Mean Dose Research Articles

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.

P.055 Corticosteroid dose tapering in patients with generalised myasthenia gravis on zilucoplan: Interim analysis of RAISE-XT

Background: In the Phase 3 RAISE study (NCT04115293), zilucoplan significantly improved MG-specific outcomes in patients with acetylcholine receptor autoantibody-positive generalised MG. After the first 12 weeks of the open-label extension study, RAISE-XT (NCT04225871), corticosteroid dose could be changed per the investigator’s discretion. We evaluate changes in corticosteroid dose during treatment with zilucoplan in RAISE-XT. Methods: In RAISE-XT, adults who completed the Phase 2 or RAISE studies (N=200) self-administered daily subcutaneous zilucoplan 0.3mg/kg, either continuing with zilucoplan or switching from placebo. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). We assessed (post-hoc) the proportion of patients who discontinued/reduced or increased corticosteroid dose relative to double-blind baseline up to Week 60. Results: At Week 60, 30% (n=18/60) and 22% (n=12/54) of patients receiving corticosteroids in the zilucoplan and placebo-switch groups, respectively, reduced/discontinued corticosteroids (mean dose reductions: 14mg and 16mg; mean [SD] CFB in MG-ADL scores: -5.00 [3.96] and -5.67 [6.89]. 12% (n=7/60) and 7% (n=4/54) of patients in the zilucoplan and placebo-switch groups, respectively, increased corticosteroid dose (~12mg mean increase in both groups). TEAEs occurred in 188 (94.0%) patients (data cut-off: 08 September 2022). Conclusions: While receiving zilucoplan, discontinuation or dose reduction in concomitant corticosteroids was possible with maintained efficacy.

#2457 Effect of belimumab in renal function and proteinuria in patients with lupus nephritis (LN): our experience

Abstract Background and Aims Belimumab was approved for systemic lupus erythematosus (SLE) after demonstrating its security and effectiveness in patients without renal activity. Recently it has been approved to treat LN [1, 2]. In this study, we analyse the experience of our centre with patients treated with Belimumab with any of the indications and renal SLE affectation. Method We retrospectively reviewed the clinical and analytical presentations and outcomes in patients diagnosed with SLE and treated with belimumab in our centre no matter the indication of the latest. We collected clinical, analytical, therapeutic and histological data of patients diagnosed with biopsy-proven LN and at least 6 months of follow-up and analyzed the evolution after belimumab was initiated. We excluded hemodialysis patients when analyzed renal function. We also reviewed clinical histories seeking potential complications related to belimumab. Results Our cohort includes 14 patients, 71% women, 71% Caucasian, 64% presented HTA and 14% were diabetic. Belimumab was initiated because of extrarenal manifestations in 43% of patients. The mean age at SLE and LN diagnosis was 31 and 36 years respectively, with a mean treatment length of 2.3 years; 71% of patients had class III or IV LN, 14% had V LN and 14% had III+V LN. Before its initiation, our cohort presented a mean SCr 0.8 mg/dL, 2g/g proteinuria, anti-DNA 172 UI/mL, C3 91 mg/dL, C4 21 mg/dL, mean SLEDAI 28.3. Of patients, 71% were under chloroquine, 93% under oral steroids (mean dose 10 mg/day), 93% under MPA (mean dose 1004 mg/day) and 43% under calcineurin inhibitors (CNI). After 6 months mean creatinine was 0.7 mg/dL, proteinuria diminished to 1.5 g/g (p &amp;lt; 0.025), anti-dsDNA were 87UI/mL, C3 was 88.5 and C4 32.7 mg/dL respectively; and after 12 months, creatinine was 0.87 mg/dL, proteinuria was 1.44g/g, anti-dsDNA were 148UI/mL, C3 was 99 and C4 24.7 mg/dL respectively and mean SLEDAI score was 7.1. After one year 66.67% of patients were under chloroquine, 88.89% under corticosteroids (mean dose 6 mg/day), 77.8% under MPA and 33.3% under CNI. After follow up we had 1 death with no secondary effects related to belimumab and reduction in proteinuria kept a trend but was no longer significative (p = 0.052). Belimumab was stopped in 5 patients, 2 of them before their inclusion in a CAR-T programme, 2 of them temporally when diagnosed with endocarditis and 1 of them after the finish of the protocol. Conclusion Our study has several limitations, mostly its reduced sample size. In our cohort, belimumab initiation is related only to a reduction of proteinuria after 6 months, but the most important aspect of this analysis may be that it proved to be safe and allowed clinicians to withdraw or reduce other immunosuppressive drugs to avoid their chronic toxicity with no undesirable side effects.

