Significant Dose Differences Research Articles

Evaluation of incidental testicular dose with thermoluminescence dosimetry during prostate radiotherapy.

The aim of this study was to investigate incidental testicular doses during intensity modulated radiation therapy (IMRT) in patients treated with prostate radiotherapy only (PORT) and whole pelvis radiotherapy (WPRT). A total of 34 prostate cancer patients with intermediate and high risk were included in this prospective study. Each patient in the intermediate risk group received a total of 78 Gy in 39 fractions for prostate and seminal vesicles. In patients in the high risk group, 2 Gy daily fraction dose for pelvic lymphatics was given to 50 Gy, and then 78 Gy was given to prostate and seminal vesicles volumes. Treatment plans were created for all patients using the IMRT technique with 6MV. Testicular doses were measured for WPRT and PORT by thermoluminescence dosimetry (TLD) detectors placed on testis surface. Testicular doses measured for WPRT and PORT were compared. The isocenter to testicular distance for WPRT and PORT was 16.83-cm (13.20 to 18.80-cm) and 11.15 cm (9.10 to 13.00-cm), respectively. The mean testicular dose measurements of TPS and TLD per fraction during PORT were 2.41 cGy (1.95 to 3.60 cGy) and 3.70 cGy (2.80 to 5.10 cGy), respectively (p = 0.00). In WPRT irradiation, mean testicular dose values of TPS and TLD per fraction were measured as 3.85 cGy (2.00 to 5.70 cGy) and 5.85 cGy (4.25 to 7.55 cGy), respectively (p = 0.00). The cumulative mean scattered dose for PORT irradiation of 78 Gy in 39 fractions was 144.30 cGy. The mean cumulative dose received by the testis for the high-risk prostate patient was 228.15 cGy. There was a significant difference in testicular dose between WPRT and PORT irradiation. Testicular doses decreased significantly with increasing isocenter-testis distance. Incidental testicular dose during prostate radiotherapy can be significantly detrimental to spermatogenesis. Therefore, the testicles should be contoured as an organ at risk for the estimation of absorbed doses. The use of in vivo dosimetry is recommended for accurate measurement of testicular dose in radiotherapy of prostate cancer for men desiring continued fertility.

The transition from conformal to advanced radiotherapy techniques in the treatment planning of gynecological cancer patients

Background/Aim. The transition from standard to highly conformal radiation therapy techniques requires the implementation of complex advanced dosimetry. The aim of the study was to compare dosimetric parameters of the three-dimensional conformal radiotherapy (3DCRT) and volumetric modulated arc therapy (VMAT) plan, as well as complications after treatment in relation to dosimetric parameters in gynecological cancer patients. Methods. A total of 49 gynecological cancer patients were included in the study. All patients were planned for 3DCRT, but due to un-acceptable doses to organs at risk (OARs), treatment plans for intensity modulated radiation therapy (IMRT), or VMAT, were generated for 21 patients. The patients were prescribed 50.4 Gy/28 fractions (4 patients) and 45 Gy/25 fractions (45 patients). The coverage of planning target volume (PTV) and doses to OARs were recorded. PTV margins were evaluated for both techniques according to the Van Herk formula. Results. ICRU 83 criteria were fulfilled in all 3DCRT/VMAT/IMRT plans providing optimal coverage of PTV. Doses to OARs, on average, the V45Gy in the small bowel in IMRT/VMAT plans was four times smaller than the same in 3DCRT plans. The V45 Gy of small bowels was, on average, 49.4 cm3 in IMRT/VMAT plans, while in 3DCRT plans, it was 211.6 cm3. In the case of the femoral head, a significant reduction in V30Gy (10.8% vs. 33.1%) and mean dose in the case of IMRT/VMAT plans was recorded (30.4 Gy in 3DCRT vs. 23.6 Gy). Rectum was planned with a significantly lower dose in terms of V30Gy (79.5% vs. 95.2%) in IMRT/VMAT plans. The bladder was better spared in VMAT plans in terms of V40Gy (51% vs. 91%), but the maximum dose was higher in VMAT plans than in 3DCRT (50.1 Gy to 48.1 Gy on average). For all OARs, there was a statistically significant difference registered at p ? 0.05. Toxicities recorded in VMAT and 3DCRT patients included mainly radiation-induced cystitis and enteritis. Patients treated with 3DCRT generally had longer recovery time. The homogeneity index was 0.11 for VMAT plans and 0.09 for 3DCRT plans. Conclusions. Analysis of dosimetric parameters revealed significant differences in normal tissue doses for the same 3DCRT and VMAT patients, which confirmed the necessity for the implementation of advanced techniques for as many patients as possible.

Impact of an ultra-low dose unenhanced planning scan on CT coronary angiography scan length and effective radiation dose.

