Michael Bassetti, MD, PhD

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT.

METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves.

RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set).

CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

PMID:38512616 | DOI:10.1007/s11547-024-01761-7

PURPOSE: To determine whether 4-dimensional computed tomography (4DCT) ventilation-based functional lung avoidance radiation therapy preserves pulmonary function compared with standard radiation therapy for non-small cell lung cancer (NSCLC).

METHODS AND MATERIALS: This single center, randomized, phase 2 trial enrolled patients with NSCLC receiving curative intent radiation therapy with either stereotactic body radiation therapy or conventionally fractionated radiation therapy between 2016 and 2022. Patients were randomized 1:1 to standard of care radiation therapy or functional lung avoidance radiation therapy. The primary endpoint was the change in Jacobian-based ventilation as measured on 4DCT from baseline to 3 months postradiation. Secondary endpoints included changes in volume of high- and low-ventilating lung, pulmonary toxicity, and changes in pulmonary function tests (PFTs).

RESULTS: A total of 122 patients were randomized and 116 were available for analysis. Median follow up was 29.9 months. Functional avoidance plans significantly (P < .05) reduced dose to high-functioning lung without compromising target coverage or organs at risk constraints. When analyzing all patients, there was no difference in the amount of lung showing a reduction in ventilation from baseline to 3 months between the 2 arms (1.91% vs 1.87%; P = .90). Overall grade ≥2 and grade ≥3 pulmonary toxicities for all patients were 24.1% and 8.6%, respectively. There was no significant difference in pulmonary toxicity or changes in PFTs between the 2 study arms. In the conventionally fractionated cohort, there was a lower rate of grade ≥2 pneumonitis (8.2% vs 32.3%; P = .049) and less of a decline in change in forced expiratory volume in 1 second (-3 vs -5; P = .042) and forced vital capacity (1.5 vs -6; P = .005) at 3 months, favoring the functional avoidance arm.

CONCLUSIONS: There was no difference in posttreatment ventilation as measured by 4DCT between the arms. In the cohort of patients treated with conventionally fractionated radiation therapy with functional lung avoidance, there was reduced pulmonary toxicity, and less decline in PFTs suggesting a clinical benefit in patients with locally advanced NSCLC.

PMID:38387810 | DOI:10.1016/j.ijrobp.2024.02.019

For MR-guided radiation therapy treatment planning, an MRI and CT of the intended treatment site are typically acquired. Patients' prior treatments or procedures can cause image artifacts in one or both scans, which may impact treatment planning or the radiation dose calculation. In this case report, a patient with several previous transcatheter arterial chemoembolization (TACE) procedures was planned for radiation therapy on a low-field MR-linac, and the impact of residual iodinated oil on the radiation dose calculation and MR-guided adaptive workflow was evaluated.

PMID:38222202 | PMC:PMC10784766 | DOI:10.7759/cureus.50459

Oligometastatic state is believed to potentially represent a transitional stage between early, locoregional state disease and widely metastatic disease. Historically, locoregional approaches, particularly in advanced colorectal cancers, have demonstrated efficacy in select patients with limited burden of metastatic disease. Recent strides in systemic therapies, including biomarker-based treatments and immunotherapy, alongside innovations in surgical techniques and novel locoregional approaches such as stereotactic radiotherapy and ablation, have ushered in a new era of therapeutic possibilities across all oligometastatic GI cancers. Despite these advancements, there remains a significant gap in high-quality prospective evidence guiding patient selection and treatment decisions across various disease types. Ongoing clinical trials are anticipated to provide crucial insights into oligometastatic states, fostering the refinement of disease-specific oligometastatic state definitions and treatment algorithms. This article reviews existing data on the management of oligometastatic GI cancer, summarizes current state of knowledge for each disease state, and provides updates on ongoing studies in this space.

PMID:38190577 | DOI:10.1200/EDBK_430152

BACKGROUND AND PURPOSE: Radiation dose escalation may improve local control (LC) and overall survival (OS) in select pancreatic ductal adenocarcinoma (PDAC) patients. We prospectively evaluated the safety and efficacy of ablative stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) for borderline resectable (BRPC) and locally advanced pancreas cancer (LAPC). The primary endpoint of acute grade ≥ 3 gastrointestinal (GI) toxicity definitely related to SMART was previously published with median follow-up (FU) 8.8 months from SMART. We now present more mature outcomes including OS and late toxicity.

MATERIALS AND METHODS: This prospective, multi-center, single-arm open-label phase 2 trial (NCT03621644) enrolled 136 patients (LAPC 56.6 %; BRPC 43.4 %) after ≥ 3 months of any chemotherapy without distant progression and CA19-9 ≤ 500 U/mL. SMART was delivered on a 0.35 T MR-guided system prescribed to 50 Gy in 5 fractions (biologically effective dose10 [BED10] = 100 Gy). Elective coverage was optional. Surgery and chemotherapy were permitted after SMART.

RESULTS: Mean age was 65.7 years (range, 36-85), induction FOLFIRINOX was common (81.7 %), most received elective coverage (57.4 %), and 34.6 % had surgery after SMART. Median FU was 22.9 months from diagnosis and 14.2 months from SMART, respectively. 2-year OS from diagnosis and SMART were 53.6 % and 40.5 %, respectively. Late grade ≥ 3 toxicity definitely, probably, or possibly attributed to SMART were observed in 0 %, 4.6 %, and 11.5 % patients, respectively.

CONCLUSIONS: Long-term outcomes from the phase 2 SMART trial demonstrate encouraging OS and limited severe toxicity. Additional prospective evaluation of this novel strategy is warranted.

PMID:38135187 | DOI:10.1016/j.radonc.2023.110064

PURPOSE: Ablative local treatment of all radiographically detected metastatic sites in patients with oligometastatic non-small cell lung cancer (NSCLC) increases progression-free survival (PFS) and overall survival (OS). Prior studies demonstrated the safety of combining stereotactic body radiation therapy (SBRT) with single-agent immunotherapy. We investigated the safety of combining SBRT to all metastatic tumor sites with dual checkpoint, anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), and anti-programmed cell death ligand 1 (anti-PD-L1) immunotherapy for patients with oligometastatic NSCLC.

METHODS AND MATERIALS: We conducted a phase 1b clinical trial in patients with oligometastatic NSCLC with up to 6 sites of extracranial metastatic disease. All sites of disease were treated with SBRT to a dose of 30 to 50 Gy in 5 fractions. Dual checkpoint immunotherapy was started 7 days after completion of radiation using anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) immunotherapy for a total of 4 cycles followed by durvalumab alone until progression or toxicity.

RESULTS: Of the 17 patients enrolled in this study, 15 patients received at least 1 dose of combination immunotherapy per protocol. The study was closed early (17 of planned 21 patients) due to slow accrual during the COVID-19 pandemic. Grade 3+ treatment-related adverse events were observed in 6 patients (40%), of which only one was possibly related to the addition of SBRT to immunotherapy. Median PFS was 42 months and median OS has not yet been reached.

CONCLUSIONS: Delivering ablative SBRT to all sites of metastatic disease in combination with dual checkpoint immunotherapy did not result in excessive rates of toxicity compared with historical studies of dual checkpoint immunotherapy alone. Although the study was not powered for treatment efficacy results, durable PFS and OS results suggest potential therapeutic benefit compared with immunotherapy or radiation alone in this patient population.

PMID:38072321 | PMC:PMC10947887 | DOI:10.1016/j.ijrobp.2023.11.040

PURPOSE: Magnetic resonance (MR) image guidance may facilitate safe ultrahypofractionated radiation dose escalation for inoperable pancreatic ductal adenocarcinoma. We conducted a prospective study evaluating the safety of 5-fraction Stereotactic MR-guided on-table Adaptive Radiation Therapy (SMART) for locally advanced (LAPC) and borderline resectable pancreatic cancer (BRPC).

METHODS AND MATERIALS: Patients with LAPC or BRPC were eligible for this multi-institutional, single-arm, phase 2 trial after ≥3 months of systemic therapy without evidence of distant progression. Fifty gray in 5 fractions was prescribed on a 0.35T MR-guided radiation delivery system. The primary endpoint was acute grade ≥3 gastrointestinal (GI) toxicity definitely attributed to SMART.

RESULTS: One hundred thirty-six patients (LAPC 56.6%, BRPC 43.4%) were enrolled between January 2019 and January 2022. Mean age was 65.7 (36-85) years. Head of pancreas lesions were most common (66.9%). Induction chemotherapy mostly consisted of (modified)FOLFIRINOX (65.4%) or gemcitabine/nab-paclitaxel (16.9%). Mean CA19-9 after induction chemotherapy and before SMART was 71.7 U/mL (0-468). On-table adaptive replanning was performed for 93.1% of all delivered fractions. Median follow-up from diagnosis and SMART was 16.4 and 8.8 months, respectively. The incidence of acute grade ≥3 GI toxicity possibly or probably attributed to SMART was 8.8%, including 2 postoperative deaths that were possibly related to SMART in patients who had surgery. There was no acute grade ≥3 GI toxicity definitely related to SMART. One-year overall survival from SMART was 65.0%.

