Radiochromic film (RCF) has several advantageous characteristics which make it an attractive dosimeter for many clinical tasks in radiation oncology. However, knowledge of and strict adherence to complicated protocols in order to produce accurate measurements can prohibit RCF from being widely adopted in the clinic. The purpose of this study was to outline some simple and straightforward RCF fundamentals in order to help clinical medical physicists perform accurate RCF measurements. We describe a process and methodology successfully used in our practice with the hope that it saves time and effort for others when implementing RCF in their clinics. Two RCF analysis software programs which differ in cost and complexity, the commercially available FilmQA Pro package and the freely available ImageJ software, were used to show the accuracy, consistency and limitations of each. The process described resulted in a majority of the measurements across a wide dose range to be accurate within ± 2% of the intended dose using either FilmQA Pro or ImageJ.

Purpose: Relative biological effectiveness (RBE) accounts for the differences in biological effect from different radiation types. The RBE for proton therapy remains uncertain, as it has been shown to vary from the clinically used value of 1.1. In this work we investigated the RBE of protons and correlated the biological differences with the underlying physical quantities. Materials and Methods: Three cell lines were irradiated (CHO, Chinese hamster ovary; A549, human lung adenocarcinoma; and T98, human glioma) and assessed for cell survival by using clonogenic assay. Cells were irradiated with 71- and 160-MeV protons at depths along the Bragg curve and 6-MV photons to various doses. The dose-averaged lineal energy (truey‒normalD) was measured under similar conditions as the cells by using a microdosimeter. Dose-averaged linear energy transfer (LETd) was also calculated by using Monte Carlo (MC) simulations. Survival data were fit by using the linear quadratic model. The RBE values were calculated by comparing the physical dose (D6MV/Dp) that results in 50% (RBE0.5) and 10% (RBE0.1) cell survival, and survival after 2 Gy (RBE2Gy). Results: Proton RBE values ranged from 0.89 to 2.40. The RBE for all 3 cell lines increased with decreasing proton energy and was higher at 50% survival than at 10% survival. Additionally, both A549 and T98 cells generally had higher RBE values relative to the CHO cells, indicating a greater biological response to protons. An increase in RBE corresponded with an increase in truey‒normalD and LETd. Conclusion: Proton RBE was found to depend on mean proton energy, survival end point, and cell type. Changes in both truey‒normalD and LETd were also found to impact proton RBE values, but consideration of the energy spectrum may provide additional information. The RBE values in this study vary greatly, indicating the clinical value of 1.1 may not be suitable in all cases.

In 2002 we fully implemented clinically a commercial Monte Carlo based treatment planning system for electron beams. The software, developed by MDS Nordion (presently Nucletron), is based on Kawrakow's VMC++ algorithm. The Monte Carlo module is integrated with our Theraplan Plustrade mark treatment planning system. An extensive commissioning process preceded clinical implementation of this software. Using a single virtual 'machine' for each electron beam energy, we can now calculate very accurately the dose distributions and the number of MU for any arbitrary field shape and SSD. This new treatment planning capability has significantly impacted our clinical practice. Since we are more confident of the actual dose delivered to a patient, we now calculate accurate three-dimensional (3D) dose distributions for a greater variety of techniques and anatomical sites than we have in the past. We use the Monte Carlo module to calculate dose for head and neck, breast, chest wall and abdominal treatments with electron beams applied either solo or in conjunction with photons. In some cases patient treatment decisions have been changed, as compared to how such patients would have been treated in the past. In this paper, we present the planning procedure and some clinical examples.

Given a fixed spot spacing of ≤4 mm, plan quality decreases as min-MU increased beyond 0.0020. The effect of min-MU needs to be taken into consideration while planning proton therapy treatments.

Various types of radiation are utilized in the treatment of cancer. Equal physical doses of different radiation types do not always result in the same amount of biological damage. In order to account for these differences, a scaling factor known as the relative biological effectiveness (RBE) can be used. 137Cesium (137Cs) has been used as a source of radiation in a significant body of radiation therapy research. However, high-energy X-rays, such as 6 MV X-rays, are currently used clinically to treat patients. To date, there is a gap in the literature regarding the RBE comparison of these two types of radiation. Therefore, the purpose of this study was to investigate the RBE of 137Cs relative to that of 6 MV X-rays. To determine the RBE, five cell lines were irradiated [Chinese hamster ovary (CHO); human lung adenocarcinoma (A549); human glioma (U251); human glioma (T98); and human osteosarcoma (U2OS)] by both types of radiation and assessed for cell survival using a clonogenic assay. Three of the five cell lines resulted in RBE values of ~1.00 to within 11% for all survival fractions, showing the physical and biological dose for these two types of radiation were equivalent. The other two cell lines gave RBE values differing from 1.00 by up to 36%. In conclusion, the results show the range in biological effect seen between cell lines, and therefore cell type must be considered when characterizing RBE.

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Proton Bragg peak irradiation has a higher ionizing density than conventional photon irradiation or the entrance of the proton beam profile. Whether targeting the DNA damage response could enhance vulnerability to the distinct pattern of damage induced by proton Bragg peak irradiation is currently unknown. Here we performed genetic or pharmacologic manipulation of key DNA damage response elements and evaluated DNA damage signaling, DNA repair, and tumor control in cell lines and xenografts treated with the same physical dose across a radiotherapy linear energy transfer spectrum. Radiotherapy consisted of 6 MV photons and the entrance beam or Bragg peak of a 76.8 MeV spot scanning proton beam. More complex DNA double strand breaks induced by Bragg peak proton irradiation preferentially underwent resection and engaged homologous recombination (HR) machinery. Unexpectedly, the ATM inhibitor AZD0156 but not an inhibitor of ATR rendered cells hypersensitive to more densely ionizing proton Bragg peak irradiation. ATM inhibition blocked resection and shunted more double strand breaks to processing by toxic ligation through nonhomologous end-joining, whereas loss of DNA ligation via XRCC4 or Lig4 knockdown rescued resection and abolished the enhanced Bragg peak cell killing. Proton Bragg peak monotherapy selectively sensitized cell lines and tumorxenografts with inherent HR defects, and the repair defect induced by ATM inhibitor coadministration showed enhanced efficacy in HR proficient models. In summary, inherent defects in HR or administration of an ATM inhibitor in HR proficient tumors selectively enhance the relative biological effectiveness of proton Bragg peak irradiation.