Current practices of craniospinal irradiation techniques in Turkey: a comprehensive dosimetric analysis.

OBJECTIVE: This study evaluates various craniospinal irradiation (CSI) techniques used in Turkish centers to understand their advantages, disadvantages and overall effectiveness, with a focus on enhancing dose distribution. METHODS: Anonymized CT scans of adult and pediatric patients, alongside target volumes and organ-at-risk (OAR) structures, were shared with 25 local radiotherapy centers. They were tasked to develop optimal treatment plans delivering 36 Gy in 20 fractions with 95% PTV coverage, while minimizing OAR exposure. The same CT data was sent to a US proton therapy center for comparison. Various planning systems and treatment techniques (3D conformal RT, IMRT, VMAT, tomotherapy) were utilized. Elekta Proknow software was used to analyze parameters, assess dose distributions, mean doses, conformity index (CI), and homogeneity index (HI) for both target volumes and OARs. Comparisons were made against proton therapy. RESULTS: All techniques consistently achieved excellent PTV coverage (V95 > 98%) for both adult and pediatric patients. Tomotherapy closely approached ideal Dmean doses for all PTVs, while 3D-CRT had higher Dmean for PTV_brain. Tomotherapy excelled in CI and HI for PTVs. IMRT resulted in lower pediatric heart, kidney, parotid, and eye doses, while 3D-CRT achieved the lowest adult lung doses. Tomotherapy approached proton therapy doses for adult kidneys and thyroid, while IMRT excelled for adult heart, kidney, parotid, esophagus, and eyes. CONCLUSION: Modern radiotherapy techniques offer improved target coverage and OAR protection. However, 3D techniques are continued to be used for CSI. Notably, proton therapy stands out as the most efficient approach, closely followed by Tomotherapy in terms of achieving superior target coverage and OAR protection.

Multi-centre evaluation of variation in cumulative dose assessment in reirradiation scenarios.

BACKGROUND AND PURPOSE: Safe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi-centre clinical pathways. MATERIAL AND METHODS: We provided DICOM planning CT, structures and doses for two reirradiation cases: head & neck (HN) and lung. Participants followed their standard pathway to assess the cumulative physical and EQD2 doses (with provided α/ß values), and submitted DVH metrics and a description of their pathways. Participants could also submit physical dose distributions from Course 1 mapped onto the CT of Course 2 using their best available tools. To assess isolated impact of image registrations, a single observer accumulated each submitted spatially mapped physical dose for every participating centre. RESULTS: Cumulative dose assessment was performed by 24 participants. Pathways included rigid (n = 15), or deformable (n = 5) image registration-based 3D dose summation, visual inspection of isodose line contours (n = 1), or summation of dose metrics extracted from each course (n = 3). Largest variations were observed in near-maximum cumulative doses (25.4 - 41.8 Gy for HN, 2.4 - 33.8 Gy for lung OARs), with lower variations in volume/dose metrics to large organs. A standardised process involving spatial mapping of the first course dose to the second course CT followed by summation improved consistency for most near-maximum dose metrics in both cases. CONCLUSION: Large variations highlight the uncertainty in reporting cumulative doses in reirradiation scenarios, with implications for outcome analysis and understanding of published doses. Using a standardised workflow potentially including spatially mapped doses improves consistency in determination of accumulated dose in reirradiation scenarios.

Effect of Multileaf Collimator Leaf Position Error Determined by Picket Fence Test on Gamma Index Value in Patient-Specific Quality Assurance of Volumetric-Modulated Arc Therapy Plans.

Aim The correlation between the MLC QA (IBA Dosimetry, Germany) results of the picket fence test created with intentional errors and the patient's quality assurance (QA) evaluation was investigated to assess the impact of multileaf collimator (MLC) positioning error on patient QA. Materials and methods The picket fence, including error-free and intentional MLC errors, defined in Bank In, Bank Out, and Bank Both were analyzed using MLC QA. The QA of 15 plans consisting of stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and conventionally fractionated volumetric-modulated arc therapy (VMAT) acquired with electronic portal imaging devices (EPID) was evaluated in the presence of error-free and MLC errors. The QA of plans were analyzed with 2%/2 mm and 3%/3 mm criteria. Results The passing rates of the picket fence test were 97%, 92%, 91%, and 87% for error-free and intentional errors. The criterion of 3%/3 mm wasn't able to detect an MLC error for either SRS/SBRT or conventionally fractionated VMAT. The criterion of 2%/2mm was more sensitive to detect MLC error for the conventionally fractionated VMAT than SRS/SBRT. While only two of SBRT plans had <90%, four of conventionally fractionated VMAT plans had a <90% passing rate. Conclusion We found that the systematic MLC positioning errors defined with picket fence have a smaller but measurable impact on SRS/SBRT than the VMAT plan for a conventionally fractionated and relatively complex plan such as head and neck and endometrium cases.

