Prospective Evaluation of Automated Contouring for CT-Based Brachytherapy for Gynecologic Malignancies.

Purpose: The use of deep learning to auto-contour organs at risk (OARs) in gynecologic radiation treatment is well established. Yet, there is limited data investigating the prospective use of auto-contouring in clinical practice. In this study, we assess the accuracy and efficiency of auto-contouring OARs for computed tomography-based brachytherapy treatment planning of gynecologic malignancies. Methods and Materials: An inhouse contouring tool automatically delineated 5 OARs in gynecologic radiation treatment planning: the bladder, small bowel, sigmoid, rectum, and urethra. Accuracy of each auto-contour was evaluated using a 5-point Likert scale: a score of 5 indicated the contour could be used without edits, while a score of 1 indicated the contour was unusable. During scoring, automated contours were edited and subsequently used for treatment planning. Dice similarity coefficient, mean surface distance, 95% Hausdorff distance, Hausdorff distance, and dosimetric changes between original and edited contours were calculated. Contour approval time and total planning time of a prospective auto-contoured (AC) cohort were compared with times from a retrospective manually contoured (MC) cohort. Results: Thirty AC cases from January 2022 to July 2022 and 31 MC cases from July 2021 to January 2022 were included. The mean (±SD) Likert score for each OAR was the following: bladder 4.77 (±0.58), small bowel 3.96 (±0.91), sigmoid colon 3.92 (±0.81), rectum 4.6 (±0.71), and urethra 4.27 (±0.78). No ACs required major edits. All OARs had a mean Dice similarity coefficient > 0.86, mean surface distance < 0.48 mm, 95% Hausdorff distance < 3.2 mm, and Hausdorff distance < 10.32 mm between original and edited contours. There was no significant difference in dose-volume histogram metrics (D2.0 cc/D0.1 cc) between original and edited contours (P values > .05). The average time to plan approval in the AC cohort was 19% less than the MC cohort. (AC vs MC, 117.0 + 18.0 minutes vs 144.9 ± 64.5 minutes, P = .045). Conclusions: Automated contouring is useful and accurate in clinical practice. Auto-contouring OARs streamlines radiation treatment workflows and decreases time required to design and approve gynecologic brachytherapy plans.

CD46 targeted 212Pb alpha particle radioimmunotherapy for prostate cancer treatment.

We recently identified CD46 as a novel prostate cancer cell surface antigen that shows lineage independent expression in both adenocarcinoma and small cell neuroendocrine subtypes of metastatic castration resistant prostate cancer (mCRPC), discovered an internalizing human monoclonal antibody YS5 that binds to a tumor selective CD46 epitope, and developed a microtubule inhibitor-based antibody drug conjugate that is in a multi-center phase I trial for mCRPC (NCT03575819). Here we report the development of a novel CD46-targeted alpha therapy based on YS5. We conjugated 212Pb, an in vivo generator of alpha-emitting 212Bi and 212Po, to YS5 through the chelator TCMC to create the radioimmunoconjugate, 212Pb-TCMC-YS5. We characterized 212Pb-TCMC-YS5 in vitro and established a safe dose in vivo. We next studied therapeutic efficacy of a single dose of 212Pb-TCMC-YS5 using three prostate cancer small animal models: a subcutaneous mCRPC cell line-derived xenograft (CDX) model (subcu-CDX), an orthotopically grafted mCRPC CDX model (ortho-CDX), and a prostate cancer patient-derived xenograft model (PDX). In all three models, a single dose of 0.74 MBq (20 µCi) 212Pb-TCMC-YS5 was well tolerated and caused potent and sustained inhibition of established tumors, with significant increases of survival in treated animals. A lower dose (0.37 MBq or 10 µCi 212Pb-TCMC-YS5) was also studied on the PDX model, which also showed a significant effect on tumor growth inhibition and prolongation of animal survival. These results demonstrate that 212Pb-TCMC-YS5 has an excellent therapeutic window in preclinical models including PDXs, opening a direct path for clinical translation of this novel CD46-targeted alpha radioimmunotherapy for mCRPC treatment.

Subset analysis of safety and efficacy in asian patients treated with RRx-001 across three clinical trials.

