Intraoperative radiation therapy with 50 kV x-rays: A multi-institutional review.

This report covers clinical implementation of a low kV intraoperative radiation therapy (IORT) program with the INTRABEAM® System (Carl Zeiss Meditec AG, Jena, Germany). Based on collective user experience from eight institutions, we discuss best methods of INTRABEAM quality assurance (QA) tests, commissioning measurements, clinical workflow, treatment planning, and potential avenues for research. The guide provides pertinent background information and clinical justification for IORT. It describes the INTRABEAM system and commissioning measurements along with a TG100 risk management analysis to ensure safety and accuracy of the IORT program. Following safety checks, dosimetry measurements are performed for verification of field flatness and symmetry, x-ray output, and depth dose. Also discussed are dose linearity checks, beam isotropy, ion chamber measurements, calibration protocols, and in-vivo dosimetry with optically stimulated luminescence dosimeters OSLDs, and radiochromic film. Emphasis is placed on the importance of routine QA procedures (daily, monthly, and annual) performed at regular intervals for a successful IORT program. For safe and accurate dose delivery, tests of important components of IORT clinical workflow are emphasized, such as, dose prescription, pre-treatment QA, treatment setup, safety checks, radiation surveys, and independent checks of delivered dose. Challenges associated with in-vivo dose measurements are discussed, along with special treatment procedures and shielding requirements. The importance of treatment planning in IORT is reviewed with reference to a Monte Carlo-based commercial treatment planning system highlighting its main features and limitations. The report concludes with suggested topics for research including CT-based image-guided treatment planning and improved prescription dose accuracy. We hope that this multi-institutional report will serve as a guidance document on the clinical implementation and use of INTRABEAM IORT.

A Retrospective Evaluation of the Benefit of Referring Pediatric Cancer Patients to an External Proton Therapy Center.

BACKGROUND: Pediatric cancer patients requiring radiation therapy (RT) have been routinely assessed and referred to proton therapy (PT) at an external institution. The benefit of the delivered PT compared to the state-of-the-art intensity modulated x-ray RT (XT) at the home institution was evaluated. PROCEDURE: Twenty-four consecutive children referred for PT during 2010-2013 for craniospinal (CSI, n = 10), localized intracranial (IC, n = 7), head/neck (HN, n = 4) or parameningeal (PM, n = 3) lesions were included. The median age was 8 years (2-16 years). XT plans were generated for each patient, blinded to the PT delivered. Dosimetry, estimated growth hormone deficiency (GHD), and neurocognitive dysfunction (NCD) risks were compared for PT and XT (Wilcoxon). RESULTS: PT started (median) 5 weeks (± 1.3 weeks, 95% CI) after referral. For CSI patients, PT was clearly superior to XT plans with median dose reductions for the heart, lungs and thyroid of 17, 2.5 and 18 Gy, respectively (P = 0.005). The median estimated NCD and GHD risks were 1-3 (max 16) and 2 (max 61) percentage points, respectively, lower for PT compared to XT. The median of the mean doses to the brain, cochleae and pituitary gland was lower with PT than XT for the IC, H/N and PM patients (P < 0.039). For a single IC patient, the dose to hippocampi and optic chiasm was higher for PT compared to XT. CONCLUSIONS: PT clearly benefitted the patients studied, except for IC disease where differences between PT and XT were modest, and comparative PT and XT treatment planning is warranted prior to referral.

Use of PET/CT instead of CT-only when planning for radiation therapy does not notably increase life years lost in children being treated for cancer.

BACKGROUND: PET/CT may be more helpful than CT alone for radiation therapy planning, but the added risk due to higher doses of ionizing radiation is unknown. OBJECTIVE: To estimate the risk of cancer induction and mortality attributable to the [F-18]2-fluoro-2-deoxyglucose (FDG) PET and CT scans used for radiation therapy planning in children with cancer, and compare to the risks attributable to the cancer treatment. MATERIALS AND METHODS: Organ doses and effective doses were estimated for 40 children (2-18 years old) who had been scanned using PET/CT as part of radiation therapy planning. The risk of inducing secondary cancer was estimated using the models in BEIR VII. The prognosis of an induced cancer was taken into account and the reduction in life expectancy, in terms of life years lost, was estimated for the diagnostics and compared to the life years lost attributable to the therapy. Multivariate linear regression was performed to find predictors for a high contribution to life years lost from the radiation therapy planning diagnostics. RESULTS: The mean contribution from PET to the effective dose from one PET/CT scan was 24% (range: 7-64%). The average proportion of life years lost attributable to the nuclear medicine dose component from one PET/CT scan was 15% (range: 3-41%). The ratio of life years lost from the radiation therapy planning PET/CT scans and that of the cancer treatment was on average 0.02 (range: 0.01-0.09). Female gender was associated with increased life years lost from the scans (P < 0.001). CONCLUSION: Using FDG-PET/CT instead of CT only when defining the target volumes for radiation therapy of children with cancer does not notably increase the number of life years lost attributable to diagnostic examinations.