Quantifying the influences of radiation therapy on deformability of human red blood cells by dual-beam optical tweezers.

Radiation therapy is widely used as a treatment tool for malignancies. However, radiation-related complications are still unavoidable risks for off-target cells. Little is known about radiation therapy's possible effects on mechanical features of the off-target cells such as human red blood cells (RBCs). RBCs are nucleus-free circulating cells that can deform without losing functionality in healthy conditions. Thus, to evaluate in vitro effects of radiation therapy on the healthy plasma membrane of cells, RBCs were selected as a primary test model. RBCs were exposed to clinically prescribed radiotherapy doses of 2 Gy, 12 Gy and, 25 Gy, and each radiotherapy dose group was compared to a non-irradiated group. Cells were characterized by stretching using dual-beam optical tweezers and compared using the resulting deformability index. The group receiving the highest radiation dose was found statistically distinguishable from the control group (DI0Gy = 0.33 ± 0.08), and revealed the highest deformability index (DI25Gy = 0.38 ± 0.11, p = 0.0068), while no significant differences were found for 2 Gy (DI2Gy = 0.33 ± 0.08, p = 0.9) and 12 Gy (DI12Gy = 0.31 ± 0.09, p = 0.2) dose groups. Based on these findings, we conclude that radiotherapy exposure may alter the deformability of red blood cells depending on the dose amount, and measurement of deformability index by dual-beam optical tweezers can serve as a sensitive biomarker to probe responses of cells to the radiotherapy.

Acoustic diagnosis of elastic properties of human tooth by 320 MHz scanning acoustic microscopy after radiotherapy treatment for head and neck cancer.

BACKGROUND: On the elastic profiles of human teeth after radiotherapy for head and neck cancers, generation of dental complications, which may bring several side effects preventing the quality of life, has not well clarified. Thus, we aimed to show the applicability of using 320 MHz Scanning Acoustic Microscopy (SAM) in the evaluation of the tooth damage acoustically at the micrometer level following radiation therapy, and also in the determination of the safe dose limits to impede severe dental damage. METHODS: This prospective study was performed by SAM employed at 320 MHz by an azimuthal resolution of 4.7 µm resolving enamel and dentin. A total of 45 sound human third molar teeth collected between September 2018 and May 2019 were used for the acoustic impedance measurements pre- and post irradiation. Nine samples for each group (control, 2 Gy, 8 Gy, 20 Gy, 30 Gy and 60 Gy) were evaluated to acquire the acoustic images and perform a qualitative analysis. Scanning Electron Microscopy (SEM) images were obtained to establish a relationship between micromechanical and morphological characteristics of the teeth. Statistical analysis was conducted using the Student t-test succeded by Mann-Whitney U investigation (p < .05), while SEM images were assessed qualitatively. RESULTS: The analysis included 45 sound teeth collected from men and women 18 to 50 years old. Post irradiation micromechanical variations of human teeth were significant only in the radiation groups of 30 Gy and 60 Gy compared to pre-irradiation group for enamel (7.24 ± 0.18 MRayl and 6.49 ± 028 MRayl; p < 0.05, respectively). Besides, the teeth subjected to radiation doses of 20, 30 and 60 Gy represented significantly lower acoustic impedance values relative to non-irradiated group for dentin (6.52 ± 0.43 MRayl, 5.71 ± 0.66 MRayl and 4.82 ± 0.53 MRayl p < 0.05), respectively. CONCLUSIONS: These results are evidence for a safe acoustic examination device which may be a useful tool to visualize and follow the safe dose limits to impede severe dental damage through the radiation therapy treatment for head and neck cancers.

Comparison of Multiple Treatment Planning Techniques for High-Grade Glioma Tumors Near to Critical Organs.