RRx-001, a CD47 antagonist via its inhibition of MYC and the γ-subtype of the peroxisome proliferator-activated receptor (PPAR) has been associated to date with minimal toxicity. The aim of this post-hoc analysis was to evaluate the toxicity and efficacy of RRx-001 in Asian patients since RRx-001, in the context of multiple Phase 3 studies, will be administered in China and Chinese territories as well as potentially throughout the rest of Asia. Patients received 4 mg of RRx-001 in three different antitumor clinical trials with chemotherapy and/or radiation and a retrospective subset efficacy and toxicity analysis was conducted for patients with Asian ancestry in comparison to patients with other ethnic backgrounds. The toxicity and efficacy data from these studies were similar between Asians and the rest of the treated patients. While the sample sizes are too small to draw definitive conclusions, at a dose of 4 mg, when RRx-001 is combined with chemotherapy, no apparent differences in terms of safety and efficacy are observed in cancer patients with Asian ancestry.

Dose Optimization for Single-Channel Vaginal Cylinder High-Dose-Rate Brachytherapy: A Double Prescription Method for Patients With Endometrial Adenocarcinoma.

Purpose This study aimed to explore the relationship between applicator surface dose and 5 mm-depth dose and to optimize both locations simultaneously for three most used cylinder sizes (2.5, 3.0, and 3.5 cm in diameter) in treating patients with endometrial adenocarcinoma. Materials and methods A total of 216 plans were created for each dose level and applicator size. For each dose level, four plans were created with single or double prescription doses. For plans with double prescription doses, the dose constraints were applied to all those points on the surface and 5 mm depth and optimize the two sites simultaneously.  Results A dose table between surface and 5 mm depth and its fifth order polynomial mapping functions were established for each applicator size, so any prescribed dose at one site can find the prescription dose on the other site in optimization on both locations. For plans with a 5 mm-depth prescription, the maximum dose on the surface can be reduced from 145% to 133% if the surface prescription dose is also used; for plans with surface dose prescription, the minimum dose and mean dose can be improved by 2% if 5 mm-depth dose prescription is also used in optimization. Conclusion Dose table and their mapping functions between surface prescription dose and their corresponding 5 mm-depth doses were created. A new optimization method that uses two prescription doses on both surface and 5 mm-depth sites was proposed to reduce the hot dose on the surface and improve the cold dose at 5 mm depth.

Incorporating Treatment Time into Butterfly Optimization to Reduce Total Treatment Time for Vaginal Cylinder Brachytherapy.

Purpose For patient comfort and safety, irradiation times should be kept at a minimum while maintaining high treatment quality. In this study of high dose rate (HDR) therapy with a vaginal cylinder, we used the butterfly optimization algorithm (BOA) to simultaneously optimize individual dwell times for precise dose conformity and for the reduction of total dwell time. Material and methods BOA is a population-based, meta-heuristic algorithm that averts local minima by conducting intensive local and global searching based on switching probability. We constructed an objective function (a stimulus intensity function) that consisted of two components. The first one was the root-mean-squared dose error (RMSE) defined as the square root of the sum of squared differences between the prescribed and delivered dose at the constraint points. The second component was weighted total treatment time. Eight previously treated cases were retrospectively reviewed by re-optimizing the clinical treatment plans with BOA.  Results Compared to the eight original plans generated with the commercial adaptive volume optimization algorithm (AVOA), the BOA-optimized plans reduced treatment times by 5.4% to 8.9%, corresponding to a time-saving of 13.1 to 47.7 seconds with the activities on the treatment day and saving from 29.3 to 64.6 seconds if treated with an activity of 5 CI. Dose deviations from the prescription were smaller than in the original plans. Conclusion  Dose optimizations based on the BOA algorithm yield closer dose conformity in vaginal HDR treatment than AVOA. Incorporating total treatment time into the optimization algorithm reduces the delivery time while having only a small effect on dose conformity.

Selection of brachytherapy applicators based on tumor size and shape for cervical cancer: simulation analysis of pear-shaped isodose dimensions.

