B Bednarz

A review of dosimetry studies on external-beam radiation treatment with respect to second cancer induction

It has been long known that patients treated with ionizing radiation carry a risk of developing a second cancer in their lifetimes. Factors contributing to the recently renewed concern about the second cancer include improved cancer survival rate, younger patient population as well as emerging treatment modalities such as intensity-modulated radiation treatment (IMRT) and proton therapy that can potentially elevate secondary exposures to healthy tissues distant from the target volume. In the past 30 years, external-beam treatment technologies have evolved significantly, and a large amount of data exist but appear to be difficult to comprehend and compare. This review article aims to provide readers with an understanding of the principles and methods related to scattered doses in radiation therapy by summarizing a large collection of dosimetry and clinical studies. Basic concepts and terminology are introduced at the beginning. That is followed by a comprehensive review of dosimetry studies for external-beam treatment modalities including classical radiation therapy, 3D-conformal x-ray therapy, intensity-modulated x-ray therapy (IMRT and tomotherapy) and proton therapy. Selected clinical data on second cancer induction among radiotherapy patients are also covered. Problems in past studies and controversial issues are discussed. The needs for future studies are presented at the end.

The development, validation and application of a multi-detector CT (MDCT) scanner model for assessing organ doses to the pregnant patient and the fetus using Monte Carlo simulations

The latest multiple-detector technologies have further increased the popularity of x-ray CT as a diagnostic imaging modality. There is a continuing need to assess the potential radiation risk associated with such rapidly evolving multi-detector CT (MDCT) modalities and scanning protocols. This need can be met by the use of CT source models that are integrated with patient computational phantoms for organ dose calculations. Based on this purpose, this work developed and validated an MDCT scanner using the Monte Carlo method, and meanwhile the pregnant patient phantoms were integrated into the MDCT scanner model for assessment of the dose to the fetus as well as doses to the organs or tissues of the pregnant patient phantom. A Monte Carlo code, MCNPX, was used to simulate the x-ray source including the energy spectrum, filter and scan trajectory. Detailed CT scanner components were specified using an iterative trial-and-error procedure for a GE LightSpeed CT scanner. The scanner model was validated by comparing simulated results against measured CTDI values and dose profiles reported in the literature. The source movement along the helical trajectory was simulated using the pitch of 0.9375 and 1.375, respectively. The validated scanner model was then integrated with phantoms of a pregnant patient in three different gestational periods to calculate organ doses. It was found that the dose to the fetus of the 3 month pregnant patient phantom was 0.13 mGy/100 mAs and 0.57 mGy/100 mAs from the chest and kidney scan, respectively. For the chest scan of the 6 month patient phantom and the 9 month patient phantom, the fetal doses were 0.21 mGy/100 mAs and 0.26 mGy/100 mAs, respectively. The paper also discusses how these fetal dose values can be used to evaluate imaging procedures and to assess risk using recommendations of the report from AAPM Task Group 36. This work demonstrates the ability of modeling and validating an MDCT scanner by the Monte Carlo method, as well as assessing fetal and organ doses by combining the MDCT scanner model and the pregnant patient phantom.

Comparison of out-of-field photon doses in 6 MV IMRT and neutron doses in proton therapy for adult and pediatric patients.

