A quick guide on implementing and quality assuring 3D printing in radiation oncology.

As three-dimensional (3D) printing becomes increasingly common in radiation oncology, proper implementation, usage, and ongoing quality assurance (QA) are essential. While there have been many reports on various clinical investigations and several review articles, there is a lack of literature on the general considerations of implementing 3D printing in radiation oncology departments, including comprehensive process establishment and proper ongoing QA. This review aims to guide radiation oncology departments in effectively using 3D printing technology for routine clinical applications and future developments. We attempt to provide recommendations on 3D printing equipment, software, workflow, and QA, based on existing literature and our experience. Specifically, we focus on three main applications: patient-specific bolus, high-dose-rate (HDR) surface brachytherapy applicators, and phantoms. Additionally, cost considerations are briefly discussed. This review focuses on point-of-care (POC) printing in house, and briefly touches on outsourcing printing via mail-order services.

Iris melanoma presenting as childhood glaucoma.

PURPOSE: To describe the natural history and management of a rare case of iris melanoma in a pediatric patient. OBSERVATIONS: A Caucasian female presented with left pupillary abnormalities at age 7, progressive iris changes at age 9, and markedly elevated intraocular pressure with advanced optic nerve cupping at 11 years of age. She was found to have a pigmented lesion overlying her iris and invading her angle. Trans-corneal fine needle aspirate biopsy demonstrated malignant melanoma of the iris. The patient subsequently underwent Iodine-125 plaque brachytherapy for the tumor. CONCLUSIONS: and Importance: Early identification and treatment of iris melanoma may be associated with decreased risk of local progression and metastatic disease. Treatment of glaucoma in conjunction with uveal melanoma is complicated by tumor specific considerations, including treatment of the tumor and prevention of metastasis.

Validation of a modern second-check dosimetry system using a novel verification phantom.

PURPOSE: To evaluate the Mobius second-check dosimetry system by comparing it to ionization-chamber dose measurements collected in the recently released Mobius Verification Phantom™ (MVP). For reference, a comparison of these measurements to dose calculated in the primary treatment planning system (TPS), Varian Eclipse with the AcurosXB dose algorithm, is also provided. Finally, patient dose calculated in Mobius is compared directly to Eclipse to demonstrate typical expected results during clinical use of the Mobius system. METHODS: Seventeen anonymized intensity-modulated clinical treatment plans were selected for analysis. Dose was recalculated on the MVP in both Eclipse and Mobius. These calculated doses were compared to doses measured using an A1SL ionization-chamber in the MVP. Dose was measured and analyzed at two different chamber positions for each treatment plan. Mobius calculated dose was then compared directly to Eclipse using the following metrics; target mean dose, target D95%, global 3D gamma pass rate, and target gamma pass rate. Finally, these same metrics were used to analyze the first 36 intensity modulated cases, following clinical implementation of the Mobius system. RESULTS: The average difference between Mobius and measurement was 0.3 ± 1.3%. Differences ranged from -3.3 to + 2.2%. The average difference between Eclipse and measurement was -1.2 ± 0.7%. Eclipse vs. measurement differences ranged from -3.0 to -0.1%. For the 17 anonymized pre-clinical cases, the average target mean dose difference between Mobius and Eclipse was 1.0 ± 1.1%. Average target D95% difference was -0.9 ± 2.0%. Average global gamma pass rate, using a criteria of 3%, 2 mm, was 94.4 ± 3.3%, and average gamma pass rate for the target volume only was 80.2 ± 12.3%. Results of the first 36 intensity-modulated cases, post-clinical implementation of Mobius, were similar to those seen for the 17 pre-clinical test cases. CONCLUSION: Mobius correctly calculated dose for each tested intensity modulated treatment plan, agreeing with measurement to within 3.5% for all cases analyzed. The dose calculation accuracy and independence of the Mobius system is sufficient to provide a rigorous second-check of a modern TPS.

Pretreatment albumin may aid in patient selection for intrahepatic Y-90 microsphere transarterial radioembolization (TARE) for malignancies of the liver.

