SEARCH · Search NASA
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
We conducted a phase 3 randomized clinical trial to assess whether radical hemithoracic radiation therapy (RHR) compared with palliative radiation therapy (PR) can achieve overall survival (OS) advantages in patients with malignant pleural mesothelioma (MPM).
Background: The role of postmastectomy radiotherapy (PMRT) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is controversial. We aimed to evaluate the effectiveness of radiotherapy in patients treated with NAC and mastectomy in the Japanese Breast Cancer Registry. Methods: We enrolled patients who received NAC and mastectomy for cT1–4 cN0–2 M0 breast cancer. We evaluated the association between radiotherapy and outcomes, locoregional recurrence (LRR), distant disease-free survival (DDFS), and overall survival (OS) based on ypN status by multivariable analysis. Results: Of the 145,530 patients, we identified 3226 who met the inclusion criteria. Among ypN1 patients, no differences were found in LRR, DDFS, or OS between groups with and without radiotherapy (p = 0.72, p = 0.29, and p = 0.36, respectively). Radiotherapy was associated with improved LRR-free survival (p < 0.001), DDFS (p = 0.01), and OS (p < 0.001) in patients with ypN2–3. Multivariable analysis demonstrated that use of radiotherapy was independently associated with improved LRR [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.45–0.82, p = 0.001] and OS [HR 0.69, 95% CI 0.53–0.89, p = 0.004) for ypN2–3 patients only. The association between radiotherapy and OS was not statistically significant among ypN0 (p = 0.22) and ypN1 patients (p = 0.51). Conclusions: The results from this nationwide database study did not show significant associations between PMRT and improved survival among ypN0 and ypN1 patients. Radiotherapy may be beneficial only for ypN2–3 breast cancer patients who receive NAC and mastectomy in the modern era.
Background: Pleural mesothelioma is a rare but aggressive form of cancer. Local recurrence represents the majority of treatment failures and overall survival (OS) outcomes remain dismal. Adding locoregional treatment with radiotherapy after surgical resection has been considered but its role remains uncertain. Objective: The purpose of this study was to evaluate the outcomes of adjuvant radiation therapy (RT) for patients with malignant pleural mesothelioma. Methods: The National Cancer Data Base (NCDB) was queried (2004–2013) for patients with malignant mesothelioma. Patients were divided into three groups: observation, surgery alone, and surgery followed by adjuvant RT. Statistics included Fisher’s exact or Chi square tests to analyze categorical proportions between groups, Kaplan–Meier analysis to evaluate OS, and Cox proportional hazards modeling to determine variables associated with OS. Propensity matching was performed to make comparisons between homogenous groups. Results: Overall, the surgery plus radiotherapy group had a higher median survival (21.4 months) compared with surgery alone (16.59 months) [p < 0.001]. RT was more likely to be delivered after extrapleural pneumonectomy than with lung-sparing surgical approaches. On multivariable analysis, receipt of surgery plus radiotherapy, chemotherapy administration, and higher socioeconomic status were associated with improved OS (p < 0.0001). After propensity matching, receipt of surgery plus radiotherapy and chemotherapy administration were still associated with improved OS (p < 0.05). Conclusions: In the treatment of malignant pleural mesothelioma, adjuvant radiotherapy after surgical intervention was associated with improved OS. This study is the largest study of adjuvant radiotherapy to date, and our findings highlight the need for additional prospective data.
Radiotherapy, where ionizing radiation is locally delivered either through an external beam or by surgically implanting radionuclide-based seeds in the tumor, is one of the gold standard treatments for cancer. Due to the non-selective nature of radiation, healthy tissue surrounding the cancerous region is usually affected by the treatment. Hence, new strategies, including targeted alpha therapy, are being studied to improve the selectivity of the treatment and minimize side effects. Several challenges, however, limit the current development of targeted radiotherapy, such as the functionalization of the therapeutic agent with targeting vectors and controlling the release of recoiling daughters. Nanoparticles offer unique opportunities as drug delivery vehicles, since they are biocompatible, enhance the cellular uptake of drugs, and are easily functionalized with targeting molecules. In this review, we examine how nanoparticles can be used for targeted radiotherapy, either as sensitizers of external beams or as delivery vehicles for therapeutic radionuclides. Further, we describe the clinical relevance of different types of nanoparticles, followed by an analysis of how these nanoconstructs can solve some of the main limitations of conventional radiotherapy. Finally, we critically discuss the current situation of nanoparticle-based radiotherapy in clinical settings and challenges that need to be overcome in the future for further development of the field.
