Energy dependence of dose and dose-rate effectiveness factor for low-let radiations: potential importance to estimation of cancer risks and relationship to biological effectiveness

A dose and dose-rate effectiveness factor (DDREF) for low-linear energy transfer (LET) radiations (photons and electrons) is used in cancer risk assessments to represent an assumption that risks at low doses and low dose rates may be less than estimates that are based mainly on linear extrapolations of observed risks at higher acute doses. DDREF generally is assumed to be independent of energy. However, a variety of radiobiological data reviewed in this paper suggest that DDREF may decrease with decreasing energy. This effect, which parallels increases in biological effectiveness with decreasing energy of photons and electrons that have been observed in many radiobiological studies, has received little attention. The importance of an overestimation of DDREF at low energies of photons and electrons is that cancer risks at low doses and low dose rates could be underestimated. This paper also discusses (1) the link between DDREF and the usual assumption of a linear-quadratic dose-response relationship for low-LET radiations and (2) concerns about the validity of estimates of DDREF and biological effectiveness used in cancer risk assessments that are raised by results of recent studies that cast doubt on whether the underlying radiobiological data can be represented by a simple linear-quadratic model.     

Induction of somatic mutations by low concentrations of tritiated water (HTO): evidence for the possible existence of a dose-rate threshold

Tritium is a low energy beta emitter and is discharged into the aquatic environment primarily in the form of tritiated water (HTO) from nuclear power plants or from nuclear fuel reprocessing plants. Although the biological effects of HTO exposures at significant doses or dose rates have been extensively studied, there are few reports concerning the biological effects of HTO exposures at very low dose rates. In the present study using a hyper-sensitive assay system, we investigated the dose rate effect of HTO on the induction of mutations. Confluent cell populations were exposed to HTO for a total dose of 0.2 Gy at dose rates between 4.9 mGy/day and 192 mGy/day by incubating cells in medium containing HTO. HTO-induced mutant frequencies and mutation spectra were then investigated. A significant inflection point for both the mutant frequency and mutation spectra was found between 11 mGy/day and 21.6 mGy/day. Mutation spectra analysis revealed that a mechanistic change in the nature of the mutation events occurred around 11 mGy/day. The present observations and published experimental results from oral administrations of HTO to mice suggest that a threshold dose-rate for HTO exposures might exist between 11 mGy/day and 21.6 mGy/day where the nature of the mutation events induced by HTO becomes similar to those seen in spontaneous events.     

Ionizing radiation alters organoid forming potential and replenishment rate in a dose/dose-rate dependent manner

Intestinal organoids are an in vitro cultured tissue model generated from intestinal stem cells, and they contain a mixture of epithelial cell types. We previously established an efficient ‘one cell/well’ sorting method, and defined organoid-forming potential (OFP) as a useful index to evaluate the stemness of individual cells. In this study, we assessed the response to radiation dose and dose-rate by measuring both OFP and the percentage of stem cells in the crypts. After high-dose-rate (HDR, 0.5 Gy/min) irradiation in vivo, the percentage of stem cells in the harvested crypt cells decreased, and the replenishment of cycling stem cells originating from dormant cells was enhanced, but OFP increased in cells irradiated with a total dose of >1 Gy. In contrast, at a total dose of 0.1 Gy the percentage of stem cells reduced slightly, but neither replenishment rate nor OFP changed. Furthermore, the response to 1 Gy of low-dose-rate (LDR) irradiation was similar to the response to 0.1 Gy HDR irradiation. These results suggest that 0.1 Gy HDR irradiation or 1 Gy LDR irradiation does not alter stemness. Additionally, the OFP increase in the colon in response to irradiation was smaller than that in the duodenum, similar to the percentage of stem cells. Understanding the differences in the response of stem cells between the colon and the duodenum to radiation is important to clarify the mechanisms underlying the development of radiation-associated intestinal cancers.     