ObjectiveImaged scan length (z-axis coverage) is a simple parameter that can reduce CT dose without compromising image quality. In CT coronary angiography (CTCA), z-axis coverage may be planned using non-contrast calcium score scan (CaCS) to identify the relevant coronary anatomy. However, standardised Agatston CaCS is acquired at 120 kV which adds a relatively high contribution to total study dose and CaCS is no longer routinely recommended in UK guidelines. We evaluate an ultra-low dose unenhanced planning scan on CTCA scan length and effective radiation dose.Methods:An ultra-low dose tin filter (Sn-filter) planning scan (100 kVp, maximum iterative reconstruction) was performed and used to plan the z-axis coverage on 48 consecutive CTCAs (62% men, 62 ± 13 years) compared with 47 CTCA planned using a localiser alone (46% men, 59 ± 12 years) between May and June 2019. Excess scanning beyond the ideal scan length was calculated for both groups. Estimations of radiation dose were also compared between the two groups.Results:Addition of an ultra-low dose unenhanced planning scan to CTCA protocol was associated with reduction in overscanning with no impact on image quality. There was no significant difference in total study effective dose with the addition of the planning scan, which had an average dose–length product of 3 mGy.cm. (total study dose: Protocol A 2.1 mSv vs Protocol B 2.2 mSv, p = 0.92).Conclusion:An ultra-low dose unenhanced planning scan facilitates optimal scan length for the diagnostic CTCA, reducing overscanning and preventing incomplete cardiac imaging with no significant dose penalty or impact on image quality.Advances in knowledge:An ultra-low dose CTCA planning is feasible and effective at optimising scan length.

An Investigation of Exposure to the Eyes and Thyroid of Personnel Near to Patient in Abdominal Radiography: A Phantom Study

Abdominal radiography is beneficial in a variety of clinical situations. Prior to the introduction of multiplanar imaging, it was considered as the main examination for gastrointestinal pathology. However, the radiation dose received is considered high since it is equivalent to the dose of at least 75 chest radiographs. Personnel including staff or relatives may be required to assist patients in many conditions, increasing unnecessary radiation and the likelihood of radiation-induced cancer. The purpose of this study was to determine the radiation dose received by personnel when eyes and thyroid are exposed during abdominal radiography. The Rando and body phantoms were used to represent personnel and patients in this experimental approach. The dose was measured as entrance surface dose (ESD) by using TLD-100, which was positioned at the Rando phantom's eyes and thyroid. The study included a total of twenty exposures, five times at each of four distinct sites. The mean doses (eyes/thyroid in mGy) were (0.083/0.081), (0.090/0.087), (0.093/0.092), and (0.092/0.089), respectively, at locations 1, 2, 3, and 4. The results indicated that there was no correlation between organ and location affecting ESD measurement (p=0.960). There was no significant difference in dose between the two organs (p=0.355), with the mean difference in the eyes being 0.002 more than in the thyroid. The proximity of the eyes to the tube source contributed for the increased dose observed at the eyes. Though ESD was substantial for location pairings 1 vs. 3 (p=0.001) and 1 vs. 4 (p=0.015) owing to the anode-cathode phenomena. In conclusion, personnel should avoid the tube source and cathode region, since they give a greater dose of radiation, particularly when the personnel are closest to the patient and does not have eyes or thyroid protection.

Local Anesthetic Injection Before Incision Decreases General Anesthesia Requirements in Pediatric Trigger Thumb Release: A Randomized Controlled Trial.

Animal studies have shown evidence of neurotoxicity from inhalational anesthesia, yet clinical studies have been less conclusive. While ongoing studies investigate the clinical significance of anesthesia-associated neurodevelopmental changes in young children, reducing anesthetic exposure in pediatric orthopaedic surgery is prudent. The primary objective of this study is to determine if local anesthetic injection before surgical incision versus after surgical release decreased inhalational anesthetic exposure in children undergoing unilateral trigger thumb release. The secondary objectives were to determine if the timing of local anesthetic injection affected postoperative pain or length of stay. This was a single-center randomized controlled trial of pediatric patients (4 y and below) undergoing unilateral trigger thumb release. Subjects were randomized into preincision or postrelease local anesthesia injection groups. The surgeon was aware of the treatment group, while the anesthesiologist was blinded. Patient demographics, operative times, cumulative sevoflurane dose, and postoperative anesthesia care unit recovery characteristics were collected. The χ2, Fisher exact, and Mann-Whitney U tests were conducted. A total of 24 subjects were enrolled, with 13 randomized to the preincision injection group and 11 to the postprocedure injection group. There was no significant difference in age, sex, operative time, or tourniquet time between groups. There was a significant difference in the cumulative sevoflurane dose between the preincision injection group (23.2 vol%; interquartile range: 21.7 to 27.6) and the postprocedure injection group (28.1 vol%; interquartile range: 27 to 30) (P=0.03), with a 21% reduction in cumulative dose. There were no significant differences in postoperative pain scores, use of rescue pain medications, the incidence of nausea, or time to discharge between groups. Administering local anesthesia before incision versus at the end of the procedure significantly decreased cumulative sevoflurane dose for unilateral trigger thumb release. The results of this study suggest that local anesthetic injection before the incision is a low risk, easy method to reduce general anesthesia requirements during trigger thumb release and could decrease sevoflurane exposure more substantially in longer procedures and mitigate risks of neurotoxicity. Preincision injection with local anesthetic should be incorporated into routine clinical practice. Level I.

