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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 -
Journal of Nuclear Medicine : Official... Mar 2022Tumor dosimetry was performed for Lu-DOTATATE with the aims of better understanding the range and variation of the tumor-absorbed doses (ADs), how different dosimetric...
Tumor dosimetry was performed for Lu-DOTATATE with the aims of better understanding the range and variation of the tumor-absorbed doses (ADs), how different dosimetric quantities evolve over the treatment cycles, and whether this evolution differs depending on the tumor grade. Such information is important for radiobiologic interpretation and may inform the design of alternative administration schemes. The data came from 41 patients with neuroendocrine tumors (NETs) of grade 1 ( = 23) or 2 ( = 18) who had received between 2 and 9 treatment cycles. Dosimetry was performed for 182 individual lesions, giving a total of 880 individual AD assessments across all cycles. Hybrid planar-SPECT/CT imaging was used, including quantitative SPECT reconstruction, voxel-based absorbed-dose-rate calculation, semiautomatic image segmentation, and partial-volume correction. Linear mixed-effect models were used to analyze changes in tumor ADs over cycles, absorbed-dose rates and activity concentrations on day 1, effective half-times, and tumor volumes. Tumors smaller than 8 cm were excluded from analyses. Tumor ADs ranged between 2 and 77 Gy per cycle. On average, the AD decreased over the cycles, with significantly different rates ( < 0.05) of 6% and 14% per cycle for grade 1 and 2 NETs, respectively. The absorbed-dose rates and activity concentrations on day 1 decreased by similar amounts. The effective half-times were less variable but shorter for grade 2 than for grade 1 ( < 0.001). For grade 2 NETs, the tumor volumes decreased, with a similar tendency in grade 1. The tumor AD, absorbed-dose rate, and activity uptake decrease, in parallel with tumor volumes, between Lu-DOTATATE treatment cycles, particularly for grade 2 NETs. The effective half-times vary less but are lower for grade 2 than grade 1 NETs. These results may indicate the development of radiation-induced fibrosis and could have implications for the design of future treatment and dosimetry protocols.
Topics: Humans; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Overtreatment; Positron-Emission Tomography; Radiometry; Radionuclide Imaging; Radiopharmaceuticals
PubMed: 34272319
DOI: 10.2967/jnumed.121.262069 -
International Journal of Radiation... Oct 2021Carbon ions are radiobiologically more effective than photons and are beneficial for treating radioresistant gross tumor volumes (GTV). However, owing to a reduced...
PURPOSE
Carbon ions are radiobiologically more effective than photons and are beneficial for treating radioresistant gross tumor volumes (GTV). However, owing to a reduced fractionation effect, they may be disadvantageous for treating infiltrative tumors, in which healthy tissue inside the clinical target volume (CTV) must be protected through fractionation. This work addresses the question: What is the ideal combined photon-carbon ion fluence distribution for treating infiltrative tumors given a specific fraction allocation between photons and carbon ions?
METHODS AND MATERIALS
We present a method to simultaneously optimize sequentially delivered intensity modulated photon (IMRT) and carbon ion (CIRT) treatments based on cumulative biological effect, incorporating both the variable relative biological effect of carbon ions and the fractionation effect within the linear quadratic model. The method is demonstrated for 6 glioblastoma patients in comparison with the current clinical standard of independently optimized CIRT-IMRT plans.
RESULTS
Compared with the reference plan, joint optimization strategies yield inhomogeneous photon and carbon ion dose distributions that cumulatively deliver a homogeneous biological effect distribution. In the optimal distributions, the dose to CTV is mostly delivered by photons and carbon ions are restricted to the GTV with variations depending on tumor size and location. Improvements in conformity of high-dose regions are reflected by a mean EQD2 reduction of 3.29 ± 1.22 Gy in a dose fall-off margin around the CTV. Carbon ions may deliver higher doses to the center of the GTV, and photon contributions are increased at interfaces with CTV and critical structures. This results in a mean EQD2 reduction of 8.3 ± 2.28 Gy, in which the brain stem abuts the target volumes.
