Significant Difference In Mean Dose Research Articles

Innovative Education Method for a More Effective, Faster, and Valued Training in Radiation Therapy Treatment Planning

Because of the automation of radiation therapy, competencies of radiation technologists (RTTs) change, and training methods are challenged. This study aims to develop, and pilot test an innovative training method based on lean management principles. A new training method was developed for lung cancer treatment planning (TP). The novelty is summarized by including a stable environment and an increased focus on the how and why of key decision making. Trainees have to motivate their decisions during TP process, and to argue their choices with peers. Six students and 6 RTTs completed this training for lung cancer TP. Effects of the training were measured by (1) quality of TP, using doses in organs at risk and target volumes, (2) perceived experiences (survey), measured at baseline (T0); after peer session (T1); and 6 months later (T2). Finally, training throughput time was measured. At T0, RTTs showed a larger intragroup interquartile range (IIR) (2.63Gy vs 1.51Gy), but lower mean doses to heart and esophagus than students (6.79Gy vs 8.49Gy; 20.87Gy vs 24.62Gy). At T1, quality of TPs was similar between RTTs and students (IIR: 1.39Gy vs 1.33Gy) and no significant differences in mean dose to heart and esophagus (4.48Gy vs 4.69Gy; 17.75Gy vs 18.47Gy). At T2, students still performed equal to RTTs (IIR: 1.07Gy vs 1.45Gy) and achieved lower maximum dose to esophagus (44.75Gy vs 46.45Gy). The training method and peer sessions were experienced positive: at baseline (T0): 8 score on a scale 1-10, directly after the peer sessions; (T1): 8 by the students and 7 by the RTTs, after 9 months; (T2): 9 by the students and 7 by the RTTs. Training throughput time decreased from 12 to 3 months. This training method based on lean management principles was successfully applied to training of RTTs for lung cancer TP. Training throughput time was reduced dramatically and TP quality sustained after 6 months. This method can potentially improve training efficiency in diverse situations with complex decision-making.

Generating deliverable DICOM RT treatment plans for prostate VMAT by predicting MLC motion sequences with an encoder-decoder network.

Deep learning-based auto-planning is an active research field; however, for some tasks a treatment planning system (TPS) is still required. To introduce a deep learning-based model generating deliverable DICOM RT treatment plans that can be directly irradiated by a linear accelerator (LINAC). The model was based on an encoder-decoder network and can predict multileaf collimator (MLC) motion sequences for prostate VMAT radiotherapy. A total of 619 treatment plans from 460 patients treated for prostate cancer with single-arc VMAT were included in this study. An encoder-decoder network was trained using 465 clinical treatment plans and validated on 77 plans. The performance was analyzed on a separate test set of 77 treatment plans. Separate L1 losses were computed for the leaf and jaw positions as well as the monitor units, with the leaf loss being weighted by a factor of 100 before being added to the other losses. The generated treatment plans were recalculated in a treatment planning system and the dose-volume metrics and gamma passing rates were compared to the original dose. All generated treatment plans showed good agreement with the original data, with an average gamma passing rate (3%/3mm) of 91.9±7.1%. However, the coverage of the PTVs. was slightly lower for the generated plans (D98% =92.9±2.6%) in comparison to the original plans (D98% =95.7±2.2%). There was no significant difference in mean dose to the bladder between the predicted and original plan (Dmean of 28.0±13.5vs. 28.1±13.3% of prescribed dose) or rectum (Dmean of 42.3±7.4vs. 42.6±7.5%). The maximum dose to bladder was only slightly higher in the predicted plans (D2% of 100.7±5.3vs. 99.8±4.0%) and for the rectum it was even lower (D2% of 100.5±3.7vs. 100.1±4.3). The deep learning-based model could predict MLC motion sequences in prostate VMAT plans, eliminating the need for sequencing inside a TPS, thus revolutionizing autonomous treatment planning workflows. This research completes the loop in deep learning-based treatment planning processes, enabling more efficient workflows for real-time or online adaptive radiotherapy.

Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non-constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet.

Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance. Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics. Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group. Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.