The purpose of study is to measure Point A pear-shaped isodose dimensions of the conventional intracavitary brachytherapy with various sizes of colpostats and analyze which size of tumor is the optimal for 3-D interstitial brachytherapy. CT simulation was performed with Fletcher type applicator using various sizes of colpostats (2.0, 2.5, and 3.0 cm diameter). The Manchester standard loading (dwell time) system was used to generate pear-shaped isodose envelopes with high-dose rate iridium-192 according to the colpostat sizes. The size of the pear-shaped envelope was measured at 5 different levels: A-level (center of the colpostats), B-level (top of the colpostats), C-level (between B and D), D-level (Point A), and E-level (1.0 cm above Point A). In this study, it was assumed that uterine tandem was located at the center of tumor. For width of pear-shape: At the A-level, 6.4, 7.3, and 8.0 cm for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the B-level, 5.8, 6.4, and 6.8 cm for 2, 2.5, and 3.0 cm colpostats, respectively. At the C-level, 4.6, 4.8, and 4.8 for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the D-level, 4.0 cm for all different size. At the E-level, 3.8 cm for all 3 different size colpostats. A-level was the largest dimension of pear-shape. However, it was located in the upper vagina below the main cervical mass. The center of the effective pear-shape size for tumor was between the C and D levels. For thickness, all 5 different levels were ranging 3.7 to 4.0 cm. For height, the length of height was dependent on the tandem length. Therefore, the pear-shape envelope was able to accommodate up to 4.0 cm diameter volume. According to our analysis of conventional pear-shape dimension, 3-D interstitial brachytherapy should be considered for tumors larger than 4.0 cm for symmetrical tumor.

[Progress on photodynamic therapy in oral diseases].

Photodynamic therapy (PDT) has developed rapidly in basic and clinical research, and its therapeutic prospects have received increasing attention. PDT has the advantages of minimally invasive, low toxicity, high selectivity, good reproducibility, protection of appearance and vital organ function, and has become a treatment. With the development of medicine, the field of application of PDT becomes more wildly, and brings a new direction for the treatment of oral diseases. This article reviews the basic principles, treatment elements and research results of PDT in the treatment of oral diseases.

Advances on mechanism and treatment of salivary gland in radiation injury.

Oral squamous cell carcinoma (OSCC) is the most frequent tumour in head and neck malignant. The current treatment is mainly based on surgery therapy, radiation therapy and chemical therapy. Meanwhile, there are many a defect in the treatment. For example, there are many defects in radiotherapy. Radioactive salivatitis is the most common. In addition, there are a series of changes such as dry mouth, oral mucositis, rampant dental caries, and radioactive osteomyelitis of jaw, which cause swallowing, chewing problems, and taste dysfunction. Currently, the research on radioactive salivatitis is progressing rapidly, but its mechanism is more complication. This paper review aims to summarize the research progress in this field.

Molecular Imaging of Prostate Cancer Targeting CD46 Using ImmunoPET.

PURPOSE: We recently identified CD46 as a novel therapeutic target in prostate cancer. In this study, we developed a CD46-targeted PET radiopharmaceutical, [89Zr]DFO-YS5, and evaluated its performance for immunoPET imaging in murine prostate cancer models. EXPERIMENTAL DESIGN: [89Zr]DFO-YS5 was prepared and its in vitro binding affinity for CD46 was measured. ImmunoPET imaging was conducted in male athymic nu/nu mice bearing DU145 [AR-, CD46+, prostate-specific membrane antigen-negative (PSMA-)] or 22Rv1 (AR+, CD46+, PSMA+) tumors, and in NOD/SCID gamma mice bearing patient-derived adenocarcinoma xenograft, LTL-331, and neuroendocrine prostate cancers, LTL-331R and LTL-545. RESULTS: [89Zr]DFO-YS5 binds specifically to the CD46-positive human prostate cancer DU145 and 22Rv1 xenografts. In biodistribution studies, the tumor uptake of [89Zr]DFO-YS5 was 13.3 ± 3.9 and 11.2 ± 2.5 %ID/g, respectively, in DU145 and 22Rv1 xenografts, 4 days postinjection. Notably, [89Zr]DFO-YS5 demonstrated specific uptake in the PSMA- and AR-negative DU145 model. [89Zr]DFO-YS5 also showed uptake in the patient-derived LTL-331 and -331R models, with particularly high uptake in the LTL-545 neuroendocrine prostate cancer tumors (18.8 ± 5.3, 12.5 ± 1.8, and 32 ± 5.3 %ID/g in LTL-331, LTL-331R, and LTL-545, respectively, at 4 days postinjection). CONCLUSIONS: [89Zr]DFO-YS5 is an excellent PET imaging agent across a panel of prostate cancer models, including in both adenocarcinoma and neuroendocrine prostate cancer, both cell line- and patient-derived xenografts, and both PSMA-positive and -negative tumors. It demonstrates potential for clinical translation as an imaging agent, theranostic platform, and companion biomarker in prostate cancer.

