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Technology in Cancer Research &... 2020There are very few studies on noncoplanar radiation in tomotherapy because deformable image registration is not implemented in the TomoTherapy Planning Station, a...
BACKGROUND
There are very few studies on noncoplanar radiation in tomotherapy because deformable image registration is not implemented in the TomoTherapy Planning Station, a treatment planning device used in tomotherapy. This study examined whether noncoplanar radiation can be performed on the head using a tilt-type head and neck fixture and deformable image registration.
METHODS
Planning target volume spheres with diameters of 2, 3, and 4 cm were set on a head phantom, and computed tomography images were taken at 0° and 40° using a tilt-type head and neck fixture. Irradiation plans were created in the Tomotherapy Planning Station. Noncoplanar radiation was simulated, and the dose volume was evaluated by adding the 0° dose distribution and 40° dose distribution using the deformable image registration of the RayStation treatment planning system.
RESULTS
The ratio of the phantom volume to the irradiation dose for 20% to 30% of the planning target volume in noncoplanar radiation was smaller than that for 40% to 90% of the planning target volume in single-section irradiation at 0° or 40°.
CONCLUSIONS
Noncoplanar radiation on the head region using tomotherapy was possible by using a tilt-type head and neck fixture, and the dose distribution could be evaluated using deformable image registration. This method helps reduce the dose of the organ-at-risk region located slightly away from the planning target volume.
Topics: Brain Neoplasms; Dose Fractionation, Radiation; Humans; Phantoms, Imaging; Radiation Dosage; Radiosurgery; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated
PubMed: 32734825
DOI: 10.1177/1533033820945776 -
Radiotherapy and Oncology : Journal of... Sep 2023Tumour hypoxia is an established radioresistance factor. A novel hypoxia-activated prodrug CP-506 has been proven to selectively target hypoxic tumour cells and to cause... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
Tumour hypoxia is an established radioresistance factor. A novel hypoxia-activated prodrug CP-506 has been proven to selectively target hypoxic tumour cells and to cause anti-tumour activity. The current study investigates whether CP-506 improves outcome of radiotherapy in vivo.
MATERIALS AND METHODS
Mice bearing FaDu and UT-SCC-5 xenografts were randomized to receive 5 daily injections of CP-506/vehicle followed by single dose (SD) irradiation. In addition, CP-506 was combined once per week with fractionated irradiation (30 fractions/6 weeks). Animals were followed-up to score all recurrences. In parallel, tumours were harvested to evaluate pimonidazole hypoxia, DNA damage (γH2AX), expression of oxidoreductases.
RESULTS
CP-506 treatment significantly increased local control rate after SD in FaDu, 62% vs. 27% (p = 0.024). In UT-SCC-5, this effect was not curative and only marginally significant. CP-506 induced significant DNA damage in FaDu (p = 0.009) but not in UT- SCC-5. Hypoxic volume (HV) was significantly smaller (p = 0.038) after pretreatment with CP-506 as compared to vehicle in FaDu but not in less responsive UT-SCC-5. Adding CP-506 to fractionated radiotherapy in FaDu did not result in significant benefit.
CONCLUSION
The results support the use of CP-506 in combination with radiation in particular using hypofractionation schedules in hypoxic tumours. The magnitude of effect depends on the tumour model, therefore it is expected that applying appropriate patient stratification strategy will further enhance the benefit of CP-506 treatment for cancer patients. A phase I-IIA clinical trial of CP-506 in monotherapy or in combination with carboplatin or a checkpoint inhibitor has been approved (NCT04954599).
Topics: Humans; Animals; Mice; Carcinoma, Squamous Cell; Prodrugs; Dose Fractionation, Radiation; Hypoxia; Probability
PubMed: 37315579
DOI: 10.1016/j.radonc.2023.109738 -
Radiotherapy and Oncology : Journal of... Aug 2022The effects of radiation on the heart are dependent on dose, fractionation, overall treatment time, and pre-existing cardiovascular pathology. Murine models have played... (Review)
Review
BACKGROUND AND PURPOSE
The effects of radiation on the heart are dependent on dose, fractionation, overall treatment time, and pre-existing cardiovascular pathology. Murine models have played a central role in improving our understanding of the radiation response of the heart yet a wide range of exposure parameters have been used. We evaluated the study design of published murine cardiac irradiation experiments to assess gaps in the literature and to suggest guidance for the harmonisation of future study reporting.