CONCLUSIONS: The primary endpoint of this study was met with no acute grade ≥3 GI toxicity definitely attributed to ablative 5-fraction SMART. Although it is unclear whether SMART contributed to postoperative toxicity, we recommend caution when pursuing surgery, especially with vascular resection after SMART. Additional follow-up is ongoing to evaluate late toxicity, quality of life, and long-term efficacy.

PMID:37210048 | DOI:10.1016/j.ijrobp.2023.05.023

PURPOSE: In this prospective phase 2 trial, we investigated the toxicity and patient-reported quality-of-life outcomes in patients treated with stereotactic body radiation therapy (SBRT) to the prostate gland and a simultaneous focal boost to magnetic resonance imaging (MRI)-identified intraprostatic lesions while also de-escalating dose to the adjacent organs at risk.

METHODS AND MATERIALS: Eligible patients included low- or intermediate-risk prostate cancer (Gleason score ≤7, prostate specific antigen ≤20, T stage ≤2b). SBRT was prescribed to 40 Gy in 5 fractions delivered every other day to the prostate, with any areas of high disease burden (MRI-identified prostate imaging reporting and data system 4 or 5 lesions) simultaneously escalated to 42.5 to 45 Gy and areas overlapping organs at risk (within 2 mm of urethra, rectum, and bladder) constrained to 36.25 Gy (n = 100). Patients without a pretreatment MRI or without MRI-identified lesions were treated to dose of 37.5 Gy with no focal boost (n = 14).

RESULTS: From 2015 to 2022, a total of 114 patients were enrolled with a median follow-up of 42 months. No acute or late grade 3+ gastrointestinal (GI) toxicity was observed. One patient developed late grade 3 genitourinary (GU) toxicity at 16 months. In patients treated with focal boost (n = 100), acute grade 2 GU and GI toxicity was seen in 38% and 4% of patients, respectively. Cumulative late grade 2+ GU and GI toxicities at 24 months were 13% and 5% respectively. Patient-reported outcomes showed no significant long-term change from baseline in urinary, bowel, hormonal, or sexual quality-of-life scores after treatment.

CONCLUSIONS: SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute and late grade 2+ GI and GU toxicity as seen in other SBRT regimens without intraprostatic boost. Moreover, no significant long-term changes were seen in patient-reported urinary, bowel, or sexual outcomes from pretreatment baseline.

PMID:37179035 | DOI:10.1016/j.ijrobp.2023.05.004

PMID:37064601 | PMC:PMC10104451 | DOI:10.1016/j.yao.2021.02.003

The liver is a common site for metastatic spread for various primary tumor histologies. Stereotactic body radiation therapy (SBRT) is a non-invasive treatment technique with broad patient candidacy for the ablation of tumors in the liver and other organs. SBRT involves focused, high-dose radiation therapy delivered in one to several treatments, resulting in high rates of local control. Use of SBRT for ablation of oligometastatic disease has increased in recent years and emerging prospective data have demonstrated improvements in progression free and overall survival in some settings. When delivering SBRT to liver metastases, clinicians must balance the priorities of delivering ablative tumor dosing while respecting dose constraints to surrounding organs at risk (OARs). Motion management techniques are crucial for meeting dose constraints, ensuring low rates of toxicity, maintaining quality of life, and can allow for dose escalation. Advanced radiotherapy delivery approaches including proton therapy, robotic radiotherapy, and real-time MR-guided radiotherapy may further improve the accuracy of liver SBRT. In this article, we review the rationale for oligometastases ablation, the clinical outcomes with liver SBRT, tumor dose and OAR considerations, and evolving strategies to improve liver SBRT delivery.

PMID:36990635 | DOI:10.1016/j.semradonc.2022.11.008

AIMS: The introduction of on-line magnetic resonance image-guided radiotherapy (MRIgRT) has led to an improvement in the therapeutic workflow of radiotherapy treatments thanks to the better visualization of therapy volumes assured by the higher soft tissue contrast. Magnetic Resonance contrast agents (MRCA) could improve the target delineation in on-line MRIgRT planning as well as reduce inter-observer variability and enable innovative treatment optimization protocols. The aim of this survey is to investigate the utilization of MRCA among centres that clinically implemented on-line MRIgRT technology.

METHODS: In September 2021, we conducted an online survey consisting of a sixteen-question questionnaire that was distributed to the all the hospitals around the world equipped with MR Linacs. The questionnaire was developed by two Italian 0.35 T and 1.5 T MR-Linac centres and was validated by four other collaborating centres, using a Delphi consensus methodology.

RESULTS: The survey was distributed to 52 centres and 43 centres completed it (82.7%). Among these centres, 23 institutions (53.5%) used the 0.35T MR-Linac system, while the remaining 20 (46.5%) used the 1.5T MR-Linac system.According to results obtained, 25 (58%) of the centres implemented the use of MRCA for on-line MRIgRT. Gadoxetate (Eovist®; Primovist®) was reported to be the most used MRCA (80%) and liver the most common site of application (58%). Over 70% of responders agreed/strongly agreed to the need for international guidelines.

CONCLUSIONS: The use of MRCA in clinical practice presents several pitfalls and future research will be necessary to understand the actual advantage derived from the use of MRCA in clinical practice, their toxicity profiles and better define the need of formulating guidelines for standardising the use of MRCA in MRIgRT workflow.

PMID:36968577 | PMC:PMC10034422 | DOI:10.1016/j.ctro.2023.100615

PMID:36503718 | PMC:PMC9784376 | DOI:10.2478/raon-2022-0044

PURPOSE/OBJECTIVE: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology.

MATERIALS/METHODS: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems.

RESULTS: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details unavailable for 1223 cobalt courses), of which 21.1% were adapted. Ultra-hypofractionation (UHfx) (1-5 fractions) was used in 70.3% of all courses. At least one adaptive fraction was used for 38.5% of courses (average 1.7 adapted fractions/course), with higher oART use in UHfx dose schedules (47.7% of courses, average 1.9 adapted fractions per course). The most commonly treated organ sites were pancreas (20.7%), liver (16.5%), prostate (12.5%), breast (11.5%), and lung (9.4%). Temporal trends show a compounded annual growth rate (CAGR) of 59.6% in treatment courses delivered, with a dramatic increase in use of UHfx to 84.9% of courses in 2020 and similar increase in use of oART to 51.0% of courses.

CONCLUSIONS: This is the first comprehensive study reporting patterns of utilization among early adopters of MRIdian in the US. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of adaptive radiation therapy has led to a substantial transition to ultra-hypofractionated regimens. 0.35 T-MRgRT has been predominantly used to treat abdominal and pelvic tumors with increasing use of on-table adaptive replanning, which represents a paradigm shift in radiation therapy.

PMID:36466748 | PMC:PMC9712826 | DOI:10.1016/j.ctro.2022.11.013

PURPOSE: Liquid biopsies in metastatic renal cell carcinoma (mRCC) provide a unique approach to understand the molecular basis of treatment response and resistance. This is particularly important in the context of immunotherapies, which target key immune-tumor interactions. Unlike metastatic tissue biopsies, serial real-time profiling of mRCC is feasible with our noninvasive circulating tumor cell (CTC) approach.

METHODS: We collected 457 longitudinal liquid biopsies from 104 patients with mRCC enrolled in one of two studies, either a prospective cohort or a phase II multicenter adaptive immunotherapy trial. Using a novel CTC capture and automated microscopy platform, we profiled CTC enumeration and expression of HLA I and programmed cell death-ligand 1 (PD-L1). Given their diametric immunological roles, we focused on the HLA I to PD-L1 ratio (HP ratio).

RESULTS: Patients with radiographic responses showed significantly lower CTC abundances throughout treatment. Furthermore, patients whose CTC enumeration trajectory was in the highest quartile (> 0.12 CTCs/mL annually) had shorter overall survival (median 17.0 months v 21.1 months, P < .001). Throughout treatment, the HP ratio decreased in patients receiving immunotherapy but not in patients receiving tyrosine kinase inhibitors. Patients with an HP ratio trajectory in the highest quartile (≥ 0.0012 annually) displayed significantly shorter overall survival (median 18.4 months v 21.2 months, P = .003).

CONCLUSION: In the first large longitudinal CTC study in mRCC to date to our knowledge, we identified the prognostic importance of CTC enumeration and the change over time of both CTC enumeration and the HP ratio. These insights into changes in both tumor burden and the molecular profile of tumor cells in response to different treatments provide potential biomarkers to predict and monitor response to immunotherapy in mRCC.

