Continuous Low Dose Rate Irradiation Research Articles

COMBINED ANALYSIS OF CANCER INCIDENCE AND LIFESPAN IN MICE EXPOSED TO CHRONIC LOW DOSE RATE RADIATION.

The authors performed a combined analysis using the data obtained from continuous low dose rate irradiation experiments on mice conducted at the Institute for Environmental Sciences, namely, cancer incidence data and lifespan data. They estimated the length of cancer progression period, which is difficult to assess experimentally. The combined analysis showed that the mean cancer progression period is 173d in the control group and 103d in the irradiated group.

Inhibition of Endoplasmic Reticulum Stress-Mediated Autophagy Enhances the Anticancer Effect of Iodine-125 Seed Radiation on Esophageal Squamous Cell Carcinoma.

Autophagy has been reported to play a radioresistance role in high-dose-rate irradiation. However, its mechanisms and roles in continuous low-dose-rate (CLDR) irradiation have not been clearly understood. Iodine-125 (I-125) seed brachytherapy is a modality of CLDR irradiation and has been used in the treatment of various cancers. In this study, we investigated the mechanisms and roles of autophagy induced by I-125 seed radiation in human esophageal squamous cell carcinoma (ESCC) cell lines (Eca-109 and EC-109) and a xenograft mouse model. The results of this work showed that I-125 seed radiation induced a dose-dependent increase in autophagy in both cell lines. In Eca-109 cells, I-125 seed radiation-induced endoplasmic reticulum (ER) stress, manifesting as the increased levels of intracellular Ca2+ and Grp78/BiP, and activated PERK-eIF2α, IRE1, and ATF6 pathways of the unfolded protein response. Knockdown of PERK led to the decreased expression of autophagy marker, LC3B-II. Inhibition of autophagy by chloroquine or knockdown of ATG5 enhanced I-125 seed radiation-induced cell proliferation inhibition and apoptosis. Interestingly, chloroquine did not aggravate ER stress but promoted apoptosis via the mitochondrial pathway. The animal experiment showed that inhibition of autophagy by chloroquine improved the efficacy of I-125 seed radiation. In summary, our data demonstrate that I-125 seed CLDR radiation induces ER stress-mediated autophagy in ESCC. Autophagy plays a pro-survival role in I-125 seed CLDR irradiation, and chloroquine is a potential candidate for use in combination therapy with I-125 seed radiation treatment to improve efficacy against ESCC.

Continuous Low-dose-rate Irradiation of Iodine-125 Seeds Inhibiting Perineural Invasion in Pancreatic Cancer.

Background:Perineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa). The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 (125I) seed implantation.Methods:The in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of 125I seeds CLDR irradiation. The orthotopic models of PNI were established, and 125I seeds were implanted in tumor. The PNI-related molecules were analyzed. In 30 patients with panCa, the pain relief was assessed using a visual analog scale (VAS). Pain intensity was measured before and 1 week, 2 weeks, and 1, 3, and 6 months after 125I seed implantation.Results:The co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites. In co-culture groups, the increased number of DRG neurites and pancreatic cells in radiation group was significantly less. In orthotopic models, the PNI-positive rate in radiation and control group was 3/11 and 7/11; meanwhile, the degrees of PNI between radiation and control groups was significant difference (P < 0.05). At week 2, the mean VAS pain score in patients decreased by 50% and significantly improved than the score at baseline (P < 0.05). The pain scores were lower in all patients, and the pain-relieving effect was retained about 3 months.Conclusions:The CLDR irradiation could inhibit PNI of PanCa with the value of further study. The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain.

I-125 Seeds Continuous Low Dose Rate Radiation Induced Severe DNA Damages on H520 Lung Cancer Cell

I-125 Seeds Continuous Low Dose Rate Radiation Induced Severe DNA Damages on H520 Lung Cancer Cell

SU‐F‐19A‐08: Optimal Time Release Schedule of In‐Situ Drug Release During Permanent Prostate Brachytherapy