Comparison of Doses in Organs at Risk of Conventional and Three-Dimensional Treatment Planning in Hybrid Brachytherapy

INTRODUCTION: This retrospective study aims to evaluate the doses of organs at risk (OARs) calculated by conventional two-dimensional (2-D) and three-dimensional (3-D) treatment planning techniques in hybrid high dose rate (HDR) brachytherapy for cervical cancer. MATERIALS AND METHODS: Data of five patients treated with combination of intracavitary and interstitial brachytherapy were used. For each implant, computed tomography (CT) images were obtained, and the clinical target volume and OARs were contoured on CT images. In 3-D planning, the volumes of OARs were derived from dose-volume histogram (DVH) on a dose volume of 2 cc for bladder, rectum, and sigmoid. The OARs defined in replanning for 2-D treatment were the ICRU-38 bladder (bICRU) and rectum (rICRU) points. Paired T-tests were used to analyse the radiation doses of bladder and rectum obtained from both techniques. RESULTS: The mean point doses evaluated via bICRU) and rICRU were 89.34 GyEQD2 and 75.92 GyEQD2, respectively. Meanwhile, the mean volumetric doses of D2cc for bladder and rectum were 80.50 GyEQD2 and 69.08 GyEQD2, respectively. There is a significant difference in mean doses of ICRU point and D2cc volume for bladder (p<0.05). However, there is no significant difference in mean doses of ICRU point and D2cc for rectum (p>0.05). Overall, ICRU point doses overestimated volumetric D2cc doses with a mean dose ratio of 1.110 for bladder and 1.099 for rectum respectively. CONCLUSION: The bICRU in 2-D planning could not represent the bladder 2 cc used in 3-D planning, thus resulting in different total dose; whereas rICRU of 2-D planning was discovered to be similar with rectum 2 cc of 3-D planning and deemed reliable in total dose estimation

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.

Doses to Organs at Risk Calculated Using Plato and Oncentra Softwares in Intracavitary Brachytherapy

This is a retrospective study, the organ doses to the bladder and rectum were compared between Nucletron PLATO V14.2.3 (BV) and newer version software Oncentra MasterPlan V4.3 (OMP) treatment planning systems (TPS). The treatment data of 32 intracavitary brachytherapy patients at Hospital Universiti Sains Malaysia from January 2010 to June 2015 were used. These data sets were used for catheter reconstruction for both PLATO and OMP TPS followed by independent verification using Excel. There is no significant difference in mean doses to organs at risk (OARs) that calculated by both TPS (p>0.05). The mean percentage of doses calculated by PLATO TPS for bladder and rectum were 66.58 ± 27.42 % and 46.27 ± 14.47 % respectively. While the mean percentage of doses for bladder and rectum calculated by OMP TPS were 65.68 ± 24.24 % and 46.46 ± 16.66 respectively. The mean percentage difference in doses comparison between independent verification calculation and PLATO TPS was 1.96 ± 6.00% and then became 6.37 ± 5.17% when it was compared with OMP TPS. Overall, the dose calculation differences for both versions of TPS were within the range recommended by Nuclear Regulatory Commission (NRC). The dose calculations of the two treatment planning systems showed good agreement and both could be used in planning intracavitary brachytherapy for cervical cancer. Whereas Excel based independent verification suitable to be implemented as routine dose verification programme prior to treatment delivery.

Radiation dose-painting with protons vs. photons for head-and-neck cancer

Background: Dose-painting has recently been investigated in early-phase trials in head-and-neck cancer (HNC) with the aim of improving local tumor control. At the same time proton therapy has been reported as potentially capable of decreasing toxicity. Here, we investigate whether protons could be applied in a dose-painting setting by comparing proton dose distributions with delivered photon plans from a phase-I trial of FDG-PET based dose-painting at our institution.Material and methods: Eleven oropharynx (5), hypopharynx (2) and larynx cancer (4) patients from the recently conducted phase I trial were used for comparison of proton and photon dose-painting techniques. Robust optimization (3.5%/3 mm) was used for proton plans. Plan robustness and difference in dose metrics to targets and organs at risk were evaluated.Results: The proton plans met target dose constraints, while having lower non-target dose than photon plans (body-minus-CTV, mean dose 3.9 Gy vs 7.2 Gy, p = .004). Despite the use of robust proton planning for plan max dose, photon plan max doses were more robust (p = .006). Max dose to medulla, brainstem and mandible were lower in the proton plans, while there was no significant difference in mean dose to submandibular- and parotid glands.Conclusion: Proton dose-painting for HNC seems feasible and can reduce the non-target dose overall, however not significantly to certain organs close to the target, such as the salivary glands. Max dose in proton plans had a lower robustness compared to photons, requiring caution to avoid unintended hot spots in consideration of the risk of mucosal toxicity.

