Quantification of Organ Motion in Male and Female Patients Undergoing Long-Course Radiation Therapy for Rectal Cancer in the Supine Position.

Purpose: Previous studies have reported data on the internal rectal motion of patients with rectal cancer treated in the prone position. With the introduction of intensity modulated techniques, more patients are treated in the more reproducible supine position. Data informing specific margins for this treatment position are sparse, as are data comparing rectal motion characteristics and factors in male and female patients. The purpose of this retrospective study was to quantify and compare the interfractional rectal movement characteristics of male and female patients with rectal cancer treated with long-course chemoradiation therapy in the supine position. The data will aid the generation of internal target volume margins accounting for this organ's internal physiological movements. Methods and Materials: Cone beam computed tomography (CBCT) images were acquired from 19 male and 16 female patients with rectal cancer on the first 3 days of treatment and weekly thereafter. The rectum, bladder, and femoral heads were delineated on the planning CT (PCT) and 6 CBCT for each patient. Overall, 245 images were analyzed. All patients were treated with a full bladder. The rectum was divided into three 5-cm segments (upper, mid, and lower). The motion of the rectum was quantified by documenting the anteroposterior and lateral distances as measured using fixed anatomic landmarks, namely from the anterior aspect of the sacrum and mid-left femoral head, respectively. These measurements were taken at 1-cm intervals from the inferior border of L5 vertebrae. The sigmoid was excluded from these measurements. Estimations of systematic and random physiological movement error were determined and margins were calculated. Results: Two hundred forty-five image sets (19 PCT + 114 CBCT for male, 16 PCT + 96 CBCT for female) on patients who had undergone long-course radiation therapy were analyzed. Rectal tumor location was 31% in the inferior rectum, 46% in the mid rectum, and 23% in the superior rectum. Random rectal motion (mean of the per-patient standard deviation [σ]) was largest for the upper and mid rectum in the anterior direction. There were statistically significant differences in σ between male and female patients in the left lateral motion of the mid and inferior rectum as well as the anterior, posterior, and right motion of the inferior rectum (mid left: P < .0005; lower left: P < .0005; lower posterior: P = .001; lower anterior: P = .032; lower right: P = .001). Suggested internal target volume margin guidelines are therefore nonisotropic and vary per segment of rectum and sex. Conclusions: In our present study, interfractional rectal motion is shown to be significantly different between male and female patients. Our data suggest that the use of asymmetrical sex-specific margins in patients with rectal cancer treated in the supine position should be considered.

Treatment of multiple intracranial metastases in radiation oncology: a contemporary review of available technologies.

The use of stereotactic radiosurgery to treat multiple intracranial metastases, frequently concurrently, has become increasingly common. The ability to accurately and safely deliver stereotactic radiosurgery treatment to multiple intracranial metastases (MIM) relies heavily on the technology available for targeting, planning, and delivering the dose. A number of platforms are currently marketed for such applications, each with intrinsic capabilities and limitations. These can be broadly categorised as cobalt-based, linac-based, and robotic. This review describes the most common representative technologies for each type along with their advantages and current limitations as they pertain to the treatment of multiple intracranial metastases. Each technology was used to plan five clinical cases selected to represent the clinical breadth of multiple metastases cases. The reviewers discuss the different strengths and limitations attributed to each technology in the case of MIM as well as the impact of disease-specific characteristics (such as total number of intracranial metastases, their size and relative proximity) on plan and treatment quality.

Determining normal tissue dose in intracranial stereotactic radiosurgery: A diameter-based predictive nomogram.

