-
Practical Radiation Oncology 2015The purpose of this study was to evaluate the dose-volume relationships of genitourinary toxicity after stereotactic body radiation therapy (SBRT) monotherapy for...
PURPOSE
The purpose of this study was to evaluate the dose-volume relationships of genitourinary toxicity after stereotactic body radiation therapy (SBRT) monotherapy for prostate cancer.
METHODS AND MATERIALS
Fifty-six patients diagnosed with low- to intermediate-risk prostate cancer treated with SBRT alone were reviewed retrospectively. All patients received a total dose of 38 Gy in 4 fractions with a planning target volume expansion of 2 mm. Overall, acute, and late genitourinary toxicity were documented according to the Common Terminology Criteria for Adverse Events (version 4) and International Prostate Symptom Scores (IPSS).
RESULTS
The median age at treatment was 68 years, and the median prostate volume was 45.5 mL, with a median baseline IPSS of 9.95. The median prescription isodose line was 68%. The median clinical follow-up was 35.49 months. Acute grade 1, 2, and 3 genitourinary toxicities occurred in 41.1%, 35.7%, and 0% of patients. All acute genitourinary toxicities resolved except 1 patient with grade 2 toxicity that progressed to grade 3 late toxicity. No dose-volume relationships were associated with acute genitourinary grade 2+ toxicity. Late grade 1, 2, and 3 genitourinary toxicity occurred in 19.6%, 19.6%, and 3.6% of cases, respectively. Of the cases with late toxicities, 16.7% were persistent. Late grade 2+ genitourinary toxicity was associated with prostate volume ≥50 mL, lower homogeneity index, and urethral maximum point dose ≥47 Gy. The overall risk of any grade 2+ genitourinary toxicity was associated with baseline IPSS >7, prostate volume ≥50 mL, urethral volume receiving 44 Gy, and bladder volume receiving 19 Gy.
CONCLUSIONS
SBRT for prostate cancer appears well tolerated, with mostly transient low-grade toxicity. Urethral sparing should be used with a maximum point dose <47 Gy, volume receiving 120 Gy <50% of the prostate, and bladder volume receiving 19 Gy <15 mL in 4 fraction treatments. Patients with prostate volumes ≥50 mL should be counseled regarding the increased risk of moderate-grade genitourinary toxicity.
Topics: Aged; Aged, 80 and over; Dose Fractionation, Radiation; Humans; Male; Middle Aged; Prostatic Neoplasms; Radiosurgery
PubMed: 25795252
DOI: 10.1016/j.prro.2015.02.001 -
Journal of Chromatography. A Jan 2020A proteomic workflow for a simple loss-less manual nano-fractionation (300 nL/fraction) for low µg sample amounts which avoids the need to dry down or transfer...
Nano volume fractionation strategy for dilute-and-shoot injections in off-line loss-less proteomic workflows for extensive protein identifications of ultra-low sample amounts.
A proteomic workflow for a simple loss-less manual nano-fractionation (300 nL/fraction) for low µg sample amounts which avoids the need to dry down or transfer fractions to autosampler vials is shown to be feasible. It is demonstrated that the conventional procedure of drying samples down followed by reconstitution negatively affects the number of protein and peptide identifications. Furthermore, these losses seem to disproportionately affect hydrophobic peptides from the drying down and reconstitution step. By collecting and concatenating the fractions while the outlet of the column is submerged in a small predefined volume of 0.2% formic acid, the content of acetonitrile in the collecting vials was lowered such that it was compatible with direct injection for the online analysis. This additionally resulted in a time gain of approx. an hour for the total fractionation time. Acetonitrile concentrations up to 7.5% do not seem to compromise the chromatographic performance in the online analysis. Using as little as 2 µg digested HeLa lysate, approx. 7000 protein groups could be easily identified with 2 or more unique peptides. This was the case when fractionation was performed at pH 10 as well as at pH 5.5.