#2362 Clinical utility Anti-human T-lymphocyte Immunoglobulin (ATLG) as an induction agent in a living donor kidney transplantation: 5-year follow-up data

Abstract Background and Aims The usage of induction agents for living donor kidney transplants in India is varied. Polyclonal antibodies currently in use are anti-thymocyte globulin (ATG) and anti-T-lymphocyte globulin (ATLG). The role and dose of ATLG need to be defined. This study is focused on ATLG usage and the outcome with long-term follow-up. Method This is an analysis of 206 patients who received ATLG as an induction agent from 2017 to 2023. Patients received triple immunosuppression therapy: Tacrolimus, Mycophenolate Mofetil (MMF), and prednisolone for maintenance immunosuppression. Results A total of 206 patients received ATLG as an induction agent for living donor kidney transplants. The mean age of the patients was 39.13 ± 12.56 years. There were 87.3% (n = 180) males and 12.6% (n = 26) females. The majority of transplants in our study were ABO-compatible (94.6%, n = 195) and ABO-incompatible (5.2%, n = 11). The mean age of donors was 41 ± 13.7 years. Males were 38.3% (n = 79), and females were 61.6% (n = 127). Overall survival observed in the current study was 98% (n = 202), Post-transplant, 4 patients died (n = 2 died due to COVID-19, 1 due to Heart failure and 1 was infectious mortality.) The mean cumulative dose of ATLG in the current study was 305.1 ± 61.8 mg, and the mean dose was 5.4 ± 1.4 mg/kg. The baseline etiologies of patients who underwent transplant were chronic glomerulonephritis (47.5% n = 98), diabetic nephropathy (16.9% n = 35), hypertension (29.1% n = 60), CIN, and other GMB diseases. In the current study, the figure shows overall 11.6% (n = 24) rejections and 5-year follow-up data of Serum creatinine within a normal range. Post-transplant BK Virus Nephropathy was observed in 3.39% (n = 7) cases, CMV infection in two cases, TB was observed in three cases and fungal pneumonia in one case. Conclusion Long-term 5 year follow-up of Living donor kidney transplant shows that ATLG is an effective and safe induction agent. Good compliance with Oral immunosuppressant can improve graft survival as per the current study.

Quantitative evaluation of 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following Yttrium-90 radioembolization.

Following yttrium-90 radioembolization (90Y-RE), 90Y-PET/CT and 90Y-SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well-established standardized dosimetry protocols for 90Y-RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel-based dosimetry between 90Y-PET/CT and 90Y-SPECT/CT. To quantitatively analyze and compare 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following 90Y-RE. 90Y-PET/CT and90Y-SPECT/CT imaging was acquired for 35 patients following 90Y-RE with TheraSphere for the treatment of unresectable hepatocellular carcinoma. Dosimetry was performed using the local deposition method with known activity and the mean dose (Dmean) was calculated for perfused liver volumes (PV), tumors (T), and perfused normal livers (NL). Additionally, the absorbed dose to x% of the volume (Dx, x [5%, 10%, …, 90%, 95%]) and the volume receiving y Gy (Vy, y [10Gy, 20Gy, …, 190Gy, 200Gy]) were calculated for T and NL, respectively. Dose metrics were compared using linear regression, Bland-Altman analysis, and statistical testing. Both 90Y-SPECT/CT and 90Y-PET/CT-based tumor Dmean were strongly correlated (R2 ≥ 0.90) with Dx, excluding metrics on the extrema. Intra-modality comparisons of various Dx and Vy metrics yielded statistically significant differences (ANOVA, p<0.001) for both90Y-PET/CT and90Y-SPECT/CT. Based on statistical testing, only Dx metrics separated by greater than 20%-30% coverage, and only Vy metrics separated by greater than 40-70Gy, reported significant differences. For PV, there was a strong correlation (R2 ≥ 0.99) between Dmean derived separately from 90Y-PET/CT and 90Y-SPECT/CT imaging. The strength of the correlation was slightly reduced for T and NL with R2=0.91 and R2=0.95, respectively. For PV, the mean bias±standard error (SE) and 95% limits of agreement (LOA) between Dmean from the two modalities was effectively zero with -0.8±0.4% (±2.5%). For T and NL, the mean bias±SE (±LOA) was -14.5±3.7% (±24%) and 9.4±4.7% (±27%), respectively. The strong correlation between Dmean and Dx suggests information from multiple dose metrics (e.g., D70 and Dmean) is largely redundant when establishing dose-response relationships in 90Y-RE. Dmean is highly correlated between 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry, for all liver VOIs. Relative to 90Y-SPECT/CT, 90Y-PET/CT, on average, yielded higher Dmean to tumors (14%) and lower Dmean to perfused normal livers (9%). Absorbed dose differences for perfused liver volumes between 90Y-SPECT/CT and 90Y-PET/CT were negligible.