Purpose: A major factor in dose-fractionation selection for intracranial metastases in stereotactic radiosurgery (SRS) is the size of the target lesion and consequently the dose-volume to the surrounding normal brain tissue (NTV), as this has been correlated with brain radiation necrosis (RN). This study outlines the development and validation of a predictive model that can estimate the NTV for a range of dose-fractionation schemes based on target diameter from a patient's MRI. Methods: Data from a cohort of historical SRS clinical treatment plans were used to extract three key input parameters for the model - conformity index, gradient index, and a scaling factor which were then defined as a function of target volume. The relationship between the measured tumour diameter and the NTV was established by approximating the target to a spherical volume covered by the prescription dose. A scaling factor (λNTV) describes the non-linear fall-off of dose beyond the target. This was then used to provide a first-order approximation of the resulting NTV. The predictive model was retrospectively validated using linear regression against actual NTV values from 39 historical SRS plans which were independent to the derivation process. The model was validated for both three-dimensional (3D) target diameter and axial-only two-dimensional (2D) estimates of target diameter values. Results: The prediction model directly relates lesion diameter to NTV volume (cc) and thus RN risk for a given dose-fractionation. The predicted NTV (cc) for both 3D- and 2D-based volume estimates could statistically significantly predict the actual NTV (cc): R2=0.942 (p<.0005) for 3D-based estimate, and R2=0.911 (p=<.0005) for axial-only 2D-based estimate. Conclusion: This knowledge-based method for NTV prediction in intracranial SRS provides the clinician with a decision support tool to appropriately select dose-fractionation prior to treatment planning.

A novel dynamic arc treatment planning solution to reduce dose to small bowel in preoperative radiotherapy for rectal cancer.

Preoperative radiotherapy or combined chemoradiotherapy for locally advanced rectal cancer (LARC) can cause acute and late gastrointestinal (GI) side-effects. There is thought to be a dose-volume relationship between small bowel irradiation and the development of these effects. A planning study was undertaken to compare small bowel sparing for a range of 3D conformal and dynamic arc planning solutions. A planning study was carried out for 20 LARC patients. Organs at risk (OAR) contoured included bowel loops and peritoneal space (PS). For each of the 20 patients, 5 plans were created: (1) standard 3D conformal plan; (2) standard dual dynamic arc plan; (3) dual dynamic arc plan with 90° avoidance sector through the anterior portion of the patient; (4) dual dynamic arc plan with an anterior avoidance structure in the optimizer; (5) dual dynamic arc plan with both an anterior avoidance structure and an avoidance sector. The prescription was 50.4 Gy in 28 fractions to the planning target volume (PTV). Five Dose Volume Levels (DVLs; V15 Gy, V20 Gy, V25 Gy, V35 Gy, V40 Gy, and V50.4 Gy) for bowel and PS were selected. The DVLs were compared between the plans using Friedman Tests and Wilcoxon Signed Rank Tests. Comparison of the 5 plans revealed that a dual dynamic arc plan containing both an anterior avoidance sector and structure significantly improved the dose to the bowel compared to a standard 3D conformal plan and to a standard dual dynamic arc plan. This improvement was achieved while maintaining PTV coverage. This novel dual dynamic arc planning technique that uses both an avoidance sector and structure reduces the dose to the bowel and PS, which may lead to a reduction in GI toxicity.

Code of ethics for the American Association of Physicists in Medicine (Revised): Report of Task Group 109.

The American Association of Physicists in Medicine (AAPM) has established a comprehensive Code of Ethics for its members. The Code is a formal part of AAPM governance, maintained as Professional Policy 24, and includes both principles of ethical practice and the rules by which a complaint will be adjudicated. The structure and content of the Code have been crafted to also serve the much broader purpose of giving practical ethical guidance to AAPM members for making sound decisions in their professional lives. The Code is structured in four major parts: a Preamble, a set of ten guiding Principles, Guidelines that elucidate the application of the Principles in various practice settings, and the formal Complaint process. Guidelines have been included to address evolving social and cultural norms, such as the use of social media and the broadening scope of considerations important in an evolving workplace. The document presented here is the first major revision of the AAPM Code of Ethics since 2008. This revision was approved by the Board of Directors to become effective 1 January 2019.

Stereotactic radiosurgery to surgical cavity post resection of brain metastases: Local recurrence and overall survival rates. A single-centre experience.