Amplitude-based gated phase-controlled rescanning in carbon-ion scanning beam treatment planning under irregular breathing conditions using lung and liver 4DCTs

Amplitude-based gating aids treatment planning in scanned particle therapy because it gives better control of uncertainty with the gate window. We have installed an X-ray fluoroscopic imaging system in our treatment room for clinical use with an amplitude-based gating strategy. We evaluated the effects of this gating under realistic organ motion conditions using 4DCT data of lung and liver tumors. 4DCT imaging was done for 24 lung and liver patients using the area-detector CT. We calculated the field-specific target volume (FTV) for the gating window, which was defined for a single respiratory cycle. Prescribed doses of 48 Gy relative biological effectiveness (RBE)/fraction/four fields and 45 Gy RBE/two fractions/two fields were delivered to the FTVs for lung and liver treatments, respectively. Dose distributions were calculated for the repeated first respiratory cycle (= planning dose) and the whole respiratory data (= treatment dose). We applied eight phase-controlled rescannings with the amplitude-based gating. For the lung cases, D95 of the treatment dose (= 96.0 ± 1.0%) was almost the same as that of the planning dose (= 96.6 ± 0.9%). D_max/D_min of the treatment dose (= 104.5 ± 2.2%/89.4 ± 2.6%) was slightly increased over that of the planning dose (= 102.1 ± 1.0%/89.8 ± 2.5%) due to hot spots. For the liver cases, D₉₅ of the treatment dose (= 97.6 ± 0.5%) was decreased by ∼ 1% when compared with the planning dose (= 98.5 ± 0.4%). D_max/D_min of the treatment dose was degraded by 3.0%/0.4% compared with the planning dose. Average treatment times were extended by 46.5 s and 65.9 s from those of the planning dose for lung and liver cases, respectively. As with regular respiratory patterns, amplitude-based gated multiple phase-controlled rescanning preserves target coverage to a moving target under irregular respiratory patterns.     

Estimation of the total rectal dose of radical external beam and intracavitary radiotherapy for uterine cervical cancer using the deformable image registration method

We adapted the deformable image registration (DIR) technique to accurately calculate the cumulative intracavitary brachytherapy (ICBT) and external beam radiotherapy (EBRT) rectal dose for treating uterine cervical cancer. A total of 14 patients with primary cervical cancer radically treated with ICRT and EBRT were analysed using the Velocity AI^TM software. Computed tomography (CT) images were registered, and EBRT and ICBT dose distributions were determined. Cumulative D_2cm³, D_1cm³ and D_0.1cm³ were calculated by simple addition of fractional values or by DIR. The accuracy of DIR was evaluated by means of a virtual phantom mimicking the rectum. The dice similarity coefficient (DSC) was calculated to evaluate rectal contour concordance between CT images before and after DIR. Virtual phantom analysis revealed that the average difference between the DIR-based phantom D_mean and the simple phantom D_mean was 1.9 ± 2.5 Gy (EQD₂), and the DIR method included an uncertainty of ∼8.0%. The mean DSC between reference CT and CT was significantly improved after DIR (EBRT: 0.43 vs 0.85, P < 0.005; ICBT: 0.60 vs 0.87, P < 0.005). The average simple rectal D_2cm³, D_1cm³ and D_0.1cm³ values were 77.6, 81.6 and 91.1 Gy (EQD₂), respectively; the DIR-based values were 76.2, 79.5 and 87.6 Gy, respectively. The simple addition values were overestimated, on average, by 3.1, 3.7 and 5.5 Gy, respectively, relative to the DIR-based values. In conclusion, the difference between the simple rectal dose–volume histogram (DVH) parameter addition and DIR-based cumulative rectal doses increased with decreasing DVH parameters.     