Purpose:Permanent prostate brachytherapy spacers can be used to deliver sustained doses of radiosentitizing drug directly to the target, in order to enhance the radiation effect. Implantable nanoplatforms for chemo‐radiation therapy (INCeRTs) have a maximum drug capacity and can be engineered to control the drug release schedule. The optimal schedule for sensitization during continuous low dose rate irradiation is unknown. This work studies the optimal release schedule of drug for both traditional sensitizers, and those that work by suppressing DNA repair processes.Methods:Six brachytherapy treatment plans were used to model the anatomy, implant geometry and calculate the spatial distribution of radiation dose and drug concentrations for a range of drug diffusion parameters. Three state partial differential equations (cells healthy, damaged or dead) modeled the effect of continuous radiation (radiosensitivities α,β) and cellular repair (time tr) on a cell population. Radiosensitization was modeled as concentration dependent change in α,β or tr which with variable duration under the constraint of fixed total drug release. Average cell kill was used to measure effectiveness. Sensitization by means of both enhanced damage and reduced repair were studied.Results:Optimal release duration is dependent on the concentration of radiosensitizer compared to the saturation concentration (csat) above which additional sensitization does not occur. Long duration drug release when enhancing α or β maximizes cell death when drug concentrations are generally over csat. Short term release is optimal for concentrations below saturation. Sensitization by suppressing repair has a similar though less distinct trend that is more affected by the radiation dose distribution.Conclusion:Models of sustained local radiosensitization show potential to increase the effectiveness of radiation in permanent prostate brachytherapy. INCeRTs with high drug capacity produce the greatest benefit with drug release over weeks. If in‐vivo drug concentrations are not able to approach saturation concentration, durations of days is optimal.DOD 1R21CA16977501; A. David Mazzone Awards Program 2012PD164

Biological Effects of 125I Seeds Radiation on A549 Lung Cancer Cells: G2/M Arrest and Enhanced Cell Death

External beam radiation (EBRT) and 125I seeds continuous low dose rate radiation (CLDR) were used to treat patients with lung cancer. We herein investigated the biological effects of EBRT and CLDR on lung cancer cells. A549 human lung cancer cell line was thus exposed to different doses of EBRT and CLDR. CLDR was more efficient to inhibit cell growth than EBRT. CLDR induced increased DNA damage as evidenced by long-lasting p-H2AX activity. The enhanced inhibitory effects of CLDR on lung cancer cell growth may be, at least in part, due to the increased Bax/Bcl2 ratio and cyclin B1-mediated G2/M arrest.

Combined effects of C225 and 125-iodine seed radiation on colorectal cancer cells

BackgroundTo characterize the effect of combined treatment of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody C225 and 125-iodine (125I) seed radiation in human colorectal cancer.MethodsWe treated LS180 cells with 125I continuous low dose rate radiation in the presence and absence of 100 nM C225. The clonogenic capacity, cellular proliferation, cell cycle distribution, apoptosis, and molecular pathways of the cells following the treatments were analyzed in vitro.ResultsThe sensitizer enhancement ratio of C225 was approximately 1.4. Treatment with C225 and radiation alone produced significant inhibition of cell growth, but combination therapy produced greater inhibition than either treatment administered alone. C225 increased the radiation-induced apoptosis and the fraction of γ-H2AX foci positive cells at 48 h after treatment. The Akt phosphorylation level was lower in the cells receiving the combination treatment than in the cells treated with radiation or C225 alone.ConclusionsThese findings indicate that C225 sensitizes LS180 cells to 125I seed radiation. Growth inhibition is mediated by inducing apoptosis and not cell cycle arrest. Additionally, we confirmed that C225 impairs DNA repair by reducing the cellular level of the DNA-PKcs and Ku70 proteins. Furthermore, the inhibition of Akt signaling activation may be responsible for the C225-mediated radiosensitization.

The different biological effects of single, fractionated and continuous low dose rate irradiation on CL187 colorectal cancer cells.