The Effect of Different Doses of Botulinum Toxin on Masseter Muscle in Patients with Bruxism.

Background and Objectives: Botulinum toxin type A is produced by clostridium botulinum. It acts by inhibiting the release of acetylcholine from cholinergic neurons. Botulinum toxin has been used for management of bruxism, which is a parafunctional disorder and characterized by clenching or grinding of the teeth or both. This study aimed to find out the effect of two different doses of injecting botulinum neurotoxin in masseter muscle in a patient with bruxism. Materials and Methods: A prospective clinical open trial study was conducted from November 2018 to November 2019. Thirty patients, aged 20‐45 years, with bruxism were subjected to injection of two different doses of botulinum toxin in masseter muscle. Patients were divided into two equal groups. The first group included 15 patients treated by 18 units of botulinum toxin, 9 units for each side and the second group included 15 patients treated by 24 units of botulinum toxin 12 unit for each side. Parameters, as visual analogue scale (VAS), Bite force, patient’s evaluation of lower facial slimming were recorded for each patient before and after the injections of botulinum neurotoxin at 2 weeks, 4 weeks and 3 months. Results: The study showed a significant reduction in VAS, bite force and patient's evaluation of facial slimming for both groups after 2 weeks, 4 weeks and 3 months of follow up (P < 0.05) with no significant differences in both group doses. Conclusion: Both doses of botulinum toxin (18 and 24) units have significantly improved pain score, and bite force and have the same efficacy in treating patients with bruxism., therefore dose of 18 units of the drug is preferable over 24 units in treating bruxism.

Radiation Exposure During Diagnostic and Therapeutic Angiography of Carotid-cavernous Fistula

PurposeThe aim of this study was to determine local diagnostic reference levels (DRLs) during endovascular diagnostics and therapy of carotid-cavernous fistulas (CCF).MethodsIn a retrospective study design, DRLs, achievable dose (AD) and mean values were assessed for all patients with CCF undergoing diagnostic angiography (I) or embolization (II). All procedures were performed with the flat-panel angiography system Allura Xper (Philips Healthcare). Interventional procedures were differentiated according to the type of CCF and the type of procedure.ResultsIn total, 86 neurointerventional procedures of 48 patients with CCF were executed between February 2010 and July 2021. The following DRLs, AD and mean values could be determined: (I) DRL 215 Gy ∙ cm2, AD 169 Gy ∙ cm2, mean 165 Gy ∙ cm2; (II) DRL 350 Gy ∙ cm2, AD 226 Gy ∙ cm2, mean 266 Gy ∙ cm2. Dose levels of embolization were significantly higher compared to diagnostic angiography (p < 0.001). No significant dose difference was observed with respect to the type of fistula or the embolization method.ConclusionThis article reports on diagnostic and therapeutic DRLs in the management of CCF that could serve as a benchmark for the national radiation protection authorities. Differentiation by fistula type or embolization method does not seem to be useful.

A Multicentre Study on Average Warfarin Dose to Maintain Therapeutic International Normalised Ratio with Time in Therapeutic Range of More than 75% in Atrial Fibrillation Patients

Large interindividual variability and over-anticoagulation resulting bleeding complications due to narrow therapeutic index of warfarin has causes its pharmacodynamic activity to be highly variable. Studies shown that ethnicity, age and gender contribute to warfarin response variability. Good coagulation control of time in therapeutic range (TTR) &gt; 75% was chosen to determine the average warfarin dose in atrial fibrillation (AF) among ethnicity, age and gender. Data from Warfarin Medication Therapy Adherence Clinic of selected Pulau Pinang hospitals were used for the analysis of average warfarin dose in AF among ethnicity, age and gender. Patients who fulfilled the inclusion criteria from 2015–2016 were followed up for a year. Five hundred and seventy-six patients were included. Two hundred and ten patients had good coagulation control of TTR &gt; 75% with mean warfarin dose of 3.05 ± 1.25 mg. Only Chinese and Indian have significant difference in average warfarin dose with 2.86 ± 1.10 mg and 4.11 ± 1.40 mg, respectively (p = 0.008). Average warfarin dose was found not significantly different among gender and age. As for TTR achievement, 210 (36.4%) were able to achieve TTR &gt; 75%, 134 patients achieved TTR 60%–75% and 232 patients has TTR &lt; 60%. The median day to achieve three consecutive targeted international normalised ratio (INR) is 186.5 days for atrial fibrillation patient newly started on warfarin therapy in 2015 until 2016. Indian patients required a higher warfarin dose than Chinese patients. This study found that mean warfarin doses were not affected by age and sex.

The impact of gadolinium-based MR contrast on radiotherapy planning for oropharyngeal treatment on the MR Linac.

