Open Field Irradiation Research Articles

Spectral characterization and comparison of EBT3, EBT4, and EBT-XD radiochromic films

This study analyzed the spectral response of EBT3, EBT4, and EBT-XD radiochromic films using absorption spectroscopy. The primary focus was on characterizing the evolution of spectral signatures across a range of absorbed doses, thereby elucidating the unique dose-dependent response profiles of each film type. Ten samples of each film type were subjected to open field irradiation within their designated dose ranges (1-20 Gy for EBT3 and EBT4, 1-50 Gy for EBT-XD). The corresponding absorption spectra were recorded and studied via decomposition and parameterization of dose-dependent spectral features. Lorentzian profiles were employed for spectral decomposition. Each film type displayed unique spectral signatures with distinct absorption peaks: nine for EBT3, eleven for EBT4, and twelve constituent profiles for EBT-XD. Notably, the EBT4 film demonstrated a slight difference in the blue part of the absorption spectrum and a change in the response, relative to its EBT3 predecessor. Orientation dependence of the film spectra was most pronounced for the EBT3 film type, followed by a declining trend across EBT4 and EBT-XD films. Absorption spectroscopy portrayed distinct spectral fingerprints of the studied film types, aiding the selection of the most suitable film for specific applications.

2D mapping of radiation dose and clonogenic survival for accurate assessment of in vitro X-ray GRID irradiation effects

Spatially fractionated radiation therapy (SFRT or GRID) is an approach to deliver high local radiation doses in an ‘on-off’ pattern. To better appraise the radiobiological effects from GRID, a framework to link local radiation dose to clonogenic survival needs to be developed. A549 lung cancer cells were irradiated in T25 cm2 flasks using 220 kV x-rays with an open field or through a tungsten GRID collimator with periodical 5 mm openings and 10 mm blockings. Delivered nominal doses were 2, 5, and 10 Gy. A novel approach for image segmentation was used to locate the centroid of surviving colonies in scanned images of the cell flasks. GafchromicTM film dosimetry (GFD) and FLUKA Monte Carlo (MC) simulations were employed to map the dose at each surviving colony centroid. Fitting the linear-quadratic (LQ) function to clonogenic survival data for open field irradiation, the expected survival level at a given dose level was calculated. The expected survival levels were then mapped together with the observed levels in the GRID-irradiated flasks. GFD and FLUKA MC gave similar dose distributions, with a mean peak-to-valley dose ratio of about 5. LQ-parameters for open field irradiation gave Gy−1 and Gy−2. The mean relative percentage deviation between observed and predicted survival in the (peak; valley) dose regions was (4.6; 3.1) %, (26.6; −1.0) %, and (129.8; −2.3) % for 2, 5 and 10 Gy, respectively. In conclusion, a framework for mapping of surviving colonies following GRID irradiation together with predicted survival levels from homogeneous irradiation was presented. For the given cell line, our findings indicate that GRID irradiation causes reduced survival in the peak regions compared to an open field configuration.

Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors

Introduction: Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear–quadratic cell survival model.Material and Methods: HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed.Results: The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1–5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2t) value of 0·5. In addition, the mean ± SD of TR values for SF2t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2t value of 0.5.Conclusion: HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

TU‐H‐BRC‐07: Therapeutic Benefit in Spatially Fractionated Radiotherapy (GRID) Using Helical Tomotherapy

Purpose:The aim of this project is to study the therapeutic ratio (TR) for helical Tomotherapy (HT) based spatially fractionated radiotherapy (GRID). Estimation of TR was based on the linear‐quadratic cell survival model by comparing the normal cell survival in a HT GRID to that of a uniform dose delivery in an open‐field for the same tumor survival.Methods:HT GRID plan was generated using a patient specific virtual GRID block pattern of non‐divergent, cylinder shaped holes using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT GRID irradiation to an open field irradiation with an equivalent dose that result in the same tumor cell SF. The ratio was estimated from DVH data on ten patient plans with deep seated, bulky tumor approved by the treating radiation oncologist. Dependence of the TR values on radio‐sensitivity of the tumor cells and prescription dose were also analyzed.Results:The mean ± standard deviation (SD) of TR was 4.0±0.7 (range: 3.1 to 5.5) for the 10 patients with single fraction dose of 20 Gy and tumor cell SF of 0.5 at 2 Gy. In addition, mean±SD of TR = 1±0.1 and 18.0±5.1 were found for tumor with SF of 0.3 and 0.7, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the TR to 2.0±0.2 and 1.2±0.04 for a tumor cell SF of 0.5 at 2 Gy. In this study, the SF of normal cells was assumed to be 0.5 at 2 Gy.Conclusion:HT GRID displayed a significant therapeutic advantage over uniform dose from an open field irradiation. TR increases with the radioresistance of the tumor cells and with prescription dose.