DNA strand break induction of aqueous plasmid DNA exposed to 30 MeV protons at ultra-high dose rate

Radiation cancer therapy with ultra-high dose rate exposure, so called FLASH radiotherapy, appears to reduce normal tissue damage without compromising tumor response. The aim of this study was to clarify whether FLASH exposure of proton beam would be effective in reducing the DNA strand break induction. We applied a simple model system, pBR322 plasmid DNA in aqueous 1 × TE solution, where DNA single strand breaks (SSBs) and double strand breaks (DSBs) can be precisely quantified by gel electrophoresis. Plasmid DNA were exposed to 27.5 MeV protons in the conventional dose rate of 0.05 Gy/s (CONV) and ultra-high dose rate of 40 Gy/s (FLASH). With both dose rate, the kinetics of the SSB and DSB induction were proportional to absorbed dose. The SSB induction of FLASH was significantly less than CONV, which were 8.79 ± 0.14 (10⁻³ SSB per Gy per molecule) and 10.8 ± 0.68 (10⁻³ SSB per Gy per molecule), respectively. The DSB induction of FLASH was also slightly less than CONV, but difference was not significant. Altogether, 27.5 MeV proton beam at 40 Gy/s reduced SSB and not DSB, thus its effect may not be significant in reducing lethal DNA damage that become apparent in acute radiation effect.     

Assessment of simulated high-dose partial-body irradiation by PCC-R assay

The estimation of the dose and the irradiated fraction of the body is important information in the primary medical response in case of a radiological accident. The PCC-R assay has been developed for high-dose estimations, but little attention has been given to its applicability for partial-body irradiations. In the present work we estimated the doses and the percentage of the irradiated fraction in simulated partial-body radiation exposures at high doses using the PCC-R assay. Peripheral whole blood of three healthy donors was exposed to doses from 0–20 Gy, with ⁶⁰Co gamma radiation. To simulate partial body irradiations, irradiated and non-irradiated blood was mixed to obtain proportions of irradiated blood from 10–90%. Lymphocyte cultures were treated with Colcemid and Calyculin-A before harvest. Conventional and triage scores were performed for each dose, proportion of irradiated blood and donor. The Papworth''s u test was used to evaluate the PCC-R distribution per cell. A dose-response relationship was fitted according to the maximum likelihood method using the frequencies of PCC-R obtained from 100% irradiated blood. The dose to the partially irradiated blood was estimated using the Contaminated Poisson method. A new D₀ value of 10.9 Gy was calculated and used to estimate the initial fraction of irradiated cells. The results presented here indicate that by PCC-R it is possible to distinguish between simulated partial- and whole-body irradiations by the u-test, and to accurately estimate the dose from 10–20 Gy, and the initial fraction of irradiated cells in the interval from 10–90%.     

VMAT–SBRT planning based on an average intensity projection for lung tumors located in close proximity to the diaphragm: a phantom and clinical validity study

The aim of the this study was to validate the use of an average intensity projection (AIP) for volumetric-modulated arc therapy for stereotactic body radiation therapy (VMAT–SBRT) planning for a moving lung tumor located near the diaphragm. VMAT–SBRT plans were created using AIPs reconstructed from 10 phases of 4DCT images that were acquired with a target phantom moving with amplitudes of 5, 10, 20 and 30 mm. To generate a 4D dose distribution, the static dose for each phase was recalculated and the doses were accumulated by using the phantom position known for each phase. For 10 patients with lung tumors, a deformable registration was used to generate 4D dose distributions. Doses to the target volume obtained from the AIP plan and the 4D plan were compared, as were the doses obtained from each plan to the organs at risk (OARs). In both phantom and clinical study, dose discrepancies for all parameters of the dose volume (D_min, D₉₉, D_max, D₁ and D_mean) to the target were <3%. The discrepancies of D_max for spinal cord, esophagus and heart were <1 Gy, and the discrepancy of V20 for lung tissue was <1%. However, for OARs with large respiratory motion, the discrepancy of the D_max was as much as 9.6 Gy for liver and 5.7 Gy for stomach. Thus, AIP is clinically acceptable as a planning CT image for predicting 4D dose, but doses to the OARs with large respiratory motion were underestimated with the AIP approach.     