Topics: Chemical Fractionation; Desiccation; HeLa Cells; Humans; Hydrogen-Ion Concentration; Nanoparticles; Peptides; Proteins; Proteomics; Trypsin; Workflow
PubMed: 31522804
DOI: 10.1016/j.chroma.2019.460507 -
Head & Neck Aug 2020A large tumor volume negatively impacts the outcome of radiation therapy (RT). Altered fractionation (AF) can improve local control (LC) compared with conventional... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A large tumor volume negatively impacts the outcome of radiation therapy (RT). Altered fractionation (AF) can improve local control (LC) compared with conventional fractionation (CF). The aim of the present study was to investigate if response to AF differs with tumor volume in oropharyngeal cancer.
METHODS
Three hundred and twenty four patients with oropharyngeal cancer treated in a randomized, phase III trial comparing CF (2 Gy/d, 5 d/wk, 7 weeks, total dose 68 Gy) to AF (1.1 Gy + 2 Gy/d, 5 d/wk, 4.5 weeks, total dose 68 Gy) were analyzed.
RESULTS
Tumor volume had less impact on LC for patients treated with AF. There was an interaction between tumor volume and fractionation schedule (P = .039). This differential response was in favor of CF for small tumors and of AF for large tumors.
CONCLUSION
AF diminishes the importance of tumor volume for local tumor control in oropharyngeal cancer.
Topics: Dose Fractionation, Radiation; Humans; Oropharyngeal Neoplasms; Tumor Burden
PubMed: 32196826
DOI: 10.1002/hed.26142 -
Clinical Oncology (Royal College of... May 2015Stereotactic body radiotherapy (SBRT) can deliver high radiation doses to small volumes with very tight margins, which has significant advantages when treating tumours... (Review)
Review
Stereotactic body radiotherapy (SBRT) can deliver high radiation doses to small volumes with very tight margins, which has significant advantages when treating tumours close to the spinal cord or at sites of retreatment. When treating spinal tumours, meticulous quality control is essential with effective immobilisation, as dose gradients at the edge of the spinal cord will be steep and excessive movements can be catastrophic. A range of dose-fractionation schedules have been used from single doses of 15-24 Gy to fractionated schedules delivering 15-35 Gy in three to five fractions. Indications include solitary or up to three vertebral metastases and primary tumours, in particular chordomas or bone sarcomas. Pain relief from metastatic disease is seen in over 80%, with similar rates of objective local control. Local control can be achieved in primary tumours of the spine in up to 95% and similar response rates are seen in non-spinal bone metastases. Toxicity rates are low, even in series that have delivered re-irradiation with myelopathy in <1%, although later vertebral fracture may occur. Further prospective studies are required to formally evaluate patient selection and optimal dose and fractionation alongside an evaluation of cost-effectiveness.
Topics: Bone Neoplasms; Dose Fractionation, Radiation; Humans; Neoplasm Metastasis; Radiosurgery; Spinal Neoplasms
PubMed: 25687175
DOI: 10.1016/j.clon.2015.01.030 -
International Journal of Radiation... May 2019Spatially fractionated radiation therapy represents a significant departure from canonical thinking in radiation oncology despite having origins in the early 1900s. The... (Review)
Review
Spatially fractionated radiation therapy represents a significant departure from canonical thinking in radiation oncology despite having origins in the early 1900s. The original and most common implementation of spatially fractionated radiation therapy uses commercially available blocks or multileaf collimators to deliver a nonconfluent, sieve-like pattern of radiation to the target volume in a nonuniform dose distribution. Dosimetrically, this is parameterized by the ratio of the valley dose in cold spots to the peak dose in hot spots, or the valley-to-peak dose ratio. The radiobiologic mechanisms are postulated to involve radiation-induced bystander effects, microvascular alterations, and/or immunomodulation. Current indications include bulky or locally advanced disease that would not be amenable to conventional radiation or that has proved refractory to chemoradiation. Early-phase clinical trials have shown remarkable success, with some response rates >90% and minimal toxicity. This has promoted technological developments in 3-dimensional formats (LATTICE), micron-size beams (microbeam), and proton arrays. Nevertheless, more clinical and biological data are needed to specify ideal dosimetry parameters and to formulate robust clinical indications and guidelines for optimal standardized care.