The purpose of this study was to assess lateral out-of-field doses in 6 MV IMRT (intensity modulated radiation therapy) and compare them with secondary neutron equivalent dose contributions in proton therapy. We simulated out-of-field photon doses to various organs as a function of distance, patients age, gender and treatment volumes based on 3, 6, 9 cm field diameters in the head and neck and spine region. The out-of-field photon doses to organs near the field edge were found to be in the range of 2, 5 and 10 mSv Gy(-1) for 3 cm, 6 cm and 9 cm diameter IMRT fields, respectively, within 5 cm of the field edge. Statistical uncertainties calculated in organ doses vary from 0.2% to 40% depending on the organ location and the organ volume. Next, a comparison was made with previously calculated neutron equivalent doses from proton therapy using identical field arrangements. For example, out-of-field doses for IMRT to lung and uterus (organs close to the 3 cm diameter spinal field) were computed to be 0.63 and 0.62 mSv Gy(-1), respectively. These numbers are found to be a factor of 2 smaller than the corresponding out-of-field doses for proton therapy, which were estimated to be 1.6 and 1.7 mSv Gy(-1) (RBE), respectively. However, as the distance to the field edge increases beyond approximately 25 cm the neutron equivalent dose from proton therapy was found to be a factor of 2-3 smaller than the out-of-field photon dose from IMRT. We have also analyzed the neutron equivalent doses from an ideal scanned proton therapy (assuming not significant amount of absorbers in the treatment head). Out-of-field doses were found to be an order of magnitude smaller compared to out-of-field doses in IMRT or passive scattered proton therapy. In conclusion, there seem to be three geometrical areas when comparing the out-of-target dose from IMRT and (passive scattered) proton treatments. Close to the target (in-field, not analyzed here) protons offer a distinct advantage due to the lower integral dose. Out-of-field, but within approximately 25 cm from the field edge, the scattered photon dose in IMRT turned out to be roughly a factor of 2 lower than the neutron equivalent dose from proton therapy for the fields considered in this study. At larger distances to the field (beyond approximately 25 cm), protons offer an advantage, resulting in doses that are roughly a factor of 2-3 lower.

Assessment of patient organ doses and effective doses using the VIP-Man adult male phantom for selected cone-beam CT imaging procedures during image guided radiation therapy

A Monte Carlo based computational procedure for determining organ doses and effective doses has been described for two procedures used in newly developed image-guided radiation treatment: kilovoltage cone-beam computed tomography (kV CBCT) and mega-voltage computed tomography (MV CBCT). A whole-body patient computational phantom, VIP-Man phantom, is employed for Monte Carlo dose calculations. Results indicate that the thyroid dose is always the highest in head and neck (H&N) scan for both kV and MV CBCT, and the bladder dose is the highest in prostate scan for both kV and MV CBCT. For the VIP-Man phantom, it has been found that the effective dose for kV CBCT (assuming a total exposure of 1350 mAs) is approximately 9.5 mSv for the two anatomical sites, whereas the effective dose for MV CBCT (assuming a total of 6 monitor unit) ranges from 5.10 mSv for the H&N case to 8.39 mSv for the prostate scan. The estimated whole-body effective doses allow different imaging procedures to be compared and evaluated.

A comparative study on the risk of second primary cancers in out-of-field organs associated with radiotherapy of localized prostate carcinoma using Monte Carlo-based accelerator and patient models

PURPOSE A physicians decision regarding an ideal treatment approach (i.e., radiation, surgery, and/or hormonal) for prostate carcinoma is traditionally based on a variety of metrics. One of these metrics is the risk of radiation-induced second primary cancer following radiation treatments. The aim of this study was to investigate the significance of second cancer risks in out-of-field organs from 3D-CRT and IMRT treatments of prostate carcinoma compared to baseline cancer risks in these organs. METHODS Monte Carlo simulations were performed using a detailed medical linear accelerator model and an anatomically realistic adult male whole-body phantom. A four-field box treatment, a four-field box treatment plus a six-field boost, and a seven-field IMRT treatment were simulated. Using BEIR VII risk models, the age-dependent lifetime attributable risks to various organs outside the primary beam with a known predilection for cancer were calculated using organ-averaged equivalent doses. RESULTS The four-field box treatment had the lowest treatment-related second primary cancer risks to organs outside the primary beam ranging from 7.3 x 10(-9) to 2.54 x 10(-5)%/MU depending on the patients age at exposure and second primary cancer site. The risks to organs outside the primary beam from the four-field box and six-field boost and the seven-field IMRT were nearly equivalent. The risks from the four-field box and six-field boost ranged from 1.39 x 10(-8) to 1.80 x 10(-5)%/MU, and from the seven-field IMRT ranged from 1.60 x 10(-9) to 1.35 x 10(-5)%/MU. The second cancer risks in all organs considered from each plan were below the baseline risks. CONCLUSIONS The treatment-related second cancer risks in organs outside the primary beam due to 3D-CRT and IMRT is small. New risk assessment techniques need to be investigated to address the concern of radiation-induced second cancers from prostate treatments, particularly focusing on risks to organs inside the primary beam.