Gadolinium-based contrast agents (GBCAs) may add value to magnetic resonance (MR)-only radiotherapy (RT) workflows including on hybrid machines such as the MR Linac. The impact of GBCAs on RT dose distributions however have not been well studied. This work used retrospective GBCA-enhanced datasets to assess the dosimetric effect of GBCAs on head and neck plans. Ten patients with oropharyngeal squamous cell carcinoma receiving RT from November 2018 to April 2020 were included in this study. RT planning included contrast-enhanced computed tomography (CT) and MR scans. A contrast agent "contour" was defined by delineating GBCA-enhanced regions using an agreed window/level threshold, transferred to the planning CT and given a standardized electron density (ED) of 1.149 in the Monaco treatment planning system (Elekta AB). Four plans were per patient calculated and compared using two methods: (1) optimized without contrast (Plan A) then recalculated with ED (Plan B), and (2) optimized with contrast ED (Plan C) then without (Plan D). For target parameters minimum and maximum doses to 1cc of PTVs, D95 values, and percent dose differences were calculated. Dose differences for organs-at-risk (OARs) were calculated as a percentage of the clinical tolerance value. For the purposes of this study,±2% over the whole treatment course was considered to be a clinically acceptable dose deviation. Wilcoxon-signed rank tests were used to determine any dose differences within and between the two methods of optimization and recalculation (p<0.05). Pearson's correlations were used to establish the relationship between gadolinium uptake volume in a structure (i.e., proportion of structure covered by a density override) and the resulting dose difference. The median percent dose differences for key reportable dosimetric parameters between non-contrast and simulated contrast plans were<1.2% over all fractions over all patients for reportable target parameters (mean 0.34%, range 0.22%-1.02%). The percent dose differences for maximum dose to 1cc of both PTV1 and PTV2 were significantly different after application of density override (p<0.05) but only in method 2 (Plan C vs. Plan D). For D95 PTV1, there was a statistically significant effect of density override (p<0.01), however only in method 1 (Plan A vs. Plan B). There were no significant differences between calculation methods of the impact of contrast in most target parameters with the exception of D95 PTV1 (p<0.01) and for D95 PTV2 (p<0.05). The median percent dose differences for reportable OAR parameters as a percentage of clinical planning tolerances were<2.0% over a full treatment course (mean 0.65%, range 0.27%-1.62%). There were no significant differences in dose to OARs within or between methods for contrast impact assessment. Dose differences to targets and OARs in oropharyngeal cancer treatment due to the presence of GBCA were minimal, and this work suggests that prospective in vivo evaluations of impact may not be necessary in this clinical site. Accounting for GBCAs may not be needed in daily adaptive workflows on the MR Linac.

Relationship between diverting stoma and adjuvant chemotherapy in patients with rectal cancer: a nationwide study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

Patients at risk of recurrence after curative surgery for rectal cancer usually receive adjuvant chemotherapy. Postoperative recovery after low anterior resection (LAR) for rectal cancer can be improved by placement of a diverting stoma to reduce anastomotic leakage. However, it remains unclear how a diverting stoma affects administration of adjuvant chemotherapy in these patients. We identified Japanese patients with rectal cancer who underwent LAR in 2014 and received adjuvant chemotherapy within 12months of surgery in the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Doses of five types of chemotherapy administered (tegafur/uracil, tegafur/gimeracil/oteracil potassium, capecitabine, 5-fluorouracil, and oxaliplatin) were assessed according to the presence or absence of diverting stoma and the timing of stoma closure. There was no significant difference in the cumulative doses of chemotherapy administered in the 12months after LAR between patients with and without diverting stoma, but more doses were administered in the early postoperative period (0-2months after LAR) in patients without diverting stoma. Also, more doses of chemotherapy, regardless of type, were administered in the late closure group (7-12months after LAR) than in the early closure (≤ 6months) and no closure groups. Presence of a diverting stoma did not influence the dose of adjuvant chemotherapy administered within 12months after LAR but could have delayed the start of adjuvant chemotherapy. Patients with late closure of a diverting stoma received more doses of adjuvant chemotherapy administered over 12months.