Diminished or inversed dose-rate effect on clonogenic ability in Ku-deficient rodent cells

The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as ‘the dose-rate effect’. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70^−/− mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.     

Implantable cardiac pacemaker failure by cumulative dose effects of flattening filter free beams

Cumulative dose effects, which are one of the main causes of errors that occur when an implantable cardiac pacemaker (ICP) is irradiated with ionizing radiation, induce permanent failure in ICPs. Although flattening filter free (FFF) beams, which are often used in stereotactic radiotherapy, are known to have different characteristics from conventional (with flattening filter [WFF]) beams, the cumulative dose effects on ICPs with FFF beams have been under-investigated. This study investigates ICP failure induced by cumulative dose effects of FFF beams. When the ICP placed in the center of the irradiation field was irradiated with 10 MV-FFF at 24 Gy/min, the cumulative dose at which failure occurred was evaluated on the basis of the failure criteria associated with high cumulative dose as described in the American Association of Physicists in Medicine Task Group 203. The ICP failures such as a mild battery depletion at a cumulative dose of 10 Gy, pacing-output voltage change >25% at a cumulative dose of 122 Gy, and the loss of telemetry capability at cumulative dose 134 Gy were induced by cumulative dose effects. The cumulative doses by which the cumulative dose effects of FFF beams induced ICP failure were not very different from those reported in previous studies with WFF beams. Therefore, radiotherapy with FFF beams (and WFF beams) for patients with ICP requires appropriate management for minimizing the cumulative dose effects.     

Dosimetric evaluation of ovaries and pelvic bones associated with clinical outcomes in patients receiving total body irradiation with ovarian shielding

Total body irradiation (TBI) with ovarian shielding is expected to preserve fertility among hematopoietic stem cell transplant (HSCT) patients with myeloablative TBI-based regimens. However, the radiation dose to the ovaries that preserves ovarian function in TBI remains poorly understood. Furthermore, it is uncertain whether the dose to the shielded organs is associated with relapse risk. Here, we retrospectively evaluated the relationship between fertility and the dose to the ovaries, and between relapse risk and the dose to the pelvic bones. A total of 20 patients (median age, 23 years) with standard-risk hematologic diseases were included. Median follow-up duration was 31.9 months. The TBI prescribed dose was 12 Gy in six fractions for three days. Patients’ ovaries were shielded with cylinder-type lead blocks. The dose–volume parameters (D_98% and D_mean) in the ovaries and the pelvic bones were extracted from the dose–volume histogram (DVH). The mean ovary D_mean for all patients was 2.4 Gy, and 18 patients recovered menstruation (90%). The mean ovary D_mean for patients with menstrual recovery and without recovery were 2.4 Gy and 2.4 Gy, respectively, with no significant difference (P = 0.998). Hematological relapse was observed in five patients. The mean pelvis D_mean and pelvis D_98% for relapse and non-relapse patients were 11.6 Gy and 11.7 Gy and 5.6 Gy and 5.3 Gy, respectively. Both parameters showed no significant difference (P = 0.827, 0.807). In conclusion, TBI with ovarian shielding reduced the radiation dose to the ovaries to 2.4 Gy, and preserved fertility without increasing the risk of relapse.     

Rectal dose-sparing effect with bioabsorbable spacer placement in carbon ion radiotherapy for sacral chordoma: dosimetric comparison of a simulation study