Safety Profile and Therapeutic Efficacy of One Cycle of Lu177-PSMA in End-Stage Metastatic Castration-Resistant Prostate Cancer Patients with Low Performance Status.

The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status. Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis. Partial response (PR), stable disease (SD) and progressive disease (PD) for PSA were seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables. We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.

Impact of pelvic bone marrow irradiation on the hematological toxicity of subsequent chemotherapy in rectal cancer

Preoperative radio(chemo)therapy in rectal cancer may irreversibly damage pelvic bone marrow (PBM) and impair the tolerance of subsequent chemotherapy. The aim of the study was to assess the relationship between the irradiated volume of PBM and the toxicity of subsequent 5-fluorouracil, oxaliplatin, leucovorin (FOLFOX-4) in rectal cancer. We included consecutive rectal cancer patients who received FOLFOX-4 postoperatively or due to cancer relapse. The PBM was divided into iliac (IM), lumbosacral (LSM), and lower pelvic (LPM) marrow. We assessed mean dose, and percentage of volume receiving 10%-90% (V10%-V90%) of the prescribed dose for PBM, IM, LSM, and LPM. Generalized linear model for repeated measures (GLM) was used to test an influence of dose-volumes distribution on toxicities grade 2 or higher (TOX2) and grade 3 or higher (TOX3). The two-sided t-test was used to evaluate the difference in mean dose, mean V20%, and mean V40% between patients who experienced TOX2 or TOX3 and those who did not. 39 patients met eligibility criteria. Because of the low occurrence of TOX3 (n=3), related analyses were abandoned. We found no influence of dose-volume distribution on TOX2 in GLM and no significant differences in mean dose, mean V20%, and mean V40% for PBM, IBM, LSM, and LPM between patients who experienced TOX2 and those who did not. To conclude, no relationship between doses received by PBM in preoperative radio(chemo)therapy in rectal cancer and hematological tolerance of subsequent FOLFOX-4 chemotherapy was found.

Dosimetric Comparison of Intensity-Modulated Radiation Therapy via Breath Hold Technique and Proton Therapy With or Without Breath Hold for Mediastinal Lymphoma

Treating patients affected with mediastinal lymphoma with radiation therapy (RT) has been associated with long-term late side effects. Deep inspiration breath-hold (BH) can result in significant dosimetric benefits to the heart and lung. We hypothesized that RT to the mediastinum with intensity modulated radiation therapy (IMRT) would be comparable to proton-free breathing (P-FB) plans but inferior to theoretical proton breath-hold (P-BH) plans in regards to dosimetry of organs at risk (OAR). Ten patients (including 5 females) that received mediastinal involved site RT with “butterfly” IMRT-BH and had 4D-CT treatment planning scans available were included. Female patients were positioned on a 15 degree inclined board for breast sparing. The Eclipse Treatment Planning System was used to generate two additional plans per patient (P-FB and P-BH), optimized to deliver 30.6 Gy or CGE in 17 fractions. We calculated total volume, mean dose, V30, V25, V15 and V5 for OAR including heart, left ventricle (LV), coronary arteries, lungs, and breasts. Comparisons were made using a non-parametric two tailed paired t test with a significant P value of < 0.05. All plans had to have comparable coverage of the PTV. Heart dose was not significantly different comparing IMRT-BH to P-FB, while P-BH significantly improved high and low doses to the heart (Table 1). There was a significant lower LV mean dose in favor of P-BH compared to IMRT-BH (1.0 Gy versus 3.3 Gy; P = 0.01). P-BH resulted in lower lung high and low doses compared to IMRT-BH and P-FB. Although lung V5 was significantly higher with IMRT-BH compared to both P-FB and P-BH, IMRT-BH significantly lowered the V30 and V25 (Table 1). In all plans, there were no statistically significant differences in mean dose, V30, V25, V15 or V5 for the left main/left anterior descending artery, right coronary artery, and bilateral breasts. Owing to its physical properties, proton RT can be advantageous for the treatment of lymphoma patients receiving RT to the mediastinum contingent on using deep inspiration BH technique; IMRT-BH was able to achieve comparable doses to the heart, breasts, and coronary arteries compared with P-FB plans.Tabled 1Abstract 130; Table 1OrganIMRT-BHP-FBP valueIMRT-BH vs. P-FBP-BHP valueIMRT-BH vs. P-BHP valueP-FB vs. P-BHLung Volume (cc)4369.62438.4.001 Mean Dose (Gy)861.9753.6.03664.7<.001.008 V306.810.8<.0018.7.004.001 V2513.916.2.00813.3.18.001 V2019.319.5.8616.4.001.001 V1524.523.4.4520.4.001.008 V540.533.8.00731.0<.001.03Heart Volume (cc)625.2653.1.23 Mean Dose (Gy)9.67.6.077.0.001.37 V3016.016.6.7415.0.43.32 V2521.719.9.5118.1.03.31 V1527.123.9.3522.1.02.35 V536.928.9.1026.8.004.36 Open table in a new tab