In vivo effects of lattice radiation therapy on local and distant lung cancer: potential role of immunomodulation.

Radiation is a potent immune-modulator that elicits cell death upon tumor, stromal and angiogenic compartments of tumor microenvironment. Here, we test a novel approach of high-dose radiation delivery using three dimensional volume based lattice radiation therapy (LRT) to understand the impact of different volume irradiation in eliciting both local and metastatic/distant tumor control through modulation of tumor immune micro-environment. To study such effects of LRT, tumors were implanted in both hind legs of C57BL/6 mice using Lewis lung carcinoma 1 (LLC1) cells. Mice were divided into five groups: untreated; partial tumor volume groups included two 10% vertices, one 20% vertex and one 50% vertex of the total tumor volume; and 100% open-field irradiation. Tumors implanted in the left flank were irradiated with a single dose of 20 Gy while the tumors in the right flank were unirradiated. Tumor growth and regression as well as immune responses (such as Th1 and Th2; T-cell infiltration) were determined after radiation treatment. Results demonstrated that both 100% open-field irradiation and 20% volume irradiation (in two 10% volumes) resulted in significant growth delay in the irradiated tumor. Further, all types of radiation exposures, partial or 100% volume, demonstrated distal effectiveness, however, 20% volume irradiation (in two 10% volumes) and 50% tumor volume irradiation led to maximum growth delay. Mice treated with partial tumor volume radiation induced a robust IFN-γ and Th1 response when compared to whole-tumor irradiation and down-modulated Th2 functions. The presence of increased CD3+ cells and TRAIL in partially irradiated tumor volumes correlated well with tumor growth delay. Further, serum obtained from any of the LRT treated mice caused growth inhibition of endothelial cells when compared to serum obtained from either untreated or open-field irradiated groups. These results indicate that high-dose partial volume irradiation can cause an improved distant effect than the total tumor volume irradiation through activating the host immune system.

Monitor units are not predictive of neutron dose for high-energy IMRT

BackgroundDue to the substantial increase in beam-on time of high energy intensity-modulated radiotherapy (>10 MV) techniques to deliver the same target dose compared to conventional treatment techniques, an increased dose of scatter radiation, including neutrons, is delivered to the patient. As a consequence, an increase in second malignancies may be expected in the future with the application of intensity-modulated radiotherapy. It is commonly assumed that the neutron dose equivalent scales with the number of monitor units.MethodsMeasurements of neutron dose equivalent were performed for an open and an intensity-modulated field at four positions: inside and outside of the treatment field at 0.2 cm and 15 cm depth, respectively.ResultsIt was shown that the neutron dose equivalent, which a patient receives during an intensity-modulated radiotherapy treatment, does not scale with the ratio of applied monitor units relative to an open field irradiation. Outside the treatment volume at larger depth 35% less neutron dose equivalent is delivered than expected.ConclusionsThe predicted increase of second cancer induction rates from intensity-modulated treatment techniques can be overestimated when the neutron dose is simply scaled with monitor units.