NCOG-11. ASSOCIATION OF HYPERGLYCEMIA AND TUMOR SUBCLASS ON SURVIVAL IN IDH-WILDTYPE GLIOBLASTOMA

Abstract BACKGROUND RNA expression and DNA methylation studies have identified different subclasses of isocitrate dehydrogenase (IDH)-wildtype (wt) glioblastoma (GBM). However, the prognostic significance of molecular subclasses is unclear. Although hyperglycemia has been previously associated with worse survival, attempts to lower glucose have yielded mixed responses. The role of hyperglycemia may be confounded by molecular heterogeneity and have different impact in molecularly distinct GBM subclasses. METHODS Clinical, laboratory, and molecular data on 89 IDH-wt GBMs profiled by clinical next-generation sequencing and treated with Stupp protocol were reviewed. IDH-wt GBMs were subclassified into RTKI (Proneural), RTKII (Classical) and Mesenchymal subtypes using DNA methylation. Average glucose was calculated by time-weighting plasma glucose measurements between diagnosis and last follow-up. RESULTS Patients were stratified into three groups using average glucose: tertile one (&amp;lt; 100mg/dL), tertile two (100-115mg/dL), and tertile three ( &amp;gt; 115mg/dL). Comparison across glucose tertiles revealed no significant differences in Karfnosky Performance Status (KPS), dexamethasone dose, MGMT methylation, or methylation subclass. Overall survival (OS) was not affected by methylation subclass (log-rank p=0.9) but decreased with higher glucose (log-rank p=0.015). Higher glucose tertiles were associated with poorer OS among RTK I (log-rank p=0.08) and mesenchymal tumors (log-rank p=0.05), but not RTK II (log-rank p=0.99). After controlling for age, KPS, dexamethasone dose, and MGMT status, glucose remained significantly associated with survival (adjusted hazard ratio=5.2, p=0.02). DNA methylation clustering did not identify a unique signature associated with high or low glucose levels. Metabolomic analysis of 23 tumors showed minimal variation across metabolites within the cohort with no differences across molecular subclasses. CONCLUSION Higher average glucose values were associated with poorer OS in RTKI and Mesenchymal IDH-wt GBM, but not RTKII. There were no discernible epigenetic or metabolomic differences between tumors in different glucose environments, suggesting a potential survival benefit with systemic glucose lowering in selected molecular subtype.

Oral immunotherapy in children with a food allergy-Where do we stand? - Review.

The number of hospitalisations due to an anaphylactic reaction to food is continuously increasing. Therefore, there is an urgent need to seek effective therapy. Currently, the only way to treat food allergies is to avoid allergens and to administer intramuscular adrenaline if an accidental allergen intake occurs. The only causal therapeutic strategy is specific oral immunotherapy. An increasing amount of data confirms this therapy's effectiveness and safety, but the results remain inconclusive due to the lack of long-term follow-up. In this state-of-the-art review, we briefly summarise the latest placebo-controlled randomised controlled trials on oral immunotherapy (OIT) to treat food allergy. During the paper's review, we asked the following questions: does the therapy permanently increase the amount of allergen consumed without symptoms? Does it significantly increase or decrease the occurrence of severe systemic reactions - requiring the administration of adrenaline or hospitalisation? Many authors describe outcomes such as an increase in the amount of allergen that can be safely ingested; however, significant clinical benefits such as decreased hospitalisations or anaphylaxis incidence are rarely included in the results. To date, there is no unified protocol of therapy, which makes comparisons between studies difficult because of significant differences in types, doses, and routes of administration of the allergen, timeline for up-dosing and maintenance, duration of the therapy, and primary outcomes of OIT.

Calcitriol and Levothyroxine Dosing for Patients With Pseudohypoparathyroidism.

Pseudohypoparathyroidism (PHP) is a rare hormone resistance syndrome caused by mutations in GNAS. This cross-sectional study investigated whether PHP patients with parathyroid hormone (PTH), thyrotropin (thyroid stimulating hormone; TSH), and free thyroxine (T4) levels at goal required higher doses of levothyroxine and calcitriol than recommended by current guidelines to overcome mineral ion abnormalities due to hormone resistance.Baseline demographic and clinical data of participants enrolled in PHP research studies between 2012-2021 were collected via retrospective chart review. Longitudinally, data were recorded at a maximum frequency of once a year starting at 1 year of age. The PTH at goal (PAG) group was defined as PTH < 150 pg/mL and calcium ≥ 8.4 mg/dL, and the TSH and free T4 at goal (TAG) group was defined as TSH < 5 mIU/L and free T4 ≥ 0.8 ng/dL.The PAG group (n = 74) was prescribed higher calcitriol doses than the PTH not at goal (PNAG) group (n = 50) (0.9 ± 1.1 vs 0.5 ± 0.9 mcg/day, P = 0.04) and 21% of individual patients were prescribed ≥ 1.5 mcg of calcitriol daily. This remained true after normalization for body weight (0.013 ± 0.015 vs 0.0067 ± 0.0095 mcg/kg/day, P = 0.008). There was no statistically significant difference in levothyroxine dosing between the TAG group (n = 122) and TSH and free T4 not at goal (TNAG) group (n = 45) when normalized for weight (2.0 ± 0.7 vs 1.8 ± 0.7 mcg/kg/day, P = 0.2).More than one-third of patients with PHP had PTH levels not at goal and some patients required calcitriol doses ≥ 1.5 mcg/day to meet current treatment goals.

The Investigation of Tissue Composition Effects on Dose Distributions Using Monte Carlo Method in Permanent Prostate Brachytherapy

Objective: Radiation dose calculations in the prostate brachytherapy practices have very high importance in terms of the success of treatment. The purpose of the present study is to determine whether there is a significant dose difference between the radiation dose calculations performed in water medium and prostate cancer-diagnosed patients by using the Monte Carlo method.&#x0D; Methods: The radiation dose calculations were performed on 20 prostate patients by using the BrachyDose Monte Carlo code. Phantom geometry derived from real patients computed tomography (CT) data was created to use in dose calculations. Water material was assigned to all voxels within the prostate volume for dose comparison with CT derived phantom. 125I (Amersham, OncoSeed, 6711), 103Pd (Theragenics Co., TheraSeed, 200) and 131Cs (IsoRay Medical) commercial brachytherapy seed models were used in dose calculations. &#x0D; Results: It was observed that there are significant dose differences between the water medium and the prostate tissue. The differences between D90 dose values in prostate tissue and water medium were calculated as 7.2-10.5%, 9.1-13.4% and 5.4-8.3% for 125I, 103Pd and 131Cs brachytherapy seed sources, respectively. &#x0D; Conclusions: It was concluded that material compositions of different organs and tissues in the human body should be considered for more accurate brachytherapy dose calculations.