PMID:35617646 | PMC:PMC9622626 | DOI:10.1200/JCO.22.00219

PURPOSE: Distant metastasis is the main cause of treatment failure in locally advanced rectal cancer (LARC) patients, despite the recent improvement in treatment strategies. This study aims to evaluate the "delta radiomics" approach in patients undergoing neoadjuvant chemoradiotherapy (nCRT) treated with 0.35-T magnetic resonance-guided radiotherapy (MRgRT), developing a logistic regression model able to predict 2-year disease-free-survival (2yDFS).

METHODS: Patients affected by LARC were enrolled in this multi-institutional study. A predictive model of 2yDFS was developed taking into account both clinical and radiomics variables. Gross tumour volume (GTV) was delineated on the magnetic resonance (MR) images acquired during MRgRT, and 1,067 radiomic features (RF) were extracted using the MODDICOM platform. The performance of RF in predicting 2yDFS was investigated in terms of the Wilcoxon-Mann-Whitney test and area under receiver operating characteristic (ROC) curve (AUC).

RESULTS: 48 patients have been retrospectively enrolled, with 8 patients (16.7%) developing distant metastases at the 2-year follow-up. A total of 1,099 variables (1,067 RF and 32 clinical variables) were evaluated in two different models: radiomics and radiomics/clinical. The best-performing 2yDFS predictive model was a delta radiomics one, based on the variation in terms of area/surface ratio between biologically effective doses (BED) at 54 Gy and simulation (AUC of 0.92).

CONCLUSIONS: The results of this study suggest a promising role of delta radiomics analysis on 0.35-T MR images in predicting 2yDFS for LARC patients. Further analyses including larger cohorts of patients and an external validation are needed to confirm these preliminary results.

PMID:35280799 | PMC:PMC8907443 | DOI:10.3389/fonc.2022.831712

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer (SCLC) provide recommended management for patients with SCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. This selection for the journal focuses on metastatic (known as extensive-stage) SCLC, which is more common than limited-stage SCLC. Systemic therapy alone can palliate symptoms and prolong survival in most patients with extensive-stage disease. Smoking cessation counseling and intervention should be strongly promoted in patients with SCLC and other high-grade neuroendocrine carcinomas. The "Summary of the Guidelines Updates" section in the SCLC algorithm outlines the most recent revisions for the 2022 update, which are described in greater detail in this revised Discussion text.

PMID:34902832 | PMC:PMC10203822 | DOI:10.6004/jnccn.2021.0058

PURPOSE: Respiration-induced tumor or organ positional changes can impact the accuracy of external beam radiotherapy. Motion management strategies are used to account for these changes during treatment. The authors report on the development, testing, and first-in-human evaluation of an electronic 4D (e4D) MR-compatible ultrasound probe that was designed for hands-free operation in a MR and linear accelerator (LINAC) environment.

METHODS: Ultrasound components were evaluated for MR compatibility. Electromagnetic interference (EMI) shielding was used to enclose the entire probe and a factory-fabricated cable shielded with copper braids was integrated into the probe. A series of simultaneous ultrasound and MR scans were acquired and analyzed in five healthy volunteers.

RESULTS: The ultrasound probe led to minor susceptibility artifacts in the MR images immediately proximal to the ultrasound probe at a depth of <10 mm. Ultrasound and MR-based motion traces that were derived by tracking the salient motion of endogenous target structures in the superior-inferior (SI) direction demonstrated good concordance (Pearson correlation coefficients of 0.95-0.98) between the ultrasound and MRI datasets.

CONCLUSION: We have demonstrated that our hands-free, e4D probe can acquire ultrasound images during a MR acquisition at frame rates of approximately 4 frames per second (fps) without impacting either the MR or ultrasound image quality. This use of this technology for interventional procedures (e.g. biopsies and drug delivery) and motion compensation during imaging are also being explored.

PMID:34218199 | PMC:PMC8403156 | DOI:10.1016/j.ejmp.2021.06.017

PURPOSE: Although SABR can improve oncologic outcomes for patients with oligometastatic disease, treatment of metastases near critical organs remains challenging. The purpose of this study is to determine the dosimetric feasibility of delivering magnetic resonance imaging (MRI)-guided adaptive SABR in a single fraction for abdominal and thoracic metastases.

METHODS AND MATERIALS: Previously delivered MRI-guided radiation therapy plans for 20 patients with oligometastatic disease in the thorax or abdomen, with 70% (14/20) of the lesions within 8 mm from dose-limiting organs at risk (OARs), were used to simulate the delivery of 24 Gy in a single fraction. Planning objectives included planning target volume (PTV) V95% >90%, optimized PTV (PTVopt) V95% >90%, and PTVopt D99% >20 Gy with no OAR dose violations, where PTVopt removed overlap with nearby planning organ at risk volume (PRV). Single-fraction plans were simulated on the first 5 daily setup breath-hold MRI scans, and the plans were reoptimized to consider variations in setup position and anatomy.

RESULTS: The mean PTV V95% for single-fraction SABR plans was lower compared with multifraction plans (mean 85.4% vs 92.6%, P = .02), but mean PTVopt V95% was not different (95.3% vs 98.2%, P = .62). After reoptimization of the single-fraction plan to the treatment day MRI, there was an increase in mean PTV V95% (85.0% vs 88.1%, P = .05), increase in mean PTVopt V95% (92.7% vs 96.3%, P = .02), increase in mean PTVopt D99% (19.7 Gy vs 23.8 Gy, P < .01), increase in mean frequency of meeting PTV D99% >20 Gy (52% vs 87%, P < .01), and increase in mean gross tumor volume minimum dose (17.5 Gy vs 19.3 Gy, P < .01). Reoptimization decreased mean frequency of OAR dose constraint violation (48% vs 0%, P < .01).

CONCLUSIONS: Single-fraction MRI-guided SABR is a dosimetrically feasible treatment for oligometastases that allows for on-table adaptation to avoid OAR dose constraint violations, but this method requires clinical validation.

PMID:34195490 | PMC:PMC8233469 | DOI:10.1016/j.adro.2021.100652

OBJECTIVE: Patients are turning to the Internet more often for cancer-related information. Oncology organizations need to ensure that appropriately written information is available for patients online. The aim of this study was to determine whether the readability of radiation oncology online patient information (OPI) provided by RTAnswers (RTAnswers.org, created by the American Society for Radiation Oncology) is written at a sixth-grade level as recommended by the National Institutes of Health (NIH), the U.S Department of Health and Human Services (HHS), and the American Medical Association (AMA).

METHODS: RTanswers.org was accessed and online patient-oriented brochures for 13 specific disease sites were analyzed. Readability of OPI from RTAnswers was assessed using 10 common readability tests: New Dale-Chall Test, Flesch Reading Ease Score, Coleman-Liau Index, Flesch-Kinkaid Grade Level, FORCAST test, Fry Score, Simple Measure of Gobbledygook, Gunning Frequency of Gobbledygook, New Fog Count, and Raygor Readability Estimate.

RESULTS: A composite grade level of readability was constructed using the 8 readability measures that provide a single grade-level output. The grade levels computed by each of these 8 tests were highly correlated (SI alpha = 0.98). The composite grade level for these disease site-specific brochures was 11.6 ± 0.83, corresponding to a senior in high school, significantly higher than the target sixth-grade level (p < 0.05) recommended by the NIH, HHS, and AMA.

CONCLUSION: Patient educational material provided by RTAnswers.org is written significantly above the target reading level. Simplifying and rewording this information could improve patients' understanding of radiation therapy and improve treatment adherence and outcomes.

PMID:34169120 | PMC:PMC8221236

INTRODUCTION: Pancreatic adenocarcinoma (PAC) has some of the worst treatment outcomes for any solid tumor. PAC creates substantial difficulty for effective treatment with traditional RT delivery strategies primarily secondary to its location and limited visualization using CT. Several of these challenges are uniquely addressed with MR-guided RT. We sought to summarize and place into context the currently available literature on MR-guided RT specifically for PAC.

METHODS: A literature search was conducted to identify manuscript publications since September 2014 that specifically used MR-guided RT for the treatment of PAC. Clinical outcomes of these series are summarized, discussed, and placed into the context of the existing pancreatic literature. Multiple international experts were involved to optimally contextualize these publications.

RESULTS: Over 300 manuscripts were reviewed. A total of 6 clinical outcomes publications were identified that have treated patients with PAC using MR guidance. Successes, challenges, and future directions for this technology are evident in these publications. MR-guided RT holds theoretical promise for the treatment of patients with PAC. As with any new technology, immediate or dramatic clinical improvements associated with its use will take time and experience. There remain no prospective trials, currently publications are limited to small retrospective experiences. The current level of evidence for MR guidance in PAC is low and requires significant expansion. Future directions and ongoing studies that are currently open and accruing are identified and reviewed.