Heterogeneous FDG-guided dose-escalation for locally advanced NSCLC (the NARLAL2 trial): Design and early dosimetric results of a randomized, multi-centre phase-III study

Background and purposeLocal recurrence is frequent in locally advanced NSCLC and is primarily located in FDG-avid parts of tumour and lymph nodes. Aiming at improving local control without increasing toxicity, we designed a multi-centre phase-III trial delivering inhomogeneous dose-escalation driven by FDG-avid volumes, while respecting normal tissue constraints and requiring no increase in mean lung dose. Dose-escalation driven by FDG-avid volumes, delivering mean doses of 95Gy (tumour) and 74Gy (lymph nodes), was pursued and compared to standard 66Gy/33F plans. Material and methodsDose plans for the first thirty patients enroled were analysed. Standard and escalated plans were created for all patients, blinded to randomization, and compared for each patient in terms of the ability to escalate while protecting normal tissue. ResultsThe median dose-escalation in FDG-avid areas was 93.9Gy (tumour) and 73.0Gy (lymph nodes). Escalation drove the GTV and CTV to mean doses for the tumour of 87.5Gy (GTV-T) and 81.3Gy (CTV-T) in median. No significant differences in mean dose to lung and heart between standard and escalated were found, but small volumes of e.g. the bronchi received doses between 66 and 74Gy due to escalation. ConclusionsFDG-driven inhomogeneous dose-escalation achieves large increment in tumour and lymph node dose, while delivering similar doses to normal tissue as homogenous standard plans.

Recovery of Salivary Function: Contralateral Parotid-sparing Intensity-modulated Radiotherapy versus Bilateral Superficial Lobe Parotid-sparing Intensity-modulated Radiotherapy

AimsTo establish whether there is a difference in recovery of salivary function with bilateral superficial lobe parotid-sparing intensity-modulated radiotherapy (BSLPS-IMRT) versus contralateral parotid-sparing IMRT (CLPS-IMRT) in patients with locally advanced head and neck squamous cell cancers. Materials and methodsA dosimetric analysis was carried out on data from two studies in which patients received BSLPS-IMRT (PARSPORT II) or CLPS-IMRT (PARSPORT). Acute (National Cancer Institute, Common Terminology Criteria for adverse events – NCI CTCAEv3.0) and late (Late Effects of Normal Tissue- subjective, objective, management analytical – LENTSOMA and Radiation Therapy Oncology Group) xerostomia scores were dichotomised: recovery (grade 0–1) versus no recovery (≥grade 2). Incidence of recovery of salivary function was compared between the two techniques and dose-response relationships were determined by fitting dose-response curves to the data using non-linear logistic regression analysis. ResultsSeventy-one patients received BSLPS-IMRT and 35 received CLPS-IMRT. Patients received 65 Gy in 30 fractions to the primary site and involved nodal levels and 54 Gy in 30 fractions to elective nodal levels. There were significant differences in mean doses to contralateral parotid gland (29.4 Gy versus 24.9 Gy, P < 0.005) and superficial lobes (26.8 Gy versus 30.5 Gy, P = 0.02) for BSLPS and CLPS-IMRT, respectively. Lower risk of long-term ≥grade 2 subjective xerostomia (LENTSOMA) was reported with BSLPS-IMRT (odds ratio 0.50; 95% confidence interval 0.29–0.86; P = 0.012). The percentage of patients who reported recovery of parotid saliva flow at 1 year was higher with BSLPS-IMRT compared with CLPS-IMRT techniques (67.1% versus 52.8%), but the difference was not statistically significant (P = 0.12). For the whole parotid gland, the tolerance doses, D50, were 25.6 Gy (95% confidence interval 20.6–30.5), k = 2.7 (0.9–4.5) (CLPS-IMRT) and 28.9 Gy (26.1–31.9), k = 2.4 (1.4–3.4) (BSLPS-IMRT). For the superficial lobe, D50 were similar: BSLPS-IMRT 23.5 Gy (19.3–27.6), k = 1.9 (0.5–3.8); CLPS-IMRT 24.0 Gy (17.7–30.1), k = 2.1 (0.1–4.1). ConclusionBSLPS-IMRT reduces the risk of developing high-grade subjective xerostomia compared with CLPS-IMRT. The D50 of the superficial lobe may be a more reliable predictor of recovery of parotid function than the whole gland mean dose.