The effect of low-dose radiation spillage during stereotactic radiosurgery for brain metastases on the development of de novo metastases.

PURPOSE/OBJECTIVES: Stereotactic radiosurgery (SRS) for metastatic disease to the brain is associated with higher in-brain failures compared to whole brain radiation therapy (WBRT). Here we investigated the relationship between low-dose fall off during SRS and location of new brain lesions. MATERIALS AND METHODS: One hundred sixty-seven patients treated with single fraction or fractionated SRS for intact or resected brain metastases at our institution from January 2016 to June 2018 were reviewed. Patients with imaging findings of new brain metastases after the initial SRS were included. Patients with WBRT before SRS were excluded. MRI scans for repeat treatments were fused with initial SRS plan. New lesions were outlined on the initial SRS planning CT. The mean dose that the site of new lesions received from initial SRS was tabulated. RESULTS: Thirty-eight patients met inclusion criteria. 165 new lesions were evaluated. There was a lower propensity to develop new brain lesions with increasing dose received by the regions from prior SRS, with 66%, 34%, 19%, 13%, 6%, 5%, 2% and 1% of new lesions appearing in regions that received less than 1 Gy, greater than or equal to 1, 2, 3, 4, 5, 6, and 7 Gy, respectively. Higher doses are received by smaller brain volumes during SRS. After accounting for volume, 14, 14, 11, 7, 2, 2, 1 and 1 new lesions appeared per 100 cm3 of brain in regions that received doses of less than 1 Gy, greater than or equal to 1, 2, 3, 4, 5, 6, and 7 Gy, respectively, from prior SRS. CONCLUSIONS: We identified low dose spillage during SRS to be associated with lower incidence of new brain metastases. Validation in larger dataset or prospective study of the combination of SRS with low dose WBRT would be crucial in order to establish causality of these findings.

Hybrid tandem and ovoids brachytherapy in locally advanced cervical cancer: impact of dose and tumor volume metrics on outcomes.

PURPOSE: To report the impact of dose and tumor volume metrics at brachytherapy on outcomes for locally advanced cervical cancer treated with tandem and ovoids intracavitary/interstitial brachytherapy. MATERIAL AND METHODS: FIGO stage IB1-IIIB locally advanced cervical cancer treated with intracavitary/interstitial brachytherapy via a tandem and ovoids hybrid applicator were analyzed. Median high-risk clinical target volume (HR-CTV), rate of tumor volume reduction, EQD2 D90, organ at risk doses, and outcomes were recorded. Univariable and multivariable Cox regression was applied for survival analysis, and logistic regression was used for toxicity analysis. RESULTS: Seventy-one patients were identified. Median follow-up was 24.9 months, with a 2-year local control of 83.6%, loco-regional control of 72.0%, and overall survival of 88.6%. Median HR-CTV D90 was 87.4 Gy (IQR = 85.7-90.2). Median HR-CTV D90 > 90 Gy10 showed a trend toward improved local control (LC) (p = 0.19). Median HR-CTV was 37.9 cm3, and median V100 was 86.5%. A median HR-CTV of ≥ 40 cm3 demonstrated worse loco-regional control (LRC) (p = 0.018) and progression-free survival (p = 0.021). Two-year LC and LRC for stage IIB patients with a median HR-CTV < 40 cm3 were significantly improved as compared to ≥ 40 cm3 at 100% and 71.8%, respectively (p = 0.019) and 100% and 56.5%, respectively (p = 0.001). However, this trend was not statistically significant for stage IIIB patients. Higher percent per day reduction in HR-CTV during brachytherapy showed improved LRC (p = 0.045). Four percent of patients experienced acute grade 3 genitourinary toxicity, 1% late grade 3 genitourinary and 1% late grade 3 gastrointestinal toxicity. CONCLUSIONS: Tandem and ovoids intracavitary/interstitial brachytherapy provides satisfactory outcomes with modest toxicity. Higher HR-CTV D90 coverage demonstrated a trend toward improved tumor control. Tumor volume based on median HR-CTV ≥ 40 cm3 at brachytherapy was prognostic for poor outcomes, even within initial FIGO stage groups warranting caution.