CONCLUSIONS: The potential promise of MR-guided RT for PAC is highlighted, the challenges associated with this novel therapeutic intervention are also reviewed. Outcomes are very early, and will require continued and long term follow up. MR-guided RT should not be viewed in the same fashion as a novel chemotherapeutic agent for which dosing, administration, and toxicity has been established in earlier phase studies. Instead, it should be viewed as a novel procedural intervention which must be robustly tested, refined and practiced before definitive conclusions on the potential benefits or detriments can be determined. The future of MR-guided RT for PAC is highly promising and the potential implications on PAC are substantial.

PMID:34046339 | PMC:PMC8144850 | DOI:10.3389/fonc.2021.628155

Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement. Seven patients with RCC were treated at our institution with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, 2 with grade 1 hematuria and 1 with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR (estimated glomerular filtration rate) preceding and following SBRT and MW ablation was 69 mL/min/1.73 m2 and 68 mL/min/1.73 m2 (P = .19), respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.

PMID:34024743 | DOI:10.1016/j.clgc.2021.04.010

INTRODUCTION: A recent study performed on 16 locally advanced rectal cancer (LARC) patients treated using magnetic resonance guided radiotherapy (MRgRT) has identified two delta radiomics features as predictors of clinical complete response (cCR) after neoadjuvant radio-chemotherapy (nCRT). This study aims to validate these features (ΔLleast and Δglnu) on an external larger dataset, expanding the analysis also for pathological complete response (pCR) prediction.

METHODS: A total of 43 LARC patients were enrolled: Gross Tumour Volume (GTV) was delineated on T2/T1* MR images acquired during MRgRT and the two delta features were calculated. Receiver Operating Characteristic (ROC) curve analysis was performed on the 16 cases of the original study and the best cut-off value was identified. The performance of ΔLleast and Δglnu was evaluated at the best cut-off value.

RESULTS: On the original dataset of 16 patients, ΔLleast reported an AUC of 0.81 for cCR and 0.93 for pCR, while Δglnu 0.72 and 0.54 respectively. The best cut-off values of ΔLleast was 0.73 for both outcomes, while Δglnu reported 0.54 for cCR and 0.93 for pCR. At the external validation, ΔLleast showed an accuracy of 81% for cCR and 79% for pCR, while Δglnu reported 63% for cCR and 40% for pCR.

CONCLUSION: The accuracy of ΔLleast in predicting cCR and pCR is significantly higher than those obtained considering Δglnu, but inferior if compared with other image-based biomarker, such as the early-regression index. Studies with larger cohorts of patients are recommended to further investigate the role of delta radiomic features in MRgRT.

PMID:33901863 | DOI:10.1016/j.ejmp.2021.03.038

This study reports dose corresponding to visible radiation induced liver damage following Stereotactic Body Radiation Therapy (SBRT) for liver metastasis, and the optimal time for follow up scans using post radiation imaging. Diagnostic magnetic resonance scans of nine patients treated with liver SBRT using a 0.35 T MRI-guided radiotherapy system were analyzed. The dice coefficients between the region of visible liver damage and the delivered dose were calculated. A median dose of 35 Gy correlated most closely with the visible radiation induced liver damage. We compared scans over two to nine months and observed maximal dice coefficients at two to five months post radiation. We have presented a new method for developing treatment planning guidelines for liver SBRT.

PMID:33898785 | PMC:PMC8058022 | DOI:10.1016/j.phro.2021.01.009

Online MRI-guided radiotherapy (MRgRT) is one of the most recent technological advances in radiotherapy. MRgRT permits the visualization of tumorous and healthy tissue while the patient is on the treatment table and online daily plan adaptations following the observed anatomical changes. In the context of rectal cancer, online MRgRT is a very promising modality due to the pronounced geographical variability of tumor tissues and the surrounding healthy tissues. This current paper will discuss the possible applications of online MRgRT, in particular, in terms of radiotherapy dose escalation and response prediction in organ preservation approaches for rectal cancer.

PMID:33859937 | PMC:PMC8042309 | DOI:10.3389/fonc.2021.619852

In this review, we outline the potential benefits and the future role of MRI and MR-guided radiotherapy (MRgRT) in the management of esophageal cancer. Although not currently used in most clinical practice settings, MRI is a useful non-invasive imaging modality that provides excellent soft tissue contrast and the ability to visualize cancer physiology. Chemoradiation therapy with or without surgery is essential for the management of locally advanced esophageal cancer. MRI can help stage esophageal cancer, delineate the gross tumor volume (GTV), and assess the response to chemoradiotherapy. Integrated MRgRT systems can help overcome the challenge of esophageal motion due to respiratory motion by using real-time imaging and tumor tracking with respiratory gating. With daily on-table MRI, shifts in tumor position and tumor regression can be taken into account for online-adaptation. The combination of accurate GTV visualization, respiratory gating, and online adaptive planning, allows for tighter treatment volumes and improved sparing of the surrounding normal organs. This could lead to a reduction in radiotherapy induced cardiac toxicity, pneumonitis and post-operative complications. Tumor physiology as seen on diffusion weighted imaging or dynamic contrast enhancement can help individualize treatments based on the response to chemoradiotherapy. Patients with a complete response on MRI can be considered for organ preservation while patients with no response can be offered an earlier resection. In patients with a partial response to chemoradiotherapy, areas of residual cancer can be targeted for dose escalation. The tighter and more accurate targeting enabled with MRgRT may enable hypofractionated treatment schedules.

PMID:33828980 | PMC:PMC8019940 | DOI:10.3389/fonc.2021.628009

Background Although CT, endoscopic US, and PET are critical in determining the appropriate management of esophageal carcinoma (squamous cell carcinoma and adenocarcinoma), previous reports show that staging accuracy remains low, particularly for nodal involvement sensitivity. Purpose To perform a systematic review and meta-analysis to determine the diagnostic performance of MRI for multiple staging thresholds in patients with biopsy-proven esophageal carcinoma (differentiation of stage T0 disease from stage T1 or higher disease, differentiation of stage T2 or lower disease from stage T3 or higher disease, and differentiation of stage N0 disease from stage N1 or higher disease [where T refers to tumor stage and N refers to nodal stage]). Materials and Methods Studies of the diagnostic performance of MRI in determining the stage of esophageal carcinoma in patients before esophagectomy and pathologic staging between 2000 and 2019 were searched in PubMed, Scopus, Web of Science, and Cochrane Library by a librarian and radiation oncologist. Pooled diagnostic performance of MRI was calculated with a bivariate random effects model. Bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (version 2) tool. Results Twenty studies with a total of 984 patients were included in the analysis. Pooled accuracy for stage T0 versus stage T1 or higher had a sensitivity of 92% (95% CI: 82, 96) and a specificity of 67% (95% CI: 51, 81). Pooled accuracy for stage T2 or lower versus stage T3 or higher had a sensitivity of 86% (95% CI: 76, 92) and a specificity of 86% (95% CI: 75, 93). Pooled accuracy for stage N0 versus stage N1 or higher had a sensitivity of 71% (95% CI: 60, 80) and a specificity of 72% (95% CI: 64, 79). The concern for applicability was low for the patient selection, index test, and reference test domains, except for 10% of studies (two of 20) that had unclear concern for patient selection applicability. Conclusion MRI has high sensitivity but low specificity for the detection of esophageal carcinoma, which shows promise for determining neoadjuvant therapy response and for detecting locally advanced disease for potential trimodality therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Leeflang in this issue.

PMID:33787334 | DOI:10.1148/radiol.2021202857

The aim of this study is to investigate the role of Delta Radiomics analysis in the prediction of one-year local control (1yLC) in patients affected by locally advanced pancreatic cancer (LAPC) and treated using Magnetic Resonance guided Radiotherapy (MRgRT). A total of 35 patients from two institutions were enrolled: A 0.35 Tesla T2*/T1 MR image was acquired for each case during simulation and on each treatment fraction. Physical dose was converted in biologically effective dose (BED) to compensate for different radiotherapy schemes. Delta Radiomics analysis was performed considering the gross tumour volume (GTV) delineated on MR images acquired at BED of 20, 40, and 60 Gy. The performance of the delta features in predicting 1yLC was investigated in terms of Wilcoxon Mann-Whitney test and area under receiver operating characteristic (ROC) curve (AUC). The most significant feature in predicting 1yLC was the variation of cluster shade calculated at BED = 40 Gy, with a p-value of 0.005 and an AUC of 0.78 (0.61-0.94). Delta Radiomics analysis on low-field MR images might play a promising role in 1yLC prediction for LAPC patients: further studies including an external validation dataset and a larger cohort of patients are recommended to confirm the validity of this preliminary experience.

