Total body irradiation for standard treatment rooms: a robust sweeping beam technique with respect to the body shape

Background: The purpose of this work is to improve a sweeping beam technique for total body irradiation (TBI) on a low flat couch using a varying patient thickness model. We designed a flat couch for total body irradiation in supine and prone position. Three generic arcs with rectangular segments for a patient torso thickness of 16, 22 and 28 cm were generated with respect to varying patient thickness of four particular parts of the body: head, torso, thighs and calves. Materials and methods: Longitudinal and transversal dose profiles were measured using an ionization chamber and the EBT3 gafchromic film in a solid water slab phantom. The robustness of the method was examined in phantoms of different thicknesses. Results: Measured dose homogeneity stays within ±10% of prescribed dose for all of the three patient thickness models. The robustness of the method was evaluated as the increase in dose in the phantom center of 0.7% per 1 cm reduction in phantom thickness. Conclusion: The method is applicable for the broad range of patient sizes, comfortable for patients, robust and suitable for standard treatment rooms with a standard linear accelerator. It requires minimal investments into equipment.

Cardiotoxicity of radiation therapy in esophageal cancer

With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data

Validation of dose distribution computation on sCT images generated from MRI scans by Philips MRCAT

AimTo evaluate calculation of treatment plans based on synthetic-CT (sCT) images generated from MRI.BackgroundBecause of better soft tissue contrast, MR images are used in addition to CT images for radiotherapy planning. However, registration of CT and MR images or repositioning between scanning sessions introduce systematic errors, hence suggestions for MRI-only therapy. The lack of information on electron density necessary for dose calculation leads to sCT (synthetic CT) generation. This work presents a comparison of dose distribution calculated on standard CT and sCT.Materials and methods10 prostate patients were included in this study. CT and MR images were collected for each patient and then water equivalent (WE) and MRCAT images were generated. The radiation plans were optimized on CT and then recalculated on MRCAT and WE data. 2D gamma analysis was also performed.ResultsThe mean differences in the majority of investigated DVH points were in order of 1% up to 10%, including both MRCAT and WE dose distributions. Mean gamma pass for acceptance criteria 1%/1mm were greater than 82.5%. Prescribed doses for target volumes and acceptable doses for organs at risk were met in almost all cases.ConclusionsThe dose calculation accuracy on MRCAT was not significantly compromised in the majority of clinical relevant DVH points. The introduction of MRCAT into practise would eliminate systematic errors, increase patients’ comfort and reduce treatment expenses. Institutions interested in MRCAT commissioning must, however, consider changes to established workflow

Transcriptional Dynamics of DNA Damage Responsive Genes in Circulating Leukocytes during Radiotherapy

External beam radiation therapy leads to cellular activation of the DNA damage response (DDR). DNA double-strand breaks (DSBs) activate the ATM/CHEK2/p53 pathway, inducing the transcription of stress genes. The dynamic nature of this transcriptional response has not been directly observed in vivo in humans. In this study we monitored the messenger RNA transcript abundances of nine DNA damage-responsive genes (CDKN1A, GADD45, CCNG1, FDXR, DDB2, MDM2, PHPT1, SESN1, and PUMA), eight of them regulated by p53 in circulating blood leukocytes at different time points (2, 6–8, 16–18, and 24 h) in cancer patients (lung, neck, brain, and pelvis) undergoing radiotherapy. We discovered that, although the calculated mean physical dose to the blood was very low (0.038–0.169 Gy), an upregulation of Ferredoxin reductase (FDXR) gene transcription was detectable 2 h after exposure and was dose dependent from the lowest irradiated percentage of the body (3.5% whole brain) to the highest, (up to 19.4%, pelvic zone) reaching a peak at 6–8 h. The radiation response of the other genes was not strong enough after such low doses to provide meaningful information. Following multiple fractions, the expression level increased further and was still significantly up-regulated by the end of the treatment. Moreover, we compared FDXR transcriptional responses to ionizing radiation (IR) in vivo with healthy donors’ blood cells exposed ex vivo and found a good correlation in the kinetics of expression from the 8-hours time-point onward, suggesting that a molecular transcriptional regulation mechanism yet to be identified is involved. To conclude, we provided the first in vivo human report of IR-induced gene transcription temporal response of a panel of p53-dependant genes. FDXR was demonstrated to be the most responsive gene, able to reliably inform on the low doses following partial body irradiation of the patients, and providing an expression pattern corresponding to the % of body exposed. An extended study would provide individual biological dosimetry information and may reveal inter-individual variability to predict radiotherapy-associated adverse health outcomes

High-Dose-Rate Brachytherapy as an Organ-Sparing Treatment for Early Penile Cancer

Background: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting. Methods: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles. Results: The median follow-up was 117.5 months (range, 5–210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7–97.7%) and 68.3% (95% CI: 44.0–92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45–97.7%) and 62.1% (95% CI: 34.8–89.4%), respectively. Conclusions: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort—the second largest reported to date in this clinical setting—prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer

Utilization of cone-beam CT for offline evaluation of target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment

AimTo assess target volume coverage during prostate image-guided radiotherapy based on bony anatomy alignment and to assess possibility of safety margin reduction.BackgroundImplementation of IGRT should influence safety margins. Utilization of cone-beam CT provides current 3D anatomic information directly in irradiation position. Such information enables reconstruction of the actual dose distribution.Materials and methodsSeventeen prostate patients were treated with daily bony anatomy image-guidance. Cone-beam CT (CBCT) scans were acquired once a week immediately after bony anatomy alignment. After the prostate, seminal vesicles, rectum and bladder were contoured, the delivered dose distribution was reconstructed. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed a 1[[ce:hsp sp="0.25"/]]cm safety margin. Alternative plans assuming a smaller 7[[ce:hsp sp="0.25"/]]mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with the initial ones. Rectal and bladder volumes irradiated with doses higher than 75[[ce:hsp sp="0.25"/]]Gy, 70[[ce:hsp sp="0.25"/]]Gy, 60[[ce:hsp sp="0.25"/]]Gy, 50[[ce:hsp sp="0.25"/]]Gy and 40[[ce:hsp sp="0.25"/]]Gy were analyzed.ResultsIn 12% of reconstructed plans the prostate coverage was not sufficient. The prostate underdosage was observed in 5 patients. Coverage of seminal vesicles was not satisfactory in 3% of plans. Most of the target underdosage corresponded to excessive rectal or bladder filling. Evaluation of alternative plans assuming a smaller 7[[ce:hsp sp="0.25"/]]mm margin revealed 22% and 11% of plans where prostate and seminal vesicles coverage, respectively, was compromised. These were distributed over 8 and 7 patients, respectively.ConclusionSufficient dose coverage of target volumes was not achieved for all patients. Reducing of safety margin is not acceptable. Initial rectal and bladder volumes cannot be considered representative for subsequent treatment

The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.

The increasing risk of acute large-scale radiological/nuclear exposures of population underlines the necessity of developing new, rapid and high throughput biodosimetric tools for estimation of received dose and initial triage. We aimed to compare the induction and persistence of different radiation exposure biomarkers in human peripheral blood in vivo. Blood samples of patients with indicated radiotherapy (RT) undergoing partial body irradiation (PBI) were obtained soon before the first treatment and then after 24 h, 48 h, and 5 weeks; i.e. after 1, 2, and 25 fractionated RT procedures. We collected circulating peripheral blood from ten patients with tumor of endometrium (1.8 Gy per fraction) and eight patients with tumor of head and neck (2.0-2.121 Gy per fraction). Incidence of dicentrics and micronuclei was monitored as well as determination of apoptosis and the transcription level of selected radiation-responsive genes. Since mitochondrial DNA (mtDNA) has been reported to be a potential indicator of radiation damage in vitro, we also assessed mtDNA content and deletions by novel multiplex quantitative PCR. Cytogenetic data confirmed linear dose-dependent increase in dicentrics (p < 0.01) and micronuclei (p < 0.001) in peripheral blood mononuclear cells after PBI. Significant up-regulations of five previously identified transcriptional biomarkers of radiation exposure (PHPT1, CCNG1, CDKN1A, GADD45, and SESN1) were also found (p < 0.01). No statistical change in mtDNA deletion levels was detected; however, our data indicate that the total mtDNA content decreased with increasing number of RT fractions. Interestingly, the number of micronuclei appears to correlate with late radiation toxicity (r2 = 0.9025) in endometrial patients suggesting the possibility of predicting the severity of RT-related toxicity by monitoring this parameter. Overall, these data represent, to our best knowledge, the first study providing a multiparametric comparison of radiation biomarkers in human blood in vivo, which have potential for improving biological dosimetry

FDXR is a biomarker of radiation exposure in vivo

Abstract Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately FDXR transcription. Finally, we provided a first in vivo dose-response showing dose-dependency even for very low doses or partial body exposure showing good correlation between physically and biologically assessed doses. In conclusion, we report the remarkable responsiveness of FDXR to ionising radiation at the transcriptional level which, when measured in the right time window, provides accurate in vivo dose estimates

Chromosomal changes in PBMCs of head and neck patients.

<p>Number of dicentric chromosomes (A) and structurally aberrant cells (B) was determined and both parameters increase with the number of RT fractions. *, statistically significant difference versus Control group (p < 0.01). Representative figures of dicentric chromosome (C) and structurally aberant cells—ring chromosome (D), double fragment (E) and break (F) are shown.</p

Incidence of micronuclei in PBMCs of endometrial patients (A) and their relation to late radiotoxicity (B).

<p>Number of MN increased with the number of RT fractions. BN, binucleated cells; *, statistically significant difference of the 2^nd and 25^th RT fraction versus Control group (p < 0.001); #, statistically significant difference of the 25^th RT fraction versus 2^nd RT fraction (p < 0.001).</p