A dosimetric phantom study of dose accuracy and build-up effects using IMRT and RapidArc in stereotactic irradiation of lung tumours

Background and purposeStereotactic lung radiotherapy (SLRT) has emerged as a curative treatment for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC) and the use of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc treatments (VMAT) have been proposed as the best practical approaches for the delivery of SLRT. However, a large number of narrow field shapes are needed in the dose delivery of intensity-modulated techniques and the probability of underdosing the tumour periphery increases as the effective field size is decreased. The purpose of this study was to evaluate small lung tumour doses irradiated by intensity-modulated techniques to understand the risk for dose calculation errors in precision radiotherapy such as SLRT.Materials and methodsThe study was executed with two heterogeneous phantoms with targets of Ø1.5 and Ø4.0 cm. Dose distributions in the simulated tumours delivered by small sliding window apertures (SWAs), IMRT and RapidArc treatment plans were measured with radiochromic film. Calculation algorithms of pencil beam convolution (PBC) and anisotropic analytic algorithm (AAA) were used to calculate the corresponding dose distributions.ResultsPeripheral doses of the tumours were decreased as SWA decreased, which was not modelled by the calculation algorithms. The smallest SWA studied was 2 mm, which reduced the 90% isodose line width by 4.2 mm with the Ø4.0 cm tumour as compared to open field irradiation. PBC was not able to predict the dose accurately as the gamma evaluation failed to meet the criteria of ±3%/±1 mm on average in 61% of the defined volume with the smaller tumour. With AAA the corresponding value was 16%. The dosimetric inaccuracy of AAA was within ±3% with the optimized treatment plans of IMRT and RapidArc. The exception was the clinical RapidArc plan with dose overestimation of 4%.ConclusionsOverall, the peripheral doses of the simulated lung tumours were decreased by decreasing the SWA. To achieve adequate surface dose coverage to small lung tumours with a difference less than 1 mm in the isodose line radius between the open and modulated field, a larger than 6 mm SWA should be used in the dose delivery of SLRT.

Measurements to predict the time of target replacement of a helical tomotherapy

Intensity‐modulated radiation therapy (IMRT) requires more beam‐on time than normal open field treatment. Consequently, the machines wear out and need more spare parts. A helical tomotherapy treatment unit needs a periodical tungsten target replacement, which is a time consuming event. To be able to predict the next replacement would be quite valuable. We observed unexpected variations towards the end of the target lifetime in the performed pretreatment measurements for patient plan verification. Thus, we retrospectively analyze the measurements of our quality assurance program. The time dependence of the quotient of two simultaneous dose measurements at different depths within a phantom for a fixed open field irradiation is evaluated. We also assess the time‐dependent changes of an IMRT plan measurement and of a relative depth dose curve measurement. Additionally, we performed a Monte Carlo simulation with Geant4 to understand the physical reasons for the measured values. Our measurements show that the dose at a specified depth compared to the dose in shallower regions of the phantom declines towards the end of the target lifetime. This reproducible effect can be due to the lowering of the mean energy of the X‐ray spectrum. These results are supported by the measurements of the IMRT plan, as well as the study of the relative depth dose curve. Furthermore, the simulation is consistent with these findings since it provides a possible explanation for the reduction of the mean energy for thinner targets. It could be due to the lowering of low energy photon self‐absorption in a worn out and therefore thinner target. We state a threshold value for our measurement at which a target replacement should be initiated. Measurements to observe a change in the energy are good predictors of the need for a target replacement. However, since all results support the softening of the spectrum hypothesis, all depth‐dependent setups are viable for analyzing the deterioration of the tungsten target. The suggested measurements and criteria to replace the target can be very helpful for every user of a TomoTherapy machine.PACS numbers: 87.55.N‐, 87.55.Qr, 87.55.T‐, 87.56.bd

Abstract LB-359: Effects of space time fractionated radiation on normal tissue toxicity