BACKGROUND: Hepatic malignancies are common including primary malignancies and metastases. Transarterial radioembolization (TARE) is an important treatment option. We reviewed safety and efficacy of (TARE) in our patients to identify factors that may impact treatment outcomes in a heterogeneous population. METHODS: All patients that received TARE at the Medical University of South Carolina from March 2006 through May of 2014 were included. Kaplan-Meier estimates on overall survival (OS) from date of first procedure are reported. Potential prognostic factors for OS were evaluated using log rank tests and Cox proportional hazards models. RESULTS: In the 114 patients that received TARE at our institution, median follow-up was 6.4 months (range, 0-86 months) with the following histologies: colorectal (CR) n=55, hepatocellular (HC) n=20, cholangiocarcinoma (CC) n=16, neuroendocrine (NE) n=12, breast (BR) n=6, other n=5. At least 1 line of prior systemic therapy was noted in 79% of patients. Median OS was significantly better with NE and BR histology, and in those with normal albumin levels. With an albumin >3.4 median OS was 10.3 months, but was only 3.1 months with an albumin <3 g/dL. Grade ≥2 toxicity was observed in 22 patients (19.3%) including 9 (7.9%) with Grade 3 and 1 (0.9%) with Grade 4 toxicity. CONCLUSIONS: TARE is a relatively safe and effective treatment for intrahepatic malignancies. Patients with NE and BR histology as well as those with better hepatic synthetic function were associated with significantly better survival. Our data suggest that patients with albumin below 3 g/dL may not derive significant benefit from TARE.

Assessment of a three-dimensional (3D) water scanning system for beam commissioning and measurements on a helical tomotherapy unit.

Beam scanning data collected on the tomotherapy linear accelerator using the TomoScanner water scanning system is primarily used to verify the golden beam profiles included in all Helical TomoTherapy treatment planning systems (TOMO TPSs). The user is not allowed to modify the beam profiles/parameters for beam modeling within the TOMO TPSs. The authors report the first feasibility study using the Blue Phantom Helix (BPH) as an alternative to the TomoScanner (TS) system. This work establishes a benchmark dataset using BPH for target commissioning and quality assurance (QA), and quantifies systematic uncertainties between TS and BPH. Reproducibility of scanning with BPH was tested by three experienced physicists taking five sets of measurements over a six-month period. BPH provides several enhancements over TS, including a 3D scanning arm, which is able to acquire necessary beam-data with one tank setup, a universal chamber mount, and the OmniPro software, which allows online data collection and analysis. Discrepancies between BPH and TS were estimated by acquiring datasets with each tank. In addition, data measured with BPH and TS was compared to the golden TOMO TPS beam data. The total systematic uncertainty, defined as the combination of scanning system and beam modeling uncertainties, was determined through numerical analysis and tabulated. OmniPro was used for all analysis to eliminate uncertainty due to different data processing algorithms. The setup reproducibility of BPH remained within 0.5 mm/0.5%. Comparing BPH, TS, and Golden TPS for PDDs beyond maximum depth, the total systematic uncertainties were within 1.4mm/2.1%. Between BPH and TPS golden data, maximum differences in the field width and penumbra of in-plane profiles were within 0.8 and 1.1 mm, respectively. Furthermore, in cross-plane profiles, the field width differences increased at depth greater than 10 cm up to 2.5 mm, and maximum penumbra uncertainties were 5.6mm and 4.6 mm from TS scanning system and TPS modeling, respectively. Use of BPH reduced measurement time by 1-2 hrs per session. The BPH has been assessed as an efficient, reproducible, and accurate scanning system capable of providing a reliable benchmark beam data. With this data, a physicist can utilize the BPH in a clinical setting with an understanding of the scan discrepancy that may be encountered while validating the TPS or during routine machine QA. Without the flexibility of modifying the TPS and without a golden beam dataset from the vendor or a TPS model generated from data collected with the BPH, this represents the best solution for current clinical use of the BPH.

Slug expression inhibits calcitriol-mediated sensitivity to radiation in colorectal cancer.

