Adjustment of the lateral and longitudinal size of scanned proton beam spots using a pre-absorber to optimize penumbrae and delivery efficiency

In scanned-beam proton therapy, the beam spot properties, such as the lateral and longitudinal size and the minimum achievable range, are influenced by beam optics, scattering media and drift spaces in the treatment unit. Currently available spot scanning systems offer fewoptions for adjusting these properties. We investigated a method for adjusting the lateral and longitudinal spot size that utilizes downstream plastic pre-absorbers located near a water phantom. The spot size adjustment was characterized usingMonte Carlo simulations of a modified commercial scanned-beam treatment head. Our results revealed that the pre-absorbers can be used to reduce the lateral full width at half maximum (FWHM) of dose spots inwater by up to 14 mm, and to increase the longitudinal extent from about 1 mm to 5 mm at residual ranges of 4 cm and less. A large factor in manipulating the lateral spot sizes is the drift space between the preabsorber and the water phantom. Increasing the drift space from 0 cm to 15 cm leads to an increase in the lateral FWHM from 2.15 cm to 2.87 cm, at a waterequivalent depth of 1 cm. These findings suggest that this spot adjustment method may improve the quality of spot-scanned proton treatments. © 2010 Institute of Physics and Engineering in Medicine

Linear energy transfer dependence of Al2O3:C optically stimulated luminescence detectors exposed to therapeutic proton beams

Currently, there are no radiation detectors that can be used for routine measurements of linear energy transfer (LET) in particle therapy clinics. In this work, we characterized the LET dependence of Al2O3:C optically stimulated luminescence (OSL) detectors (OSLDs) exposed to therapeutic proton beams in order to evaluate their potential for clinical LET measurements. We evaluated OSLDs that were irradiated with an absorbed dose to water of 0.2 Gy in therapeutic proton beams with average energies ranging between approximately 25 MeV and 200 MeV, resulting in LET in water values between 0.45 and 2.29 keV/μm. We examined two properties of the OSL emission signal in terms of LET dependence: the signal intensities of the blue and ultraviolet (UV) emission bands, and the shapes of the OSL curves. We found that the signal intensity of the UV emission band increased consistently with LET within the range investigated, whereas the intensity of the blue emission band remained constant. Our results also demonstrated that the OSL curve shapes were more LET dependent for signals containing both the blue and UV emission bands than for signals containing only one of the bands. Both metrics we examined in this study - the relative UV/blue emission signal intensities and OSL curve shapes - show potential for LET detection in proton therapy

Ionization density dependence of the curve shape and ratio of blue to UV emissions of Al\u2082O\u2083:C optically stimulated luminescence detectors exposed to 6-MV photon and therapeutic proton beams

In this work we characterized the dose and linear energy transfer (LET) (ionization density) dependence of commercial Al\u2082O\u2083:C optically stimulated luminescence (OSL) detectors (OSLDs) exposed to clinical photon and proton beams. We characterized the dose-dependence of the OSL signal, OSL curve shape, and the relative intensities of the blue and ultraviolet (UV) OSL emission bands using different readout protocols and beam qualities. We irradiated OSLDs with absorbed doses ranging from 0.1 Gy to 100 Gy in a 6-MV photon beam and from 0.1 Gy to 50 Gy in 140- and 250-MeV proton beams. Readouts were done with both continuous-wave (CWOSL) and pulsed (POSL) stimulation. The linearity of the OSLD dose\u2013response depended on readout protocol and radiation type. Improved linearity was found for OSLDs irradiated with beams of increased LET, and for OSL signals containing only the blue emission band of Al\u2082O\u2083:C (which remained linear for doses up to 10 Gy for 140-MeV proton beam irradiations). The OSL curve shape did not vary with dose in the low-dose region (below 5 Gy depending on readout protocol), but beyond this, curves decayed more rapidly with increasing dose. Similarly, the ratio of blue to UV emission band intensities in the OSL signal did not vary with dose up to 5 Gy (depending on readout protocol), beyond which the ratio decreased with increasing dose. Because both the OSL curve shape and the ratio of blue to UV emission intensities have been investigated as potential parameters for measurements of LET, the constancy of these two quantities at doses relevant to radiotherapy is encouraging for the potential development of novel OSL methods to measure LET. Our findings are expected to contribute to the development of (i) improved readout protocols for commercially available Al\u2082O\u2083:C OSLDs and (ii) methods to measure radiation quality and LET.Peer reviewed: YesNRC publication: Ye

