Prescription Dose Analysis of Quetiapine in the Elderly and Insomnia

Objective: The purpose of this study is to investigate the appropriate dose of quetiapine in clinical psychiatric diseases by examining the drug prescription dose in the elderly and insomnia group through an analysis of the tendency of quetiapine dose prescribed by psychiatric diagnosis.Methods: Among the patients who had been taking outpatient treatment to the mental health department for about 7 years and 8 months from May 1, 2010 to December 31, 2017, 2,794 patients who were continuously taking quetiapine immediate-release form drugs were retrospectively tested. In addition, all subjects were classified into a total of four groups according to their maintenance dose, four mental diseases that most commonly prescribe quetiapine were selected and grouped, and further analyzed whether there was a difference in prescription capacity by age and comorbidities for the insomnia group.Results: Prescription dose of quetiapine was found to be less than 50 mg in depressive disorders and insomnia, which is a relatively low dose prescribed compared to schizophrenia and bipolar disorder. In the case of insomnia, quetiapine prescribed in the elderly patient group was 30.03±9.14 mg, which was relatively high compared to the non-elderly group. And in the case of insomnia accompanied by depressive disorder, 50.28±11.41 mg was prescribed, more than 60% higher doses than that of primary insomnia.Conclusion: In the case of primary insomnia, quetiapine dose prescribed in the elderly patient group is higher than that in the non-elderly patient group.

The POLO (Partially Omitted Lobe) approach to safely treat in-breast recurrence after intraoperative radiotherapy with electrons

Objectives: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). Methods: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. Results: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. Conclusion: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. Advances in knowledge: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

Analytical setup margin for spinal stereotactic body radiotherapy based on measured errors

Background No consensus currently exists about the correct margin size to use for spinal SBRT. Margins have been proposed to account for various errors individually, but not with all errors combined to result in a single margin value. The purpose of this work was to determine a setup margin for five-fraction spinal SBRT based on known errors during radiotherapy to achieve at least 90% coverage of the clinical target volume with the prescription dose for at least 90% of patients and not exceed a 30 Gy point dose or 23 Gy to 10% of the spinal cord subvolume. Methods The random and systematic error components of intrafraction motion, residual setup error, and end-to-end system accuracy were measured. The patient’s surface displacement was measured to quantify intrafraction motion, the residual setup error was quantified by re-registering accepted daily cone beam computed tomography setup images, and the displacement between measured and planned dose profiles in a phantom quantified the end-to-end system accuracy. These errors and parameters were used to identify the minimum acceptable margin size. The margin recommendation was validated by assessing dose delivery across 140 simulated patient plans suffering from various random shifts representative of the measured errors. Results The errors were quantified in three dimensions and the analytical margin generated was 2.4 mm. With this margin applied in the superior/inferior direction only, at least 90% of the CTV was covered with the prescription dose for 96% of the 140 patients simulated with minimal negative effect on the spinal cord dose levels. Conclusions The findings of this work support that a 2.4 mm margin applied in the superior/inferior direction can achieve at least 90% coverage of the CTV for at least 90% of dual-arc volumetric modulated arc therapy spinal SBRT patients in the presence of errors when immobilized with vacuum bags.

Re-Irradiation With Stereotactic Body Radiotherapy for In-Field Recurrence of Pancreatic Cancer After Prior Stereotactic Body Radiotherapy: Analysis of 24 Consecutive Cases