PurposeTo determine the biological effectiveness of single, fractionated and continuous low dose rate irradiation on the human colorectal cancer cell line CL187 in vitro and explore the cellular mechanisms.Materials and methodsThe CL187 cells were exposed to radiation of 6 MV X-ray at a high dose rate of 4Gy/min and 125I seed at a low dose rate of 2.77 cGy/h. Three groups were employed: single dose radiation group (SDR), fractionated dose radiation group (FDR) by 2Gy/f and continuous low dose rate radiation group (CLDR). Four radiation doses 2, 4, 6 and 8Gy were chosen and cells without irradiation as the control. The responses of CL187 cells to distinct modes of radiation were evaluated by the colony-forming assay, cell cycle progression as well as apoptosis analysis. In addition, we detected the expression patterns of DNA-PKcs, Ku70 and Ku80 by Western blotting.ResultsThe relative biological effect for 125I seeds compared with 6 MV X-ray was 1.42. 48 hrs after 4Gy irradiation, the difference between proportions of cells at G2/M phase of SDR and CLDR groups were statistically significant (p = 0.026), so as the FDR and CLDR groups (p = 0.005). 48 hrs after 4Gy irradiation, the early apoptotic rate of CLDR group was remarkably higher than SDR and FDR groups (CLDR vs. SDR, p = 0.001; CLDR vs. FDR, p = 0.02), whereas the late apoptotic rate of CLDR group increased significantly compared with SDR and FDR group (CLDR vs. SDR, p = 0.004; CLDR vs. FDR, p = 0.007). Moreover, DNA-PKcs and Ku70 expression levels in CLDR-treated cells decreased compared with SDR and FDR groups.ConclusionsCompared with the X-ray high dose rate irradiation, 125I seeds CLDR showed more effective induction of cell apoptosis and G2/M cell cycle arrest. Furthermore, 125I seeds CLDR could impair the DNA repair capability by down-regulating DNA-PKcs and Ku70 expression.

The Direct Biologic Effects of Radioactive 125I Seeds on Pancreatic Cancer Cells PANC-1, at Continuous Low-Dose Rates

The relative biologic effectiveness of model 6711 125I seeds (Ningbo Junan Pharmaceutical Technology Company,Ningbo, China) and their effects on growth, cell cycle, and apoptosis in human pancreatic cancer cell line PANC-1 were examined in the present study. PANC-1 cells were exposed to the absorbed doses of 1, 2, 4, 6, 8, and 10 Gyeither with 125I seeds (initial dose rate, 2.59 cGy=h) or with 60Co g-ray irradiation (dose rate, 221 cGy=min),respectively. Significantly greater numbers of apoptotic PANC-1 cells were detected following the continuouslow-dose-rate (CLDR) irradiation of 125I seeds, compared with cells irradiated with identical doses of 60Co g-ray. The D(0) for 60Co g-ray and 125I seed irradiation were 2.30 and 1.66, respectively. The survival fraction after 125Iseed irradiation was significantly lower than that of 60Co g-ray, with a relative biologic effectiveness of 1.39.PANC-1 cells were dose dependently arrested in the S-phase by 60Co g-rays and in the G2=M phase by 125I seeds,24 hour after irradiation. CLDR irradiation by 125I seeds was more effective in inducing cell apoptosis in PANC-1cells than acute high-dose-rate 60Co g irradiation. Interestingly, CLDR irradiation by 125I seeds can cause PANC-1cell-cycle arrest at the G2=M phase and induce apoptosis, which may be an important mechanism underlying 125Iseed-induced PANC-1 cell inhibition.

Method of simulation of low dose rate for total dose effect in 0.18 μm CMOS technology

Three methods for simulating low dose rate irradiation are presented and experimentally verified by using 0.18 μm CMOS transistors. The results show that it is the best way to use a series of high dose rate irradiations, with 100 °C annealing steps in-between irradiation steps, to simulate a continuous low dose rate irradiation. This approach can reduce the low dose rate testing time by as much as a factor of 45 with respect to the actual 0.5 rad (Si)/s dose rate irradiation. The procedure also provides detailed information on the behavior of the test devices in a low dose rate environment.

The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells

BackgroundTo investigate the effectiveness and mechanism of 125I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro.MethodsThe CL187 cell line was exposed to radiation of 60Coγ ray at high dose rate of 2 Gy/min and 125I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under 125I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI) staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR) and Raf under continuous low dose rate irradiation (CLDR) and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence.ResultsThe relative biological effect (RBE) for 125I seeds compared with 60Co γ ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% ± 1.63%, 32.58% ± 3.61%, and 46.27% ± 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% ± 0.19%. G2/M cell cycle arrests of CL187 cancer cells were 42.59% ± 3.21%, 59.84% ± 4.96%, and 34.61% ± 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% ± 2.53%. P < 0.05 vs. control groups by Student's t-test were found in every treated group both in apoptosis and in G2/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change.Conclusion125I seeds resulted in more effective inhibition than 60Co γ ray high dose rate irradiation in CL187 cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could influence the proliferation of cells via MAPK signal transduction.