AIM: The purpose of this study was to compare 6 treatment planning methods (5-beam coplanar intensity-modulated radiotherapy (IMRT), 7-beam coplanar IMRT, 7-beam noncoplanar IMRT, 2 full arc coplanar volumetric modulated arc therapy (VMAT), 2 half partial arc coplanar VMAT, and 2 half partial arc noncoplanar VMAT) for high-grade gliomas with planning target volumes (PTVs) overlapping the optic pathway and/or brainstem. PATIENTS AND METHODS: 27 previously-treated patients with high-grade gliomas were replanned for treatment with IMRT5, IMRT7, IMRT7-non, VMAT2f, VMAT2h, and VMAT2h-non. In order to perform a comparative study of the treatment outcomes, 3 tumor localizations (right-sided, left-sided, and central tumors) were selected. Patients were administered a PTV dose of 60 Gy in 30 fractions with a maximum permitted dose of 110%. RESULTS: Comparison of the 3 IMRT plans and 3 VMAT plans was performed for all 27 patients. The median conformity index was significantly higher (p < 0.05) in all IMRT plans compared to all VMAT plans in the case of right sided tumors. Significant differences were also observed between coplanar and noncoplanar plans in IMRT and VMAT in right-sided tumors (p < 0.05). Differences in brainstem mean doses were only found to be significant between coplanar and noncoplanar plans in centrally-located tumors. In right- and left-sided tumors, the VMAT2f plans demonstrated higher values than all IMRT plans in their mean values for radiation doses to the ipsilateral optic nerves, contralateral optic nerves, ipsilateral lens, ipsilateral eye, contralateral lens, contralateral eye, and contralateral optic nerves, as well in the maximums for the optic chiasm and contralateral optic nerves. Significantly faster treatment times were achieved with all VMAT plans compared to IMRT plans. CONCLUSION: IMRT techniques provided better target coverage than VMAT plans. However, VMAT techniques reduced treatment delivery time more than IMRT techniques. Technique selection for tumors located in 3 different localizations should be individualized in accordance with patients' specific parameters.

Alterations in cellular metabolism triggered by URA7 or GLN3 inactivation cause imbalanced dNTP pools and increased mutagenesis.

Eukaryotic DNA replication fidelity relies on the concerted action of DNA polymerase nucleotide selectivity, proofreading activity, and DNA mismatch repair (MMR). Nucleotide selectivity and proofreading are affected by the balance and concentration of deoxyribonucleotide (dNTP) pools, which are strictly regulated by ribonucleotide reductase (RNR). Mutations preventing DNA polymerase proofreading activity or MMR function cause mutator phenotypes and consequently increased cancer susceptibility. To identify genes not previously linked to high-fidelity DNA replication, we conducted a genome-wide screen in Saccharomyces cerevisiae using DNA polymerase active-site mutants as a "sensitized mutator background." Among the genes identified in our screen, three metabolism-related genes (GLN3, URA7, and SHM2) have not been previously associated to the suppression of mutations. Loss of either the transcription factor Gln3 or inactivation of the CTP synthetase Ura7 both resulted in the activation of the DNA damage response and imbalanced dNTP pools. Importantly, these dNTP imbalances are strongly mutagenic in genetic backgrounds where DNA polymerase function or MMR activity is partially compromised. Previous reports have shown that dNTP pool imbalances can be caused by mutations altering the allosteric regulation of enzymes involved in dNTP biosynthesis (e.g., RNR or dCMP deaminase). Here, we provide evidence that mutations affecting genes involved in RNR substrate production can cause dNTP imbalances, which cannot be compensated by RNR or other enzymatic activities. Moreover, Gln3 inactivation links nutrient deprivation to increased mutagenesis. Our results suggest that similar genetic interactions could drive mutator phenotypes in cancer cells.

Re-Irradiation of Locoregional NSCLC Recurrence Using Robotic Stereotactic Body Radiotherapy.

BACKGROUND: We evaluated the efficacy, toxicity, and dose responses of re-irradiation with stereotactic body radiotherapy (SBRT) in patients with recurrent non- small cell lung cancer (NSCLC) after previous irradiation. PATIENTS AND METHODS: 28 patients were included. Previous median radiation doses were 54 and 66 Gy. The median interval time between previous radiotherapy and SBRT was 14 months. The median follow-up time after SBRT was 9 months (range 3-93 months). To evaluate the effectiveness of SBRT, local control, overall survival, and treatment-related toxicity were reported. RESULTS: SBRT doses and fractionation ranged from 60 to 30 Gy and from 3 to 8, respectively, according to previous doses, location of the recurrence, and interval time. 65% of tumor recurrences overlapped with previous treatment, while 35% of tumors recurred outside of the previous treatment. 4 patients had local progression after SBRT at their first follow-up. The Kaplan-Meier estimates of the 1- and 2-year actuarial overall survival were 71 and 42%, respectively. The mean survival following SBRT was 32.8 months, and the median survival was 21 months. No grade 3 or higher toxicities were observed. CONCLUSION: Robotic SBRT is a tolerable treatment option with manageable toxicity which can be used with radical or palliative intent in carefully selected patients with locally recurrent tumors after previous irradiation.