Comprehensive Patient-Specific Intensity-Modulated Radiation Therapy Quality Assurance Comparing Mobius3D/FX to Conventional Methods of Evaluation.

Purpose To determine the appropriateness of implementing Mobius3D/FX (Varian Medical Systems, Inc., Palo Alto, CA, USA) as not only a pretreatment secondary check but as an alternative to measurement-based patient-specific intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods Mobius3D/FX was commissioned and stock beam models were tweaked so that an independent recalculated 3D dose distribution can be obtained. Then, 50 patient-specific treatment plans for various indications were delivered across a 2D ion chamber array, radiochromic film setup, and electronic portal imager and analyzed with MobiusFX and gamma analysis. The concordance of plans scored as passing between MobiusFX and the conventional methods of QA was determined. Results All analyzed treatment plans passed with a gamma passing rate >90% across all conventional QA methods, most commonly using a 3%/3mm gamma criterion except for film measurements where a 5%/3mm criterion was applied. There was good agreement and concordance between MobiusFX and conventional methods when using a 3%/3mm criteria for MobiusFX, whereas a 2%/2mm criteria appeared too stringent as it failed treatment plans deemed clinically acceptable using conventional methods. Conclusions Using a 50-sample subset of clinically delivered treatment plans this non-inferiority-type comparison shows Mobius3D/FX based on log file analysis to be a suitable alternative to conventional QA methods when utilizing the 3%/3mm gamma criterion. Methods based on log file analysis can provide an opportunity for resource sparing, improving the efficiency, and workflow for evaluating IMRT treatment plans.

Nestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate.

In the prostate, stem and progenitor cell regenerative capacities have been ascribed to both basal and luminal epithelial cells. Here, we show that a rare subset of mesenchymal cells in the prostate are epithelial-primed Nestin-expressing cells (EPNECs) that can generate self-renewing prostate organoids with bipotential capacity. Upon transplantation, these EPNECs can form prostate gland tissue grafts at the clonal level. Lineage-tracing analyses show that cells marked by Nestin or NG2 transgenic mice contribute to prostate epithelium during organogenesis. In the adult, modest contributions in repeated rounds of regression and regeneration are observed, whereas prostate epithelial cells derived from Nestin/NG2-marked cells are dramatically increased after severe irradiation-induced organ damage. These results indicate that Nestin/NG2 expression marks a novel radioresistant prostate stem cell that is active during development and displays reserve stem cell activity for tissue maintenance.

In Vitro Photoirradiation System for Simultaneous Irradiation with Different Light Doses at a Fixed Temperature.

OBJECTIVE: In this work an irradiance and temperature controlled in-vitro system for conducting investigations in PDT and phototherapy is presented. BACKGROUND DATA: The development of new light sources has caused a considerable increase in research and application of several photodynamic (PDT) therapeutic methods, as well as other light-based therapeutic techniques. However, further work is needed to fully understand and elucidate the mechanisms as well as to increase the effectiveness of PDT. Nowadays, there are no commercial systems to perform automated light exposure experiments with cultured cells. Also, there are very few reports of similar photoirradiation systems. MATERIALS AND METHODS: The system is composed of 24 independent light-emitting diodes that can be used to irradiate separate wells in a microwell plate. The system includes a module to measure changes in temperature within each irradiated well without contact. The light sources are placed on a plate that can easily be changed in order to irradiate at different wavelengths. The performance of the system is fully controlled with a computer, and all the experimental data are properly recorded. RESULTS: The design, construction, operation, and a full characterization of the system are presented. CONCLUSIONS: A novel fully automated photoirradiation system has been developed. The system allows the design of the experiments in this area with precise dosimetry, temperature, and irradiation regime controls reducing manipulation of the samples and saving time.