Relationship of HepG2 cell sensitivity to continuous low dose-rate irradiation with ATM phosphorylation

Objective To investigate the change of ATM phosphorylation in HepG2 cells and its effect on HepG2 cell survival under a continuous low dose-rate irradiation.

Radiobiological responses for two cell lines following continuous low dose-rate (CLDR) and pulsed dose rate (PDR) brachytherapy

The iso-effective irradiation of continuous low-dose-rate (CLDR) irradiation was compared with that of various schedules of pulsed dose rate (PDR) irradiation for cells of two established human lines, T-47D and NHIK 3025. Complete single-dose response curves were obtained for determination of parameters α and β by fitting of the linear quadratic formula. Sublethal damage repair constants µ and T1/2 were determined by split-dose recovery experiments. On basis of the acquired parameters of each cell type the relative effectiveness of the two regimens of irradiation (CLDR and PDR) was calculated by use of Fowler's radiobiological model for iso-effect irradiation for repeated fractions of dose delivered at medium dose rates. For both cell types the predicted and observed relative effectiveness was compared at low and high iso-effect levels. The results indicate that the effect of PDR irradiation predicted by Fowlers model is equal to that of CLDR irradiation for both small and large doses with T-47D cells. With NHIK 3025 cells PDR irradiation induces a larger effect than predicted by the model for small doses, while it induces the predicted effect for high doses. The underlying cause of this difference is unclear, but cell-cycle parameters, like G2-accumulation is tested and found to be the same for the two cell lines.

The biological effect of pentoxifylline on the survival of human head and neck cancer cells treated with continuous low and high dose-rate irradiation

The aim of this study was to compare the radiosensitivity effect of the G2/M arrest-abrogating substance, pentoxifylline (PTX), with high dose-rate irradiation (HDRI) and low dose-rate irradiation (LDRI), during which DNA repair and cell proliferation occur. Three squamous cell carcinoma cell lines, FaDu, RPMI 2650 and SCC-61, with differences in genomic imbalance and intrinsic radiosensitivity, were irradiated with 140 cGy/min (HDRI) and 0.7 cGy/min (LDRI) in the presence and absence of 2.0 mM PTX. The surviving fraction at 2.0 Gy (SF2) and cell-cycle phase distribution were assessed by DNA flow cytometry analysis and bromodeoxyuridine incorporation. With HDRI and LDRI the SF2 of FaDu cells decreased by 38.5% and 27.6%, respectively, while the corresponding figures for RPMI 2650 were 28.5% and 48.5%, and for SCC-61 were 44.2% and 28.6%. Increases in G2 populations were evident after both HDRI and LDRI of all cell lines. The enhancement in the cytotoxic effect of PTX was statistically significant after HDRI as well as after LDRI in all three cell lines. We therefore conclude that PTX in combination with LDRI is worth further study, both in vitro, for disclosing underlying mechanisms, and in vivo, to confirm the findings.

Dose rate dependence of the relative biological effectiveness of 103Pd for continuous low dose rate irradiation of BA1112 rhabdomyosarcoma cells in vitro relative to acute exposures

Purpose: To measure the relative biological effectiveness (RBE) of continuous low dose rate irradiation (CLDRI) using 103Pd sources relative to acute high dose rate irradiations (AHDRI) from a 250 kVp x-ray beam and an x-ray beam having an equivalent mono-energetic photon energy equal to the average energy of the 103Pd source for BA1112 rhabdomyosarcoma cells.Materials and methods: A customized 103Pd irradiator was built to provide CLDRI using 103Pd at different dose rates relevant to clinical interstitial brachytherapy to BA1112 rhabdomyosarcoma cells growing in exponential phase in culture. A special x-ray beam that simulates the photon energies emitted by the 103Pd source was also developed to provide acute high dose rate irradiation at those energies. Cell survival curves from different irradiation conditions were measured. The RBE with respect to AHDRI using standard 250 kVp x-rays was determined from the doses required to achieve a cell surviving faction of 0.01.Results: For acute irradiation, the RBE of the x-rays simulating 103Pd was 1.24 relative to 250 kVp x-rays. A profound dose rate effect was observed at low dose rates in the range of 6.8 – 14.4 cGy/h that are typical of permanent interstitial brachytherapy. At cell-surviving fraction of 0.01, the RBE of CLDRI at 6.8 and 14.4 cGy/h using 103Pd sources was reduced by a factor of 3 and 2, respectively, relative to the acute exposure. This observation is in good agreement with recent in vivo tumor cure studies performed on BA1112 tumor.Conclusion: The relative biological effectiveness of the photons emitted by 103Pd depends on both the linear energy transfer (LET) of the low energy photons and the dose rate of the irradiation. The higher LET of 103Pd photons is biologically more effective in killing BA1112 tumor cells compared to conventional 250 kVp x-rays when both are delivered at the same dose rate. But the gain in RBE that results from the higher LET can be quickly negated by the reduced dose rate of the irradiation.