#3140 Investigating the impact of Anti-IL5 therapy in eosinophilic granulomatosis with polyangiitis (EGPA): a three year longitudinal perspective

Abstract Background and Aims In the randomized, placebo-controlled MIRRA trial [1] for relapsing and refractory eosinophilic granulomatosis with polyangiitis (EGPA), adjuvant therapy with 300 mg anti-IL5 mAB Mepolizumab [MEPO] for 12 months (M), accrued longer times in remission, reduced steroid exposure and reduced relapse rates [1]. The aim of this study is to analyze the outcome of 100 mg MEPO monthly s/c for a minimum of 36 months. Changes to adjuvant immunosuppression and indications for anti-IL5 class switch from MEPO 100 mg s/c to Benralizumab (BRZ) or Reslizumab (Res) were assessed. Method In this observational study, 20 EGPA patients received anti-IL5 therapy for a minimum of 36M (range 49-68M). All commenced on 100 mg s/c MEPO every four weeks. Anti-IL5 therapy switched to BRZ or Res due to partial response or intolerance. Assessment time points included MEPO commencement, 6, 12, 18, 24 and 36 months. Results Overall, there was a 50% reduction in steroid dose by 12 months. This continued to reduce to 24M, by which time 2 were off steroids and a further 10/20 (50%) on weaning dose ≤ prednisolone 5 mg/day. Mean steroid dose continued to decrease to 36 months. The number on adjuvant conventional immunosuppressants (ACIS), reduced over time from 10/20 (50%) at M0 to 4/20 (20%) by M24. Clinical benefits included ANCA serology normalized in all four positive patients by 12 months. Mean eosinophil count reduced from 0.42 mg ± 0.33 × 109/L at M0 to 0.04 ± 0.03 × 109/L at 12 and 24M. BVAS reduced from median 5 [3-7], to 0 [0-1] by 24M. The change in mean FEV1 over 12 months was from (M0) 2.11 ± 0.66 to (M12) 2.39 ± 0.62 and FVC (M0) 3.42 ± 0.87 to (M12) 3.67 ± 0.93/105.60 ± 20.47 respectively. All 20 EGPA patients receiving anti -IL5 therapy, ranging from 49-68M remain on therapy. At 36M, 9 have remained on 100 mg s/c MEPO. 10 (50%) have switched to an alternative anti-IL5 agent—10 switched to benralizumab, 1 initially on benralizumab to reslizumab. 9/10 had achieved partial response prior to switch (reduction in steroids / relapse rate), 1/10 had no response.. During the duration of the study, 3 patients had a break of therapy, but all resumed anti-IL5 treatment with good response. Hence, all 20 remain on anti-IL5 beyond 24M. After 36M, one patient required cyclophosphamide along with anti-IL5 therapy for myocarditis. A further patient had Rituximab for EGPA/ Rheumatoid arthritis overlap between anti-IL5 agents. Conclusion In this study, there was a 50% reduction in steroid dosage by 12 months and steroid requirements continue to decrease to 36M. By 24 months 2 are steroid free and a further 10 on weaning dose ≤5 mg. Furthermore, the number on adjuvant conventional immunosuppression reduced over the 24M (n = 4 at 24M). This study demonstrates that anti-IL5 therapy serves as a favorable model for steroid and conventional immunosuppressant minimization in EGPA. Clinical benefits of reduction in BVAS, improved pulmonary function tests and reduced serum eosinophilia were recorded. The relapsing nature of EGPA places a dependency of therapy on steroids and this study demonstrated sustained and ongoing improvement annually with continued anti-IL5 therapy. Some participants required a switch in anti-IL5 agent.

#1681 Efficacy and safety of combined treatment with rituximab and low doses of cyclophosphamide for ANCA associated renal vasculitis