Nerve growth factor protects salivary glands from irradiation-induced damage.

AIMS: Radiotherapy has become a basic treatment modality for head and neck cancer. However, radiotherapy results in inevitable side effects, particularly radiation sialadenitis, that significantly impairs quality of life. A previous study indicated that nerve growth factor (NGF) has a radio-protective effect, but the mechanism was not determined in salivary glands. In this study, we explored the functional role and mechanism regarding how NGF protects salivary glands against IR-induced damage. MAIN METHODS: Human salivary gland (HSG) cells and C57BL/6 mice were selected to establish an IR-induced salivary gland damage model in vitro and in vivo. Recombinant NGF protein and NGF siRNA and over-expression plasmids were applied to manipulate NGF expression in vitro. AAV-NGF was retrogradely perfused into the submandibular gland (SMG) through the SMG duct to manipulate NGF expression in vitro. Small-molecule inhibitors and siRNAs were applied to inhibit AKT and JNK. Western blotting, quantitative PCR, flow cytometry and histology assays were performed to analyse the functional role and mechanism of NGF. KEY FINDINGS: Our study demonstrated that NGF expression was upregulated following radiotherapy both in human HSG cells and mouse SMG tissues. NGF could reduce IR-induced HSG cell apoptosis, and AAV-mediated gene therapy could restore the salivary flow rate and protect the salivary gland against IR-induced apoptosis in vivo. Mechanistically, NGF protects salivary glands from IR-induced apoptosis by de-phosphorylating JNK kinase rather than promoting AKT phosphorylation. SIGNIFICANCE: The current study findings indicated that the modulation of the NGF pathway might prevent IR-induced salivary hypo-function.

Progress on photodynamic therapy in oral diseases / 华西口腔医学杂志

Photodynamic therapy (PDT) has developed rapidly in basic and clinical research, and its therapeutic prospects have received increasing attention. PDT has the advantages of minimally invasive, low toxicity, high selectivity, good reproducibility, protection of appearance and vital organ function, and has become a treatment. With the development of medicine, the field of application of PDT becomes more wildly, and brings a new direction for the treatment of oral diseases. This article reviews the basic principles, treatment elements and research results of PDT in the treatment of oral diseases.

Advances on mechanism and treatment of salivary gland in radiation injury / 华西口腔医学杂志

Oral squamous cell carcinoma (OSCC) is the most frequent tumour in head and neck malignant. The current treatment is mainly based on surgery therapy, radiation therapy and chemical therapy. Meanwhile, there are many a defect in the treatment. For example, there are many defects in radiotherapy. Radioactive salivatitis is the most common. In addition, there are a series of changes such as dry mouth, oral mucositis, rampant dental caries, and radioactive osteomyelitis of jaw, which cause swallowing, chewing problems, and taste dysfunction. Currently, the research on radioactive salivatitis is progressing rapidly, but its mechanism is more complication. This paper review aims to summarize the research progress in this field.

Epidemiologic relationship between periodontitis and type 2 diabetes mellitus.

BACKGROUND: To systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM). METHODS: Four electronic databases were searched up until December 2018. The manual search included the reference lists of the included studies and relevant journals. Observational studies evaluating the relationship between T2DM and periodontitis were included. Meta-analyses were conducted using STATA. RESULTS: A total of 53 observational studies were included. The Adjusted T2DM prevalence was significantly higher in periodontitis patients (OR = 4.04, p = 0.000), and vice versa (OR = 1.58, p = 0.000). T2DM patients had significantly worse periodontal status, as reflected in a 0.61 mm deeper periodontal pocket, a 0.89 mm higher attachment loss and approximately 2 more lost teeth (all p = 0.000), than those without T2DM. The results of the cohort studies found that T2DM could elevate the risk of developing periodontitis by 34% (p = 0.002). The glycemic control of T2DM patients might result in different periodontitis outcomes. Severe periodontitis increased the incidence of T2DM by 53% (p = 0.000), and this result was stable. In contrast, the impact of mild periodontitis on T2DM incidence (RR = 1.28, p = 0.007) was less robust. CONCLUSIONS: There is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding. Our results suggest that both dentists and physicians need to be aware of the strong connection between periodontitis and T2DM. Controlling these two diseases might help prevent each other's incidence.