Background: The prognosis of advanced nodal (N3) squamous cell carcinoma of the head and neck (HNSCC) is poor. We investigated whether surgery or radiotherapy of early (T1–2) primary stage HSNCC is preferable to limit the overall morbidity after upfront neck dissection (uND) for N3 disease. Methods: This retrospective multicentric Groupe d’Étude des Tumeurs de la Tête Et du Cou study included patients undergoing uND and surgery or radiotherapy of their primary. Prognostic factors were evaluated using propensity score matching to account for biases in performing surgery depending on primary site and stage. Results: Of 189 T1–2, N3 HNSCC patients, 70 (37.0%) underwent uND: 42 with surgery of their primary and 28 with radiotherapy only. Radiotherapy alone was more frequent in patients with hypopharyngeal primaries. All local (N = 3) and regional (N = 10) relapses (included 2 locoregional relapses) occurred within the first 2 years. There were 16 distant metastatic failures. Five-year locoregional relapse and survival incidences were 15.7% and 66.5% and were similar regardless of the treatment of the primary. The overall morbidity rate was 65.2% and was similar after weighting by the inverse propensity score (p = 0.148). The only prognostic factor for morbidity was the radicality of the uND. Prolonged parenteral feeding was not more frequent in patients only irradiated to their primary (p = 0.118). Prolonged tracheostomy was more frequent after surgery of the primary. Conclusions: In patients with T1–2, N3 HNSCC undergoing uND, radiotherapy and surgery of the primary yield similar oncological outcomes. Morbidity was related to the extent of neck dissection.
To report toxicity and efficacy outcome of moderately hypofractionated image-guided external-beam radiotherapy in a large series of patients treated for prostate cancer (PCa). Between 10/2006 and 12/2015, 572 T1-T3N0M0 PCa patients received 70.2 Gy in 26 fractions at 2.7 Gy/fraction: 344 patients (60%) with three-dimensional conformal radiotherapy (3D-CRT) and 228 (40%) with intensity-modulated radiotherapy (IMRT). Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median age was 74 years (interquartile range 69–77). Compared with 3D-CRT, in IMRT group more high-risk patients (29% vs 18%; P = 0.002) and more high-volume target (75% vs 60%; P < 0.001) were included. Acute gastro-intestinal (GI) toxicity G > 1 were registered in 8% and in 11% IMRT and 3D-CRT patients, respectively, whereas late GI G > 1 were observed in 2% and 16% IMRT and 3D-CRT patients, respectively. Acute genito-urinary (GU) toxicity G > 1 were registered in 26% and 40% IMRT and 3D-CRT patients, respectively, whereas late GU G > 1 occurred in 5% IMRT and 15% 3D-CRT patients. Multivariate proportional hazard Cox models confirmed significantly greater risk of late toxicity with 3D-CRT compared to IMRT for GU > 1 (P = 0.004) and for GI > 1 (P < 0.001). With a median 4-year follow-up, overall survival (OS), clinical progression-free survival (cPFS) and biochemical PFS (bPFS) for the whole series were 91%, 92% and 91%, respectively. cPFS and bPFS were significantly different by risk groups. Multivariate Cox models for bPFS and cPFS showed no difference between irradiation techniques and a significant impact of risk group and initial PSA. Moderately hypofractionated radiotherapy is a viable treatment option for localized PCa with excellent tumour control and satisfactory toxicity profile. IMRT seems associated with a reduction in toxicity, whereas tumour control was equal between IMRT and 3D-CRT patients and depended mainly on the risk category.