METHODS AND MATERIALS
A systematic review of mouse/rat studies published 1981-2021 that examined the effect of radiation on the heart was performed. The protocol was published on PROSPERO (CRD42021238921) and the findings were reported in accordance with the PRISMA guidance. Risk of bias was assessed using the SYRCLE checklist.
RESULTS
159 relevant full-text original articles were reviewed. The heart only was the target volume in 67% of the studies and simulation details were unavailable for 44% studies. Dosimetry methods were reported in 31% studies. The pulmonary effects of whole and partial heart irradiation were reported in 13% studies. Seventy-eight unique dose-fractionation schedules were evaluated. Large heterogeneity was observed in the endpoints measured, and the reporting standards were highly variable.
CONCLUSIONS
Current murine models of radiation cardiotoxicity cover a wide range of irradiation configurations and latency periods. There is a lack of evidence describing clinically relevant dose-fractionations, circulating biomarkers and radioprotectants. Recommendations for the consistent reporting of methods and results of in vivo cardiac irradiation studies are made to increase their suitability for informing the design of clinical studies.
Topics: Animals; Cardiotoxicity; Disease Models, Animal; Dose Fractionation, Radiation; Heart; Mice; Radiometry; Rats
PubMed: 35533784
DOI: 10.1016/j.radonc.2022.04.030 -
Clinical Lung Cancer Nov 2019Higher cardiac radiotherapy (RT) doses when treating lung cancer are associated with worse overall survival (OS), although the direct association between cardiac dose...
BACKGROUND
Higher cardiac radiotherapy (RT) doses when treating lung cancer are associated with worse overall survival (OS), although the direct association between cardiac dose and early cardiotoxicity is poorly understood. We hypothesized that RT doses to the heart and cardiac substructures are associated with under-reported early cardiotoxicity and worse OS.
PATIENTS AND METHODS
We conducted an institutional retrospective review of lung cancer patients treated with conventionally fractionated RT from 2010 to 2015. Collected data included pre-RT cardiac risk factors, post-RT cardiotoxicities, and dose-volume parameters for cardiac substructures. Univariate and multivariate analyses were performed to identify predictors of cardiotoxicity and OS.
RESULTS
Seventy-six cases were evaluated with 1.2 years median follow-up. Cardiotoxicities included atrial arrhythmia (n = 5), pericardial effusion (n = 16), and valvular disease (n = 1). In univariate analysis, significant dose-volume predictors for cardiotoxicity included mean RT dose to structure of interest, volume of structure of interest receiving ≥30 Gy RT dose, and volume of structure of interest receiving ≥45 Gy RT dose (V45) to the atria, ventricles, and pericardium. Higher ventricular V45 was associated with post-RT cardiotoxicity in multivariate analysis (hazard ratio [HR], 1.50; P = .027). Cardiotoxicity occurrence was a highly significant predictor of OS in multivariate analysis (HR, 12.7; P < .001), but higher ventricular V45 alone was not (HR, 0.78; P = .450).
CONCLUSION
Early cardiac events were relatively common after lung cancer RT and associated with multiple cardiac dose-volume parameters. Occurrence of early cardiotoxicity was strongly associated with worse OS. In practice, early cardiotoxicity is under-reported, supporting the need for more detailed cardiac evaluations in high-risk patients to detect and address early cardiotoxicity.
Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Dose Fractionation, Radiation; Female; Follow-Up Studies; Heart Valve Diseases; Humans; Lung Neoplasms; Male; Middle Aged; Patient Selection; Pericardial Effusion; Prognosis; Radiometry; Radiotherapy; Retrospective Studies; Risk
PubMed: 31303452
DOI: 10.1016/j.cllc.2019.05.014 -
International Journal of Radiation... Dec 2020Our purpose was to investigate the association between imaging biomarkers of radiation-induced white matter (WM) injury within perisylvian regions and longitudinal...
PURPOSE
Our purpose was to investigate the association between imaging biomarkers of radiation-induced white matter (WM) injury within perisylvian regions and longitudinal language decline in patients with brain tumors.