Topics: Animals; Bystander Effect; Clinical Trials as Topic; Dose Fractionation, Radiation; Humans; Immunomodulation; Mice; Microvessels; Neoplasms; Radiation Oncology
PubMed: 30684666
DOI: 10.1016/j.ijrobp.2019.01.073 -
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 Neurosurgery Dec 2012Dose-volume data concerning the brainstem in stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN) were analyzed in relation to associated complications. The...
OBJECT
Dose-volume data concerning the brainstem in stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN) were analyzed in relation to associated complications. The authors present their set of data and compare it with currently cited information on brainstem dose tolerance associated with conventional fractionated radiation therapy and hypofractionated radiation treatment of other diseases.
METHODS
Stereotactic radiosurgery for TN delivers a much higher radiation dose to the brainstem in a single fraction than doses delivered by any other procedures. A literature survey of articles on radiosurgery for TN revealed no incidences of severe toxicity, unlike other high-dose procedures involving the brainstem. Published data on brainstem dose tolerance were investigated and compared with dose-volume data in TN radiosurgery. The authors also performed a biological modeling study of dose-volume data involving the brainstem in cases of TN treated with the Gamma Knife, CyberKnife, and linear accelerator-based systems.
RESULTS
The brainstem may receive a maximum dose as high as 45 Gy during radiosurgery for TN. The major complication after TN radiosurgery is mild to moderate facial numbness, and few other severe toxic responses to radiation are observed. The biologically effective dose of 45 Gy in a single fraction is much higher than any brainstem dose tolerance currently cited in conventional fractionation or in single or hypofractionated radiation treatments. However, in TN radiosurgery, the dose falloff is so steep and the delivery so accurate that brainstem volumes of 0.1-0.5 cm(3) or larger receive lower planned and delivered doses than those in other radiation-related procedures. Current models are suggestive, but an extensive analysis of detailed dose-volume clinical data is needed.
CONCLUSIONS
Patients whose TN is treated with radiosurgery are a valuable population in which to demonstrate the dose-volume effects of an extreme hypofractionated radiation treatment on the brainstem. The result of TN radiosurgery suggests that a very small volume of the brainstem can tolerate a drastically high dose without suffering a severe clinical injury. The authors believe that the steep dose gradient in TN radiosurgery plays a key role in the low toxicity experienced by the brainstem.
Topics: Adult; Aged; Brain Stem; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Female; Humans; Hyperesthesia; Hypesthesia; Male; Middle Aged; Radiosurgery; Radiotherapy Dosage; Trigeminal Neuralgia
PubMed: 23205809
DOI: 10.3171/2012.7.GKS12962 -
Journal of Neuro-oncology Sep 2022Fractionated stereotactic radiotherapy (FSRT) using gamma knife is useful for brain metastases. However, several uncertainties derived from fractionation pose issues for...
PURPOSE
Fractionated stereotactic radiotherapy (FSRT) using gamma knife is useful for brain metastases. However, several uncertainties derived from fractionation pose issues for maintaining high-level accuracy. This study analyzed interfractional tumor change by performing radiological reassessment at the midterm of FSRT with ≥ 10 fractions, and the significance of replanning was evaluated.
METHODS
Data of FSRT using gamma knife with ≥ 10 fractions were retrospectively collected. Interfractional volume changes in MRI at the midterm of the irradiation period were analyzed. Radiological changes after FSRT and final outcomes were also investigated.
RESULTS
Overall, 114 lesions in 74 treatments from 66 patients were included, with previously irradiated lesions accounting for 46%. The median interval between planning and the interfractional MRI was 7 days. The interfractional change rates of tumor volume ranged from - 48 to + 72%. Significant interfractional enlargement was observed in 16 lesions (14%); evident regression was confirmed in 17 lesions (15%). Predictive factors for interfractional enlargement were small tumor and cystic lesion; high biologically effective dose was associated with regression. After FSRT, most lesions regressed within 6 months despite interfractional change type. The incidences of tumor control and radiation necrosis indicated no differences between interfractionally-regressed lesions and others.