Background: Postmastectomy radiotherapy currently is used for locally advanced breast cancers that carry a high risk of locoregional failure. However, radiotherapy can have deleterious effects on immediate breast reconstruction (IBR). Neoadjuvant radiotherapy (NART) to facilitate postmastectomy IBR is an emerging new therapeutic sequence. A systematic review was undertaken to evaluate the current evidence on the feasibility and safety of this sequence. Methods: A comprehensive search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception to 2018 was conducted, resulting in 592 records. The review included 18 retrospective and prospective studies of NART and IBR. Results: The majority of the studies used whole-breast radiotherapy with 50 Gy, conventionally fractionated, and waited 6–8 weeks before surgery. The IBR methods were varied, with both implant and autologous reconstructions. No intraoperative complications occurred, and the postoperative complication rates ranged from 3 to 36%. The partial and total flap loss rates were very low. Studies reporting cosmetic outcomes rated the majority of cases as good or excellent. The pathologic complete response rates ranged from 17 to 55%, and the locoregional recurrence rates were low (≤ 10%), with a short follow-up period. The current MD Anderson Cancer Center prospective clinical trial is described. Conclusions: The initial results of NART and IBR demonstrate the safety of this treatment both technically and oncologically. Longer follow-up evaluation of these studies and larger prospective controlled clinical trials are needed to establish this new therapeutic sequence as a standard of care.
Abstract Introduction The immune system and hypoxia are major factors influencing radiosensitivity in patients with different cancer types. This study aimed at developing a model to predict radiotherapy response in patients with head and neck squamous cell carcinoma (HNSCC) based on the tumor immune microenvironment and hypoxia signature. Materials and Methods We first evaluated the hypoxia status and tumor immune microenvironment in the Cancer Genome Atlas (TCGA) cohort by using transcriptomic data. Differentially expressed genes (DEGs) were identified between the “high immunity and low hypoxia” and “low immunity and high hypoxia” groups and those DEGs significantly associated with disease‐specific survival in the univariate Cox regression analysis were selected as the prognostic DEGs. We selected the immune hypoxia–related genes (IHRGs) by intersecting prognostic DEGs with immune and hypoxia gene sets. We used the IHRGs to train a multivariate Cox regression model in the TCGA cohort, based on which we calculated the IHRG prognostic index (IHRGPI) for each patient and validated its efficacy in predicting radiotherapy response in the Gene Expression Omnibus cohorts. Furthermore, we explored potential mechanisms and effective combinational treatment strategies for different IHRGPI groups. Results Five IHRGs were used to construct the IHRGPI, which was used to dichotomize the cohorts. The patients with lower IHRGPI showed a better radiotherapy response across different cohorts and endpoints, including overall survival, progression‐free survival, and recurrence‐free survival ( p < 0.05). Patients with higher IHRGPI showed greater hypoxia and lesser immune cell infiltration. A lower IHRGPI indicated a better immunotherapy response, while a higher IHRGPI indicated a better chemotherapy response. Conclusions IHRGPI is promising for predicting radiotherapy response and guiding combinational treatment strategies in patients with HNSCC.
Methods, devices and systems for ultra-high dose radiotherapy are disclosed. The described techniques rely in-part on active switching control of a photoconductive switch during the time the accelerator is accelerating charged particles to produce the output radiation at the desired dose rates. One flash radiotherapy system includes an induction accelerator, and a controllable switch coupled to the induction accelerator. The switch is operable to produce a plurality of voltage pulses to drive the induction accelerator. The radiotherapy system also includes a radiation measurement device to measure output radiation produced by the radiotherapy system and provide feedback to the controllable switch. The controllable switch is operable to, based on the received feedback, modify an amplitude, shape, spacing, number or width of the voltage pulses that are supplied to the particle accelerator to deliver the desired output radiation.