METHODS AND MATERIALS
Patients with primary brain tumors (n = 44) on a prospective trial underwent brain magnetic resonance imaging, diffusion-weighted imaging, and language assessments of naming (Boston Naming Test [BNT]) and fluency (Delis-Kaplan Executive Function System Category Fluency [DKEFS-CF]) at baseline and 3, 6, and 12 months after fractionated radiation therapy (RT). Reliable change indices of language function (0-6 months), accounting for practice effects (RCI-PE), evaluated decline. Bilateral perisylvian WM regions (superficial WM subadjacent to Broca's area and the superior temporal gyrus [STG], inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], and arcuate fasciculus) were autosegmented. We quantified volume and diffusion measures of WM microstructure: fractional anisotropy (FA; lower values indicate disruption) and mean diffusivity (MD; higher values indicate injury). Linear mixed-effects models assessed mean dose as predictor of imaging biomarker change and imaging biomarkers as longitudinal predictors of language scores.
RESULTS
DKEFS-CF scores declined at 6 months post-RT (RCI-PE, -0.483; P = .01), whereas BNT scores improved (RCI-PE, 0.262; P = .04). Higher mean dose to left and right regions was predictive of decreased volume (left-STG, P = .02; right-ILF and IFOF, P = .03), decreased FA (left-WM tracts, all P < .01; right-STG and IFOF, P < .02), and increased MD of left-WM tracts (all P < .03). Volume loss within left-Broca's area (P = .01), left-ILF (P = .01), left-IFOF (P = .01), and left-arcuate fasciculus (P = .04) was associated with lower BNT scores. Lower FA correlated with poorer DKEFS-CF and BNT scores within left-ILF (P = .02, not significant), left-IFOF (P = .02, .04), and left-arcuate fasciculus (P = .01, .01), respectively. Poorer DKEFS-CF scores correlated with increased MD values within the left-arcuate fasciculus (P = .03). Right-sided biomarkers did not correlate with language scores.
CONCLUSIONS
Patients with primary brain tumors experience language fluency decline post-RT. Poorer fluency and naming function may be explained by microstructural injury to left-sided perisylvian WM, representing potential dose-avoidance targets for language preservation.
Topics: Adult; Aged; Brain Neoplasms; Broca Area; Cerebral Aqueduct; Cranial Irradiation; Diffusion Magnetic Resonance Imaging; Dose Fractionation, Radiation; Female; Humans; Language Disorders; Male; Middle Aged; Prospective Studies; Radiation Injuries; Subthalamus; Temporal Lobe; Time Factors; White Matter; Young Adult
PubMed: 32712255
DOI: 10.1016/j.ijrobp.2020.07.032 -
La Radiologia Medica Aug 2023Reirradiation (reRT) of local recurrent/second primary tumors of the head and neck represents a potential curative treatment for patients not candidate to a salvage... (Review)
Review
INTRODUCTION
Reirradiation (reRT) of local recurrent/second primary tumors of the head and neck represents a potential curative treatment for patients not candidate to a salvage surgery. Aim of the present study is to summarize literature data on modern radiation techniques and fractionations used in this setting of patients.
MATERIALS AND METHODS
A narrative review of the literature was conducted on three topics: (1) target volume delineation (2) reRT dose and techniques and (3) ongoing studies. Patients treated with postoperative reRT and palliative intent were not considered for the current analysis.
RESULTS
Recommendations on the target volume contouring have been reported. 3D-Conformal Radiotherapy, Intensity Modulated Radiotherapy, Stereotactic body Radiotherapy Intraoperative Radiotherapy, Brachytherapy and Charged Particles have been analyzed in terms of indication and fractionation in the field of reRT. Ongoing studies on the topic have been reported for IMRT and Charged Particles. Moreover, according to literature data a stepwise approach has been proposed aiming to provide a useful tool to select patients candidate to a curative reRT in daily clinical practice. Two clinical cases were also provided for its application.
CONCLUSION
Different radiation techniques and fractionations can be used for a second course of radiotherapy in patients with recurrent/second primary tumor of head and neck region. Tumor characteristics as well as radiobiological considerations should be take into account to define the best reRT approach.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Re-Irradiation; Dose Fractionation, Radiation; Radiotherapy, Intensity-Modulated; Radiotherapy Dosage; Neoplasm Recurrence, Local; Head and Neck Neoplasms
PubMed: 37415056
DOI: 10.1007/s11547-023-01671-0 -
Journal of Chromatography. B,... Apr 2021A green, novel and efficacious method for the simultaneous extraction and enrichment of rutin and narcissoside from the compound Anoectochilus roxburghii (Wall.) Lindl....
