Integrating Overall Survival and Tumor Control Probability Models to Predict Local Progression After Brain Metastasis Radiosurgery.

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is frequently prescribed to the maximum tolerated dose to minimize the probability of local progression. However, many patients die from extracranial disease prior to local progression and may not require maximally aggressive treatment. Recently, improvements in models of SRS tumor control probability (TCP) and overall survival (OS) have been made. We predicted that by combining models of OS and TCP, we could better predict the true risk of local progression after SRS than by using TCP modeling alone. Methods and Materials: Records of patients undergoing SRS at a single institution were reviewed retrospectively. Using established TCP and OS models, for each patient, the probability of 1-year survival [p(OS)] was calculated, as was the probability of 1-year local progression [p(LP)]) for each treated lesion. Joint-probability was used to combine the models [p(LP,OS)=p(LP)*p(OS)]. Analyses were conducted at the individual metastasis and whole-patient levels. Fine-Gray regression was used to model p(LP) or p(LP,OS) on the risk of local progression after SRS, with death as a competing risk. Results: At the patient level, 1-year local progression was 0.08 (95% CI, 0.03-0.15), median p(LP,OS) was 0.13 (95% CI, 0.07-0.2), and median p(LP) was 0.29 (95% CI, 0.22-0.38). At the metastasis level, 1-year local progression was 0.02 (95% CI, 0.01-0.04), median p(LP,OS) was 0.05 (95% CI, 0.02-0.07), and median p(LP) was 0.10 (95% CI, 0.07-0.13). p(LP,OS) was found to be significantly associated with the risk of local progression at the patient level (P = .048) and metastasis level (P = .007); however, p(LP) was not (P = .16 and P = .28, respectively). Conclusions: Simultaneous modeling of OS and TCP more accurately predicted local progression than TCP modeling alone. Better understanding which patients with brain metastases are at risk of local progression after SRS may help personalize treatment to minimize risk without sacrificing efficacy.

Radiation therapy practice changes in the COVID-19 pandemic era: A pilot study in California.

PURPOSE: This study aims to investigate practice changes among Southern and Northern California's radiation oncology centers during the COVID-19 pandemic. METHODS: On the online survey platform SurveyMonkey, we designed 10 survey questions to measure changes in various aspects of medical physics practice. The questions covered patient load and travel rules; scopes to work from home; new protocols to reduce corona virus disease-2019 (COVID-19) infection risk; availability of telemedicine; and changes in fractionation schedules and/or type of treatment plans. We emailed the survey to radiation oncology centers throughout Northern and Southern California, requesting one completed survey per center. All responses were anonymized, and data were analyzed using both qualitative and quantitative research methods. RESULTS: At the end of a 4-month collection period (July 2, 2021 to October 11, 2021), we received a total of 61 responses throughout Southern and Northern California. On average, 4111 patients were treated per day across the 61 centers. New COVID-19-related department and hospital policies, along with hybrid workflow changes, infectious control policies, and changes in patient load have been reported. Results also showed changes in treatment methods during the pandemic, such as increased use of telemedicine, hypofractionation for palliative, breast cancer, and prostate cancer cases; and simultaneous boosts, compared to sequential boosts. CONCLUSION: Our California radiation oncology center population study shows changes in various aspects of radiation oncology practices during the COVID-19 pandemic. This study serves as a pilot study to identify possible correlations and new strategies that allow radiation oncology centers to continue providing quality patient care while ensuring the safety of both staff and patients.

A preliminary safety assessment of vertebral augmentation with32P brachytherapy bone cement.

Comprehensive treatment for vertebral metastatic lesions commonly involves vertebral augmentation (vertebroplasty or kyphoplasty) to relieve pain and stabilize the spine followed by multiple sessions of radiotherapy. We propose to combine vertebral augmentation and radiotherapy into a single treatment by adding32P, aß-emitting radionuclide, to bone cement, thereby enabling spinal brachytherapy to be performed without irradiating the spinal cord. The goal of this study was to address key dosimetry and safety questions prior to performing extensive animal studies. The32P was in the form of hydroxyapatite powder activated by neutron bombardment in a nuclear reactor. We performedex vivodosimetry experiments to establish criteria for safe placement of the cement within the sheep vertebral body. In anin vivostudy, we treated three control ewes and three experimental ewes with brachytherapy cement containing 2.23-3.03 mCi32P ml-1to identify the preferred surgical approach, to determine if32P leaches from the cement and into the blood, urine, or feces, and to identify unexpected adverse effects. Ourex vivoexperiments showed that cement with 4 mCi32P ml-1could be safely implanted in the vertebral body if the cement surface is at least 4 mm from the spinal cord in sheep and 5 mm from the spinal cord in humans.In vivo, a lateral retroperitoneal surgical approach, ventral to the transverse processes, was identified as easy to perform while allowing a safe distance to the spinal cord. The blood, urine, and feces of the sheep did not contain detectable levels of32P, and the sheep did not experience any neurologic or other adverse effects from the brachytherapy cement. These results demonstrate, on a preliminary level, the relative safety of this brachytherapy cement and support additional development and testing.