Background: Although the false-negative rate of the sentinel lymph node biopsy (SLNB) in breast cancer patients is 5–7%, reported regional recurrence (RR) rates after negative SLNB are much lower. Adjuvant treatment modalities probably contribute to this discrepancy. This study assessed the 5-year RR risk after a negative SLNB in the subset of patients who underwent breast amputation without radiotherapy or any adjuvant treatment. Methods: All patients operated for primary unilateral invasive breast cancer between 2005 and 2008 were identified in the Netherlands Cancer Registry. Patients with a negative SLNB who underwent breast amputation and who were not treated with axillary lymph node dissection, radiotherapy, or any adjuvant systemic treatment were selected. The cumulative 5-year RR rate was estimated by Kaplan–Meier analysis. Results: A total of 13,452 patients were surgically treated for primary breast cancer and had a negative SLNB, and 2012 patients fulfilled the selection criteria. Thirty-eight RRs occurred during follow-up. Multifocal disease was associated with a higher risk of developing RR (P = 0.04). The median time to RR was 27 months and was significantly shorter in patients with estrogen receptor-negative (ER−) breast cancer (9.5 months; P = 0.003). The 5-year RR rate was 2.4% in the study population compared with 1.1% in the remainder of 11,440 SLNB-negative patients (P = 0.0002). Conclusions: Excluding the effect of radiotherapy and systemic treatment resulted in a twofold 5-year RR risk in breast cancer patients with a tumor-free SLNB. This 5-year RR rate was still much lower than the reported false-negative rate of the SLNB procedure.
A recent addition to the treatment options in external beam therapy, so-called FLASH radiotherapy, shows remarkable healthy-tissue-sparing properties in a number of pre-clinical studies without impacting the overall treatment efficacy. Its potential in clinical applications is attracting a great deal of interest in the medical community. The use of ultra-high dose rates at extremely short irradiation times has been shown to significantly enhance the differential effects between normal and tumor tissue. This makes it possible to increase treatment doses without further harming the surrounding healthy tissue. While most studies to date have focused on the use of electron beams, X-ray and proton FLASH radiotherapy have also shown beneficial effects, although for these latter two the results still need to be independently confirmed. Additionally, the mechanisms underlying the biological effects remain to be elucidated. Very recently, the FLASH effect has been demonstrated in the first human patient, with promising results, supporting further clinical studies. In this work, we present an overview of the investigations into FLASH radiotherapy to date.
Despite significant dosimetric gains, clinical implementation of the 4π non-coplanar radiotherapy on the widely available C-arm gantry system is hindered by limited clearance, and the need to perform complex coordinated gantry and couch motion. A robotic radiotherapy platform would be conducive to such treatment but a new conflict between field size and MLC modulation resolution needs to be managed for versatile applications. This study investigates the dosimetry and delivery efficiency of purposefully creating many isocenters to achieve simultaneously high MLC modulation resolution and large tumor coverage. An integrated optimization framework was proposed for simultaneous beam orientation optimization (BOO), isocenter selection, and fluence map optimization (FMO). The framework includes a least-square dose fidelity objective, a total variation term for regularizing the fluence smoothness, and a group sparsity term for beam selection. A minimal number of isocenters were identified for efficient target coverage. Colliding beams excluded, high-resolution small-field 4π intensity-modulated radiotherapy (IMRT) treatment plans with 50 cm source-to-isocenter distance (SID-50) on 10 Head and Neck (H&N) cancer patients were compared with low-resolution large-field plans with 100 cm SID (SID-100). With the same or better target coverage, the average reduction of [Dmean, Dmax] of 20-beam SID-50 plans from 20-beam SID-100 plans were [2.09 Gy, 1.19 Gy] for organs at risk (OARs) overall, [3.05 Gy, 0.04 Gy] for parotid gland, [3.62 Gy, 5.19 Gy] for larynx, and [3.27 Gy, 1.10 Gy] for mandible. R50 and integral dose were reduced by 5.3% and 9.6%, respectively. Wilcoxon signed-rank test showed significant difference (p < 0.05) in planning target volume (PTV) homogeneity, PTV Dmax, R50, Integral dose, and OAR Dmean and Dmax. The estimated delivery time of 20-beam [SID-50, SID-100] plans were [19, 18] min and [14, 9] min, assuming 5 fractions and 30 fractions, respectively. Finally, with clinically acceptable delivery efficiency, many-isocenter optimization is dosimetrically desirable for treating large targets with high modulation resolution on the robotic platform.