Intravascular Placement of Metallic Coils as Lung Tumor Markers for CyberKnife Stereotactic Radiation Therapy.

OBJECTIVE: To present our experience with placing endovascular coils in pulmonary arteries used as a fiducial marker for CyberKnife therapy and to describe the technical details and complications of the procedure. MATERIALS AND METHODS: Between June 2005 and September 2013, 163 patients with primary or secondary lung malignancies, referred for fiducial placement for stereotactic radiosurgery, were retrospectively reviewed. Fourteen patients (9 men, 5 women; mean age, 70 years) with a history of pneumonectomy (n = 3), lobectomy (n = 3) or with severe cardiopulmonary co-morbidity (n = 8) underwent coil (fiducial marker) placement. Pushable or detachable platinum micro coils (n = 49) 2-3 mm in size were inserted through coaxial microcatheters into a small distal pulmonary artery in the vicinity of the tumor under biplane angiography/fluoroscopy guidance. RESULTS: Forty nine coils with a median number of 3 coils per tumor were placed with a mean tumor-coil distance of 2.7 cm. Forty three (87.7%) of 49 coils were successfully used as fiducial markers. Two coils could not be used due to a larger tumor-coil distance (> 50 mm). Four coils were in an acceptable position but their non-coiling shape precluded tumor tracking for CyberKnife treatment. No major complications needing further medication other than nominal therapy, hospitalization more than one night or permanent adverse sequale were observed. CONCLUSION: Endovascular placement of coil as a fiducial marker is safe and feasible during CyberKnife therapy, and might be an option for the patients in which percutaneous transthoracic fiducial placement might be risky.

A microfluidic microbial fuel cell array that supports long-term multiplexed analyses of electricigens.

Microbial fuel cells (MFCs) are green energy technologies that exploit microbial metabolism to generate electricity. The widespread implementation of MFC technologies has been stymied by their high cost and limited power. MFC arrays in which device configurations or microbial consortia can be screened have generated significant interest because of their potential for defining aspects that will improve performance featuring high throughput characteristics. However, current miniature MFCs and MFC array systems do not support long-term studies that mimic field conditions, and hence, have limitations in fully characterizing and understanding MFC performances in varieties of conditions. Here, we describe an MFC array device that incorporates microfluidic technology to enable continuous long-term analysis of MFC performance at high throughput utilizing periodic anolyte/catholyte replenishment. The system showed 360% higher power output and 700% longer operating time when compared to MFC arrays without catholyte replenishment. We further demonstrate the utility of the system by reporting its successful use in screening microbial consortia collected from geographically diverse environments for communities that support enhanced MFC performance. Taken together, this work demonstrates that anolyte/catholyte replenishment can significantly improve the long-term performance of microfabricated MFC arrays, and support the characterization of diverse microbial consortia.

Comparison of dose distributions and organs at risk (OAR) doses in conventional tangential technique (CTT) and IMRT plans with different numbers of beam in left-sided breast cancer.