Synergic cloud-point extraction using [Cmim][PF] and Triton X-114 as extractant combined with HPLC for the determination of rutin and narcissoside in Anoectochilus roxburghii (Wall.) Lindl. and its compound oral liquid.
A green, novel and efficacious method for the simultaneous extraction and enrichment of rutin and narcissoside from the compound Anoectochilus roxburghii (Wall.) Lindl. oral liquid (CAROL) and Anoectochilus roxburghii (Wall.) Lindl. was developed. Ionic liquid-surfactant synergic cloud-point extraction (IL-CPE) was used to enrich two analytes, which were determined by high-performance liquid chromatography (HPLC). Some parameters affecting IL-CPE were optimized, such as ratio and volume of 1-butyl-3-methyl-imidazolium hexafluorophosphate and Triton X-114, pH of the sample, NaCl concentration, total extraction volume, incubation temperature and time, centrifuge rate and time. The corresponding linearity range for two analytes exhibited good linearity (r>0.9997), with the average added recoveries ranging from 92.1% to 98.9%. The limits of detection of rutin and narcissoside were 0.26 and 0.30 ng/mL, respectively. The method was successfully applied for the determination of two flavonoids in the complex-matrix sample, i.e. CAROL and the water extract of A. roxburghii. The mass spectrum data showed that the sample contained rutin and narcissoside. Compared with conventional extraction methods, IL-CPE exhibited higher extraction efficiency and better extraction selectivity. This method may provide a novel platform for the determination of active ingredients in compound Chinese medicine oral liquid and herb.
Topics: Chemical Fractionation; Chromatography, High Pressure Liquid; Flavonoids; Imidazoles; Limit of Detection; Linear Models; Octoxynol; Orchidaceae; Reproducibility of Results; Rutin
PubMed: 33640667
DOI: 10.1016/j.jchromb.2021.122589 -
International Journal of Radiation... Jan 2020To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved...
PURPOSE
To develop and validate combined ion-beam with constant relative biological effectiveness (RBE) (CICR) particle therapy in single field arrangements for improved treatment efficacy, robustness, and normal tissue sparing.
METHODS AND MATERIALS
The PRECISE (PaRticle thErapy using single and Combined Ion optimization StratEgies) treatment planning system was developed to investigate clinical viability of CICR treatments. Single-field uniform dose (SFUD) with a single ion (proton [p], helium [He], or carbon [C]) and CICR (C-p and C-He) treatments were generated for 3 patient cases with a clinically prescribed dose of 3 Gy (RBE) per fraction. Spread-out Bragg peak plans were irradiated in homogenous and clinical-like settings using an anthropomorphic head phantom. A dosimetric and biological verification of CICR treatments using a murine glioma cell line (GL261) was performed.
RESULTS
CICR treatment plans for the 3 patients presented highly uniform physical dose while reducing high dose-averaged linear energy transfer gradients compared with carbon ions alone. When considering uncertainty in tissue parameter (α/β) assignment and RBE modeling, the CICR treatment exhibited enhanced biophysical stability within the target volume, similar to protons alone. CICR treatments reduced dose to normal tissue surrounding the target, exhibiting similar or improved dosimetric features compared with SFUD. For both CICR and SFUD treatments, measurements verified the planned dose in the target within ∼3%. Planned versus measured target RBE values were 1.38 ± 0.02 and 1.39 ± 0.07 (<1% deviation), respectively, for the CICR treatment in heterogenous settings.
CONCLUSIONS
Here, we demonstrate that by combining 2 (or more) ions in a single field arrangement, more robust biological and more conformal dose distributions can be delivered compared with conventional particle therapy treatment planning. This work constitutes the first dosimetric and biological verification of multi-ion particle therapy in homogeneous as well as heterogenous settings.
