after fractionated irradiation simulating IMRT were higher than those simulating conventional external beam radiotherapy (p < 0.05). The dose-modifying factors for a fraction dose of 2 Gy increased from 1.05 to 1.18 for CNE1 and from 1.05 to 1.11 for CNE2 with the FDT being prolonged from 15 to 50 minutes. This study showed that the prolonged FDTs simulating IMRT significantly decreased the cell killing in both CNE1 and CNE2 cell lines, and these negative effects increased with the FDT being prolonged from 15 to 50 minutes. These effects, if confirmed by in vivo and clinical studies, need to be considered in designing IMRT treatments for NPC.

Significant dose can be lost by extended delivery times in IMRT with x rays but not high-LET radiations

To experimentally simulate IMRT delivery using two human cell models in vitro and test the hypothesis that a loss in effective dose resulting from the prolongation of megavoltage x-ray treatment delivery time would be greatly reduced in corresponding IMRT simulations using higher-LET radiation. The effect of prolonging the delivery time of a treatment fraction was investigated in vitro using human PC-3 prostate and HGL21 glioblastoma tumor cell lines. Cells were irradiated with x rays from a conventional linear accelerator or with neutrons from a clinical d(48.5)+Be radiotherapy beam and maintained at 37 degrees C throughout. The delivery time for six closely spaced doses, simulating six multiple-port segments, was varied from acute to 60 min for x-ray irradiation, and acute to 120 min for neutron irradiation. Cell survival was measured following summed doses for the six segments of 0.5-6 Gy for x rays and 0.16-2 Gy for neutrons, covering the most likely range of dose per fraction used in clinical radiotherapy. Prolonging x-ray delivery time (from initiation of segment 1 to initiation of segment 6) from 5 to 45 min resulted in a loss in effective total dose (in equivalent 2 Gy multifraction treatments) of 5.6% in the PC-3 cell line and 11.7% in the HGL21 cell line. More clinically common prolongations of 5-30 and 5-15 min resulted in effective dose reductions of 3.8% and 1.7% for PC-3, and 7.3% and 2.9% for HGL21. A loss of less than 0.5% in effective dose was observed for prolongations up to 45 min of similarly effective neutron irradiation of PC-3 and HGL21 cells. Prolonged delivery times of photon fractions could have a significant impact on treatment outcome especially for tumors with a low alpha/beta ratio and short repair halftime. These effects are significant at delivery times commonly associated with IMRT and are variable with cell type. X-ray IMRT should therefore always be planned to minimize dose-fraction delivery time. However, if IMRT treatments are delivered with high-LET radiation, this considerably reduces the dependence of the biological effect on fraction delivery time even out to 2 h.

SU‐FF‐T‐486: The Impact of Prolonged Fraction Delivery Time in Advanced Radiotherapy Techniques On Cell Survival and DNA Damage

Purpose: Currently, the advanced radiotherapy techniques such as Stereotactic radiotherapy (SRT) and Intensity modulated radiotherapy (IMRT) have been implemented in radiotherapy centers to improve the efficiency of cancer treatment. Due to their complexity, these techniques require the longer fraction delivery time comparing to conventional technique. This study aimed to prove a hypothesis that prolonged treatment time had a significant impact on cell sterilizing effect due to an increasing in DNA damage repair. Method and Materials: HeLa cells were irradiated by 6 MV linear accelerator using 3 different protocols simulated the advanced radiotherapy techniques. The absorbed dose of 200 cGy were given in 15, 30 and 45 min. Colony formation assay was used to determine cell survival while DNA damages were detected by Comet assay. The results were then compared to that of conventional technique with 5 min delivery time and analyzed by student T‐test. The Linear‐Quadratic model with α/β ratio and repair half‐time taken into account was used to calculate the dose compensating for prolonged time. Results: It revealed that, the relative percentage DNA in tail of cervical cancer cell line observed in comet assay were significantly decreased to 0.724 – 0.905 (p &lt; 0.05) while relative surviving fraction increased to 1.02 – 1.17 to that of conventional technique. Although the surviving fraction tended to increase with increasing delivery time, only the surviving fraction at 30 min delivery time was statistical different. The absorbed dose of 204 cGy calculated by LQ model should be used to compensate for this impact. Conclusions: Prolonging treatment time allowed sublethal damage repair to take place during irradiation demonstrated by decreasing in DNA damage and subsequently increasing in cell survival. Therefore, biological effective dose should be compensated in advanced radiotherapy techniques which delivery time longer or close to repair half‐time of tumor cell.