Abstract Purpose: Space-Time Fractionation (STF) proposed herein is a novel concept based on the long-standing clinical data of Spatially Fractionated GRID Radiotherapy. The conventional GRID therapy, or the recently proposed LATTICE therapy is generally intended for single-fraction treatment. The STF extends the concept to definitive, fractionated radiation therapy, aiming at maximum tumor control with significantly reduced normal tissue toxicity. Methods: In this fractionation scheme, treatment volume was divided into segments or slices, consecutively numbered 1,2,3,4,5,6,7,8…, with typical slice thickness of 1–2 cm. This formed the spatially fractionated structure. Alternated time fraction numbers (time fractionation), were delivered to their corresponding spatial segments, i.e., the odd fractions 1,3,5,7,9, … were delivered to spatial slices 1,3,5,7… and the even fractions 2,4,6,8,… were delivered to spatial slices 2,4,6,8. To demonstrate the normal tissue sparing effect, three groups of C57/BL6 mice (16/group) were used: untreated (UT); STF, 500cGy/fx × 10 (5x Position 1 + 5x Position 2) delivered through a block of multiple equally spaced open/closed slits of 2 mm width; Conventional 310cGy × 10, open field. The two irradiated groups having the same biological equivalent dose (BED) delivered to the whole abdomen. Two mice were sacrificed immediately, 24h and 7 days after radiation and intestines, kidneys and liver tissues were collected. The formalin fixed tissues were stained with hematoxylin and eosin and pathological analysis was carried out to assess the damage. Remaining mice were followed for overall survival. Results: Although mice from all the treatment groups survived for at least 90 days after the treatment, pathological analysis of the tissues clearly showed maximal damage with open field irradiation compared to STF. Intestinal epithelial cells from open field irradiated mice showed severe damage with cell loss in intestinal crypts and thus villi were shortened and blunted. Even one month after irradiation, amphophilic cytoplasm, variation in the size of the nuclei, clumping of chromatin and prominent nucleoli were observed in the intestinal tissues. Number of mitotic figures increased with time indicating regeneration but recovery was only partial. In case of the STF irradiated mice, negligible damage was observed at all the time points studied. Again, kidney tissues obtained from open field irradiated mice showed highly disorganized tubule cells structure compared to kidney tissue from mice subjected to STF. Currently, we are assessing the effects in the liver tissue. Conclusions: Results show that STF could be a new approach in treating advanced/recurrent cancers with improved local tumor control without increasing normal tissue toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-359. doi:10.1158/1538-7445.AM2011-LB-359

WE-C-AUD B-07: Comparison of Time-Fractionated and Space-Fractionated Radiotherapy

Purpose: To study the potential advantage of space-fractionation (SF) over time-fractionation (TF) in radiotherapy. Method and Materials: The back skin of mouse was stretched and fixed with two thin titanium plates, exposing a circular window of 1.5cm in diameter. Tumor cells were implanted at the center of the window. When the tumor grew to 6mm, the window was irradiated with either TF or SF schemes: open field irradiation of 13Gy per fraction each day for four days for 52Gy total dose; or 52Gy per fraction through 2mm×2mm grid covering 25% of the open field, but then shifting the grid each day to a previously untreated area so that the entire window received an acute dose of 52Gy over four days. The animals were observed for 51 days and the number of hair within the irradiation window was counted after the mice were euthanized. Results: 17 animals in the TF arm and 12 in the SF arm completed the study. After four days of irradiation, the tumors shrank to completely disappear within 2–3 days for both cohorts. Similar skin reaction and complete fur loss on both sides of the window were observed for both arms. The fur started to grow back at 4 weeks and was white rather than the original gray color. On the beam entry side, the average number of fur was 452 for the TF arm and 860 for the SF arm (p=0.0003). On the beam exit side, the number of fur strands was 223 for the TF arm and 730 for the SF arm (p=0.0001). These results strongly indicate less skin damage with SF. Conclusion: SF allowed us to deliver a higher acute dose but showed much less late-term normal tissue toxicities. The results show strong evidence that SF has protective effects to normal structures.

A Measurement and Analysis of Buildup Region Dose for Open Field Photon Beams (Cobalt-60 through 24 MV)

The central axis depth dose in the build-up region (surface to dmax) of single open field photon beams (cobalt-60 through 24MV) has been measured utilizing parallel plate and extrapolation chamber methodology. These data were used to derive, for a prescription dose of 100cGy, values of surface dose, the maximum value of dose along the central axis (Dmax) and the depth (nearest the surface) at which 90% of the prescription dose occurs (d90). For both single and parallel opposed pair (POP) open field configurations, data are presented at field sizes of 5 × 5, 15 × 15 and 25 × 25cm2 for prescription depths of 10, 15 and 20cm (midplane for POP). For the treatment machines, field sizes, and prescription depths studied, it is possible to conclude that: for single open field irradiation, surface dose values (as a percentage of the prescription dose) can be either low (<10%) or comparable to the prescription dose itself; for POP open fields, surface dose values are relatively independent of photon energy and midplane depth, and range between 30% and 70% of prescription dose, being principally dependent on field size; the depth of the initial 90cGy point for a prescription dose of 100cGy, d90, was larger for POP fields. For either single or POP open field treatments, d90 was always less than 22mm, while for 6MV or less, values of d90 were less than 4mm; Dmax values can be very large (e.g., above 300 cGy) for certain treatment situations and are reduced significantly for POP treatments; for open field POP treatments, the percent reduction in Dmax with each increment in beam energy above 10MV is reduced over that seen at 10MV or less and, possibly, this further reduction may be clinically insignificant; for open field POP treatments, changes in surface dose, d90 and Dmax with beam energy above 10MV do not suggest, with regard to these specific build-up curve parameters, any obvious advantage for treatment with beam energies greater than 10MV for the specific machines and situations studied.