Purpose/ObjectivesLocally recurrent pancreatic cancer is a therapeutic challenge, and aggressive approaches are needed to improve its clinical outcomes. Stereotactic body radiotherapy (SBRT) is a promising treatment for pancreatic cancer with an excellent local control and acceptable toxicity. However, the safety and efficacy of SBRT for in-field recurrence after initial SBRT remain unknown. The aim of the study was to investigate the feasibility of re-irradiation with SBRT for locally recurrent pancreatic cancer after prior definitive SBRT.Material/MethodsTwenty-four consecutive patients with pancreatic cancer received two courses of SBRT in our center between January 2014 and December 2016. The median prescription dose of the initial and second courses of SBRT was 35.5 Gy/5–7f and 32 Gy/5–8f, respectively. Clinical outcomes including overall survival (OS), disease control, and toxicity were evaluated after treatment.ResultsThe median interval between two courses of SBRT was 13 months (range: 6–29 months). From the first SBRT, the median OS of 18 patients with limited diseases was 26 months (95% CI: 19.1–32.95 months). The median OS of 12 patients without metastasis was 14 months (95% CI: 10.6–17.4 months) from re-irradiation of SBRT. The overall response rate and disease control rate were 50% and 13%, and 100% and 86.9% after each SBRT, respectively. Carbohydrate antigen 19-9 (CA19-9) levels declined dramatically after re-irradiation within 1 month (p = 0.002) and 3 months (p = 0.028). Twelve (75%) out of 16 patients had pain relief after re-irradiation. None of the patients experienced gastrointestinal toxicity.ConclusionsRe-irradiation with SBRT can provide favorable outcomes and effective analgesia with mild toxicity after prior SBRT for in-field recurrent pancreatic cancer, which might be feasible for locally relapsed pancreatic cancer.

Stereotactic radiosurgery for glioblastoma considering tumor genetic profiles: an international multicenter study

OBJECTIVE Molecular profiles, such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) methylation status, have important prognostic roles for glioblastoma patients. The authors studied the efficacy and safety of stereotactic radiosurgery (SRS) for glioblastoma patients with consideration of molecular tumor profiles. METHODS For this retrospective observational multiinstitutional study, the authors pooled consecutive patients who were treated using SRS for glioblastoma at eight institutions participating in the International Radiosurgery Research Foundation. They evaluated predictors of overall and progression-free survival with consideration of IDH mutation and MGMT methylation status. RESULTS Ninety-six patients (median age 56 years) underwent SRS (median dose 15 Gy and median treatment volume 5.53 cm3) at 147 tumor sites (range 1 to 7). The majority of patients underwent prior fractionated radiation therapy (92%) and temozolomide chemotherapy (98%). Most patients were treated at recurrence (85%), and boost SRS was used for 12% of patients. The majority of patients harbored IDH wild-type (82%) and MGMT-methylated (62%) tumors. Molecular data were unavailable for 33 patients. Median survival durations after SRS were similar between patients harboring IDH wild-type tumors and those with IDH mutant tumors (9.0 months vs 11 months, respectively), as well as between those with MGMT-methylated tumors and those with MGMT-unmethylated tumors (9.8 vs. 9.0 months, respectively). Prescription dose > 15 Gy (OR 0.367, 95% CI 0.190–0.709, p = 0.003) and treatment volume > 5 cm3 (OR 1.036, 95% CI 1.007–1.065, p = 0.014) predicted overall survival after controlling for age and IDH status. Treatment volume > 5 cm3 (OR 2.215, 95% CI 1.159–4.234, p = 0.02) and absence of gross-total resection (OR 0.403, 95% CI 0.208–0.781, p = 0.007) were associated with inferior local control of SRS-treated lesions in multivariate models. Nine patients experienced adverse radiation events after SRS, and 7 patients developed radiation necrosis at 59 to 395 days after SRS. CONCLUSIONS Post-SRS survival was similar as a function of IDH mutation and MGMT promoter methylation status, suggesting that molecular profiles of glioblastoma should be considered when selecting candidates for SRS. SRS prescription dose > 15 Gy and treatment volume ≤ 5 cm3 were associated with longer survival, independent of age and IDH status. Prior gross-total resection and smaller treatment volume were associated with superior local control.

Extracranial Dose and the Risk of Radiation-Induced Malignancy after Intracranial Stereotactic Radiosurgery: is it Time to Establish a Therapeutic Reference Level?