Calculated organ doses from selected prostate treatment plans using Monte Carlo simulations and an anatomically realistic computational phantom

There is growing concern about radiation-induced second cancers associated with radiation treatments. Particular attention has been focused on the risk to patients treated with intensity-modulated radiation therapy (IMRT) due primarily to increased monitor units. To address this concern we have combined a detailed medical linear accelerator model of the Varian Clinac 2100 C with anatomically realistic computational phantoms to calculate organ doses from selected treatment plans. This paper describes the application to calculate organ-averaged equivalent doses using a computational phantom for three different treatments of prostate cancer: a 4-field box treatment, the same box treatment plus a 6-field 3D-CRT boost treatment and a 7-field IMRT treatment. The equivalent doses per MU to those organs that have shown a predilection for second cancers were compared between the different treatment techniques. In addition, the dependence of photon and neutron equivalent doses on gantry angle and energy was investigated. The results indicate that the box treatment plus 6-field boost delivered the highest intermediate- and low-level photon doses per treatment MU to the patient primarily due to the elevated patient scatter contribution as a result of an increase in integral dose delivered by this treatment. In most organs the contribution of neutron dose to the total equivalent dose for the 3D-CRT treatments was less than the contribution of photon dose, except for the lung, esophagus, thyroid and brain. The total equivalent dose per MU to each organ was calculated by summing the photon and neutron dose contributions. For all organs non-adjacent to the primary beam, the equivalent doses per MU from the IMRT treatment were less than the doses from the 3D-CRT treatments. This is due to the increase in the integral dose and the added neutron dose to these organs from the 18 MV treatments. However, depending on the application technique and optimization used, the required MU values for IMRT treatments can be two to three times greater than 3D CRT. Therefore, the total equivalent dose in most organs would be higher from the IMRT treatment compared to the box treatment and comparable to the organ doses from the box treatment plus the 6-field boost. This is the first time when organ dose data for an adult male patient of the ICRP reference anatomy have been calculated and documented. The tools presented in this paper can be used to estimate the second cancer risk to patients undergoing radiation treatment.

AXL Is a Logical Molecular Target in Head and Neck Squamous Cell Carcinoma

Purpose: Head and neck squamous cell carcinoma (HNSCC) represents the eighth most common malignancy worldwide. Standard-of-care treatments for patients with HNSCC include surgery, radiation, and chemotherapy. In addition, the anti-EGFR monoclonal antibody cetuximab is often used in combination with these treatment modalities. Despite clinical success with these therapeutics, HNSCC remains a difficult malignancy to treat. Thus, identification of new molecular targets is critical. Experimental Design: In the current study, the receptor tyrosine kinase AXL was investigated as a molecular target in HNSCC using established cell lines, HNSCC patient-derived xenografts (PDX), and human tumors. HNSCC dependency on AXL was evaluated with both anti-AXL siRNAs and the small-molecule AXL inhibitor R428. Furthermore, AXL inhibition was evaluated with standard-of-care treatment regimens used in HNSCC. Results: AXL was found to be highly overexpressed in several models of HNSCC, where AXL was significantly associated with higher pathologic grade, presence of distant metastases, and shorter relapse-free survival in patients with HNSCC. Further investigations indicated that HNSCC cells were reliant on AXL for cellular proliferation, migration, and invasion. In addition, targeting AXL increased HNSCC cell line sensitivity to chemotherapy, cetuximab, and radiation. Moreover, radiation-resistant HNSCC cell line xenografts and PDXs expressed elevated levels of both total and activated AXL, indicating a role for AXL in radiation resistance. Conclusions: This study provides evidence for the role of AXL in HNSCC pathogenesis and supports further preclinical and clinical evaluation of anti-AXL therapeutics for the treatment of patients with HNSCC. Clin Cancer Res; 21(11); 2601–12. ©2015 AACR.