A preclinical radiotherapy system producing FLASH dose rates with 12 MV bremsstrahlung x rays is being developed at Stanford University and SLAC National Accelerator Laboratory. Because of the high expected workload of 6,800 Gy w –1 at the isocenter, an efficient shielding methodology is needed to protect operators and the public while the preclinical system is operated in a radiation therapy vault designed for 6 MV x rays. Here, in this study, an analysis is performed to assess the shielding of the local treatment head and radiation vault using the Monte Carlo code FLUKA and the empirical methodology given in the National Council on Radiation Protection and Measurements Report 151. Two different treatment head shielding designs were created to compare single-layer and multilayer shielding methodologies using high-Z and low-Z materials. The multilayered shielding methodology produced designs with a 17% reduction in neutron fluence leaking from the treatment head compared to the single layered design of the same size, resulting in a decreased effective dose to operators and the public. The conservative assumptions used in the empirical methods can lead to over-shielding when treatment heads use polyethylene or multilayered shielding. High-Z/Low-Z multilayered shielding optimized via Monte Carlo is shown to be effective in the case of treatment head shielding and provide more effective shielding design for external beam radiotherapy systems that use 12 MV bremsstrahlung photons. Modifications to empirical methods used in the assessment of MV radiotherapy systems may be warranted to capture the effects of polyethylene in treatment head shielding.
In this work, we investigated the delivery of a clinically acceptable pediatric whole brain radiotherapy plan at FLASH dose rates using two lateral opposing 40-MeV electron beams produced by a practically realizable linear accelerator system. The EGSnrc Monte Carlo software modules, BEAMnrc and DOSXYZnrc, were used to generate whole brain radiotherapy plans for a pediatric patient using two lateral opposing 40-MeV electron beams. Electron beam phase space files were simulated using a model of a diverging beam with a diameter of 10 cm at 50 cm SAD (defined at brain midline). The electron beams were collimated using a 10-cm-thick block composed of 5 cm of aluminum oxide and 5 cm of tungsten. For comparison, a 6-MV photon plan was calculated with the Varian AAA algorithm. Electron beam parameters were based on a novel linear accelerator designed for the PHASER system and powered by a commercial 6-MW klystron. Calculations of the linear accelerator's performance indicated an average beam current of at least 6.25 µA, providing a dose rate of 115 Gy/s at isocenter, high enough for cognition-sparing FLASH effects. The electron plan was less homogenous with a homogeneity index of 0.133 compared to the photon plan's index of 0.087. Overall, the dosimetric characteristics of the 40-MeV electron plan were suitable for treatment. In conclusion, Monte Carlo simulations performed in this work indicate that two lateral opposing 40-MeV electron beams can be used for pediatric whole brain irradiation at FLASH dose rates of >115 Gy/s and serve as motivation for a practical clinical FLASH radiotherapy system, which can be implemented in the near future.
Neutron transport simulations are ubiquitous in nuclear engineering because they allow one to model experimental systems and render a model platform for easy perturbation of experimental designs. In addition, simulations allow one to gain experimental insight without actually having to go through the trouble of building a physical experiment. Neutron transport simulations can be stochastic or deterministic based. Stochastic neutron transport simulations are typically simulated using the Monte Carlo method and yield very accurate solutions but are computationally expensive, while deterministic methods are typically faster but can be less accurate. Here we focus on optimizing the accuracy of deterministic neutron transport simulations for radiotherapy simulations. Deterministic neutron transport requires discretization of angle, energy, and space to appropriately analyze the system one is trying to model. Discretization of energy is challenging because of the highly variable neutron flux at certain neutron energies. Improper discretization of energy in the transport model can lead to erroneous results and therefore inaccurate interpretations of the solution. In this study, we evaluate Particle Swarm Optimization (PSO) as a mechanism for selecting optimal group structures for radiotherapy shielding. We tested the particle swarm optimization algorithm on radiotherapy shielding problems using Los Alamos National Laboratory's (LANL) main deterministic transport code PARTISN. Results show that the optimized energy group structures generated from the optimization algorithm outperformed LANL's standard energy group structures, and therefore demonstrate utility in using PSO to expedite computation times due to the increased accuracy obtained with a smaller but optimized group structure. (authors)
Breast cancer is the most common cancer occurring in women. The standard of breast cancer treatment is based on breast-conserving surgery with administration of adjuvant whole breast radiotherapy. Research shows that in-breast relapse is most likely to occur in the tumour bed, i.e. around the scar. Intraoperative radiotherapy (IORT), in which radiation is delivered to the tumour bed, reduces the risk of local recurrence not only through direct cell killing, but also through modification of local microenvironment. Additionally IORT modifies the composition and biological activity of surgical wound fluid. Since many researchers show that radiation damage is mediated through factors secreted to the environment by irradiated cells, we hypothesized that this radiation-induced bystander effect is partly responsible for the change observed in surgical wound fluids. We collected conditioned medium from irradiated breast cancer cells (CM) and surgical wound fluids from patients who underwent IORT (RT-WF) and from patients after breast-conserving surgery alone (WF). We incubated two breast cancer cell lines (MCF-7 and MDA-MB-468) with WF, RT-WF, CM or WF + CM and measured radiobiological response of cells. We measured the level of double-strand breaks, induction of apoptosis and the changes in expression of genes related to DNA damage repair. We observed that stimulation with RT-WF and with WF + CM-induced double-strand breaks and increased expression of DNA damage repair-related genes, which was not observed after stimulation with WF. These results suggest that IOERT induces secretion of bystander factors mediating the genotoxic effect of ionizing radiation.