Development of a rat solid tumor model for continuous low-dose-rate irradiation studies using 125I and 103Pd sources

Purpose To develop an experimental technique for studying the radiobiology of continuous low-dose-rate irradiation (CLDRI) using clinical brachytherapy sources emitting low energy photons for a rat solid tumor model. Methods and materials BA1112 tumors were grown between the ears of 14-week-old male WAG/Rij rats by interdermal inoculation. A radioactive source afterloading system, which consists of a lightweight helmet sutured to the rat and a nine-source polystyrene applicator, was fabricated for in vivo tumor irradiation by 125I and 103Pd brachytherapy sources. This system has a 12 × 12 mm opening in the center to accommodate the tumor and its growth during irradiation (the diameter of a typical BA1112 tumor was about 6 mm when radiation was applied). The spatial locations of the nine sources were optimized to produce an as uniform as possible three-dimensional dose distribution to the central portion of the applicator for both the 125I and 103Pd sources. Absolute dose delivered by the applicator was verified by point dose measurements using calibrated TLD in a polystyrene phantom that mimics the scattering environment of the tumor on the rat. Results The feasibility of tumor cure experiments using the experimental technique presented in this work was demonstrated. The technique was used to study the influence of initial dose rate on the in vivo tumor cure probability of BA1112 tumors irradiated by 125I and 103Pd sources at dose rates varying from 8–20 cGy/h. The technique was also used for studying the in vitro tumor cell survival following in vivo CLDRI irradiation of the tumor. Conclusion An experimental technique using an in vivo tumor model has been developed for studying the radiobiological effects of continuous low-dose-rate irradiations using 125I sources alone, 103Pd sources alone, or a mixture of 125I and 103Pd sources.

Biologically effective dose (BED) for interstitial seed implants containing a mixture of radionuclides with different half-lives

Purpose: To develop a tool for evaluating interstitial seed implants that contain a mixture of radionuclides with different half-lives and to demonstrate its utility by examining the clinical implications of prescribing to an isodose surface for such an implant. Methods and Materials: A linear-quadratic model for continuous low dose rate irradiation was developed for permanent implants containing a mixture of radionuclides. Using a generalized equation for the biologically effective dose (BED), the effects of cell proliferation and sublethal damage repair were examined systematically for implants containing a mixture of radionuclides. A head-and-neck permanent seed implant that contained a mixture of 125I and 103Pd seeds was used to demonstrate the utility of the generalized BED. Results: An equation of BED for implants containing a mixture of radionuclides with different half-lives was obtained. In such an implant, the effective cell kill was shown to depend strongly on the relative dose contributions from each radionuclide type; dose delivered by radionuclides with shorter half-life always resulted in more cell kill for any given sublethal damage repair and cell proliferation rates. Application of the BED formula to an implant containing a mixture of 125I and 103Pd seeds demonstrates that the conventional dose prescription to an isodose surface is not unique for such an implant. When the prescription dose was based on existing clinical experience of using 125I seeds alone, mixing 103Pd seeds with 125I seeds would increase the cell kill. On the other hand, if the prescription dose were based on existing clinical experience of using 103Pd seeds alone, mixing 125I seeds with 103Pd seeds in the same implant would create radiobiologically “cold” spots (i.e., an increase in cell survival) at locations where a major portion of the prescription dose is contributed by the 125I seeds. For fast-growing tumors, these “cold” spots can become significant. Conclusions: Total dose alone is no longer sufficient for a complete characterization of a permanent seed implant containing a mixture of radionuclides with different half-lives due to the presence of cell proliferation and sublethal damage repair in the protracted dose delivery. BED provides a tool for evaluating the radiobiologic effects of mixing different type of radionuclides in the same implant. When radionuclides of different half-lives are mixed in a permanent implant, using the dose prescription established from existing clinical experience of implants with the longer half-life radionuclide would help to avoid radiobiologic “cold” spots.