A FEASIBILITY STUDY TO CALCULATE UNSHIELDED FETAL DOSES TO PREGNANT PATIENTS IN 6- MV PHOTON TREATMENTS USING MONTE CARLO METHODS AND ANATOMICALLY REALISTIC PHANTOMS

A Monte Carlo-based procedure to assess fetal doses from 6-MV external photon beam radiation treatments has been developed to improve upon existing techniques that are based on AAPM Task Group Report 36 published in 1995 [M. Stovall et al., Med. Phys. 22, 63-82 (1995)]. Anatomically realistic models of the pregnant patient representing 3-, 6-, and 9-month gestational stages were implemented into the MCNPX code together with a detailed accelerator model that is capable of simulating scattered and leakage radiation from the accelerator head. Absorbed doses to the fetus were calculated for six different treatment plans for sites above the fetus and one treatment plan for fibrosarcoma in the knee. For treatment plans above the fetus, the fetal doses tended to increase with increasing stage of gestation. This was due to the decrease in distance between the fetal body and field edge with increasing stage of gestation. For the treatment field below the fetus, the absorbed doses tended to decrease with increasing gestational stage of the pregnant patient, due to the increasing size of the fetus and relative constant distance between the field edge and fetal body for each stage. The absorbed doses to the fetus for all treatment plans ranged from a maximum of 30.9 cGy to the 9-month fetus to 1.53 cGy to the 3-month fetus. The study demonstrates the feasibility to accurately determine the absorbed organ doses in the mother and fetus as part of the treatment planning and eventually in risk management.

Comparison of MCNPX and Geant4 proton energy deposition predictions for clinical use

Several different Monte Carlo codes are currently being used at proton therapy centers to improve upon dose predictions over standard methods using analytical or semi-empirical dose algorithms. There is a need to better ascertain the differences between proton dose predictions from different available Monte Carlo codes. In this investigation Geant4 and MCNPX, the two most-utilized Monte Carlo codes for proton therapy applications, were used to predict energy deposition distributions in a variety of geometries, comprising simple water phantoms, water phantoms with complex inserts and in a voxelized geometry based on clinical CT data. The Gamma analysis was used to evaluate the differences of the predictions between the codes. The results show that in all the cases the agreement was better than clinical acceptance criteria.

A study of the shielding used to reduce leakage and scattered radiation to the fetus in a pregnant patient treated with a 6-MV external X-ray beam.

A Monte Carlo-based procedure has been developed to assess the shielded fetal doses from 6 MV external photon beam radiation treatments and improve upon existing techniques that are based on AAPM Task Group Report 36 (TG-36). Anatomically realistic models of the pregnant patient representing 3- and 6-mo gestational stages were implemented into the MCNPX code together with a detailed accelerator model that is capable of simulating scattered and leakage radiation from the accelerator head. The phantom was shielded using suggested lead and Cerrobend in different locations and with different thicknesses. Absorbed doses to the fetus both with and without shielding were calculated considering typical mantle, head and neck, and brain treatment plans. The unshielded fetal doses tended to increase with decreasing distance from the field edge to the nearest fetal point and increasing of the field size. The unshielded absorbed doses to the fetus for all treatment plans ranged from a maximum of 4.08 μGy/MU (monitor unit) to a minimum 0.09 μGy/MU. The use of lead or Cerrobend shielding reduced the fetal doses by factors of up to 4. For an optimal shield half-value layer, the dose reduction between lead and Cerrobend was statistically insignificant. The maximum permitted MUs for the mantle treatments with shielding were calculated based on 5 cGy dose limits suggested by TG-36. The study demonstrates an accurate assessing tool that can be used to determine the absorbed dose to the fetus and to design the shielding as part of the treatment planning and risk management.