PMID:33466307 | PMC:PMC7824764 | DOI:10.3390/diagnostics11010072

Treatment of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) with chemoradiation may be associated with high rates of symptomatic cardiac toxicity. Large margins are typically required to ensure coverage of GEJ tumors with free-breathing volumetric modulated arc therapy (VMAT) radiotherapy. The purpose of this study is to determine whether treatment with tighter margins enabled by maximum-inhalation breath hold (MIBH)-gated intensity modulated radiation therapy (IMRT) on an integrated MRI-linear accelerator system (MR-linac) can decrease radiation doses to the heart and cardiac substructures. Ten patients with locally advanced GEJ adenocarcinoma underwent both free breathing 4-dimensional computed tomography (4DCT) and MIBH MRI simulation scans. MR-linac IMRT plans were created with a 3 mm clinical target volume (CTV) to planning target volume (PTV) isotropic margin and 4DCT VMAT plans were created with a 11, 13, and 9 mm CTV to PTV anisotropic margins in the left-right, cranial-caudal, and anterior-posterior directions according to GEJ-specific PTV expansion recommendations by Voncken et al. Prescription dose to PTV was 50.4 Gy in 28 fractions. Dosimetry to the heart and cardiac substructures was compared with paired t test; p < 0.05 was considered significant. Mean PTV on the MR-linac IMRT plans was significantly smaller compared to the 4DCT VMAT plans (689 cm3vs 1275 cm3, p < 0.01). Mean dose to the heart and all cardiac substructures was significantly lower in the MR-linac IMRT plans compared to the 4DCT VMAT plans: heart 20.9 Gy vs 27.8 Gy, left atrium 29.6 Gy vs 39.4 Gy, right atrium 20.5 Gy vs 25.6 Gy, left ventricle 21.6 Gy vs 29.6 Gy, and right ventricle 18.7 Gy vs 25.2 Gy (all p values <0.05). MIBH-gated MR-linac IMRT treatment of locally advanced GEJ adenocarcinoma can significantly decrease doses to the heart and cardiac substructures and this may translate to reduced rates of cardiac toxicity.

PMID:33097372 | DOI:10.1016/j.meddos.2020.10.002

PURPOSE: The role of neoadjuvant radiation for resectable pancreatic adenocarcinoma is controversial. We performed a prospective dose-escalation study of neoadjuvant stereotactic body radiation therapy (SBRT) with concurrent capecitabine and elective nodal irradiation (ENI) followed by surgical resection to explore the toxicity and feasibility of this approach.

METHODS AND MATERIALS: Patients with biopsy proven, resectable cancers of the pancreatic head were enrolled. A 4 + 4 dose-escalation design was employed delivering 5 fractions of 5 to 7 Gy to primary tumor with concurrent capecitabine. The maximum tolerated dose level was expanded for an additional 4 patients. Patients at all dose levels were treated with ENI delivering 25 Gy in 5 fractions. Dose-limiting toxicity was defined as any grade ≥3 nonhematologic toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0) attributable to chemoradiation occurring within 90 days of SBRT.

RESULTS: A total of 17 patients were enrolled with 16 patients evaluable and 13 patients ultimately proceeding to surgery. The most common toxicity was nausea (56%). There were no dose-limiting toxicities, and SBRT was maximally dose escalated to 35 Gy in 5 fractions for 8 patients. All patients completing surgery had R0 resections. Seven patients (54%) had moderate treatment effect identified in pathologic specimens. Three patients (23%) developed locoregional recurrences, with 2 (15%) partially included within the treated volume.

CONCLUSIONS: SBRT was safely dose escalated to 35 Gy in 5 fractions along with concurrent capecitabine and ENI. This regimen will be used in a future expansion cohort.

PMID:32942002 | DOI:10.1016/j.ijrobp.2020.09.010

PURPOSE: Tumor control probability (TCP)-based early regression index (ERITCP) is a radiobiological parameter that showed promising results in predicting pathologic complete response (pCR) on T2-weighted 1.5 T magnetic resonance (MR) images of patients with locally advanced rectal cancer. This study aims to validate the ERITCP in the context of low-tesla MR-guided radiation therapy, using images acquired with different magnetic field strength (0.35 T) and image contrast (T2/T1). Furthermore, the optimal timing for pCR prediction was estimated, calculating the ERI index at different biologically effective dose (BED) levels.

METHODS AND MATERIALS: Fifty-two patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy were enrolled in this multi-institutional retrospective study. For each patient, a 0.35 T T2/T1-weighted MR image was acquired during simulation and on each treatment day. Gross tumor volume was contoured according to International Commission on Radiation Units Report 83 guidelines. According to the original definition, ERITCP was calculated considering the residual tumor volume at BED = 25 Gy. ERI was also calculated in correspondence with several BED levels: 13, 21, 32, 40, 46, 54, 59, and 67. The predictive performance of the different ERI indices were evaluated in terms of receiver operating characteristic curve. The robustness of ERITCP with respect to the interobserver variability was also evaluated considering 2 operators and calculating the intraclass correlation index.

RESULTS: Fourteen patients showed pCR. ERITCP correctly 47 of 52 cases (accuracy = 90%), showing good results in terms of sensitivity (86%), specificity (92%), negative predictive value (95%), and positive predictive value (80%). The analysis at different BED levels shows that the best predictive performance is obtained when this parameter is calculated at BED = 25 Gy (area under the curve = 0.93). ERITCP results are robust with respect to interobserver variability (intraclass correlation index = 0.99).

CONCLUSIONS: This study confirmed the validity and the robustness of ERITCP as a pCR predictor in the context of low-tesla MR-guided radiation therapy and indicate 25 Gy as the best BED level to perform predictions.

PMID:32758641 | DOI:10.1016/j.ijrobp.2020.07.2323

PURPOSE: Accurate liver tumor delineation is crucial for radiation therapy, but liver tumor volumes are difficult to visualize with conventional single-energy CT. This work investigates the use of split-filter dual-energy CT (DECT) for liver tumor visibility by quantifying contrast and contrast-to-noise ratio (CNR).

METHODS: Split-filter DECT contrast-enhanced scans of 20 liver tumors including cholangiocarcinomas, hepatocellular carcinomas, and liver metastases were acquired. Analysis was performed on the arterial and venous phases of mixed 120 kVp-equivalent images and VMIs at 57 keV and 40 keV gross target volume (GTV) contrast and CNR were calculated.

RESULTS: For the arterial phase, liver GTV contrast was 12.1 ± 10.0 HU and 43.1 ± 32.3 HU (P < 0.001) for the mixed images and 40 keV VMIs. Image noise increased on average by 116% for the 40 keV VMIs compared to the mixed images. The average CNR did not change significantly (1.6 ± 1.5, 1.7 ± 1.4, 2.4 ± 1.7 for the mixed, 57 keV and 40 keV VMIs (P > 0.141)). For individual cases, however, CNR increases of up to 607% were measured for the 40 keV VMIs compared to the mixed image. Venous phase 40 keV VMIs demonstrated an average increase of 35.4 HU in GTV contrast and 121% increase in image noise. Average CNR values were also not statistically different, but for individual cases CNR increases of up to 554% were measured for the 40 keV VMIs compared to the mixed image.

CONCLUSIONS: Liver tumor contrast was significantly improved using split-filter DECT 40 keV VMIs compared to mixed images. On average, there was no statistical difference in CNR between the mixed images and VMIs, but for individual cases, CNR was greatly increased for the 57 keV and 40 keV VMIs. Therefore, although not universally successful for our patient cohort, split-filter DECT VMIs may provide substantial gains in tumor visibility of certain liver cases for radiation therapy treatment planning.

PMID:32410336 | PMC:PMC7484851 | DOI:10.1002/acm2.12904

BACKGROUND AND PURPOSE: To investigate deformable image registration (DIR) and multi-fractional dose accumulation accuracy of a clinical MR-guided online adaptive radiotherapy (MRgoART) program, utilizing clinically-based magnitudes of abdominal deformation vector fields (DVFs).

MATERIALS AND METHODS: A heterogeneous anthropomorphic multi-modality abdominal deformable phantom was comprised of MR and CT anatomically-relevant materials. Thermoluminescent dosimeters (TLDs) were affixed within regions of interest (ROIs). CT and MR simulation scans were acquired. CT was deformed to MR for dose calculations. MRgoART was executed on a MR-linac (MRIdian) for 5 Gy/5 fractions. Before each fraction, a deformation was applied. Ground truth was known for ROI volume, TLD position, and TLD dose measured by an accredited dosimetry calibration laboratory. To validate the range of applied deformations, phantom DVFs were compared to DVFs of clinical abdominal MRgoART fractions. MR-MR deformation accuracy was quantified through dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and as mean-absolute-error (MAE) for CT-MR-MR deformation. Arithmetic-summation of calculated dose at respective TLD positions and deform-accumulated dose (MIM) was compared to TLD measured dose, respectively. MR-MR deformation statistics were quantified for MRIdian and MIM.