CONCLUSIONS
We have developed a biophysical model to optimize combined photon-carbon ion treatments. For 6 glioblastoma patient cases, we show that our approach results in a more targeted application of carbon ions that (1) reduces dose in normal tissues within the target volume, which can only be protected through fractionation; and (2) boosts central target volume regions to reduce integral dose. Joint optimization of IMRT-CIRT treatments enable the exploration of a new spectrum of plans that can better address physical and radiobiological treatment planning challenges.
Topics: Brain Neoplasms; Glioblastoma; Heavy Ion Radiotherapy; Humans; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 34058258
DOI: 10.1016/j.ijrobp.2021.05.126 -
Cureus Oct 2019We aimed to evaluate the feasibility of a one-day two-fraction Gamma Knife radiosurgery (GKRS) for brain metastases.
OBJECTIVE
We aimed to evaluate the feasibility of a one-day two-fraction Gamma Knife radiosurgery (GKRS) for brain metastases.
CASES AND METHODS
Ten cases with ten brain metastases (four cases of lung adenocarcinoma, one small cell lung carcinoma (SCLC), two renal cell carcinoma, one breast cancer, one esophageal carcinoma, and one bile duct carcinoma) were treated by one-day two-fraction (with an interval of more than six hours) GKRS under rigid skull frame fixation. Of the ten brain metastases, five lesions were in the frontal lobe, one in temporal, one in occipital, and three in the cerebellar hemisphere. The mean planning target volume (PTV) of the ten brain tumors was 7.8 ml (median, 8.0; range, 3.8 - 11.8). The ten targets of the mean prescription isodose volume (PIV) of 10.1 ml (median, 10.1; range, 4.4 - 15.9) were treated with a mean margin dose of 20.4 Gy (median, 20.5; range, 16.4 - 22) in two fractions. In five cases, other small brain metastases (one to seven tumors) were also treated simultaneously in a single fraction GKRS. The indication of two-fraction radiosurgery was large lesion size in eight, retreatment in three, the proximity of the motor area in three, and pre-existing perifocal edema symptom of dysarthria in two, nausea and vomiting in one, and dementia in one.
RESULTS
Eight cases were alive at the end of the follow-up period of one to nine months (median, 6). One patient with SCLC died four and a half months after GKRS, from aggressive regrowth of the treated frontal lesion after transient marked shrinkage. Another patient died four months after GKRS due to the progression of other brain tumors treated by single fraction GKRS at the same time. In nine of 10 cases, the size of the treated tumors was controlled until the end of the follow-up period or the patient's death. In two cases, an additional GKRS was performed for newly developed brain metastases at distant locations at six months and five months after one-day two-fraction GKRS, respectively, and controlled at the end of the follow-up period.
CONCLUSIONS
A relatively high dose may be safely delivered to large lesions, to those close to the important structures, or those with perifocal edema by one-day two-fraction radiosurgery. Local control was good except for a relapsed SCLC metastasis case. Evaluation in more cases with a longer follow-up period is necessary to determine definite indications and optimal prescription doses.
PubMed: 31824793
DOI: 10.7759/cureus.6026 -
Radiation Oncology (London, England) Jun 2022Delivered organs at risk (OARs) dose may vary from planned dose due to interfraction and intrafraction motion during kidney SABR treatment. Cases of bowel stricture...
BACKGROUND
Delivered organs at risk (OARs) dose may vary from planned dose due to interfraction and intrafraction motion during kidney SABR treatment. Cases of bowel stricture requiring surgery post SABR treatment were reported in our institution. This study aims to provide strategies to reduce dose deposited to OARs during SABR treatment and mitigate risk of gastrointestinal toxicity.
METHODS
Small bowel (SB), large bowel (LB) and stomach (STO) were delineated on the last cone beam CT (CBCT) acquired before any dose had been delivered (PRE CBCT) and on the first CBCT acquired after any dose had been delivered (MID CBCT). OAR interfraction and intrafraction motion were estimated from the shortest distance between OAR and the internal target volume (ITV). Adaptive radiation therapy (ART) was used if dose limits were exceeded by projecting the planned dose on the anatomy of the day.