Hybrid isocenter technique for Gamma-Knife Perfexion treatment of trigeminal neuralgia

Gamma-Knife (GK), Perfexion (PFX) has 8 sectors that can be blocked compared with the older model 4C, which has 201 independent source blocking options using plugs. This limits the ability of PFX to shape a single isocenter plan, such as trigeminal neuralgia. In this retrospective review and prospective re-planning comparison study of trigeminal neuralgia radiosurgery plans, a hybrid isocenter technique (HIT) is compared with single isocenter GK radiosurgery plans on 2 models (4C and PFX) dosimetric parameters. With ethics approval, patients treated on 4C (n = 100) and PFX (n = 50) between 2005 and 2014 for trigeminal neuralgia were reviewed. All clinical plans were produced using 1 isocenter with a 4-mm collimator and a prescription dose of 80Gy at 100% while limiting brainstem dose to < 15Gy (D1mm3). Dose shaping was performed using plugs in 4C and sector blocking in PFX to optimize the plan, if required. Re-planning using HIT was retrospectively attempted for PFX plans with brainstem dose > 15Gy. In the implementation of HIT, we used 2 shots at the same isocenter, but with different sector block configuration and weights, to further reduce brainstem dose while optimizing dose coverage of the nerve. Planning parameters such as dose to the treated nerve, brainstem, and surrounding tissue were compared between the clinical plans and the new plans with HIT. Source blocking was applied in 66/100 4C plans with mean blocked sources of 40.2/201 (ranging 1 to 99) and in 36/50 PFX plans with mean blocked sectors of 2.2/8 (1 to 4). There is no significant differences in mean dose, integral dose, irradiated volume of the treated nerve between 4C, and PFX plans. The 4C plans had smaller irradiated volume of tissue (90.6mm3) than PFX plans (103.5mm3) (p < 0.001). The irradiated volume of tissue increases by 17% when half of the sources are blocked for both 4C and PFX plans. In 9/50 PFX plans, brainstem D1mm3 was 15.8Gy on average (15.2 to 16.5Gy) and D10mm3 was 12.2Gy (11.4 to 13.2Gy). Re-plans of these 9 cases using HIT resulted in a significant reduction in D1mm3 to 13.5Gy (12.2 to 15.1) and D10mm3 to 10.5Gy (8.1 to 12.2) (p < 0.001). There was < 1% difference between the original PFX and re-planned HIT plans in dose to the nerve, and treatment time (p = 0.186). It is noted that the increase in the irradiated volume of tissue is proportional to the use of source blocking. Larger irradiated volume may be a reason that higher pain control rate and complication rate at the same time. Hybrid isocenter technique results in greater sparing of the brainstem without compromise in the dose to the nerve or treatment time on GK PFX planning for the treatment of trigeminal neuralgia.