The purpose of this study is to evaluate if, in elderly HNC patients, loco-regional control (LRC) is influenced by average weekly radiation dose (AWD). From 2009 to 2017, 150 consecutive HNC elderly patients were analyzed. AWD was calculated by dividing total dose in Gray by overall treatment time in weeks. Patients were divided in 2 groups: Group 1 (70–75 years) and Group 2 (> 75 years). Primary endpoint was LRC; secondary endpoints were overall survival (OS) and compliance to treatment. The median age was 76 years (range 70–92), the distribution of patients by age was 72 and 78 patients in Group 1 and in Group 2, respectively; overall median follow-up was 23 months. Optimal cut-off of AWD for LRC was 9.236 (p = 0.018). Median OS was 73 months. In univariate survival analysis low PS (p = 0.005), T3–T4 (p = 0.021), Stage III–IV (p = 0.046) and AWD{sup Low} (< 9.236) (p = 0.018) were significantly associated with lower LRC; low PS (p < 0.001) and Group 2 (p = 0.006) were also associated with lower OS. Considering patients treated with radiotherapy alone AWD{sup Low} was significantly associated with lower LRC (p = 0.04) whereas among patient treated with chemoradiotherapy AWD did not affected LRC (p = 0.18). The multivariate analysis confirmed the significant value of PS for the prediction of LRC and OS (p = 0.035 and p < 0.001, respectively). In elderly patients an AWD of > 9.236 Gy was found to be beneficial for RT alone regimen. When radiotherapy alone is indicated in elderly patients an effort should be made to maintain an increased AWD in order to improve LRC.
This study aimed to investigate experimentally the effect of translational and rotational setup errors on 3-dimensional dose distributions by using the gamma index and dose volumetric indices for spine stereotactic body radiotherapy. Treatment plans were designed in accordance with the Radiation Therapy Oncology Group (RTOG) 0631 protocol. Measurements were taken using a Delta4 phantom (ScandiDos, Uppsala, Sweden). Setup errors were generated using the HexaMotion 6D moving platform (ScandiDos). Dose distributions in the presence of setup errors were evaluated, according to the γ passing rate with the 3% and 2 mm criteria (γ{sub 3%/2 mm}) and dose volumetric indices (D{sub 90} for the target volume and D{sub 2} for the spinal cord), using the Delta4 device (ScandiDos). The sensitivity coefficient, which represented the correlation between the γ{sub 3%/2 mm} passing rate and dose volumetric indices, was determined to assess robustness against setup errors. Rotational setup errors of 2° were equivalent to translational setup errors of 2 mm for the γ{sub 3%/2 mm} passing rate, D{sub 90} for the target, and D{sub 2} for the spinal cord. D{sub 90} for the target had low robustness against a translational setup error in the vertical direction and a rotational setup error in the pitch direction. D{sub 2} for the spinal cord was sensitive to a translational setup error in the lateral direction and a rotational setup error in the roll direction. The positioning accuracy of the rotational setup error, corresponding to the tolerance level of image-guided radiotherapy in the RTOG 0631 protocol, was required to be ≤ 2°.