INTRODUCTION: We reviewed local control (LC) and overall survival (OS) post intracranial SRS to cavity post resection of brain metastases at one institution, and factors affecting LC. METHODS: A retrospective review was conducted of adjuvant SRS at one institution from 2013 to 2016. Patient records, treatment plans and diagnostic images were reviewed. Local failure was MRI defined. Categorical variables were analysed using chi-square and Fisher's exact tests. Continuous variables were analysed using Mann-Whitney tests. The Kaplan-Meier method was used to estimate survival times and the log-rank test was used to compare differences in survival. RESULTS: Forty-seven patients with 48 cavities were treated with SRS post operatively. LC rate was 69%, and the distant intracranial failure rate was 47% for entirety of the follow-up period. The 12-month freedom from local recurrence (FFLR) was 77% (63-91%). Median OS (95% CI) was 22.7 (14.6-30.8) months. Patients with a single metastasis had longer FFLR (30.1 vs 14.4 months; P = 0.014). Median interval from surgery to SRS was 6.3 weeks. Patients with interval >7 weeks had increased local recurrence (LR) (62%) than <7 weeks (37%), P = 0.025. Patients with a margin < 2 mm were more likely to experience LR (48%) than those with margin equal to 2 mm (20%); this approached statistical significance (P = 0.063). The median follow-up for all patients was 15.4 months (2-41). CONCLUSIONS: We determined LC and OS post adjuvant SRS at our institution. Based on the findings of this retrospective review SRS should be given promptly post operatively with a 2 mm PTV margin.

Efficacy evaluation of retrospectively applying the Varian normal breathing predictive filter for volume definition and artifact reduction in 4D CT lung patients.

Phase-based sorting of four-dimensional computed tomography (4D CT) datasets is prone to image artifacts due to patient's breathing irregularities that occur during the image acquisition. The purpose of this study is to investigate the effect of the Varian normal breathing predictive filter (NBPF) as a retrospective phase-sorting parameter in 4D CT. Ten 4D CT lung cancer datasets were obtained. The volumes of all tumors present, as well as the total lung volume, were calculated on the maximum intensity projection (MIP) images as well as each individual phase image. The NBPF was varied retrospectively within the available range, and changes in volume and image quality were recorded. The patients' breathing trace was analysed and the magnitude and location of any breathing irregularities were correlated to the behavior of the NBPF. The NBPF was found to have a considerable effect on the quality of the images in MIP and single-phase datasets. When used appropriately, the NBPF is shown to have the ability to account for and correct image artifacts. However, when turned off (0%) or set above a critical level (approximately 40%), it resulted in erroneous volume reconstructions with variations in tumor volume up to 26.6%. Those phases associated with peak inspiration were found to be more susceptible to changes in the NBPF. The NBPF settings selected prior to exporting the breathing trace for patients evaluated using 4D CT directly affect the accuracy of the targeting and volume estimation of lung tumors. Recommendations are made to address potential errors in patient anatomy introduced by breathing irregularities, specifically deep breath or cough irregularities, by implementing the proper settings and use of this tool.

Sensitivity of volumetric modulated arc therapy patient specific QA results to multileaf collimator errors and correlation to dose volume histogram based metrics.

PURPOSE: This study investigates the impact of systematic multileaf collimator (MLC) positional errors on gamma analysis results used for quality assurance (QA) of Rapidarc treatments. In addition, this study evaluates the relationship of these gamma analysis results and clinical dose volume histogram metrics (DVH) for Rapidarc treatment plans. METHODS: Five prostate plans were modified by the introduction of systematic MLC errors. The MLC shifts to each individual active leaf introduced were 0.25, 0.5, 0.75, and 1 mm. All QA verification plans were delivered and estimated 3D patient dose or high density phantom dose were obtained based on the ArcCHECK measurement files. QA gamma analysis of 3%/3 mm and 2%/2 mm were implemented and relationships to dose differences in DVH metrics encountered due to MLC errors were determined. Tolerances of 3% and 5% for DVH metric were implemented to determine the sensitivity of gamma analysis to MLC errors. A calculation of sensitivity was determined from the number of incidences of false negative and false positive cases in gamma analysis results. RESULTS: The sensitivity of global gamma analysis for criteria of 3%/3 mm was 0.78 and for 2%/2 mm was 0.82. A number of instances occurred for an acceptable VMAT QA gamma index which did not indicate a DVH metric dose error greater than 5%. The correlation between global gamma analysis using criteria 3%/3 mm and DVH metric dose error were all <0.8 indicating less than a strong correlation. CONCLUSIONS: There is a greater sensitivity for detection of dosimetric errors occurring in a Rapidarc plan using gamma criteria of 2%/2 mm than 3%/3 mm. However, there is lack of consistently strong correlation between global gamma indexes and clinical DVH metrics for PTV and bladder and rectum for Rapidarc plans. It is recommended that the sole use of gamma index for Rapidarc QA plan evaluation could be insufficient and a methodology for evaluation of delivered dose to patient is required.