It is difficult to treat patients with an inoperable sarcoma adjacent to the gastrointestinal (GI) tract using carbon ion radiotherapy (C-ion RT), owing to the possible development of serious GI toxicities. In such cases, spacer placement may be useful in physically separating the tumor and the GI tract. We aimed to evaluate the usefulness of spacer placement by conducting a simulation study of dosimetric comparison in a patient with sacral chordoma adjacent to the rectum treated with C-ion RT. The sacral chordoma was located in the third to fourth sacral spinal segments, in extensive contact with and compressing the rectum. Conventional C-ion RT was not indicated because the rectal dose would exceed the tolerance dose. Because we chose spacer placement surgery to physically separate the tumor and the rectum before C-ion RT, bioabsorbable spacer sheets were inserted by open surgery. After spacer placement, 67.2 Gy [relative biological effectiveness (RBE)] of C-ion RT was administered. The thickness of the spacer was stable at 13–14 mm during C-ion RT. Comparing the dose–volume histogram (DVH) parameters, D_max for the rectum was reduced from 67 Gy (RBE) in the no spacer plan (simulation plan) to 45 Gy (RBE) in the spacer placement plan (actual plan) when a prescribed dose was administered to the tumor. Spacer placement was advantageous for irradiating the tumor and the rectum, demonstrated using the DVH parameter analysis.     

Reducing radiation exposure using commonly available objects

Objectives

One and a half years have passed since the Fukushima Daiichi nuclear power plant disaster. The environmental radiation dose rate was not critical, but an existing exposure situation has been identified in a large part of Fukushima Prefecture. Although people continue to live and work in the contaminated area, they are not provided with sufficient information to reduce their exposure to radiation by themselves. In this study, we attempt to evaluate the efficiency of radiation shielding by using everyday items widely available to people.

Methods

NaI scintillation and Geiger–Müller survey meters were used to measure the radiation dose of (1) contaminated soil and (2) soil covered with commonly available items.

Results

In the soil at a depth of 10 cm from the surface, the radiation dose rate decreased from 3.36 to 0.65 μSv/h, and the count rate decreased from 3,120 to 352 cpm. Both the radiation dose rate and count rate reduced when the soil was covered with everyday items, such as a magazine more than 20 mm thick, a polystyrene foam board, and a wooden board of the same thickness.

Conclusions

To protect residents from unnecessary radiation exposure in the existing exposure situation, covering contaminated soil with a wooden board or a magazine, either of them 20 mm thick, is useful to reduce the radiation dose.     

Dose rate in the highest irradiation area of the rectum correlates with late rectal complications in patients treated with high-dose-rate computed tomography-based image-guided brachytherapy for cervical cancer

The purpose of this study was to evaluate the effect of dose rate to the rectum on late rectal complications in patients treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) for cervical cancer. The subjects were 142 patients with cervical cancer who underwent Ir-192 high-dose-rate (HDR)-IGBT between March 2012 and January 2018. The dose rate to the rectum was calculated using in-house software. The minimum, mean and maximum effective dose rate (EDR) was calculated for voxels of the rectal volume covered by cumulative doses >D_0.1cc, >D_2cc, and > D_5cc. The average EDR of three to four brachytherapy sessions was calculated (EDR for patients; EDR_p). The total dose of the rectum was calculated as the biologically equivalent dose in 2-Gy fractions (EQD₂). The associations between EDR_p for D_0.1cc, D_2cc, and D_5cc and the respective rectal EQD₂ values with late rectal complications were then analyzed. The median follow-up period was 40 months. Patients with rectal complications of ≥Grade 1 received a significantly higher mean EDR_p for D_0.1cc–5cc and had a greater EQD₂ for D_0.1cc–5cc. Multivariate analysis was performed using the mean EDR_p for D_2cc, EQD₂ for D_2cc, heavy smoking and BMI. Of these four variables, mean EDR_p for D_2cc (HR = 3.38, p = 0.004) and EQD₂ for D_2cc (HR = 2.59, p = 0.045) emerged as independent predictors for late rectal complications. In conclusion, mean EDR_p and EQD₂ were associated with late rectal complications in patients treated with HDR CT-based IGBT for cervical cancer.     