Quantifying the impact of optical surface guidance in the treatment of cancers of the head and neck.

Surface guided radiation therapy (SGRT) is increasingly being adopted for use in radiation treatment delivery for Head and Neck (H&N) cancer patients. This study investigated the improvement of patient setup accuracy and reduction of setup time for SGRT compared to a conventional setup. A total of 60 H&N cancer patients were retrospectively included. Patients were categorized into three groups: oral cavity, oropharynx and nasopharynx/sinonasal sites with 20 patients in each group. They were further separated into two (2) subgroups, depending on whether they were set up with the aid of SGRT. The Align-RT™ system was used for SGRT in this work. Positioning was confirmed by daily kV-kV imaging in conjunction with weekly CBCT scans. Translational and rotational couch shifts along with patient setup times were recorded. Imaging setup time, which was defined as the elapsed time from the acquisition of the first image set to the end of the last image set, was recorded. Average translational shifts were larger in the non-SGRT group. Vertical shifts showed the most significant reduction in the SGRT group for both oropharynx and oral cavity groups. Pitch corrections were significantly higher in the SGRT group for oropharynx patients and higher pitch corrections were also observed in the SGRT groups of oral cavity and nasopharynx/sinonasal patients. The average setup time when SGRT guidance was employed was shorter for all three treatment sites although this did not reach statistical significance. The largest time reduction between the SGRT and non-SGRT groups was seen in the nasopharynx/sinonasal group. This study suggests that the use of SGRT decreases the magnitude of translational couch shifts during patient setup. However, the rotational corrections needed were generally higher with SGRT group. When SGRT was employed, a definite reduction in patient setup time was observed for nasopharynx/sinonasal and hypopharynx cancer patients.

Dosimetric comparison of deep-inspiration breath-hold and free-breathing treatment delivery techniques for left-sided breast cancer using 3D surface tracking.

INTRODUCTION: While radiation therapy has been shown to increase local control and overall survival for breast cancer, late cardiac toxicity remains a concern. Morbidity and mortality have been shown to increase proportionally to the mean heart dose. Deep inspiration breath-hold (DIBH) can reduce heart dose compared to free-breathing (FB) by increasing the heart-to-chest wall distance, especially in left-sided breast cancer. We present our clinical experience with DIBH in left breast and chest-wall irradiation using 3D optical surface tracking. MATERIALS & METHODS: 29 patients were treated with DIBH using a surface tracking system that provides a real time 3D surface image of the patient. Comparisons of maximum and mean heart dose, heart-chest wall separation, and the percentage of lung volume that receives 20 or more Gy (V20) between the DIBH and hypothetical FB treatment plans were conducted with the Student's t-test. Correlation coefficients were also calculated for heart-chest wall separation, heart volume, and lung volume. RESULTS: Comparing DIBH and FB plans showed a decrease in mean and maximum heart doses in all patients. Individual mean heart doses decreased by an average of 1.12 Gy, and the average mean heart dose for DIBH plans was significantly lower than corresponding FB plans (1.02 vs. 2.12 Gy; p < 0.0001). Maximum heart dose decreased by an average of 11.88 Gy and was significantly lower in DIBH versus FB plans (28.33 vs. 43.7 Gy; p = 0.0001). The average difference in heart to chest-wall separation between DIBH and FB images was 2.41 cm. DIBH left lung volume and measured increases in volume on inspiration inversely correlated with maximum heart dose (R = 0.39) and left lung V20 (R = 0.32). CONCLUSIONS: DIBH with 3D surface tracking can significantly benefit patients with left sided disease by limiting the mean and maximum heart dose. DIBH appears to viably reduce heart dose for left-breast cancer patients and thus potentially reduce long-term complications without prolonging treatment delivery.