Background. To measure extracranial doses from Gamma Knife Perfexion (GKP) intracranial stereotactic radiosurgery (SRS) and model the risk of malignancy after SRS for different treatment platforms. Methods. Doses were measured for 20 patients undergoing SRS on a GKP at distances of 18, 43 and 75 cm from the target, corresponding to the approximate positions of the thyroid, breast and gonads respectively. The National Cancer Institute (NCI) RadRAT calculator was used to estimate excess lifetime cancer risk from this exposure. Five different age groups covering childhood and younger adults were modelled for both sexes. Results. Extracranial doses delivered during SRS with the GKP were a median 0.04 %, 0.008 % and 0.002 % of prescription dose at 18 cm, 43 cm and 70 cm from the isocentre respectively. Comparison with the literature revealed that the extracranial dose was lowest from GKP, then linacs equipped with micro-multileaf collimators (mMLC), then linacs equipped with circular collimators (cones), and highest from Cyberknife (CK). Estimated lifetime risks of radiation-induced malignancy in the body for patients treated with SRS aged 5–45 years were 0.03 0.88 %, 0.36–11 %, 0.61–18 % and 2.2–39 % for GKP, mMLC, cones and CK respectively. Conclusions. We have compared typical extracranial doses from different platforms and quantified the lifetime risk of radiation-induced malignancy. The risk varies with platform. This should be taken into account when treating children and young adults with SRS. The concept of a therapeutic reference level (TRL), similar to the diagnostic reference level (DRL) established in radiology, is proposed.

A Dosimetric Comparison of CT- and Photogrammetry- Generated 3D Printed HDR Brachytherapy Surface Applicators

In this study, we investigate whether an acceptable dosimetric plan can be obtained for a surface applicator designed using photogrammetry and compare the plan quality to a CT-derived applicator. The nose region of a RANDO anthropomorphic phantom was selected as the treatment site due to its high curvature. Photographs were captured using a Nikon D5600 DSLR camera and reconstructed using Agisoft Metashape while CT data was obtained using a Canon Aquillion scanner. Virtual surface applicators were designed in Blender and printed with ABS plastic. Treatment plans with a prescription dose of 3.85 Gy x 10 fractions with 100 % dose to PTV on the bridge of the nose at 2 mm depth were generated separately using AcurosBV in the Varian BrachyVision TPS. PTV D98%, D90% and V100%, and OAR D0.1cc, D2cc and V50% dose metrics and dwell times were evaluated, with the applicator fit assessed by air-gap volume measurements. Both types of surface applicators were printed with minimal defects and visually fitted well to the target area. The measured air-gap volume between the photogrammetry applicator and phantom surface was 44 % larger than the CT-designed applicator, with a mean air gap thickness of 3.24 and 2.88 mm, respectively. The largest difference in the dose metric observed for the PTV and OAR was the PTV V100% of -1.27 % and skin D0.1cc of -0.28 %. PTV D98% and D90% and OAR D2cc and V50% for the photogrammetry based plan were all within 0.5 % of the CT based plan. Total dwell times were also within 5 %. A 3D printed surface applicator for the nose was successfully constructed using photogrammetry techniques. Although it produced a larger air gap between the surface applicator and phantom surface, a clinically acceptable dose plan was created with similar PTV and OAR dose metrics to the CT-designed applicator. Additional future work is required to comprehensively evaluate its suitability in a clinically environment.

Influence of target dose heterogeneity on dose sparing of normal tissue in peripheral lung tumor stereotactic body radiation therapy

Objective To evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT). Methods Based on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff. Results When MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V5, V10, V20 of whole lung, D2%, D1cc, D2cc of the rib, V30 of the rib, D2% and the maximum dose (Dmax) of the skin, and D2% and Dmax of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median Dmax, D2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R50% and D2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively. Conclusions For peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.

Effect of the dwell time deviation constraint on brachytherapy treatment planning for cervical cancer

Objective This study aimed to quantify the effect of the dwell time deviation constraint (DTDC) on brachytherapy treatment for cervical cancer. Methods A retrospective study was carried out on 20 patients with radical cervical cancer. The DTDC values changed from 0.0 to 1.0 by a step size of 0.2. We adjusted the optimization objectives to ensure that all plans were optimized to a high-risk clinical target volume (HRCTV) D90 (the dose to 90% of the HRCTV) = 6 Gy, while keeping the dose to the organs at risk as low as possible. The dose–volume histogram parameters and the dwell time data were compared between plans with different DTDC values. Results The HRCTV volume covered by 150% of the prescription dose gradually increased with increasing DTDC values. As the DTDC value increased from 0.0 to 1.0, the effective dwell point proportion increased from 61.78% to 90.30%. The mean dwell time initially decreased with an increase in the DTDC value, reached the minimum value at DTDC = 0.8, then slightly increased at DTDC = 1.0. Conclusions When using inverse planning simulated annealing optimization for radical cervical cancer cases, the recommended DTDC value is approximately 0.6 if the organ dose needs to be limited.