Comparison of predictive performance for toxicity by accumulative dose of DVH parameter addition and DIR addition for cervical cancer patients

We compared predictive performance between dose volume histogram (DVH) parameter addition and deformable image registration (DIR) addition for gastrointestinal (GI) toxicity in cervical cancer patients. A total of 59 patients receiving brachytherapy and external beam radiotherapy were analyzed retrospectively. The accumulative dose was calculated by three methods: conventional DVH parameter addition, full DIR addition and partial DIR addition. , and (minimum doses to the most exposed 2 cm³, 1cm³ and 0.1 cm³ of tissue, respectively) of the rectum and sigmoid were calculated by each method. V50, V60 and V70 Gy (volume irradiated over 50, 60 and 70 Gy, respectively) were calculated in full DIR addition. The DVH parameters were compared between toxicity (≥grade1) and non-toxicity groups. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves were compared to evaluate the predictive performance of each method. The differences between toxicity and non-toxicity groups in were 0.2, 5.7 and 3.1 Gy for the DVH parameter addition, full DIR addition and partial DIR addition, respectively. The AUCs of were 0.51, 0.67 and 0.57 for DVH parameter addition, full DIR addition and partial DIR addition, respectively. In full DIR addition, the difference in dose between toxicity and non-toxicity was the largest and AUC was the highest. AUCs of V50, V60 and V70 Gy were 0.51, 0.63 and 0.62, respectively, and V60 and V70 were high values close to the value of of the full DIR addition. Our results suggested that the full DIR addition may have the potential to predict toxicity more accurately than the conventional DVH parameter addition, and that it could be more effective to accumulate to all pelvic irradiation by DIR.     

Evaluation of triple channel correction acquisition method for radiochromic film dosimetry

The purpose of this study was to evaluate the triple channel correction acquisition (TCCA) method for radiochromic film dosimetry performed with a flatbed scanner. The study had two parts: a fundamental and a clinical examination. In the fundamental examination, we evaluated the accuracy of calibration curves for Gafchromic EBT2 (EBT2). The films were calibrated using a field-by-field method with 13 dose steps. Seven calibration curves obtained by TCCA were compared with those produced by a single channel acquisition (SCA) method. For the clinical examination, we compared relative dose distributions obtained by TCCA and SCA for four cases of intensity-modulated radiation therapy (IMRT) and intensity-modulated arc therapy (IMAT). The fundamental examination showed that the consistency of the calibration curves was better for TCCA than for SCA, particularly for the dose range between 0.25 Gy and 1.00 Gy. The clinical examination showed that the dose differences between the measured and calculated doses in high-gradient regions were smaller with TCCA than with SCA. The average pass rates in gamma analysis for the TCCA and SCA methods were 97.2 ± 0.8% (n = 20) and 93.0 ± 1.2% (n = 20), respectively. In conclusion, TCCA can acquire accurate average dose values when creating the calibration curve. The potential advantage of TCCA for EBT2 film dosimetry was seen in high-gradient regions in clinically relevant IMRT and IMAT cases. TCCA is useful to verify dose distribution.     

Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions

During interplanetary missions, astronauts are exposed to mixed types of ionizing radiation. The low ‘flux’ of the high atomic number and high energy (HZE) radiations relative to the higher ‘flux’ of low linear energy transfer (LET) protons makes it highly probable that for any given cell in the body, proton events will precede any HZE event. Whereas progress has been made in our understanding of the biological effects of low-LET protons and high-LET HZE particles, the interplay between the biochemical processes modulated by these radiations is unclear. Here we show that exposure of normal human fibroblasts to a low mean absorbed dose of 20 cGy of 0.05 or 1-GeV protons (LET ∼ 1.25 or 0.2 keV/μm, respectively) protects the irradiated cells (P < 0.0001) against chromosomal damage induced by a subsequent exposure to a mean absorbed dose of 50 cGy from 1 GeV/u iron ions (LET ∼ 151 keV/μm). Surprisingly, unirradiated (i.e. bystander) cells with which the proton-irradiated cells were co-cultured were also significantly protected from the DNA-damaging effects of the challenge dose. The mitigating effect persisted for at least 24 h. These results highlight the interactions of biological effects due to direct cellular traversal by radiation with those due to bystander effects in cell populations exposed to mixed radiation fields. They show that protective adaptive responses can spread from cells targeted by low-LET space radiation to bystander cells in their vicinity. The findings are relevant to understanding the health hazards of space travel.     