AIM: Our aim was to improve dose distribution to the left breast and to determine the dose received by the ipsilateral lung, heart, contralateral lung and contralateral breast during primary left-sided breast irradiation by using intensity modulated radiotherapy (IMRT) techniques compared to conventional tangential techniques (CTT). At the same time, different beams of IMRT plans were compared to each other in respect to CI, HI and organs at risk (OAR) dose. BACKGROUND: Conventional early breast cancer treatment consists of lumpectomy followed by whole breast radiation therapy. CTT is a traditional method used for whole breast radiotherapy and includes standard wedged tangents (two opposed wedged tangential photon beams). The IMRT technique has been widely used for many treatment sites, allowing both improved sparing of normal tissues and more conformal dose distributions. IMRT is a new technique for whole breast radiotherapy. IMRT is used to improve conformity and homogeneity and used to reduce OAR doses. MATERIALS AND METHODS: Thirty patients with left-sided breast carcinoma were treated between 2005 and 2008 using 6, 18 or mixed 6/18 MV photons for primary breast irradiation following breast conserving surgery (BCS). The clinical target volume [CTV] was contoured as a target volume and the contralateral breast, ipsilateral lung, contralateral lung and heart tissues as organs at risk (OAR). IMRT with seven beams (IMRT7), nine beams (IMRT9) and 11 beams (IMRT11) plans were developed and compared with CTT and among each other. The conformity index (CI), homogeneity index (HI), and doses to OAR were compared to each other. RESULTS: ALL OF IMRT PLANS SIGNIFICANTLY IMPROVED CI (CTT: 0.76; IMRT7: 0.84; IMRT9: 0.84; IMRT11: 0.85), HI (CTT: 1.16; IMRT7: 1.12; IMRT9: 1.11; IMRT11: 1.11), volume of the ipsilateral lung receiving more than 20 Gy (>V20 Gy) (CTT: 14.6; IMRT7: 9.08; IMRT9: 8.10; IMRT11: 8.60), and volume of the heart receiving more than 30 Gy (>V30 Gy) (CTT: 6.7; IMRT7: 4.04; IMRT9: 2.80; IMRT11: 2.98) compared to CTT. All IMRT plans were found to significantly decrease >V20 Gy and >V30 Gy volumes compared to conformal plans. But IMRT plans increased the volume of OAR receiving low dose radiotherapy: volume of contralateral lung receiving 5 and 10 Gy (CTT: 0.0-0.0; IMRT7: 19.0-0.7; IMRT9: 17.2-0.66; IMRT11: 18.7-0.58, respectively) and volume of contralateral breast receiving 10 Gy (CTT: 0.03; IMRT7: 0.38; IMRT9: 0.60; IMRT11: 0.68). The differences among IMRT plans with increased number of beams were not statistically significant. CONCLUSION: IMRT significantly improved conformity and homogeneity index for plans. Heart and lung volumes receiving high doses were decreased, but OAR receiving low doses was increased.

Dosimetric and physical comparison of IMRT and CyberKnife plans in the treatment of localized prostate cancer.

AIM: The aim of our study was the dosimetric and physical evaluation of the CK and IMRT treatment plans for 16 patients with localized prostate cancer. BACKGROUND: Intensity modulated radiation therapy (IMRT) is one of the recent technical advances in radiotherapy. The prostate is a well suited site to be treated with IMRT. The challenge of accurately delivering the IMRT needs to be supported by new advances such as image-guidance and four-dimensional computed conformal radiation therapy (4DCRT) tomography. CyberKnife (CK) provides real time orthogonal X-ray imaging of the patient during treatment course to follow gold fiducials installed into the prostate and to achieve motion correlation between online acquired X-ray imaging and digital reconstructed radiographs (DRRs) which are obtained from planning computed tomography images by translating and rotating the treatment table in five directions. METHODS AND MATERIALS: Sixteen IMRT and CK plans were performed to be compared in terms of conformity (CI), heterogeneity indices (HI), percentage doses of 100% (V100), 66% (V66), 50% (V50), 33% (V33) and 10% (V10) volumes of the bladder and rectum. Dose-volume histograms for target and critical organs, (CI) and indices (HI) and isodose lines were analyzed to evaluate the treatment plans. RESULTS: Statistically significant differences in the percentage rectal doses delivered to V10, V33, and V50 of the rectum were detected in favor of the CK plans (p values; <0.001, <0.001 and 0.019, respectively). The percentage doses for V66 and V100 of the rectum were larger in CK plans (13%, 2% in IMRT and 21%, 3% in CK plans, respectively). Percentage bladder doses for V10 and V33 were significantly lower in CK plans [96% in IMRT vs 48% in CK (p < 0.001) and 34% in IMRT vs 24% in CK (p = 0.047)]. Lower percentage doses were observed for V50, V66 of the bladder for the IMRT. They were 5.4% and 3.45% for IMRT and 13.4% and 8.05% for CK, respectively. Median CI of planning target volume (PTV) for IMRT and CK plans were 0.94 and 1.23, respectively (p < 0.001). CONCLUSION: Both systems have a very good ability to create highly conformal volumetric dose distributions. Median HI of PTV for IMRT and CK plans were 1.08 and 1.33, respectively (p < 0.001).