Reduced Margin Stereotactic Body Radiation Therapy for Early Stage Non-Small Cell Lung Cancers.

Purpose Our study reports the clinical outcomes of patients treated with 5-mm isotropic margin, fiducial-guided stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC). We also sought to assess the effect of histological subtype on local control. Methods We retrospectively reviewed the charts of all patients treated with SBRT for NSCLC between 2007 and 2017 at our institution. All patients who had implanted fiducial markers, planning target volume (PTV) margins of 5 mm or less, early stage disease (T1-T2, N0), and at least one follow-up CT were included in this analysis. Estimates of local control were generated using the Kaplan-Meier method, and differences between survival curves were assessed using the log-rank test. Results A total of 152 patients met the inclusion criteria for this analysis, with a median follow-up of 27.9 months. Patients received 54 Gy in three fractions for peripheral tumors and 48-52.5 Gy in four to five fractions for central tumors. NSCLC histology was adenocarcinoma in 69 (45.4%) cases, squamous cell carcinoma in 65 (42.8%) cases, and other or non-subtyped in 18 (11.8%) cases. Across the entire cohort, the two-year estimate of local control was 95.1%. When histology was considered, the two-year estimate of local control among patients with adenocarcinoma was 95.6% as compared with 85.0% for patients with other subtypes (p=0.044). Conclusions Fiducial-guided, isotropic 5-mm PTV margin for thoracic SBRT did not compromise local control compared with historical standards. In this series, patients with adenocarcinoma experienced improved local control compared with squamous cell carcinoma.

Semi-permanent transcorneal filter support and in vivo surgical implantation technique for open-angle glaucoma treatment.

Primary open-angle glaucoma is a progressive disease affecting nearly 60 million people worldwide which, if left untreated, can lead to optic nerve head damage and complete loss of sight. Current interventions include: pharmaceutical drops, laser surgery, shunts, and bleb; however, these methods provide insufficient long-term efficacy in intraocular pressure management. We developed a semi-permanent, implantable transcorneal duct as a new aid in the treatment of this disease. The duct, composed of an intracorneal stabilizing washer and hollow screw, creates an interface between the anterior chamber and the external environment, allowing for the outflow of excess aqueous humor. We discuss the fluid mechanics behind designing and implementing a filter material capable of preventing the ingress of bacteria and viruses while modifying aqueous humor outflow resistances to pre-glaucomatous levels, finding the effective radius of such a material to be 10.44 µm. After performing surgical implantation in four rabbit eyes, subsequent testing showed successful integration between the screw and washer. Colored saline injections highlighted fluid flow progression out of the eye through the duct, suggesting that the device may be a viable approach to treating high intraocular pressure created by open-angle glaucoma.

Dose perturbation and inhomogeneity of multi-arrays of 125I seed-loaded stent for treatment of portal vein tumor thrombosis.

PURPOSE: To investigate the dosimetry of 125I seed-loaded stent system currently used for an adjuvant treatment of portal vein tumor thrombosis (PVTT). METHODS: The stent system consisted of an inner metallic stent and outer seed-loaded capsules. Four arrays of 125I seeds were attached longitudinally to the outer surface of the stent at 90° separation. 145 Gy was prescribed at 5 mm from the axes of seed-arrays. For the geometries of the 4-array, and potential 6- and 8-array configurations, treatment planning system (TPS) and Monte Carlo (MC) calculations were performed to evaluate 3D dose distributions and dosimetric impact of the metallic stent. RESULTS: The MC simulations indicated the metallic stent reduced a dose to the prescription points by over 10%, compared to the water-based TPS results. The total activity calculated by the water-based TPS to deliver the prescription dose should compensate for this amount of reduction. The MC- and TPS-calculated doses normalized to the prescription points for the current configuration were in agreements within 4.3% on a cylindrical surface along 5 mm from the axes of seed-arrays. The longitudinal underdosage worsened as approaching the edge of arrays, and ranged from 2.8% to 25.5%. The angular underdosage between neighboring arrays was 2.1%-8.9%. CONCLUSIONS: With this compensation and a special care of near-edge underdosage, the current 4-array system can provide adequate dose coverage for treatment of PVTT. Further dosimetric homogeneity can be achieved using 6-or 8-array configurations.