Minimal long-term cardiopulmonary dysfunction following treatment for Hodgkin's disease

We studied the long term cardiopulmonary function, at rest and during exercise, of 57 patients who were at least 1 year (mean 5 years) post-treatment for Hodgkin's disease. To establish the maximum degree of dysfunction we studied 40 patients who had extensive intrathoracic disease treated with radiotherapy alone (Exten-X; n = 20) or combined modality therapy (Exten-XC; n = 20). Patients without intrathoracic disease given either prophylactic mantle therapy (Proph-X, n = 10) or no chest irradiation ( n = 7) were used as controls. An abnormal electrocardiogram, by virtue of a conduction defect, was observed in seven patients, six in the Exten-X or Exten-XC groups. Borderline abnormalities including ST-T changes, prolonged QT interval, or axis deviation occurred in 14 patients distributed evenly throughout the groups. Resting mean pulmonary function test values were normal in all treatment groups. Exercise tolerance, as indicated by peak oxygen consumption (VO2), was significantly lower for the Exten-XC group compared to Proph-X (p less than 0.01). However, the mean value of VO2 for group Exten-XC was only 15% below that predicted. Of the 12 patients with abnormally low VO2 (greater than 20% below their predicted value), 11 were in the Exten-X or Exten-XC group with no difference between the two groups. Patients who received radiotherapy to at least one lung field, using either the thin lung block technique or open field irradiation, had significantly lower exercise tolerance than those treated with full thickness blocks (p less than 0.05). Despite these abnormalities only a single patient complained of marked dyspnea. We conclude that extensive treatment to the mantle field, especially when followed by chemotherapy in patients with extensive intrathoracic Hodgkin's disease, can result in minimal cardiopulmonary dysfunction in approximately one-third of patients.

Ovarian carcinoma: A decade of progress

Significant and dramatic progress has been made in the diagnosis and treatment of women with ovarian carcinoma in the last 10 years, the results of which are now just being reflected in an increase in survival and cure rates. In early staged disease (Stage I and II) significant progress has been made concerning our understanding of the sites of subclinical metastasis when at surgery the tumor is clinically limited to the ovary or pelvis. A prospective study of 100 patients with Stages IA to IIB ovarian cancer who underwent restaging within 4 weeks of initial surgery will report this. Moreover, preliminary results of the first randomized therapeutic trials (melphalan versus observation; melphalan versus chromic phosphate [P-32]) in patients surgically staged and found to be Stage IA to IIB carcinoma will be discussed. For Stages IB to III, the 5-year survival rates comparing whole abdominal radiation by the moving strip technique to open field irradiation will be discussed. For advanced (Stage III and IV) ovarian carcinoma, the new techniques in debulking surgery will be illustrated. Finally, the significant progress in response rates, median duration of survival, disease-free survival, and 5-year survival rates made during the past 10 years will be presented. This will be done by comparing a unique group of 117 patients treated with melphalan alone, all of whom have been followed for 5 years or until death, to patients who received cisplatin combination chemotherapy--cyclophosphamide, hexamethylmelamine, Adriamycin (doxorubicin), and cisplatin (CHAD) or cisplatin, Adriamycin, and cyclophosphamide (PAC)--and have now been followed 3.4+ and 4+ years, respectively. What is clearly evident is that in the last decade there has been significant increase in response rates, median duration of survival, 3.4+-, 4+-, and 5-year survival rates and cure rates with the advent of debulking surgery and platinum-containing combination chemotherapy.