Recently, a reciprocal relationship between calcitriol and epithelial-to-mesenchymal transition has been described. Therefore, we hypothesized that calcitriol (1α,25-dihydroxyvitamin D3) would enhance radiation sensitivity in colorectal cancer regulated by epithelial mesenchymal transition. Vitamin-D receptor, E-cadherin and vimentin protein as well as E-cadherin, Snail and Slug mRNA levels were assessed in a panel of human colorectal cancer cell lines at baseline and in response calcitriol. We defined cell lines as calcitriol sensitive based on demonstrating an enhanced epithelial phenotype with increased E-cadherin, reduced vimentin and decreased expression of Snail and Slug as well as decreased cellular migration in response to calcitriol. In calcitriol sensitive cells, including DLD-1 and HCT116, 24 h calcitriol pre-treatment enhanced the radiation sensitivity by 2.3- and 2.6-fold, respectively, at 4 Gy (P < 0.05). In contrast, SW620 cells with high baseline mesenchymal features including high Slug and vimentin expression with low E-cadherin expression demonstrated no significant radiation sensitizing response to calcitriol treatment. Similarly, transfection of Slug in the calcitriol sensitive colon cancer cell lines, DLD-1 and HCT 116, completely inhibited the radiation sensitizing effect of calcitriol. Collectively, we demonstrate that calcitriol can enhance the therapeutic effects of radiation in colon cancer cells and Slug expression mitigates this observed effect potentially representing an effective biomarker for calcitriol therapy.

Comparison of radiation treatment delivery for pancreatic cancer: Linac intensity-modulated radiotherapy versus helical tomotherapy.

INTRODUCTION: Intensity-modulated radiotherapy (IMRT) has been shown to reduce dose to organs at risk (OAR) while adequately treating tumour volume. This study quantitatively compares the dosimetric differences from step-and-shoot IMRT compared with helical tomotherapy (HT) for pancreatic head cancer. METHODS: Twelve consecutive patients with non-metastatic, stage T3 or T4, unresectable pancreatic head cancer were planned for step-and-shoot IMRT as well as HT. Radiotherapy was planned to deliver 45.9 Gy to the clinical target volume in 30 fractions with an integrated boost to 54 Gy to the gross tumour volume (planning target volume 5400 including a 1-cm set-up margin). The uniformity index (UI) and conformity index (CI) were used to compare the quality of target coverage, while the quality index (QI) compared the dosimetric performance for OAR. RESULTS: Both methods were effective at covering the tumour with no significant difference in UI or CI. However, HT dosimetry exhibited superior sparing of OAR with significantly less stomach (mean QI(StomV30) = 0.84, P = 0.006) and small bowel dosing (mean small bowel QI(SBV30) = 0.84, P = 0.005). HT reduced dose to the kidney receiving the highest dose but the overall volume of kidney receiving 18 Gy was not significantly different between the two systems, indicating that HT spread the dose more uniformly through the kidneys. CONCLUSIONS: Target coverage is equivalent between the two systems; however, HT shows significantly better sparing of the stomach and small bowel. The decreased dose to OAR with HT is likely to improve the therapeutic ratio in the radiotherapy of pancreatic head cancers.

Calibration of the Gamma Knife Perfexion using TG-21 and the solid water Leksell dosimetry phantom.