Electromagnetic Transponder Based Tracking and Gating in the Radiotherapeutic Treatment of Thoracic Malignancies.

PURPOSE: This report details our institutional workflow and technique for use of the Calypso electromagnetic transponder system with respiratory gating for localization and tracking of lung tumors during stereotactic radiation therapy for early stage thoracic malignancies. METHODS AND MATERIALS: Sixteen patients underwent bronchoscopic fiducial placement of 3 transponders in small airways in proximity to the primary tumor. Transponders were placed <19 cm from the most anterior skin location of the patient for appropriate tracking functionality. Patients underwent simulation with 4-dimensional assessment and were treated with transponder based positional gating if tumors moved >5 mm in any direction. Tumor motion <5 mm was not gated and treated using an internal target volume approach. A 5 mm uniform planning target volume was used. Before treatment, fiducial placement and tumor location were verified by daily kilovoltage (kV) and cone beam computed tomography image guidance. Tracking limits were placed based on the movement of the transponders from the centroid of the structures on the maximum intensity projection image. The Calypso treatment system paused treatment automatically if beacons shifted beyond the predefined tracking limits. RESULTS: All 16 patients underwent successful implantation of the electromagnetic transponders. Eight patients exhibited tumor motion sufficient to require respiratory gating, and the other 8 patients were treated using a free breathing internal target volume technique. Difficulty with transponder sensing was experienced in 3 patients as a result of anatomic interference with the placement of the sensing arrays; each of these cases was successfully treated after making setup modifications. Triggered imaging of fiducials during treatment was consistent with real-time positioning determined by the Calypso tracking system. CONCLUSIONS: Respiratory gated electromagnetic based transponder guided stereotactic body radiation therapy using the workflow described is feasible and well tolerated in selected patients with early stage lung malignancies.

Stereotactic radiosurgery with MLC-defined arcs: Verification of dosimetry, spatial accuracy, and end-to-end tests.

PURPOSE: To measure dosimetric and spatial accuracy of stereotactic radiosurgery (SRS) delivered to targets as small as the trigeminal nerve (TN) using a standard external beam treatment planning system (TPS) and multileaf collimator-(MLC) equipped linear accelerator without cones or other special attachments or modifications. METHODS: Dosimetric performance was assessed by comparing computed dose distributions to film measurements. Comparisons included the γ-index, beam profiles, isodose lines, maximum dose, and spatial accuracy. Initially, single static 360° arcs of MLC-shaped fields ranging from 1.6 × 5 to 30 × 30 mm2 were planned and delivered to an in-house built block phantom having approximate dimensions of a human head. The phantom was equipped with markings that allowed accurate setup using planar kV images. Couch walkout during multiple-arc treatments was investigated by tracking a ball pointer, initially positioned at cone beam computed tomography (CBCT) isocenter, as the couch was rotated. Tracks were mapped with no load and a 90 kg stack of plastic plates simulating patient treatment. The dosimetric effect of walkout was assessed computationally by comparing test plans that corrected for walkout to plans that neglected walkout. The plans involved nine 160° arcs of 2.4 × 5 mm2 fields applied at six different couch angles. For end-to-end tests that included CT simulation, target contouring, planning, and delivery, a cylindrical phantom mimicking a 3 mm lesion was constructed and irradiated with the nine-arc regimen. The phantom, lacking markings as setup aids was positioned under CBCT guidance by registering its surface and internal structures with CTs from simulation. Radiochromic film passing through the target center was inserted parallel to the coronal and the sagittal plane for assessment of spatial and dosimetric accuracy. RESULTS: In the single-arc block phantom tests computed maximum doses of all field sizes agreed with measurements within 2.4 ± 2.0%. Profile widths at 50% maximum agreed within 0.2 mm. The largest targeting error was 0.33 mm. The γ-index (3%, 1 mm) averaged over 10 experiments was >1 in only 1% of pixels for field sizes up to 10 × 10 mm2 and rose to 4.4% as field size increased to 20 × 20 mm2 . Table walkout was not affected by load. Walkout shifted the target up to 0.6 mm from CBCT isocenter but, according to computations shifted the dose cloud of the nine-arc plan by only 0.16 mm. Film measurements verified the small dosimetric effect of walkout, allowing walkout to be neglected during planning and treatment. In the end-to-end tests average and maximum targeting errors were 0.30 ± 0.10 and 0.43 mm, respectively. Gamma analysis of coronal and sagittal dose distributions based on a 3%/0.3 mm agreement remained <1 at all pixels. To date, more than 50 functional SRS treatments using MLC-shaped static field arcs have been delivered. CONCLUSION: Stereotactic radiosurgery (SRS) can be planned and delivered on a standard linac without cones or other modifications with better than 0.5 mm spatial and 5% dosimetric accuracy.