RESULTS: Mean phantom DVFs were 5.0 ± 2.9 mm compared to mean DVF of clinical abdominal patients at 5.2 ± 3.0 mm. Respective mean DSC, HD, MDA was 0.93 ± 0.03, 0.74 ± 0.80 cm, 0.08 ± 0.03 cm for MRIdian and 0.93 ± 0.03, 0.54 ± 0.27 cm, 0.08 ± 0.03 cm for MIM (N = 80 ROIs). Mean MAE was 20.5 HU. Respective mean and median dose differences were 0.3%, -0.3% for arithmetic-summation and 4.1%, 0.6% for deformed-accumulation. Maximum differences were 0.21 Gy (arithmetic-summation), 0.31 Gy (deformed-accumulation).

CONCLUSIONS: MRgoART deformation and dosimetric accuracy has been benchmarked for mean fractional DVFs of 5 mm in a multiple-rigid-body deformable phantom. Deformation accuracy was within TG132 criteria and clinically acceptable end-to-end MRgoART dosimetric agreement was observed for this phantom. Further efforts are needed in validation of deform-accumulated dose.

PMID:32146260 | DOI:10.1016/j.radonc.2020.02.012

MRI-guided radiotherapy is a novel and rapidly evolving technology that might enhance the risk-benefit ratio. Through direct visualisation of the tumour and the nearby healthy tissues, the radiation oncologist can deliver highly accurate treatment even to mobile targets. Each individual treatment can be customised to changing anatomy, potentially reducing the risk of radiation-related toxicities while simultaneously increasing the dose delivered to the tumour. MRI-guided radiotherapy offers a new tool for the radiation oncologist, and creates an opportunity to achieve durable local control of liver tumours that might not otherwise be possible. Future work will allow us to expand the population eligible for curative-intent radiotherapy, optimise and customise radiation doses to specific tumours, and hopefully create opportunities for improving outcomes through machine learning and radiomics-based approaches. This Review outlines the current and future applications for MRI-guided radiotherapy with respect to metastatic and primary liver cancers.

PMID:32007208 | DOI:10.1016/S1470-2045(20)30034-6

This work describes a novel application of MR-guided online adaptive radiotherapy (MRgoART) in the management of patients whom urgent palliative care is indicated using statum-adaptive radiotherapy (STAT-ART). The implementation of STAT-ART, as performed at our institution, is presented including a discussion of the advantages and limitations compared to the standard of care for palliative radiotherapy on conventional c-arm linacs. MR-based treatment planning techniques of STAT-ART for density overrides and deformable image registration (DIR) of diagnostic CT to the treatment MR are also addressed.

PMID:31696053 | PMC:PMC6817496 | DOI:10.3389/fonc.2019.01013

Radiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment. These impacts extend beyond improved imaging and dose deposition. Real-time MRI-guided RT is actively transforming the work flows and capabilities of virtually every aspect of RT. It has the opportunity to change entirely the delivery methods and response assessments of numerous malignancies. This review intends to approach the topic of MRI-based RT guidance from a vendor neutral and international perspective. It also aims to provide an introduction to this topic targeted towards oncologists without a speciality focus in RT. Speciality implications, areas for physician education and research opportunities are identified as they are associated with MRI-guided RT. The uniquely disruptive implications of MRI-guided RT are discussed and placed in context. We further aim to describe and outline important future changes to the speciality of radiation oncology that will occur with MRI-guided RT. The impacts on RT caused by MRI guidance include target identification, RT planning, quality assurance, treatment delivery, training, clinical workflow, tumour response assessment and treatment scheduling. In addition, entirely novel research areas that may be enabled by MRI guidance are identified for future investigation.

PMID:31614288 | PMC:PMC8447225 | DOI:10.1016/j.ejca.2019.07.021

PURPOSE: The aim of this study was to determine whether a higher biological effective dose (BED) would result in improved local control in patients treated with fractionated stereotactic radiotherapy (FSRT) for their resected brain metastases.

METHODS: Patients with newly diagnosed brain metastases without previous brain radiotherapy were retrospectively reviewed. Patients underwent surgical resection of at least one brain metastasis and were treated with adjuvant FSRT, delivering 25-36 Gy in 5-6 fractions. Outcomes were computed using Kaplan-Meier survival analysis and univariate analysis.

RESULTS: Fifty-four patients with 63 post-operative cavities were included. Median follow-up was 16 months (3-60). Median metastasis size at diagnosis was 2.9 cm (0.6-8.1) and median planning target volume was 19.7 cm3 (6.3-68.1). Two-year local control (LC) was 83%. When stratified by dose, 2 years LC rate was 95.1% in those treated with 30-36 Gy in 5-6 fractions (BED10 of 48-57.6 Gy10) versus 59.1% lesions treated with 25 Gy in 5 fractions (BED10 of 37.5 Gy10) (p < 0.001). LC was not associated with resection cavity size. One year overall survival was 68.7%, and was independent of BED10. Symptomatic radiation necrosis occurred in 7.9% of patients and was not associated with dose.

CONCLUSION: In the post-operative setting, high-dose FSRT (BED10 > 37.5 Gy10) were associated with a significantly higher rate of LC compared to lower BED regimens. Overall, 25 Gy in 5 fractions is not an adequate dose to control microscopic disease. If selecting a 5-fraction regimen, 30 Gy in five fractions appears to provide excellent tumor bed control.

PMID:31606876 | DOI:10.1007/s11060-019-03308-7

Background Stereotactic body radiation therapy (SBRT) given in 1-5 fractions is an effective treatment for vertebral metastases. Real-time magnetic resonance-guided radiotherapy (MRgRT) improves soft tissue contrast, which translates into accurate delivery of spine SBRT. Here we report on clinical implementation of MRgRT for spine SBRT, the quality of MRgRT plans compared to TrueBeam based volumetric modulated arc therapy (VMAT) plans in the treatment of spine metastases and benefits of MRgRT MR scan. Patients and methods Ten metastatic lesions were included in this study for plan comparison. Lesions were spread across thoracic spine and lumbosacral spine. Three fraction spine SBRT plans: 27Gy to planning target volume (PTV) and 30Gy to gross tumor volume (GTV) were generated on the ViewRay MRIdian Linac system and compared to TrueBeamTM STx based VMAT plans. Plans were compared using metrics such as minimum dose, maximum dose, mean dose, ratio of the dose to 50% of the volume (R50), conformity index, homogeneity index and dose to the spinal cord. Results MRIdian plans achieved equivalent target coverage and spinal cord dose compared to VMAT plans. The maximum and minimum PTV doses and homogeneity index were equivalent for both planning systems. R50 was lower for MRIdian plans compared to VMAT plans, indicating a lower spread of intermediate doses with MRIdian system (5.16 vs. 6.11, p = 0.03). Conclusions MRgRT can deliver high-quality spine SBRT plans comparable to TrueBeam volumetric modulated arc therapy (VMAT) plans.

PMID:31553704 | PMC:PMC6765155 | DOI:10.2478/raon-2019-0042

PURPOSE: The purpose of this study was to evaluate predictors of cardiac events in esophageal cancer patients treated with neoadjuvant chemoradiotherapy (NA CRT) followed by surgery compared with surgery alone.

MATERIALS AND METHODS: We retrospectively identified patients treated for esophageal cancer between 2006 and 2016. A total of 123 patients were identified; 70 were treated with surgery alone, and 53 were treated with NA CRT. Cardiac events were scored based on Common Terminology Criteria for Adverse Events (version 4.03), and dosimetric data was compiled for all patients who received radiation. Univariate analysis and multivariable analysis (MVA) were performed to identify predictors of cardiac events. Competing risk of death regression was performed to a model the cumulative incidence of cardiac events.

RESULTS: The overall rates of grade ≥3 cardiac events were 24.5% in the NA CRT group versus 10% in the surgery group (P=0.04). On MVA, use of NA CRT (P<0.01, hazard ratio [HR]: 3.45, 95% confidence interval [CI]: 1.35-9.09) predicted for grade ≥3 cardiac events, though no dosimetric variable predicted for grade ≥3 cardiac events or overall survival. On MVA, NA CRT predicted for pericardial effusions of any grade (P<0.01, HR: 3.70, 95% CI: 1.67-8.33). The V45 Gy was the most significant predictor of pericardial effusions (P=0.012, HR: 1.03, 95% CI: 1.01-1.06) CONCLUSIONS:: NA CRT significantly increased the rate of grade ≥3 cardiac events compared with patients treated with surgery alone. Although no dosimetric parameter predicted for grade ≥3 cardiac events or survival, the V45 Gy predicted for pericardial effusions.

PMID:31313677 | PMC:PMC6828548 | DOI:10.1097/COC.0000000000000573

PURPOSE: Cancer treatment is limited by inaccurate predictors of patient-specific therapeutic response. Therefore, some patients are exposed to unnecessary side effects and delays in starting effective therapy. A clinical tool that predicts treatment sensitivity for individual patients is needed.