Quantification and Dosimetric Impact of Normal Organ Motion During Adaptive Radiation Therapy Plan Verification Using a 1.5 Tesla Magnetic Resonance Equipped Linear Accelerator (MR LINAC)

<h3>Purpose/Objective(s)</h3> Patients receiving adaptive radiation therapy (RT) undergo contour and plan modification prior to treatment delivery. This process takes time to complete, ranging from 15 to 60 minutes or longer. We hypothesize that during the time required to create an adapted RT plan, normal organ movement will result in unanticipated doses delivered to local organs at risk. This study quantifies the dosimetric impact of abdominal organ motion during the time required to create an adaptive RT plan. <h3>Materials/Methods</h3> Patients receiving 5-fraction treatments with MR guided adaptive RT using a 1.5 Tesla MR LINAC were prospectively enrolled in an ongoing imaging study (NCT03500081). Two sets of MRIs were acquired: the first (pre-beam MRI) used to contour organs at the start of treatment, and the second (verification MRI) used to verify organ position immediately before beam-on. Both MRIs were collected in commercially available software. Each normal organ within 1cm of radiation targets was contoured on the verification MRI. The differences in organ position between the two MRIs represents the normal organ movement during the time required for plan adaptation. Max dose (Dmax), volumetric 0.5 cubic centimeter (cc) dose (D0.5cc), volumetric 3000cGy (V30), and volumetric 2000cGy (V20) were calculated. Mixed model tests analyzing differences between the MRI sets were performed using a data management and decision management software. <h3>Results</h3> Thirty adapt-to-shape patients were included. Recontoured normal organs included colon, duodenum, small bowel, and stomach, for a total of 120 new individually created contour volumes. The table below summarizes the mean differences of Dmax in the normal organs between the MRI sets for various organs at risk. Note that only small bowel demonstrated a statistically significant difference in Dmax doses. The D0.5cc, and V30 were also statistically significant for small bowel. <h3>Conclusion</h3> Statistically significant differences in small bowel doses are demonstrated when doses are calculated using the verification MRI. This is likely due to the small bowel's increased mobility compared to other organs analyzed. There is an absence of statistically significant differences in all other abdominal organ doses between these scans. These results reflect that highly mobile structures, such as small bowel, benefit from acquisition of a verification MRI following daily adaptive plan generation. Future research should focus on methods to shorten the adaption duration and/or account for these unanticipated doses, as they represent a significant limitation of adaptive MR guidance.

Cardiotoxicity in Patients With Lung Cancer Receiving Thoracic Radiotherapy and Immune-Checkpoint Therapy

Immune checkpoint inhibitors (ICIs) have been widely adapted as part of the treatment of locally advance and metastatic lung cancer. ICIs can lead to severe immunogenic related cardiotoxicities, however, the overall cardiotoxic profile of these agents when combined with thoracic radiation therapy is not well defined. Here, we assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy.Retrospective data was collected on Stage III-IV small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) patients who received ICIs between 2015 and 2018 at a large academic tertiary care hospital. All cardiotoxicities associated with ICI were assessed by a cardiologist and in correlation with history of thoracic radiotherapy (RT), the timing of RT in relation to ICI, and the mean RT heart dose. Multivariate analysis was performed on multiple logistic regression including the Framingham risk score and steroid use during the ICI therapy.Of 194 ICI-treated patients evaluated, 66 (34.02%) and 128 (65.98%) had Stage III and IV SCLC or NSCLC, respectively, the median age was 64 years (range, 36-88), and 42.47% were female. Within the total cohort, 55.2% (n = 107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (P = 0.87). There were 38 patients who received RT concurrently with ICI and did not develop any cardiotoxicity whereas cardiotoxicity was observed in 14.1% (n = 22/156) of those who did not receive concurrent RT (univariate, P = 0.030; multivariate, P = 0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI.ICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy. Univariate analysis suggests a potential cardioprotective effect of thoracic RT with ICI's, which may be due to modulation of the immune response through reduction of lymphocytes involved in autoimmune processes. A larger cohort study will be conducted to further evaluate this potential cardioprotective effect.