SU‐E‐T‐762: Toward Volume‐Based Independent Dose Verification as Secondary Check

Purpose:Lung SBRT plan has been shifted to volume prescription technique. However, point dose agreement is still verified using independent dose verification at the secondary check. The volume dose verification is more affected by inhomogeneous correction rather than point dose verification currently used as the check. A feasibility study for volume dose verification was conducted in lung SBRT plan.Methods:Six SBRT plans were collected in our institute. Two dose distributions with / without inhomogeneous correction were generated using Adaptive Convolve (AC) in Pinnacle3. Simple MU Analysis (SMU, Triangle Product, Ishikawa, JP) was used as the independent dose verification software program, in which a modified Clarkson‐based algorithm was implemented and radiological path length was computed using CT images independently to the treatment planning system. The agreement in point dose and mean dose between the AC with / without the correction and the SMU were assessed.Results:In the point dose evaluation for the center of the GTV, the difference shows the systematic shift (4.5% ± 1.9 %) in comparison of the AC with the inhomogeneous correction, on the other hands, there was good agreement of 0.2 ± 0.9% between the SMU and the AC without the correction. In the volume evaluation, there were significant differences in mean dose for not only PTV (14.2 ± 5.1 %) but also GTV (8.0 ± 5.1 %) compared to the AC with the correction. Without the correction, the SMU showed good agreement for GTV (1.5 ± 0.9%) as well as PTV (0.9% ± 1.0%).Conclusion:The volume evaluation for secondary check may be possible in homogenous region. However, the volume including the inhomogeneous media would make larger discrepancy. Dose calculation algorithm for independent verification needs to be modified to take into account the inhomogeneous correction.

Technique for comprehensive head and neck irradiation using 3-dimensional conformal proton therapy

Owing to the technical and logistical complexities of matching photon and proton treatment modalities, we developed and implemented a technique of comprehensive head and neck radiation using 3-dimensional (3D) conformal proton therapy. A monoisocentric technique was used with a 30-cm snout. Cervical lymphatics were treated with 3 fields: a posterior-anterior field with a midline block and a right and a left posterior oblique field. The matchline of the 3 cervical nodal fields with the primary tumor site fields was staggered by 0.5cm. Comparative intensity-modulated photon plans were later developed for 12 previously treated patients to provide equivalent target coverage, while matching or improving on the proton plans׳ sparing of organs at risk (OARs). Dosimetry to OARs was evaluated and compared by treatment modality. Comprehensive head and neck irradiation using proton therapy yielded treatment plans with significant dose avoidance of the oral cavity and midline neck structures. When compared with the generated intensity-modulated radiation therapy (IMRT) plans, the proton treatment plans yielded statistically significant reductions in the mean and integral radiation dose to the oral cavity, larynx, esophagus, and the maximally spared parotid gland. There was no significant difference in mean dose to the lesser-spared parotid gland by treatment modality or in mean or integral dose to the spared submandibular glands. A technique for cervical nodal irradiation using 3D conformal proton therapy with uniform scanning was developed and clinically implemented. Use of proton therapy for cervical nodal irradiation resulted in large volume of dose avoidance to the oral cavity and low dose exposure to midline structures of the larynx and the esophagus, with lower mean and integral dose to assessed OARs when compared with competing IMRT plans.

Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

AimThe aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methodsOptimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. ResultsThe quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. ConclusionsOptimization shortens very much time planning. The average planning time was 5min and less than a minute for forward and computer optimization, respectively.

Ethambutol induced toxic optic neuropathy in HIV positive patients.

To determine whether HIV and the use of antiretroviral therapy is a risk factor for the development of ethambutol toxic optic neuropathy. To describe the clinical course of ethambutol toxic optic neuropathy in patients with HIV and to identify prognostic factors. The case notes of 14 consecutive patients referred to the neuro-ophthalmology clinic were reviewed. Data regarding HIV status, antiretroviral therapy, visual function, ethambutol therapy dosage, and ethambutol therapy duration were collected and analysed. Eleven of the 14 patients were HIV positive. Ten of the HIV positive patients were receiving antiretroviral therapy. The mean dose of ethambutol was 17.25mg/kg/day. No statistically significant difference in mean dose, duration of therapy, age or CD4 count was found between those who showed visual improvement and those who did not. Delay in presentation of more than one month post symptom onset was correlated with poor visual outcome (P=0.001). HIV and, perhaps more importantly, the potential mitochondrial toxic effects of Nucleoside analogue reverse transcriptase inhibitors (NRTIs) may be a risk factor for the development of toxic optic neuropathy from ethambutol therapy via a multiple hit effect. Delay in presentation results in poor visual outcome. Regular monitoring is recommended for HIV positive patients receiving antiretrovirals and requiring ethambutol therapy in order to avoid permanent visual loss.