RESULTS
In 36 patients, OARs were segmented on 76 PRE CBCTs and 30 MID CBCTs. Interfraction motion was larger than intrafraction motion in STO (p-value = 0.04) but was similar in SB (p-value = 0.8) and LB (p-value = 0.2). LB was inside the planned 100% isodose in all PRE CBCTs and MID CBCTs in the three patients that suffered from bowel stricture. SB D0.03cc was exceeded in 8 fractions (4 patients). LB D1.5cc was exceeded in 4 fractions (2 patients). Doses to OARs were lowered and limits were all met with ART on the anatomy of the day.
CONCLUSIONS
Interfraction motion was responsible for OARs overdosage. Dose limits were respected by using ART with the anatomy of the day.
Topics: Constriction, Pathologic; Dose Fractionation, Radiation; Humans; Kidney; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 35761291
DOI: 10.1186/s13014-022-02041-2 -
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 -
International Journal of Radiation... Jul 2021To explore the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in high-risk prostate cancer (HRPCa) in a consortium of 7 institutional phase 2 trials... (Clinical Trial)
Clinical Trial
PURPOSE
To explore the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in high-risk prostate cancer (HRPCa) in a consortium of 7 institutional phase 2 trials and prospective registries.
METHODS AND MATERIALS
Individual patient data were pooled for 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework. Fine and Gray competing risk and Cox proportional hazards regression models were developed to assess the association between time to BCR and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade ≥2 genitourinary and gastrointestinal and the following a priori-specified variables: age, dose per fraction, ADT use, and nodal radiation therapy.
RESULTS
Median follow-up was 49.5 months. Seventy-two percent of patients received ADT, with a median duration of 9 months, and 19% received elective nodal radiation therapy. Estimated 4-year BCRFS and DMFS rates were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%). The crude incidences of late grade ≥3 genitourinary and gastrointestinal toxicity were 2.3% and 0.9%.
CONCLUSIONS
These data support a favorable toxicity and efficacy profile for SBRT for HRPCa. Further prospective studies are needed to evaluate the optimal dose and target volume in the context of SBRT for HRPCa.
Topics: Aged; Aged, 80 and over; Dose Fractionation, Radiation; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Radiosurgery; Treatment Outcome
PubMed: 33493615
DOI: 10.1016/j.ijrobp.2021.01.016 -
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 -
Cancers Aug 2023The new biological interaction cross-section-based repairable-homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair,... (Review)
Review
The new biological interaction cross-section-based repairable-homologically repairable (RHR) damage formulation for radiation-induced cellular inactivation, repair, misrepair, and apoptosis was applied to optimize radiation therapy. This new formulation implies renewed thinking about biologically optimized radiation therapy, suggesting that most TP53 intact normal tissues are low-dose hypersensitive (LDHS) and low-dose apoptotic (LDA). This generates a fractionation window in LDHS normal tissues, indicating that the maximum dose to organs at risk should be ≤2.3 Gy/Fr, preferably of low LET. This calls for biologically optimized treatments using a few high tumor dose-intensity-modulated light ion beams, thereby avoiding secondary cancer risks and generating a real tumor cure without a caspase-3-induced accelerated tumor cell repopulation. Light ions with the lowest possible LET in normal tissues and high LET only in the tumor imply the use of the lightest ions, from lithium to boron. The high microscopic heterogeneity in the tumor will cause local microscopic cold spots; thus, in the last week of curative ion therapy, when there are few remaining viable tumor clonogens randomly spread in the target volume, the patient should preferably receive the last 10 GyE via low LET, ensuring perfect tumor coverage, a high cure probability, and a reduced risk for adverse normal tissue reactions. Interestingly, such an approach would also ensure a steeper rise in tumor cure probability and a higher complication-free cure, as the few remaining clonogens are often fairly well oxygenated, eliminating a shallower tumor response due to inherent ion beam heterogeneity. With the improved fractionation proposal, these approaches may improve the complication-free cure probability by about 10-25% or even more.
PubMed: 37686565
DOI: 10.3390/cancers15174286