EXPERIMENTAL DESIGN: Patient-derived cancer organoids were derived across multiple histologies. The histologic characteristics, mutation profile, clonal structure, and response to chemotherapy and radiation were assessed using bright-field and optical metabolic imaging on spheroid and single-cell levels, respectively.

RESULTS: We demonstrate that patient-derived cancer organoids represent the cancers from which they were derived, including key histologic and molecular features. These cultures were generated from numerous cancers, various biopsy sample types, and in different clinical settings. Next-generation sequencing reveals the presence of subclonal populations within the organoid cultures. These cultures allow for the detection of clonal heterogeneity with a greater sensitivity than bulk tumor sequencing. Optical metabolic imaging of these organoids provides cell-level quantification of treatment response and tumor heterogeneity allowing for resolution of therapeutic differences between patient samples. Using this technology, we prospectively predict treatment response for a patient with metastatic colorectal cancer.

CONCLUSIONS: These studies add to the literature demonstrating feasibility to grow clinical patient-derived organotypic cultures for treatment effectiveness testing. Together, these culture methods and response assessment techniques hold great promise to predict treatment sensitivity for patients with cancer undergoing chemotherapy and/or radiation.

PMID:31175091 | PMC:PMC6726566 | DOI:10.1158/1078-0432.CCR-18-3590

BACKGROUND: Adaptive magnetic resonance imaging-guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation.

METHODS: We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high-dose (biologically effective dose [BED10 ] >70) and standard-dose groups (BED10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan-Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT.

RESULTS: Median follow-up was 17 months. High-dose patients (n = 24, 55%) had statistically significant improvement in 2-year OS (49% vs 30%, P = 0.03) and trended towards significance for 2-year FFLF (77% vs 57%, P = 0.15) compared to standard-dose patients (n = 20, 45%). FFDF at 18 months in high-dose vs standard-dose groups was 24% vs 48%, respectively (P = 0.92). High-dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21-0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72-0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard-dose group and did not occur in the high-dose group.

CONCLUSIONS: Patients treated with dose-escalated MRgRT demonstrated improved OS. Prospective evaluation of high-dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted.

PMID:30932367 | PMC:PMC6536981 | DOI:10.1002/cam4.2100

PURPOSE: Daily magnetic resonance (MR)-guided radiation has the potential to improve stereotactic body radiation therapy (SBRT) for tumors of the liver. Magnetic resonance imaging (MRI) introduces unique variables that are untested clinically: electron return effect, MRI geometric distortion, MRI to radiation therapy isocenter uncertainty, multileaf collimator position error, and uncertainties with voxel size and tracking. All could lead to increased toxicity and/or local recurrences with SBRT. In this multi-institutional study, we hypothesized that direct visualization provided by MR guidance could allow the use of small treatment volumes to spare normal tissues while maintaining clinical outcomes despite the aforementioned uncertainties in MR-guided treatment.

METHODS AND MATERIALS: Patients with primary liver tumors or metastatic lesions treated with MR-guided liver SBRT were reviewed at 3 institutions. Toxicity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4. Freedom from local progression (FFLP) and overall survival were analyzed with the Kaplan-Meier method and χ2 test.

RESULTS: The study population consisted of 26 patients: 6 hepatocellular carcinomas, 2 cholangiocarcinomas, and 18 metastatic liver lesions (44% colorectal metastasis). The median follow-up was 21.2 months. The median dose delivered was 50 Gy at 10 Gy/fraction. No grade 4 or greater gastrointestinal toxicities were observed after treatment. The 1-year and 2-year overall survival in this cohort is 69% and 60%, respectively. At the median follow-up, FFLP for this cohort was 80.4%. FFLP for patients with hepatocellular carcinomas, colorectal metastasis, and all other lesions were 100%, 75%, and 83%, respectively.

CONCLUSIONS: This study describes the first clinical outcomes of MR-guided liver SBRT. Treatment was well tolerated by patients with excellent local control. This study lays the foundation for future dose escalation and adaptive treatment for liver-based primary malignancies and/or metastatic disease.

PMID:30706022 | PMC:PMC6349638 | DOI:10.1016/j.adro.2018.08.005

PURPOSE: Tumor delineation using conventional CT images can be a challenge for pancreatic adenocarcinoma where contrast between the tumor and surrounding healthy tissue is low. This work investigates the ability of a split-filter dual-energy CT (DECT) system to improve pancreatic tumor contrast and contrast-to-noise ratio (CNR) for radiation therapy treatment planning.

MATERIALS AND METHODS: Multiphasic scans of 20 pancreatic tumors were acquired using a split-filter DECT technique with iodinated contrast medium, OMNIPAQUETM . Analysis was performed on the pancreatic and portal venous phases for several types of DECT images. Pancreatic gross target volume (GTV) contrast and CNR were calculated and analyzed from mixed 120 kVp-equivalent images and virtual monoenergetic images (VMI) at 57 and 40 keV. The role of iterative reconstruction on DECT images was also investigated. Paired t-tests were used to assess the difference in GTV contrast and CNR among the different images.

RESULTS: The VMIs at 40 keV had a 110% greater image noise compared to the mixed 120 kVp-equivalent images (P < 0.0001). VMIs at 40 keV increased GTV contrast from 15.9 ± 19.9 HU to 93.7 ± 49.6 HU and CNR from 1.37 ± 2.05 to 3.86 ± 2.78 in comparison to the mixed 120 kVp-equivalent images. The iterative reconstruction algorithm investigated decreased noise in the VMIs by about 20% and improved CNR by about 30%.

CONCLUSIONS: Pancreatic tumor contrast and CNR were significantly improved using VMIs reconstructed from the split-filter DECT technique, and the use of iterative reconstruction further improved CNR. This gain in tumor contrast may lead to more accurate tumor delineation for radiation therapy treatment planning.

PMID:30117641 | PMC:PMC6123148 | DOI:10.1002/acm2.12435

Magnetic resonance-guided radiation therapy (MRgRT) offers advantages for image guidance for radiotherapy treatments as compared to conventional computed tomography (CT)-based modalities. The superior soft tissue contrast of magnetic resonance (MR) enables an improved visualization of the gross tumor and adjacent normal tissues in the treatment of abdominal and thoracic malignancies. Online adaptive capabilities, coupled with advanced motion management of real-time tracking of the tumor, directly allow for high-precision inter-/intrafraction localization. The primary aim of this case series is to describe MR-based interventions for localizing targets not well-visualized with conventional image-guided technologies. The abdominal and thoracic sites of the lung, kidney, liver, and gastric targets are described to illustrate the technological advancement of MR-guidance in radiotherapy.

PMID:29872602 | PMC:PMC5985918 | DOI:10.7759/cureus.2422

PURPOSE: Accurate identification of the gross tumor volume (GTV) in pancreatic adenocarcinoma is challenging. We sought to understand differences in GTV delineation using pancreatic computed tomography (CT) compared with magnetic resonance imaging (MRI).

METHODS AND MATERIALS: Twelve attending radiation oncologists were convened for an international contouring symposium. All participants had a clinical and research interest in pancreatic adenocarcinoma. CT and MRI scans from 3 pancreatic cases were used for contouring. CT and MRI GTVs were analyzed and compared. Interobserver variability was compared using Dice's similarity coefficient (DSC), Hausdorff distances, and Jaccard indices. Mann-Whitney tests were used to check for significant differences. Consensus contours on CT and MRI scans and constructed count maps were used to visualize the agreement. Agreement regarding the optimal method to determine GTV definition using MRI was reached.

RESULTS: Six contour sets (3 from CT and 3 from MRI) were obtained and compared for each observer, totaling 72 contour sets. The mean volume of contours on CT was significantly larger at 57.48 mL compared with a mean of 45.76 mL on MRI, P = .011. The standard deviation obtained from the CT contours was significantly larger than the standard deviation from the MRI contours (P = .027). The mean DSC was 0.73 for the CT and 0.72 for the MRI (P = .889). The conformity index measurement was similar for CT and MRI (P = .58). Count maps were created to highlight differences in the contours from CT and MRI.

CONCLUSIONS: Using MRI as a primary image set to define a pancreatic adenocarcinoma GTV resulted in smaller contours compared with CT. No differences in DSC or the conformity index were seen between MRI and CT. A stepwise method is recommended as an approach to contour a pancreatic GTV using MRI.

PMID:29426692 | DOI:10.1016/j.prro.2017.11.005

PURPOSE: Magnetic resonance imaging-guided radiation therapy has entered clinical practice at several major treatment centers. Treatment of early-stage non-small cell lung cancer with stereotactic body radiation therapy is one potential application of this modality, as some form of respiratory motion management is important to address. We hypothesize that magnetic resonance imaging-guided tri-cobalt-60 radiation therapy can be used to generate clinically acceptable stereotactic body radiation therapy treatment plans. Here, we report on a dosimetric comparison between magnetic resonance imaging-guided radiation therapy plans and internal target volume-based plans utilizing volumetric-modulated arc therapy.