Chidamide shows synergistic cytotoxicity with cytarabine via inducing G0/G1 arrest and apoptosis in myelodysplastic syndromes.

Chidamide is a newly designed and synthesized histone deacetylase (HDAC) inhibitor that selectively inhibits HDAC 1, 2, 3, and 10. Our previous study demonstrated that chidamide induces G0/G1 arrest and apoptosis in myelodysplastic syndromes (MDS). Low-dose chemotherapy is effective in treating higher risk MDS patients, and here, we sought to determine whether the combination of chidamide with cytarabine at lowdoses would increase the cytotoxicity to MDS cells. In this study, the combination of chidamide (50 nM) with cytarabine (50 nM) showed synergistic inhibition on cell growth.The mean combination index values were 0.068, 0.158, and 0.226 in SKM-1, MUTZ-1, and KG-1 MDS cell lines, respectively. The combination increased the acetylation levels of histone H3 and decreased HDAC activity in MDS cells.A low concentration (25 and 50 nM) of chidamide combined with low-dose cytarabine (50 nM) inhibited cell proliferation and arrested the cell cycle in the G0/G1 phasevia down-regulating CDK2 and up-regulating p21. Furthermore, the combined treatment induced cell apoptosis via down-regulating Bcl-2 and up-regulating cleaved caspase-3 protein. These results demonstrate the potential utility of combining chidamide and cytarabine in the treatment of MDS.

Radiation dermatitis caused by a bolus effect from an abdominal compression device.

American Association of Physicists in Medicine (AAPM) Task Group 176 evaluated the dosimetric effects caused by couch tops and immobilization devices. The report analyzed the extensive physics-based literature on couch tops, stereotactic body radiation therapy (SBRT) frames, and body immobilization bags, while noting the scarcity of clinical reports of skin toxicity because of external devices. Here, we present a clinical case report of grade 1 abdominal skin toxicity owing to an abdominal compression device. We discuss the dosimetric implications of the utilized treatment plan as well as post hoc alternative plans and quantify differences in attenuation and skin dose/build-up between the device, a lower-density alternative device, and an open field. The description of the case includes a 66-year-old male with HER2 amplified poorly differentiated distal esophageal adenocarcinoma treated with neoadjuvant chemo-radiation and the use of an abdominal compression device. Radiation was delivered using volumetric modulated arc therapy (VMAT) with 2 arcs using abdominal compression and image guidance. The total dose was 50.4Gy delivered over 40 elapsed days. With 2 fractions remaining, the patient developed dermatitis in the area of the compression device. The original treatment plan did not include a contour of the device. Alternative post hoc treatment plans were generated, one to contour the device and a second with anterior avoidance. In conclusion, replanning with the device contoured revealed the bolus effect. The skin dose increased from 27 to 36Gy. planned target volume (PTV) coverage at 45Gy was reduced to 76.5% from 95.8%. The second VMAT treatment plan with an anterior avoidance sector and more oblique beam angles maintained PTV coverage and spared the anterior wall, however at the expense of substantially increased dose to lung. This case report provides an important reminder of the bolus effect from external devices such as abdominal compression. Special consideration must be given to contour and/or avoiding beam entrance to the device, and to the use of such devices in patients who may have heightened radiosensitivity, such as those who are human immunodeficiency virus (HIV)-positive.

Comparative failure load values of acrylic resin denture teeth bonded to three different heat cure denture base resins: An in vitro study.

AIM AND OBJECTIVES: Acrylic teeth are used for fabrication of dentures. Debonding of tooth - denture base bond is routine problem in dental practice. The aim of this study was to comparatively evaluate failure load of acrylic resin denture teeth bonded to three different heat resin. MATERIALS AND METHODS: Four groups were created out of test samples central incisors (11). Group I: Control, whereas Group II, Group III and Group IV were experimental groups modified with diatoric hole, cingulum ledge lock and Teeth modified with both diatoric hole and cingulum ledge lock, respectively. These test specimens with 3 teeth (2 central [11, 21] and 1, lateral [12] incisors) positioned imitating arrangement of teeth in the conventional denture, prepared by three different heat cure materials (DPI, Trevalon, Acralyn-H). A shear load was applied at cingulum of central incisor (11) at 130° to its long axis using universal tester at a cross head speed of 5 mm/min until failure occurred. Failure load test was conducted and statistical analysis was performed using SPSS 16 software package (IBM Company, New York, U.S). RESULTS: Highest failure load was seen in Group IV specimens, prepared by Trevalon but did not significantly differ from that of DPI. CONCLUSION: The failure load of bonding denture teeth to three different heat cure materials was notably affected by modifications of ridge lap before processing. The specimens with a combination of diatoric hole and cingulum ledge lock, prepared by Trevalon showed highest failure load but did not significantly vary from that of DPI. The control group prepared by Acralyn-H showed lowest failure load but did not significantly differ from that of DPI.