Non-homologous end joining repair pathway determines cell radiosensitivity in helium and carbon ion beams

Purpose: To highlight the importance of non-homologous end-joining (NHEJ) repair in governing a cell’s radiosensitivity to helium and carbon ion beams of varying linear energy transfer (LET).Method and Materials: We selected a pair of isogenic cancer cell lines with differing proficiency in non-homologous end joining (NHEJ) repair: M059K (NHEJ-proficient) and M059J (NHEJ-deficient) and as additional reference cell lines, we selected the H1299 non-small cell lung cancer and H460 large cell lung cancer cell lines. These cells were exposed to unmodulated helium and carbon ion beams of nominal energy 150 MeV/u (helium) and 290 MeV/u (carbon) and energy degraders were used to achieve LETs ranging from 2.2 to 60 keV/µm. We performed clonogenic assays to calculate the relative biological effectiveness (RBE) of each cell line in these conditions, relative to their survival in 6 MV x-rays, using the dose for 10% survival as the biological endpoint. To support the survival data, we performed immunohistochemical staining of DNA double strand break (DSB) markers (including γH2AX and 53BP1) 30 min and 24 h post irradiation to identify persistent radiation induced foci.Results: The RBE of the NHEJ-deficient M059J cell line showed significantly less LET dependence than the reference cell lines (increasing only to 1.37± 0.07 at 60 keV/μm for M059J versus 1.80 ± 0.10, 1.79 ± 0.04 and 1.98 ± 0.05 for M059K, H460 and H1299, respectively), despite M059J being more radiosensitive to all LETs. Preliminary analysis of foci data for proton-exposed cells indicate that the M059J cells have more persistent DSB repair foci 24 h post-irradiation, consistent with their deficiency in DNA DSB repair. Conclusions: Our results indicate that proficiency status in NHEJ is extremely important in determining how cell radiosensitivity varies with He- and C-ion LET.The 61st AAPM Annual Meeting and Exhibitio

Glutaminase Inhibition Radiosensitizes Non-Small Cell Lung Cancer Cells to X-rays and Protons

https://openworks.mdanderson.org/sumexp21/1035/thumbnail.jp

Dose escalation for locally advanced pancreatic cancer: How high can we go?

Purpose: There are limited treatment options for locally advanced, unresectable pancreatic cancer (LAPC) and no likelihood of cure without surgery. Radiation offers an option for local control, but radiation dose has previously been limited by nearby bowel toxicity. Advances in on-board imaging and treatment planning may allow for dose escalation not previously feasible and improve local control. In preparation for development of clinical trials of dose escalation in LAPC, we undertook a dosimetric study to determine the maximum possible dose escalation while maintaining known normal tissue constraints. Methods and Materials: Twenty patients treated at our institution with either SBRT or dose-escalated hypofractionated IMRT (DE-IMRT) were re-planned using dose escalated SBRT to 70 Gy in 5 fractions to the GTV and 40 Gy in 5 fractions to the PTV. Standard accepted organ at risk (OAR) constraints were used for planning. Descriptive statistics were generated for homogeneity, conformality, OAR's and GTV/PTV. Results: Mean iGTV coverage by 50 Gy was 91% (±0.07%), by 60 Gy was 61.3% (±0.08%) and by 70 Gy was 24.4% (±0.05%). Maximum PTV coverage by 70 Gy was 33%. Maximum PTV coverage by 60 Gy was 77.5%. The following organ at risk (OAR) constraints were achieved for 90% of generated plans: Duodenum V20 < 30 cc, V30 < 3 cc, V35 < 1 cc; Small Bowel V20 < 15 cc, V30 < 1 cc, V35 < 0.1 cc; Stomach V20 < 20 cc, V30 < 2 cc, V35 < 1 cc. V40 < 0.5 cc was achieved for all OAR. Conclusions: Dose escalation to 60 Gy is dosimetrically feasible with adequate GTV coverage. The identified constraints for OAR's will be used in ongoing clinical trials