Tissue permittivity: a monitor for progressive tissue fibrosis as observed in bystander tissues following experimental high dose rate irradiation.

Fibrosis is a pathological condition resulting from radiation injury which often limits the prescription of higher (or boost) doses of radiation, risking inadequate tumor control in patients. Recent studies have documented reduction in fibrotic lesions after administration of pentoxyfilline and tocopherol combinations to breast cancer patients receiving adjuvant radiation therapy. Despite the promise of these findings, no techniques or markers are available which can be used to identify the onset or progression of fibrosis in such patients at stages early enough to allow maximum benefit from these types of pharmacological agents. Relative permittivity of skeletal muscle has been investigated in an animal model utilizing high dose rate radiation both at the treatment site as well as on the contralateral site, and was found to be directly related to the formation and progression of fibrotic lesions. A cubic increase in the quantified fibrotic fraction of the tissue (2.7%-13.9% over 11 w post irradiation) was reflected in a linear increase in the tissue's relative permittivity (epsilon(r) = 6.3-8.8 over 11 w post irradiation). These findings mandate further investigation of the relationship between tissue's relative permittivity and subcellular injury leading to fibrosis using electrical impedance spectroscopy (EIS).

High dose rate radiation treatment of experimental intramuscular prostate carcinoma.

PURPOSE: The Dunning R3327-MLL is a well established transplanted tumour line, and as such it makes a desirable model for evaluative studies of therapy. In the current study, the interstitial growth characteristics as well as the response of this tumour to a single fraction of high dose rate radiation is investigated. MATERIALS AND METHODS: The in vitro response to radiation of the Dunning R3327-MLL was studied via a colony forming assay using a Cs-137 irradiator. In vitro radiosensitivity was determined on tumours implanted intramuscularly in the left gastrocnemius muscle of the rat and irradiated using an Ir-192 afterloader. RESULTS: The results demonstrate a faster growth rate when compared to the reported subcutaneous growth rates. The Dunning R3327-MLL's radiosensitivity is comparable to that of late response tissues. The dose required to achieve a specific radiobiological response (the alpha:beta ratio) of the in vitro cell line is 2.4 Gy, whereas the ratio for the intramuscularly growing tumour was 0.99 Gy. CONCLUSIONS: These findings signify the intramuscularly implanted Dunning R3327-MLL tumour model as a desirable model for the study of single fraction high dose rate radiation treatments.

In vivo EIS characterization of tumour tissue properties is dominated by excess extracellular fluid.

Electrical impedance spectroscopy (EIS) is a non-ionizing, non-invasive technique which can be used to detect the presence of malignant tumours based on their electrical properties. Although it has been suggested that the edema which accompanies tumours strongly influences EIS tumour characterization, such information has not, until now, been documented in the literature. Growing intramuscular rodent tumours were imaged using magnetic resonance imaging (MRI) and EIS at several time points post-tumour implantation. The amount of edema associated with the tumours was calculated from the MRI images. Electrical parameters (resistivity, permittivity, fluid index ratio and peak frequency) were extracted from the EIS spectra. Taken together, the resulting electrical parameters strongly indicate that edema is the dominating pathological feature in EIS characterization and can at times conceal the presence of the tumour. Receiver operating characteristic analysis supports these findings.

Feasibility studies of electrical impedance spectroscopy for early tumor detection in rats.

Electrical impedance spectroscopy (EIS) has been previously reported as a technique for non invasive assessment of tissue change. Our previous in vivo studies demonstrated the ability of EIS to non-invasively detect and longitudinally follow tumor growth. This study was designed to determine the ability of EIS to detect tumors at a very early stage post-implantation. Complex impedance measurements were collected from eight rats with one control and one tumor implanted leg six or seven days after tumor cell inoculation. Legs were also imaged with computed tomography (CT) and ultrasound (US) in an effort to determine EIS resolution and sensitivity. Six of the animals were sacrificed immediately after imaging, and tissue was collected for histology and later co-registration of the pathology with the imaging techniques. Results show that EIS is able to repeatedly detect small tumors (<3 mm) and tumor-associated changes, whereas CT and US were not routinely capable of detecting pathological developments on this scale.