Ovarian Transposition Prior to Pelvic Radiotherapy: Spatial Distribution and Dose Volume Analysis

<h3>Purpose/Objective(s)</h3> Pelvic radiotherapy (RT) is an integral component of local therapy for anorectal and gynecologic malignances. Ovaries are exquisitely radiosensitive, with even 6 Gy exposure leading to a moderate risk of ovarian failure, and 14 Gy resulting in ovarian failure in nearly all patients. To facilitate ovary dose reduction, surgical transposition prior to pelvic RT can be performed, however ovarian function preservation rates remain approximately 50%. Moreover, there is a paucity of data in the modern treatment era analyzing the anatomic locations and dose volume metrics achieved for transposed ovaries, which was examined herein. <h3>Materials/Methods</h3> Retrospective study including women who underwent ovarian transposition prior to pelvic RT between 2010 and 2020. Measurements (cm) were obtained for 1) the craniocaudal (CC) distance from the plane of the sacral promontory to the ovary centroid and 2) the distance between the nearest edge of the ovary and RT planning target volume (PTV) in any dimension. Area under the receiver operating characteristic curve (AUC) and cut-point analysis estimating ovary location outside the PTV was performed. <h3>Results</h3> Thirty-one ovaries were analyzed from 18 patients. Fourteen (77.8%) were treated for cervical cancer and three (16.7%) for rectal cancer. Most (72.2%, n = 13) were treated with intensity-modulated RT while 27.8% (n = 5) were treated with 3D-CRT. The median CC distance from the ovaries to sacral promontory was 0.8 cm (interquartile range [IQR] -0.83 - 1.59 cm) and the median distance between the ovary and PTV was 0.9 cm (IQR, -1.0 - 1.9 cm). The majority of ovaries were located above the sacral promontory (64.5%, n = 20) and outside the PTV (61.3%, n = 19). AUC and cut-point analysis demonstrated that CC distance from the sacral promontory predicted an ovary to be outside the PTV with an optimal cut-point of 1.2 cm (C-index = 0.72). The median mean and maximum (Dmax) ovary doses were 15.5 Gy (IQR, 9.6 - 19.4 Gy) and 32.2 Gy (IQR, 24.8 - 45.9 Gy), respectively. When comparing the RT dose of transposed ovaries located outside (n = 19) vs. within (n = 12) the PTV, there was a significant decrease in median Dmax (25.4 Gy vs. 46.1 Gy; <b>P</b> < .001), but no significant difference in median mean dose (15.5 Gy vs. 16.4 Gy; <b>P</b> = .19). There was a significant inverse correlation between CC distance of transposed ovaries to the sacral promontory and ovary mean dose (-0.73, <b>P</b> < .0001) and Dmax (-0.76, <b>P</b> < .0001). <h3>Conclusion</h3> There was a significant inverse correlation between ovary CC distance from the sacral promontory and ovary RT dose. However, despite the majority of transposed ovaries being located outside the PTV, most patients still received ovary doses associated with a high risk of ovarian failure. These findings provide a deeper understanding of the relationship between ovary location and dose to inform pre-RT planning and suggest that more aggressive ovary-sparing strategies are warranted.

Machine Learning Based Analysis of Heart and Cardiac Substructures for Radiation-Induced Cardiac Toxicity From Breast Cancer Radiotherapy

Radiation-induced cardiac toxicity is an importantissue of breast RT. Although a relationship between mean heart dose and acute coronary event (ACE) risk was reported in previous study, the specific relationships between doses to cardiac structures or their sub-regions and subsequent toxicity have not been well defined. In this study, we studied the effect of radiation on specific heart segments on subsequent cardiac toxicity.From the 1294 patients with breast cancer where previously demonstrated a relationship between mean heart dose and ACE, 21 patients who developed HF following breast RT and 39 with ACE were identified after an independent review by cardiologists. The study included 21 and 39 controls for respective toxicity who were matched according to age, comorbidities, and physical activity. For each patient who received radiotherapy, substructures were manually drawn, and then dose-distribution parameters of heart and substructures (Mean, Maximum (Max) dose, Relative volume at least given dose from 5-50 Gy in 5 Gy increments) were collected from CT planning data. To specify most critical regions for developing ACE, analysis using High-dimensional Cox regression model (SNet) was performed to reveal the effect of radiation on specific heart segments on subsequent cardiac toxicity.In HF (n = 42) and ACE (n = 78) cohorts, characteristics between case and control were well matched. Mean time to develop heart failure, acute coronary events were 40.0 months and 42.2 months, respectively. In HF cohort, there was no significant difference not only in the mean heart dose (3.7 Gy vs 3.1 Gy, P = 0.652), but also in the mean left ventricle (LV) (5.0 Gy vs 4.1 Gy, P = 0.587), mean right ventricle (RV) (4.8 Gy vs 3.6 Gy, P = 0.473). On the other hand, in ACE cohort, there was significant difference in mean dose of heart (2.9 Gy vs 1.3 Gy, P = 0.015), left atrium (LA) (1.0 Gy vs 0.5 Gy, P = 0.008), LV (3.7 Gy vs 1.5 Gy, P = 0.028), left anterior descending artery (LAD) (6.6 Gy vs 2.4 Gy, P = 0.028) and right atrium (RA) (1.5 Gy vs 0.9 Gy, P = 0.025). In univariate analysis, mean dose of heart, LA, LV, LAD and RA was significant factors for acute coronary event free survival. ((Heart; P = 0.006, Hazard ratio (HR) 1.139, 95% Confidence Interval (CI) 1.035-1.253) (LA; P = 0.002, HR 1.735, 95% CI 1.209-2.490), (LV; P = 0.018, HR 1.079, 95% CI 1.012-1.150), (LAD; P = 0.031, HR 1.032, 95% CI 1.002-1.064), (RA; P = 0.008, HR = 1.307, 95% CI 1.068-1.598)). For predicting ACE risk for breast cancer patients, SNet model suggested nomogram based on mean and max LA dose, LAD V10, 15, 20, mean heart dose, mean RA dose and RV V35 in the order of higher predicted point variation. Based on this risk stratification model, event free survival significantly showed difference (P = 0.013).There was significant difference between cardiac substructure dose parameters in ACE cohort, but not in HF cohort. Further analysis using convolution neural network will be performed to specify most critical region to be spared.