Bone mineral density loss in thoracic and lumbar vertebrae following radiation for abdominal cancers.

PURPOSE: To investigate the relationship between abdominal chemoradiation (CRT) for locally advanced cancers and bone mineral density (BMD) reduction in the vertebral spine. MATERIALS AND METHODS: Data from 272 patients who underwent abdominal radiation therapy from January 1997 to May 2015 were retrospectively reviewed. Forty-two patients received computed tomography (CT) scans of the abdomen prior to initiation and at least twice after radiation therapy. Bone attenuation (in Hounsfield unit) (HU) measurements were collected for each vertebral level from T7 to L5 using sagittal CT images. Radiation point dose was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (Δ%HU) between baseline and post-radiation therapy were computed for each vertebral body. The Δ%HU was compared against radiation dose using Pearson's linear correlation. RESULTS: Abdominal radiotherapy caused significant reduction in vertebral BMD as measured by HU. Patients who received only chemotherapy did not show changes in their BMD in this study. The Δ%HU was significantly correlated with the radiation point dose to the vertebral body (R=-0.472, P<0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R=-0.578, P<0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (ß=0.830) on determining post-RT HU, while number of months post RT (ß=-0.213) and radiation point dose (ß=-1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R=0.883, P<0.001) with the slope of the best linear fit=0.81. Our model's predicted HU were within ±20 HU of the actual value in 53% of cases, 70% of the predictions were within ±30 HU, 81% were within ±40 HU, and 90% were within ±50 HU of the actual post-RT HU. Four of 42 patients were found to have vertebral body compression fractures in the field of radiation. CONCLUSIONS: Patients who receive abdominal chemoradiation develop significant BMD loss in the thoracic and lumbar vertebrae. Treatment-related BMD loss may contribute to the development of vertebral compression fractures. A predictive model for post-CRT BMD changes may inform bone protective strategies in patients planned for abdominal CRT.

The dosimetric impact of image guided radiation therapy by intratumoral fiducial markers.

PURPOSE: Pancreatic fiducials have proven superior over other isocenter localization surrogates, including anatomical landmarks and intratumoral or adjacent stents. The more clinically relevant dosimetric impact of image guided radiation therapy (IGRT) using intratumoral fiducial markers versus bony anatomy has not yet been described and is therefore the focus of the current study. METHODS AND MATERIALS: Using daily orthogonal kV or cone beam computed tomography (CBCT) images and positional and dosimetric data were analyzed for 12 consecutive patients treated with fiducial based IGRT and volumetric modulated arc therapy to the intact pancreas. The shifts from fiducial to bone (ΔFid-Bone) required to realign the daily fiducial-matched pretreatment images (kV, CBCTs) to the planning computed tomography (CT) using bony anatomic landmarks were recorded. The isocenter was then shifted by (ΔFid-Bone) for 5 evenly spaced treatments, and the dosimetric impact of ΔFid-Bone was calculated for planning target volume coverage (PTV50.4 and PTV47.9) and organs at risk (liver, kidney, and stomach/duodenum). RESULTS: The ΔFid-Bone were greatest in the superoinferior direction (ΔFid-Bone anteroposterior, 2.7 ± 3.0; left-right, 2.8 ± 2.8; superoinferior, 6.3 ± 7.9 mm; mean ± standard deviation; P = .03). PTV50.4 coverage was reduced by 13% (fiducial plan 95 ± 2.0 vs bone plan 82 ± 12%; P = .005; range, 5%-52%; >5% loss in all; and >10% loss in 42% of patients), and to a lesser degree for PTV47.9 (difference, -8%; range, 1%-30%; fiducial plan 100 ± 0.3% vs bone plan 92 ± 7.6%; P = .003; with reductions of >5% in 66% and >10% in 33% of patients). The dosimetric impact of ΔFid-Bone on the organs at risk was not significant. Positional shifts for kV- and CBCT-based realignments were nearly identical. CONCLUSION: Compared with matching by fiducial markers, IGRT matched by bony anatomy substantially reduces the PTV50.4 and PTV47.9 coverage, supporting the use of intratumoral pancreatic markers for improved targeting in IGRT for pancreatic cancer.

Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90Y microsphere brachytherapy in the treatment of hepatic malignancies.

Yttrium-90 microsphere brachytherapy of the liver exploits the distinctive features of the liver anatomy to treat liver malignancies with beta radiation and is gaining more wide spread clinical use. This report provides a general overview of microsphere liver brachytherapy and assists the treatment team in creating local treatment practices to provide safe and efficient patient treatment. Suggestions for future improvements are incorporated with the basic rationale for the therapy and currently used procedures. Imaging modalities utilized and their respective quality assurance are discussed. General as well as vendor specific delivery procedures are reviewed. The current dosimetry models are reviewed and suggestions for dosimetry advancement are made. Beta activity standards are reviewed and vendor implementation strategies are discussed. Radioactive material licensing and radiation safety are discussed given the unique requirements of microsphere brachytherapy. A general, team-based quality assurance program is reviewed to provide guidance for the creation of the local procedures. Finally, recommendations are given on how to deliver the current state of the art treatments and directions for future improvements in the therapy.

Experimental investigation of the implementation of Fermi-Eyges-Hogstrom electron beam model of the Pinnacle3 system at extended SSDs.

A commercially available ADAC Pinnacle(3) radiation treatment planning system has been used to model electron beams from a Varian Clinac 2300C/D in the energy range of 6 to 22 MeV. Prior to clinical use, the dosimetric characteristics of the beams have to be modeled accurately. As a first step for beam modeling, a number of dose profile and depth dose measurements were taken at standard source-to-surface distance (SSD) of 100 cm. Dose profiles and depth dose measurements at extended SSDs up to 120 cm are important for ascertaining accuracy of the model, as well as their clinical usefulness in the treatment of some sites (e.g., head-and-neck tumors). Modeled and measured beam data were compared. Over 98% of comparison points (modeled vs. measured) at 100-cm SSD were within 2.5% or 2.5 mm. At 110 cm SSD, over 98% of compared points were within 4% or 4 mm, and at 120-cm SSD, over 98% of compared points were within 5% or 5 mm. Overall, more than 98% of compared points were within 4% or 4 mm. Better models were produced for lower energies (6 to 15 MeV) than higher energies (18 and 22 MeV). For 6, 9, 12, and 15 MeV, 89% of compared points were within 2% or 2 mm. For 18- and 22-MeV electron energies, 75% and 67%, respectively, were within 2% or 2 mm. These results are consistent with the recommendations of AAPM Task Group Report 53.

Application of imaging-derived parameters to dosimetry of intravascular brachytherapy sources: perturbation effects of residual plaque burden.

The dosimetric effect of geometric and material heterogeneities on intravascular brachytherapy dose delivery has been studied recently. Residual plaque within the coronary vessel appears to have an impact on the uniform delivery of radiation dose to the arterial tissue. In this study, we have examined the effect of residual plaque burden and post-PCI (percutaneous coronary intervention) plaque configuration on the dose to the arterial wall from clinical intravascular brachytherapy beta-emitting sources containing 32P and 90Sr/90Y. Monte Carlo simulations using the MCNP4B code were performed for these catheter-based sources with residual plaque burden ranging between 25% and 50%. The residual plaque burden values were derived from post-PCI data provided in several recent clinical studies. Dose calculations were performed for three different values of plaque density (1.45 g cm(-3), 2.20 g cm(-3), and 3.1 g cm(-3)) and three different plaque morphologies for the same residual plaque burden. The dose perturbation factor (DPF), defined as the ratio of dose at 2 mm radial distance for a given case to the dose at the same radial distance in homogeneous water medium, was determined for each of the three different plaque densities. The range of DPF values was 0.81-1.01, 0.62-0.99, and 0.41-0.97 for different plaque densities for the 32P source. Corresponding DPF values for the 90Sr/90Y source were 0.90-1.01, 0.84-1.01, and 0.62-1.01. The results indicate the need for accurate assessment of post-PCI clinical measurements such as minimal lumen diameter and residual plaque burden and incorporation of these values into dose calculations.