PURPOSE: To calibrate a Gamma Knife (GK) Perfexion using TG-21 with updated chamber-dependent values for modern microionization chambers in the new solid water Leksell dosimetry phantom. This work illustrates a calibration method using commercially available equipment, instruments, and an established dosimetry protocol that may be adopted at any GK center, thus reducing the interinstitutional variation in GK calibration. The calibration was verified by three third-party dosimetry checks. In addition, measurements of the relative output factors are presented and compared to available data and the new manufacturer-provided relative output factors yet to be released. METHODS: An absolute dose calibration based on the TG-21 formalism, utilizing recently reported phantom material and chamber-dependent factors, was performed using a microionization chamber in a spherical solid water phantom. The result was compared to other calibration protocols based on TG-51. Independent verification of the machine output was conducted through M.D. Anderson Dosimetry Services (MDADS), using thermoluminescent dosimeters (TLDs) in an anthropomorphic head phantom; the Radiological Physics Center (RPC), using TLDs in the standard Elekta ABS plastic calibration phantom (gray phantom), included with the GK; and through a collaborative international calibration survey by the University of Pittsburgh Medical Center (UPMC) using alanine dosimeters, also in the gray phantom. The alanine dosimeters were read by the National Institute of Standards and Technology. Finally, Gafchromic EBT film was used to measure relative output factors and these factors were compared to values reported in the literature as well as new values announced for release by Elekta. The films were exposed in the solid water phantom using an included film insert accessory. RESULTS: Compared to the TG-21 protocol in the solid water phantom, the modified and unmodified TG-51 calibrations resulted in dose rates which were 1.8% and 1.3% lower, respectively. Ratios of the doses measured by third parties to the dose reported showed excellent agreement. MDADS returned ratios of 1.00 and 0.98 for the two TLDs irradiated. The RPC returned a mean ratio of 0.98 of the dose reported and the UPMC alanine study returned a mean ratio of 1.008. Relative output factors were found to be 0.817 +/- 0.009 and 0.897 +/- 0.008 for the 4 and 8 mm collimators, respectively, which are in excellent agreement with revised Monte Carlo-derived relative output factors Elekta is expected to recommend with the next version of the GK treatment planning software (GAMMAPLAN version 10). CONCLUSIONS: The TG-21 dosimetry protocol, performed in a solid water phantom in conjunction with modern dosimeters and phantom material and chamber-dependent factors, can yield an accurate dose measurement in the unique GK treatment geometry. The technique described here can be easily adopted by institutions worldwide since all equipment and instruments used are commercially available, thus reducing the existing interinstitutional variation in GK calibration techniques. Relative output factor measurements made in this same solid water phantom were used to verify the relative output factors provided by Elekta and agreed excellently with output factors expected to be released in conjunction with GAMMAPLAN version 10.

Comparison of intraoperatively built custom linked seeds versus loose seed gun applicator technique using real-time intraoperative planning for permanent prostate brachytherapy.

PURPOSE: To report our dosimetric results using a novel push-button seed delivery system that constructs custom links of seeds intraoperatively. METHODS AND MATERIALS: From 2005 to 2007, 43 patients underwent implantation using a gun applicator (GA), and from 2007 to 2008, 48 patients underwent implantation with a novel technique allowing creation of intraoperatively built custom links of seeds (IBCL). Specific endpoint analyses were prostate D90% (pD90%), rV100% > 1.3 cc, and overall time under anesthesia. RESULTS: Final analyses included 91 patients, 43 GA and 48 IBCL. Absolute change in pD90% (ΔpD90%) between intraoperative and postoperative plans was evaluated. Using GA method, the ΔpD90% was -8.1 Gy and -12.8 Gy for I-125 and Pd-103 implants, respectively. Similarly, the IBCL technique resulted in a ΔpD90% of -8.7 Gy and -9.8 Gy for I-125 and Pd-103 implants, respectively. No statistically significant difference in ΔpD90% was found comparing methods. The GA method had two intraoperative and 10 postoperative rV100% >1.3 cc. For IBCL, five intraoperative and eight postoperative plans had rV100% >1.3 cc. For GA, the mean time under anesthesia was 75 min and 87 min for Pd-103 and I-125 implants, respectively. For IBCL, the mean time was 86 and 98 min for Pd-103 and I-125. There was a statistical difference between the methods when comparing mean time under anesthesia. CONCLUSIONS: Dosimetrically relevant endpoints were equivalent between the two methods. Currently, time under anesthesia is longer using the IBCL technique but has decreased over time. IBCL is a straightforward brachytherapy technique that can be implemented into clinical practice as an alternative to gun applicators.

Imaging applications in multicatheter brachytherapy for soft tissue sarcomas.

Multicatheter brachytherapy can be applied as a monotherapy or in combination with external beam radiotherapy as an adjuvant treatment for soft tissue sarcoma. Successful application of brachytherapy in the treatment of soft tissue sarcoma requires implementation of multiple imaging modalities during preoperative and postoperative planning. Preoperative imaging is essential in planning local therapy for soft tissue sarcoma in that it defines the proximity of the tumor to adjacent critical structures, predicts the likelihood of close or positive surgical margins, and aids in defining the target volume for a brachytherapy implant. In the postoperative setting, imaging is utilized to assess the accuracy of target volume coverage and integrity of the implant, as well as in three-dimensional treatment planning.

Feasibility of postmastectomy treatment with helical TomoTherapy.