Development and Validation of a Spatial Dose Pattern Based Model Predicting Acute Pulmonary Toxicity in Patients Treated With Volumetric Arc-Therapy for Locally Advanced Lung Cancer

<h3>Purpose/Objective(s)</h3> (Chemo)-radiotherapy is the standard treatment for patients with locally advanced lung cancer (LALC) not accessible to surgery. Despite strict application of dose constraints, acute toxicities such as acute pulmonary toxicity (APT) remain frequent, and may impact treatment's compliance and patients' quality of life. Previously, on a population treated with intensity-modulated photon therapy or passive scattering proton therapy, spatial dose patterns associated with APT were identified in the lower lungs, especially in the lower right lung. In the present study, we aim to define these spatial dose patterns on a retrospective cohort treated by volumetric-arc therapy (VMAT) and to validate our findings prospectively. <h3>Materials/Methods</h3> For the training cohort, we retrospectively included all patients treated in our institution by VMAT for a LALC between 2015 and 2018. APT was scored according to the CTCAE v4.0 scale. All dose maps were registered to a thorax phantom using a segmentation-based elastic registration. Voxel-based analysis of local dose differences was performed with a non-parametric permutation test accounting for <i>n = 10.000</i> permutations, producing a 3-dimensional significance maps on which clusters of voxels that exhibited significant dose differences (<i>P < 0.05</i>) between the two toxicity groups (APT ≥ grade 2 vs APT < grade 2) were identified. A dose cut-off was defined by maximizing the Youden-Index derived from the Receiver Operative Curve. For the validation cohort, we applied the predefined spatial dose pattern and the dose cut-off to an observational prospective cohort. The model was evaluated using the Area under the curve (AUC) and the balanced accuracy (Bacc: mean of the sensitivity and specificity). <h3>Results</h3> 167 and 42 patients were included in the training and validation cohorts, with respective APT rates of 22.2% and 21.4%. In the training cohort, a cluster of voxels was identified in the lower right lung with a cut off of 30.3 Gy for the D_mean(mean-dose). This spatial-based model resulted in an AUC of 0.69 and a Bacc of 0.71. Using the same voxel cluster and the D_meancut-off on the validation cohort, the model resulted in an AUC of 0.74 and a Bacc of 0.69. <h3>Conclusion</h3> Our model corroborates previous findings regarding the possible role of the lower right lung regarding the development of APT and successfully evaluates its robustness in a prospective cohort treated by VMAT. Regional radiosensitivity should be considered in usual lung dose constraints.

A model for calculating beta exposure doses to tracheobronchial cells during movement of a point source

The article describes a model and method for calculating beta-exposure doses to secretory and basal cells of the tracheobronchial part of the respiratory tract when a point source of 1 Bq activity moves along the inner surface of respiratory formations. The calculations, that used for proposed model, were performed by using a 90Y point source as an example. The dose calculation model takes into account the speed o f movement of the radiation source in each respiratory formation, the size of the respiratory formations, and the depth of the secretory and basal cells. The dose calculation is based on the dose rate attenuation functions published by W. G. Cross et al. (DOI: 10.1097/00004032-199208000-00002). The calculations were performed for a cylindrical model of a respiratory formation. Two kinds of cells were considered for the dose estimation: cells irradiated without beta-particle exit into bronchial lumen (type 1 cells) and cells irradiated due to beta-par­ticle exit into bronchial lumen (type 2 cells). The results of calculations showed, that as far as the generation number increasing, the average irradiation doses of the type 1 cells are 10 or more times greater than those of the type 2 cells. With increasing generation number in the tracheobronchial tree, doses per cells increase by several orders of magnitude. The highest doses are formed in bronchioles of generations 9-15, reaching units and tens of mGy. In spite of the fact that the number of generation increases, the total number of irradiated cells decreases, the collective doses of irradiated cells (sum of doses to all cells of the respiratory formation) in the last generations are 30-50 times higher than the doses of the first generations. Thus, in case of a single point source, there is a significant (by many orders of magnitude) scatter of doses to individual cells in indi­vidual respiratory formation, as well as significant differences in average doses of trachea, individual bronchi and bronchioles.