CONCLUSION
This is the first study to evaluate interfractional tumor change in FSRT using gamma knife with ≥ 10 fractions, indicating significant volume changes in 29% of the lesions. These preliminary results suggest that interfractional reassessment of a treatment plan in FSRT with irradiation periods exceeding a week is necessary for more adaptive treatment.
Topics: Brain Neoplasms; Dose Fractionation, Radiation; Humans; Radiosurgery; Retrospective Studies; Treatment Outcome; Tumor Burden
PubMed: 35809149
DOI: 10.1007/s11060-022-04075-8 -
International Journal of Molecular... Apr 2023Extracellular vesicles (EV) have many attributes important for biomedicine; however, current EV isolation methods require long multi-step protocols that generally...
Extracellular vesicles (EV) have many attributes important for biomedicine; however, current EV isolation methods require long multi-step protocols that generally involve bulky equipment that cannot be easily translated to clinics. Our aim was to design a new cyclic olefin copolymer-off-stoichiometry thiol-ene (COC-OSTE) asymmetric flow field fractionation microfluidic device that could isolate EV from high-volume samples in a simple and efficient manner. We tested the device with large volumes of urine and conditioned cell media samples, and compared it with the two most commonly used EV isolation methods. Our device was able to separate particles by size and buoyancy, and the attained size distribution was significantly smaller than other methods. This would allow for targeting EV size fractions of interest in the future. However, the results were sample dependent, with some samples showing significant improvement over the current EV separation methods. We present a novel design for a COC-OSTE microfluidic device, based on bifurcating asymmetric flow field-flow fractionation (A4F) technology, which is able to isolate EV from large volume samples in a simple, continuous-flow manner. Its potential to be mass-manufactured increases the chances of implementing EV isolation in a clinical or industry-friendly setting, which requires high repeatability and throughput.
Topics: Extracellular Vesicles; Polymers; Chemical Fractionation; Fractionation, Field Flow; Lab-On-A-Chip Devices; Culture Media, Conditioned
PubMed: 37175677
DOI: 10.3390/ijms24097971 -
PloS One 2019Nine patients with recurrent head and neck (H&N) cancer received boron neutron capture therapy (BNCT) in one fraction at the Tsing-Hua Open pool reactor (THOR) utilizing... (Clinical Trial)
Clinical Trial Comparative Study
A comparison of dose distributions in gross tumor volume between boron neutron capture therapy alone and combined boron neutron capture therapy plus intensity modulation radiation therapy for head and neck cancer.
Nine patients with recurrent head and neck (H&N) cancer received boron neutron capture therapy (BNCT) in one fraction at the Tsing-Hua Open pool reactor (THOR) utilizing the THORplan treatment planning system (TPS). The aims of the present study were to evaluate the use of intensity modulated radiation therapy (IMRT) of 45 Gy in 20 fractions to compensate for the dose heterogeneity in gross tumor volume observed with single-fraction BNCT with mean prescription dose 19 Gy (w), and to evaluate planning quality indices of simulated BNCT+IMRT versus single-fraction BNCT alone. All IMRT plans were generated using the Eclipse TPS which employs the analytical anisotropic algorithm. The conformity index for the gross tumor volume (GTV) was better for the BNCT+IMRT plan than for the BNCT-alone plan (p = 0.003). In addition, the BNCT+IMRT plan provided significantly better homogeneity in the GTV (p = 0.03). The cold spots in inhomogeneous dose distribution in the BNCT plan may be a key factor for H&N cancer recurrence. Our results suggest that single-fraction BNCT combined with compensated multi-fraction IMRT improves treatment homogeneity and conformity than single-fraction BNCT alone, especially for tumor volumes >100 cm3, and possibly increases local tumor control.
Topics: Boron Neutron Capture Therapy; Combined Modality Therapy; Dose Fractionation, Radiation; Feasibility Studies; Head and Neck Neoplasms; Humans; Neoplasm Recurrence, Local; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Tomography, X-Ray Computed; Tumor Burden
PubMed: 30947267
DOI: 10.1371/journal.pone.0210626