Topics: Animals; Brain Neoplasms; Carbon; Carcinoma, Adenoid Cystic; Cell Line, Tumor; Chordoma; Combined Modality Therapy; Dose Fractionation, Radiation; Glioma; Heavy Ion Radiotherapy; Helium; Humans; Linear Energy Transfer; Mice; Organ Sparing Treatments; Organs at Risk; Phantoms, Imaging; Proton Therapy; Radiation Injuries; Radiotherapy Planning, Computer-Assisted; Relative Biological Effectiveness; Sacrum; Spinal Neoplasms
PubMed: 31610250
DOI: 10.1016/j.ijrobp.2019.10.008 -
International Journal of Radiation... Mar 2021Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy....
PURPOSE
Magnetic resonance image (MRI) guided radiation therapy has the potential to improve outcomes for glioblastoma by adapting to tumor changes during radiation therapy. This study quantifies interfraction dynamics (tumor size, position, and geometry) based on sequential magnetic resonance imaging scans obtained during standard 6-week chemoradiation.
METHODS AND MATERIALS
Sixty-one patients were prospectively imaged with gadolinium-enhanced T1 (T1c) and T2/FLAIR axial sequences at planning (Fx0), fraction 10 (Fx10), fraction 20 (Fx20), and 1 month after the final fraction of chemoradiation therapy (P1M). Gross tumor volumes (GTVs) and clinical target volumes (CTVs) were contoured at all time points. Target dynamics were quantified by absolute volume (V), volume relative to Fx0 (V), and the migration distance (d; the linear displacement of the GTV or CTV relative to Fx0). Temporal changes were assessed using a linear mixed-effects model.
RESULTS
Median volumes at Fx0, Fx10, Fx20, and P1M for the GTV were 18.4 cm (range, 1.1-110.5 cm), 14.7 cm (range, 0.9-115.1 cm), 13.7 cm (range, 0.6-174.2 cm), and 13.0 cm (range, 0.9-76.3 cm), respectively, with corresponding median V of 0.88 at Fx10, 0.77 at Fx20, and 0.71 at P1M relative to Fx0 (P < .001 for all). The GTV (CTV) migration distances were greater than 5 mm in 46% (54%) of patients at Fx10, 50% (58%) of patients at Fx20, and 52% (57%) of patients at P1M. Dynamic tumor morphologic changes were observed, with 40% of patients exhibiting a decreased GTV (V ≤1) with a d >5 mm during chemoradiation therapy.
CONCLUSIONS
Clinically meaningful tumor dynamics were observed during chemoradiation therapy for glioblastoma, supporting evaluation of daily MRI guided radiation therapy and treatment plan adaptation.
Topics: Adult; Aged; Brain Neoplasms; Chemoradiotherapy; Dose Fractionation, Radiation; Female; Gadolinium; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Radiotherapy, Image-Guided; Tumor Burden; Young Adult
PubMed: 33068687
DOI: 10.1016/j.ijrobp.2020.10.002 -
Radiotherapy and Oncology : Journal of... Aug 2022For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and... (Review)
Review
For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and delineation variability. For pediatric patients no standardized margins are defined. Moreover, studies on these geometrical uncertainties are relatively scarce. Therefore, this systematic review presents an overview of organ motion, applied margin sizes and delineation variability in patients <18 years. A search from January 2000 to March 2021 in Medline, Embase, Web of Science, ClinicalTrials.gov and the International Trials Registry Platform resulted in the inclusion of 117 studies reporting on organ motion, margin sizes and/or delineation variability. Studies were heterogeneous concerning age, tumor types, the use of general anesthesia, imaging modalities; image guidance techniques were reported in 39% of the studies. Inter- and intrafractional motion as reported for different organs was largest in cranio-caudal direction and ranged from -9.1 to 10.0 mm and -4.4 to 19.5 mm, respectively. Motion quantification methodologies differed between studies regarding measures of displacement and definitions of motion direction. Reported CTV-PTV margins varied from 3 to 20 mm for both thoracic and abdominal targets, and for spinal and pelvic from 3to 15 mm and 3 to 10 mm, respectively. Studies reported wide variation in interobserver variability of target volume delineation, which may affect dose distributions to both target volumes and organs at risk. Results of this review indicate possible reduction of margin sizes for children, however, wide variation in organ motion and delineation variability caused by differences in methodologies and outcomes hamper the use of standardized margins.
Topics: Child; Dose Fractionation, Radiation; Humans; Organ Motion; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided
PubMed: 35640771
DOI: 10.1016/j.radonc.2022.05.021