Dynamics of the vaginal wall dose in HDR interstitial brachytherapy for gynecological cancer: Systematic analysis of phantom vs patient case.

This study aimed to investigate the dynamics of the vaginal wall dose for interstitial brachytherapy (ISBT). A patient undergoing ISBT was selected as the patient case. The phantom case was generated to simulate the patient case in all regards with the exception of parallel needle positions. The vaginal wall was contoured as a 0.5-cm expansion around the vaginal surface of the obturator. The prescribed ISBT dose was 20 Gy in 4 fractions. Six treatment plans were generated by modifying relative dwell times and needle positions (DTNP). The volume of the vaginal wall receiving > 150% of prescription dose (V> 150%) and D2cc of the vaginal wall were compared among plans. The V> 150% was much larger in the patient case (49.3%) due to unparallel needles compared with the phantom case (14.3%) without modification (plan 1). Among the 6 plans, reduced dwell time (plan 3) and no dwell time (plans 5 and 6) on the vaginal surface needles had the lowest vaginal wall doses with the use of a central obturator needle in both cases. In comparison of patient case plans 1, 3, 5, and 6, V150% was 49.2%, 19.0%, 21.3%, and 28.7%, respectively, and D2cc was 41.15 Gy, 33.10 Gy, 36.51 Gy, and 34.37 Gy, respectively, which was limited around each loaded needle. Modification of DTNP is able to reduce the vaginal wall volume exceeding 150% of the prescription dose in the patient case. Understanding these dynamics of the vaginal wall dose will improve dose optimization of ISBT and may reduce vaginal morbidities.

A novel phantom and procedure providing submillimeter accuracy in daily QA tests of accelerators used for stereotactic radiosurgery*.

Stereotactic radiosurgery (SRS) places great demands on spatial accuracy. Steel BBs used as markers in quality assurance (QA) phantoms are clearly visible in MV and planar kV images, but artifacts compromise cone-beam CT (CBCT) isocenter localization. The purpose of this work was to develop a QA phantom for measuring with sub-mm accuracy isocenter congruence of planar kV, MV, and CBCT imaging systems and to design a practical QA procedure that includes daily Winston-Lutz (WL) tests and does not require computer aid. The salient feature of the phantom (Universal Alignment Ball (UAB)) is a novel marker for precisely localizing isocenters of CBCT, planar kV, and MV beams. It consists of a 25.4mm diameter sphere of polymethylmetacrylate (PMMA) containing a concentric 6.35mm diameter tungsten carbide ball. The large density difference between PMMA and the polystyrene foam in which the PMMA sphere is embedded yields a sharp image of the sphere for accurate CBCT registration. The tungsten carbide ball serves in finding isocenter in planar kV and MV images and in doing WL tests. With the aid of the UAB, CBCT isocenter was located within 0.10 ± 0.05 mm of its true positon, and MV isocenter was pinpointed in planar images to within 0.06 ± 0.04mm. In clinical morning QA tests extending over an 18 months period the UAB consistently yielded measurements with sub-mm accuracy. The average distance between isocenter defined by orthogonal kV images and CBCT measured 0.16 ± 0.12 mm. In WL tests the central ray of anterior beams defined by a 1.5 × 1.5 cm2 MLC field agreed with CBCT isocenter within 0.03 ± 0.14 mm in the lateral direction and within 0.10 ± 0.19 mm in the longitudinal direction. Lateral MV beams approached CBCT isocenter within 0.00 ± 0.11 mm in the vertical direction and within -0.14 ± 0.15 mm longitudinally. It took therapists about 10 min to do the tests. The novel QA phantom allows pinpointing CBCT and MV isocenter positions to better than 0.2 mm, using visual image registration. Under CBCT guidance, MLC-defined beams are deliverable with sub-mm spatial accuracy. The QA procedure is practical for daily tests by therapists.