MATERIALS AND METHODS: Ten patients with early-stage non-small cell lung cancer who underwent radiation therapy planning and treatment were studied. Following 4-dimensional computed tomography, patient images were used to generate clinically deliverable plans. For volumetric-modulated arc therapy plans, the planning tumor volume was defined as an internal target volume + 0.5 cm. For magnetic resonance imaging-guided plans, a single mid-inspiratory cycle was used to define a gross tumor volume, then expanded 0.3 cm to the planning tumor volume. Treatment plan parameters were compared.

RESULTS: Planning tumor volumes trended larger for volumetric-modulated arc therapy-based plans, with a mean planning tumor volume of 47.4 mL versus 24.8 mL for magnetic resonance imaging-guided plans ( P = .08). Clinically acceptable plans were achievable via both methods, with bilateral lung V20, 3.9% versus 4.8% ( P = .62). The volume of chest wall receiving greater than 30 Gy was also similar, 22.1 versus 19.8 mL ( P = .78), as were all other parameters commonly used for lung stereotactic body radiation therapy. The ratio of the 50% isodose volume to planning tumor volume was lower in volumetric-modulated arc therapy plans, 4.19 versus 10.0 ( P < .001). Heterogeneity index was comparable between plans, 1.25 versus 1.25 ( P = .98).

CONCLUSION: Magnetic resonance imaging-guided tri-cobalt-60 radiation therapy is capable of delivering lung high-quality stereotactic body radiation therapy plans that are clinically acceptable as compared to volumetric-modulated arc therapy-based plans. Real-time magnetic resonance imaging provides the unique capacity to directly observe tumor motion during treatment for purposes of motion management.

PMID:28168936 | PMC:PMC5616053 | DOI:10.1177/1533034617691407

Improvements in surgical technique and perioperative care have resulted in increased long-term survival for patients with congenital heart disease. As these patients begin to reach their later years, clinicians are challenged with determining optimal management of noncardiac diseases in this complex patient population, including surgically treatable malignancies. We present a case of esophageal cancer in a patient with previously repaired tetralogy of Fallot and right-sided aortic arch, treated with neoadjuvant therapy followed by laparoscopic and left thoracoscopic esophagectomy.

PMID:28007281 | DOI:10.1016/j.athoracsur.2016.06.092

PURPOSE: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy.

METHODS AND MATERIALS: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching.

RESULTS: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses).

CONCLUSIONS: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.

PMID:27869098 | DOI:10.1016/j.ijrobp.2016.08.016

PURPOSE: Nearly two-thirds of cancer patients seek information about their diagnosis online. We assessed the readability of online patient education materials found on academic radiation oncology department Web sites to determine whether they adhered to guidelines suggesting that information be presented at a sixth-grade reading level.

METHODS AND MATERIALS: The Association of American Medical Colleges Web site was used to identify all academic radiation oncology departments in the United States. One-third of these department Web sites were selected for analysis using a random number generator. Both general information on radiation therapy and specific information regarding various radiation modalities were collected. To test the hypothesis that the readability of these online educational materials was written at the recommended grade level, a panel of 10 common readability tests was used. A composite grade level of readability was constructed using the 8 readability measures that provide a single grade-level output.

RESULTS: A mean of 5605 words (range, 2058-12,837) from 30 department Web sites was collected. Using the composite grade level score, the overall mean readability level was determined to be 13.36 (12.83-13.89), corresponding to a collegiate reading level. This was significantly higher than the target sixth-grade reading level (middle school, t (29) = 27.41, P < .001).

CONCLUSIONS: Online patient educational materials from academic radiation oncology Web sites are significantly more complex than recommended by the National Institutes of Health and the Department of Health and Human Services. To improve patients' comprehension of radiation therapy and its role in their treatment, our analysis suggests that the language used in online patient information should be simplified to communicate the information at a more appropriate level.

PMID:27663932 | PMC:PMC5219938 | DOI:10.1016/j.prro.2016.07.008

BACKGROUND: The NIH and Department of Health & Human Services recommend online patient information (OPI) be written at a sixth grade level. We used a panel of readability analyses to assess OPI from NCI-Designated Cancer Center (NCIDCC) Web sites.

METHODS: Cancer.gov was used to identify 68 NCIDCC Web sites from which we collected both general OPI and OPI specific to breast, prostate, lung, and colon cancers. This text was analyzed by 10 commonly used readability tests: the New Dale-Chall Readability Formula, Flesch Reading Ease scale, Flesch-Kinaid Grade Level, FORCAST scale, Fry Readability Graph, Simple Measure of Gobbledygook test, Gunning Frequency of Gobbledygook index, New Fog Count, Raygor Readability Estimate Graph, and Coleman-Liau Index. We tested the hypothesis that the readability of NCIDCC OPI was written at the sixth grade level. Secondary analyses were performed to compare readability of OPI between comprehensive and noncomprehensive centers, by region, and to OPI produced by the American Cancer Society (ACS).

RESULTS: A mean of 30,507 words from 40 comprehensive and 18 noncomprehensive NCIDCCs was analyzed (7 nonclinical and 3 without appropriate OPI were excluded). Using a composite grade level score, the mean readability score of 12.46 (ie, college level: 95% CI, 12.13-12.79) was significantly greater than the target grade level of 6 (middle-school: P<.001). No difference between comprehensive and noncomprehensive centers was identified. Regional differences were identified in 4 of the 10 readability metrics (P<.05). ACS OPI provides easier language, at the seventh to ninth grade level, across all tests (P<.01).

CONCLUSIONS: OPI from NCIDCC Web sites is more complex than recommended for the average patient.

PMID:27283166 | PMC:PMC7236813 | DOI:10.6004/jnccn.2016.0075

This study investigated the dosimetric differences in treatment plans from flattened and flattening filter-free (FFF) beams from the TrueBeam System. A total of 104 treatment plans with static (sliding window) intensity-modulated radiotherapy beams and volumetric-modulated arc therapy (VMAT) beams were generated for 15 patients involving three cancer sites. In general, the FFF beam provides similar target coverage as the flattened beam with improved dose sparing to organ-at-risk (OAR). Among all three cancer sites, the head and neck showed more important differences between the flattened beam and FFF beam. The maximum reduction of the FFF beam in the mean dose reached up to 2.82 Gy for larynx in head and neck case. Compared to the 6 MV flattened beam, the 10 MV FFF beam provided improved dose sparing to certain OARs, especially for VMAT cases. Thus, 10 MV FFF beam could be used to improve the treatment plan.

PMID:27217620 | PMC:PMC4871009 | DOI:10.4103/0971-6203.181636

SBRT is increasingly utilized in liver tumor treatment. MRI-guided RT allows for real-time MRI tracking during therapy. Liver tumors are often poorly visualized and most contrast agents are transient. Gadoxetate may allow for sustained tumor visualization. Here, we report on the first use of gadoxetate during real-time MRI-guided SBRT.

PMID:26627702 | DOI:10.1016/j.radonc.2015.10.024

PMID:26615141 | DOI:10.1053/j.seminoncol.2015.09.033

In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective of relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences. The TF was further charged with making suggestions as to critical areas of biological basic research investigation that might be most likely to maintain and build further the scientific foundation and vitality of radiation oncology as an independent and vibrant medical specialty. It was not within the scope of service of the TF to consider the quality of ongoing research efforts within the broader radiation oncology space, to presume to consider their future potential, or to discourage in any way the investigators committed to areas of interest other than those targeted. The TF charge specifically precluded consideration of research issues related to technology, physics, or clinical investigations. This document represents an Executive Summary of the Task Force report.

PMID:24246724 | DOI:10.1016/j.ijrobp.2013.09.040

As research in synthetic biology and genomic sciences becomes more widespread, the need for diverse oligonucleotide populations has increased. To limit reagent cost, it would be advantageous to obtain high quality populations in minute amounts. Towards that end, synthesis of DNA strands in capillaries utilizing photolabile 3-nitrophenylpropyloxycarbonyl (NPPOC) chemistry and ultraviolet-light emitting diodes (UV-LEDs) was examined. Multiple oligonucleotides were made in single capillaries and were characterized by hybridization, sequencing and gene synthesis. DNA synthesized in capillaries was capable of being hybridized and signal intensities correlated with microarray data. Sequencing demonstrated that the oligonucleotides were of high quality (up to 44% perfect sequences). Oligonucleotides were combined and used successfully for gene synthesis. This system offers a novel, scalable method to synthesize high quality oligonucleotides for biological applications.

PMID:16963493 | PMC:PMC1636377 | DOI:10.1093/nar/gkl641