1075 Poster Equivalence of fractionated irradiation, continuous low dose rate irradiation, and I-131 exposure in human thyroid cancer cells grown as megacolonies

1075 Poster Equivalence of fractionated irradiation, continuous low dose rate irradiation, and I-131 exposure in human thyroid cancer cells grown as megacolonies

Experimental determination of the anisotropy function for the Model 200 “light seed” and derivation of the anisotropy constant based upon the linear quadratic model

Since the publication of the AAPM Task Group 43 report in 1995, Model 200 103Pd seed, which has been widely used in prostate seed implants and other brachytherapy procedures, has undergone some changes in its internal geometry resulting from the manufacturer's transition from lower specific activity reactor-produced 103Pd ("heavy seeds") to higher specific activity accelerator-produced radioactive material ("light seeds"). Based on previously reported theoretical calculations and measurements, the dose rate constants and the radial dose functions of the two types of seeds are nearly the same and have already been reported. In this work, the anisotropy function of the "light seed" was experimentally measured and an averaging method for the determination of the anisotropy constant from distance-dependent values of anisotropy factors is presented based upon the continuous low dose rate irradiation linear quadratic model for cell killing. The anisotropy function of Model 200 103Pd "light seeds" was measured in a Solid Water phantom using 1 X 1 x 1 mm micro LiF TLD chips at radial distances of 1, 2, 3, 4, 5, and 6 cm and at angles from 0 to 90 degrees with respect to the longitudinal axis of the seeds. At a radial distance of 1 cm, the measured anisotropy function of the 103Pd "light seed" is considerably lower than that of the 103Pd "heavy seed" reported in the TG 43 report. Our measured values at all radial distances are in excellent agreement with the results of a Monte Carlo simulation reported by Weaver, except for points along and near the seed longitudinal axis. The anisotropy constant of the 103Pd "light seed" was calculated using the linear quadratic biological model for cell killing in 30 clinical implants. For the model 200 "light seed," it has a value of 0.865. However, our biological model calculations lead us to conclude that if the anisotropy factors of an interstitial brachytherapy seed vary significantly over radial distances anisotropy constant should not be used as an approximation for anisotropy characteristics of a brachytherapy seed.

Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants—a bio-mathematical model

Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125I and 103Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T) = Vp (1 + M exp(−0.693T/Te)) where Vp is the prostate volume before implantation, M is the edema magnitude and Te is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. Ḋ = SkΛg(r) ϕ̄an/r2, where r is the distance between a seed and a given point. The distance r is now a function of time because of edema. The g(r) was approximated as 1/r0.4 and 1/r0.8 for 125I and 103Pd, respectively. By expanding the mathematical expression of the resultant dose rate in a Taylor series of exponential functions of time, the dose rate was made equivalent to that produced from multiple fictitious radionuclides of different decay constants and strengths. The biologically effective dose (BED) for an edematous prostate implant was then calculated using a generalized Dale equation. The cell surviving fraction was computed as exp(−αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125I and 103Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days and a magnitude of 50%, the edema increased tumour cell survival by about 1 and 2 orders of magnitude for 125I and 103Pd seed implants respectively. At the extreme (95% edema magnitude and an edema half-life of 30 days), the increase was more than 3 and 5 orders of magnitude for 125I and 103Pd seed implants respectively. The absolute increases were almost independent of TPDT and the prostate edema did not significantly change the effective treatment time. Tumour cell survival for prostate undergoing CLDRI using 125I or 103Pd seeds may be increased substantially due to the presence of edema caused by surgical trauma. This effect appears to be more pronounced for 103Pd than 125I because of the shorter half-life of 103Pd. If significant edema is observed post implantation, then a boost to the prostate using external beam radiotherapy may be considered as a part of the treatment strategy.