PURPOSE: To investigate the potential of helical tomotherapy for postmastectomy radiation therapy. METHODS AND MATERIALS: By use of the TomoTherapy Hi-Art II treatment-planning system (TomoTherapy Inc., Madison, WI), helical tomotherapy dose plans were developed for 5 patients and compared with the mixed-beam (electron-photon) plans with which they had been treated. The TomoTherapy plans were evaluated by use of dose-volume quantities, tumor control probability, normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). RESULTS: The TomoTherapy plans showed better dose homogeneity in the planning treatment volume containing the chest wall and internal mammary nodes (p = 0.001) and eliminated the need for abutting fields. For the normal tissues, the TomoTherapy plans showed a smaller fractional volume receiving 20 Gy or greater for the ipsilateral lung (p = 0.05), no change in NTCP for postradiation pneumonitis, increased SCCP for each lung and both lungs together (p < 0.02), no change in the volume of the heart receiving more than 15 Gy, no change in NTCP for excess cardiac mortality, and a larger mean dose and SCCP in the contralateral breast (p < 0.001). For nonspecific tissues, the volume receiving between 5 Gy and 25 Gy and SCCP were both larger for the TomoTherapy plans (p < 0.01). Total SCCP was larger for the TomoTherapy plans (p = 0.001). CONCLUSIONS: Overall, the TomoTherapy plans had comparable tumor control probability and NTCP to the mixed-beam plans and increased SCCP. The TomoTherapy plans showed significantly greater dose homogeneity in the chest wall, which offers the potential for improved cosmesis after treatment. These factors have resulted in TomoTherapy often being the treatment of choice for postmastectomy radiation therapy in our clinic.

Incidence and prognostic factors for seroma development after MammoSite breast brachytherapy.

PURPOSE: Describe the incidence and identify risk factors for seroma development after MammoSite breast brachytherapy (MBT). METHODS AND MATERIALS: MBT patient data were prospectively recorded into a quality assurance database. Departmental and electronic records were reviewed to extract patient-, treatment-, and outcome-specific data. Stepwise logistic regression analysis was performed to identify factors associated with development of any seroma including the subset of clinically significant seroma (CSS). CSS was defined as a symptomatic seroma requiring multiple aspirations, biopsy, and/or excision. Variables analyzed included age, weight, number of excisions, time from resection to catheter placement, placement technique, balloon volume, dosimetric factors, and postbrachytherapy infection. RESULTS: MBT was performed in 109 patients, of whom 97 had minimum 6 months (median, 36) post-MBT follow-up or earlier development of seroma. All patients received 34 Gy to 1cm depth from balloon surface, delivered twice daily in 10 fractions. Seroma developed in 41% of patients at a median of 3 months (range, 0.1-25) post-MBT. One-third of seromas (13% of all patients) were CSS. The only factor identified as statistically significant for development of any seroma was catheter placement on day of resection vs. > or =1 day later (59% vs. 33%; p = 0.0066). Post-MBT infection was highly statistically significant for development of CSS (64% vs. 7%; p<0.0001). Prophylactic antibiotics reduced the risk of post-MBT infection from 37.5% to 6% (p = 0.011). CONCLUSIONS: The incidence of CSS after MBT is low. Post-MBT infection is statistically significantly associated with CSS development, the incidence of which is reduced with prophylactic antibiotics.

Helical tomotherapy for total lymphoid irradiation.

Total lymphoid irradiation is employed in the preparative regimens for allogeneic bone marrow and solid organ transplantation, solid organ transplant rejection, and chronic graft-versus-host disease. Linear accelerator-based radiotherapy, typically involving opposed anteroposterior and posteroanterior beams, has been commonly used; however, extended source-to-skin patient setup and/or field matching are required, and all organs within the beam coverage receive the entire prescribed dose. Megavoltage helical tomotherapy represents a technological advance in terms of both treatment delivery and patient positioning. The continuously rotating multileaf collimated fan beam allows highly conformal coverage of complex target geometries, in turn allowing avoidance of radiosensitive adjacent organs. In addition, the megavoltage computed tomographic scans allow potentially more accurate, targetbased setup verification. The present case report describes tomotherapy-based total lymphoid irradiation in an adult patient with late-onset cardiac transplant rejection. Treatment planning allowed dose minimization to the spinal cord, kidneys, intestinal compartment, and lungs. The patient tolerated treatment well without acute adverse effects, and he is now in early follow-up.