Inverse planning for combination of intracavitary and interstitial brachytherapy for locally advanced cervical cancer

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V₁₀₀ achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D₁₀₀ was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D₉₀ was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D_2cm³: 408 ± 71 cGy vs manual optimization D_2cm³: 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D_2cm³: 452 ± 60 cGy vs manual optimization D_2cm³: 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.     

Evaluation of dosimetric variance in whole breast forward-planned intensity-modulated radiotherapy based on 4DCT and 3DCT

This study was performed to explore and compare the dosimetric variance caused by respiratory movement in the breast during forward-planned IMRT after breast-conserving surgery. A total of 17 enrolled patients underwent the 3DCT simulation scans followed by 4DCT simulation scans during free breathing. The treatment planning constructed using the 3DCT images was copied and applied to the end expiration (EE) and end inspiration (EI) scans and the dose distributions were calculated separately. CTV volume variance amplitude was very small (11.93 ± 28.64 cm³), and the percentage change of CTV volumes receiving 50 Gy and 55 Gy between different scans were all less than 0.8%. There was no statistically significant difference between EI and EE scans (Z =–0.26, P = 0.795). However, significant differences were found when comparing the D_mean at 3DCT planning with the EI and EE planning (P = 0.010 and 0.019, respectively). The homogeneity index at EI, EE and 3D plannings were 0.139, 0.141 and 0.127, respectively, and significant differences existed between 3D and EI, and between 3D and EE (P = 0.001 and 0.006, respectively). The conformal index (CI) increased significantly in 3D treatment planning (0.74 ± 0.07) compared with the EI and EE phase plannings (P = 0.005 and 0.005, respectively). The V₃₀, V₄₀, V₅₀ and D_mean of the ipsilateral lung for EE phase planning were significantly lower than for EI (P = 0.001–0.042). There were no significant differences in all the DVH parameters for the heart among these plannings (P = 0.128–0.866). The breast deformation during respiration can be disregarded in whole breast IMRT. 3D treatment planning is sufficient for whole breast forward-planned IMRT on the basis of our DVH analysis, but 4D treatment planning, breath-hold, or respiratory gate may ensure precise delivery of radiation dose.     

Effects of single-pulse (< or = 1 ps) X-rays from laser-produced plasmas on mammalian cells

The effects of low linear energy transfer (LET) radiation on mammalian cells have been studied at dose-rates as high as 10(9) Gy/sec delivered as a single 3-nanosecond pulse, and no increase in cytotoxicity was shown compared with delivery at a conventional dose-rate. There have been no observations on the effects of radiation delivered at even higher dose-rates on the picosecond time-scale. Here we examined, for the first time, the effects on cultured mouse L5178Y cells and its radiosensitive XRCC4-deficient mutant M10 cells of sub-picosecond X-rays emitted from laser-produced plasmas at the ultrahigh dose-rate of 10(12)-10(13) Gy/sec. No increase in the sensitivity to the X-rays was observed compared with gamma-rays at a conventional dose-rate. The increase in the sensitivity of L5178Y cells by labeling with 5-iododeoxyuridine was smaller than those irradiated with gamma-rays at a conventional dose-rate, while the difference was apparently the reverse in M10 cells. The D10 ratio between L5178Y cells and M10 cells produced by the X-rays at temporally dense ionization was the same as that produced by X(gamma)-rays at the conventional dose-rate, while the ratio is greatly reduced in the case of particle radiation. These results suggest that there is no increase in the cytotoxic effects of X-rays at dose-rates as high as 10(13) Gy/sec, and that the increased cytotoxicity of particle radiation is not attributable to temporally dense ionization. It is discussed that the mechanism for the induction of radiation damage responsible for cytotoxicity may be slightly modified at ultrahigh dose-rates.