Plasma amisulpride in relation to prescribed dose, clozapine augmentation, and other factors: data from a therapeutic drug monitoring service, 2002–2010

ObjectiveThis study aimed to investigate the effect of dose and other factors on plasma amisulpride concentrations in clinical practice.MethodAmisulpride therapeutic drug monitoring data 2002–2010 have been studied.ResultsThere were 296 samples (196 adult patients). Amisulpride was not detected in 10% of samples. In the remainder, the mean plasma amisulpride in relation to the prescribed dose (mg/day) was as follows: 100–200 (111 µg/L), 201–400 (254 µg/L), 400–800 (421 µg/L), and 800–1200 (494 µg/L). For prescribed doses up to 800 mg/day, only 51% of results were within 100–319 µg/L. There were no significant sex differences in mean plasma amisulpride or mean dose. The mean plasma amisulpride, but not the dose, was significantly higher in smokers. Linear regression analysis showed that dose explained only 42% of the variation in plasma amisulpride after log10 transformation of both variables. There was no significant difference in the mean dose or mean plasma amisulpride in patients co‐prescribed clozapine as compared with the remaining samples.ConclusionIn practice, dose is a poor predictor of plasma amisulpride concentration. Therapeutic drug monitoring may not only help assess adherence, but also guide dosage. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Evaluation of Anemia Management by Algorithms in Patients with Chronic Kidney Disease Who Are Not Receiving Dialysis

Anemia commonly develops in patients with chronic kidney disease and is strongly associated with adverse clinical outcomes. There are currently no published studies evaluating the efficacy of a nurse-driven anemia-management protocol for patients with chronic kidney disease who are not receiving dialysis. To evaluate the efficacy of an anemia-management protocol in terms of achieving hemoglobin and transferrin saturation levels within the target range, as well as associated utilization of medications, relative to individualized dosing of medications by nephrologists. An algorithm for nurse-driven management of anemia was introduced in April 2009 at a kidney function clinic in a large urban centre. The charts of patients with chronic kidney disease who were not undergoing dialysis were reviewed before (July to December 2007) and after (July to December 2009) implementation of the protocol. Patients' data for hemoglobin, transferrin saturation, and doses of iron and erythropoiesis-stimulating agents were collected for each of the 6-month study periods. In total, 390 patients were treated for anemia before and 434 patients after introduction of the protocol. The anemia-management protocol was non-inferior to individualized dosing for maintenance of hemoglobin levels within the target range of 110-120 g/L: percentage of measured levels within target range 33.3% (485/1456) before versus 34.2% (504/1472) after (absolute difference 0.9 percentage points, 95% confidence interval [CI] -2.5 to 4.4). The criteria for non-inferiority were not met for maintenance of transferrin saturation within the target range of 22%-50%: percentage of levels within target range 58.8% (374/636) before versus 56.9% (403/708) after (absolute difference 1.9 percentage points, 95% CI -3.4 to 7.2). There were no statistically significant differences in mean doses of epoetin alfa, darbepoetin, or iron before and after introduction of the protocol. Similarly, there were no statistically significant differences in number of dose changes for epoetin alfa, darbepoetin, or iron. The nurse-driven anemia-management protocol was non-inferior to dosing by nephrologists in terms of managing hemoglobin levels. It would be reasonable to use an anemia-management protocol for patients with chronic kidney disease who are not receiving dialysis.

Prevalence of osteoporosis and osteopenia in advanced chronic obstructive pulmonary disease patients

Background:Reduction of bone mineral density (BMD) is a known and established phenomenon in chronic obstructive pulmonary disease (COPD). However, there have been no data regarding osteoporosis/osteopenia in COPD patients in India.Aim:To look for the degree and frequency of osteoporosis/osteopenia in our OPD patients being diagnosed as COPD.Materials and Methods:Thirty-seven randomly selected patients with COPD were assessed for BMD with commercially available ultrasound bone densitometer (HOLOGIC SAHARA) in a pulmonary OPD. Some cofactors for reduced BMD were also noted.Results:Out of the 37 COPD (all belonging to the GOLD III/IV category) patients studied, the BMD was found to be normal in 10 (27%) patients, while 27 (73%) patients were found to have osteopenia/osteoporosis [19 (51.35%) and 8 (21.62%) patients having osteopenia and osteoporosis, respectively].Conclusion:Frequency of osteoporosis and osteopenia was found to be very high (73%) in our population of advanced COPD. The data suggest a need for further in-depth study regarding the issue.