Abstract Background and Aims Current guidelines recommend the use of rituximab (RTX) or cyclophosphamide (CP) as induction treatment for ANCA-associated vasculitis (AAV) with renal involvement. Some authors have described the combination of CP and RTX in the treatment of severe AAV, and recently a regimen of 6 cycles of low-dose CP combined with RTX has been used with good results. The aim our study was to compare the efficacy and safety of combined treatment with even lower doses of intravenous CP (2-3 cycles) and RTX, compared to standard treatment with RTX. Method We conducted a retrospective study that included 14 patients with histologically confirmed AAV, treated with an induction treatment scheme of corticosteroids, RTX and 2-3 cycles of intravenous CP. A case-control analysis was performed with 16 patients who received only corticosteroids and RTX in the same period, matched by propensity score for age, creatinine at presentation and histological parameters (sclerosed glomeruli, epithelial crescents and normal glomeruli). We compared renal and overall survival, and complications from immunosuppression in both groups. Results At presentation, patients treated with the combined regimen had a mean age of 67 ± 12.1 years, a mean glomerular filtration rate estimated by CKD-EPI of 19.8 ± 11.1 ml/min/1.73 m2, proteinuria of 1.6 (0.81- 1.84) g/24 hours and initial BVAS score of 18.5 ± 6.9. 78.6% of the patients were anti-MPO positive and 21.4% were anti-PR3 positive. According to Berden's classification, 85.7% had a mixed variant, 7.1% crescentic and 7.1% sclerotic, in the renal biopsy. The mean dose of CP was 1445 ± 384 mg, and of RTX was 2g. 28.6% required dialysis at presentation, of which 75% recovered kidney function. The duration of steroid treatment was 8 (4.6-16.9) months. Remission rate at 6 months was 71.4%, and after a median follow-up of 20 (15-35) months, 92.9% had remitted. During follow-up, 50% had serious infections; and at the end, 7.1% progressed to end-stage chronic kidney disease (ESKD). 21.4% of the patients included ended up dying. In comparison with the control group, patients who received the combined treatment had a higher remission rate (92.9% vs. 75%), a lower relapse rate (15.4% vs. 35.7%), lower progression to ESKD (7.1% vs. 20%) and lower mortality (21.4% vs 37.5%), with no differences for serious infections. Conclusion The association of low doses of cyclophosphamide to rituximab induction treatment could improve the prognosis in patients with severe ANCA-associated renal vasculitis.

A comparison of methods for in vivo activity and absorbed dose quantification with PET/CT following yttrium-90 radioembolization.

Yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after 90Y-radioembolization (90Y-RE). Yet, the accuracy of in vivo 90Y-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and 90Y-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood. The purpose of this study was to investigate the accuracy of 90Y-PET/CT-based activity estimates following 90Y-RE and characterize differences between 90Y-PET/CT-based voxel dosimetry algorithms. Thirty-five patients underwent 90Y-PET/CT imaging after 90Y-RE with TheraSphere. The net administered 90Y activity (Aadmin) was determined using a dose calibrator and pre- and post-procedure exposure rate measurements. The summation of image-based activity (Aimage) was extracted from perfused volume (PV) and 3D-isotropically 2-cm expanded PV contour (PV+2cm). Absorbed doses were calculated using voxel S-value (VSV), local deposition method (LDM), and LDM with known activity (LDMKA) dosimetry algorithms. Linear regression and Bland-Altman analysis quantified the relationship between Aimage and Aadmin and between mean dose estimates (DLDM, DVSV, DLDM-KA) for PV, T, and perfused NL volumes. While Aadmin and Aimage in PV were highly correlated (R2>0.95), the mean bias±standard error (SE) and (95% limits of agreement, LOA) was significantly non-zero with -22.7±4.7% (±28.4%). In PV+2cm, the mean bias±SE (±LOA) decreased to 1.3±3.4% (±18.0%) consistent with zero mean error. DLDM and DVSV were highly correlated (R2>0.99) for all volumes of interest (VOIs) and the meanbias±SE(±LOA) was 2.2±0.2% (±1.0%), 0.7±0.4% (±2.8%), and 3.2±0.5% (±2.8%) for PV, T, and NL, respectively. DLDM-KA and DVSV were correlated with R2=0.86, 0.80, and 0.86 for PV, T, and NL, respectively. The meanbias±SE(±LOA) between DLDM-KA and DVSV was significantly non-zero with -19.6±5.1% (±31.0%), -20.8±4.4% (±29.0%), and -18.1±5.3% (±31.1%) for PV, T, and NL, respectively. The summation of Aimage in PV was underestimated relative to Aadmin. Only by accounting for respiratory motion, limited spatial resolution, and PET/CT co-registration errors through VOI expansion was Aimage, on average, equal to Aadmin. The differences between DLDM and DVSV were not clinically relevant, though DLDM-KA was approximately 20% greater than DVSV. Given the high quantitative accuracy of dose calibrators and challenges associated with accurate 90Y-PET/CT quantification, LDMKA is the preferred algorithm for accurate 90Y-PET/CT-based dosimetry following 90Y-RE.

Urinary methotrexate dosage in rheumatoid arthritis, in patients treated for at least 6 months: a potential marker of adherence

ObjectivesNon-adherence to rheumatoid arthritis (RA) treatments must be identified. A methotrexate (MTX) urinary dosage (METU) was recently developed. The aim of our study was to assess adherence to MTX in...

The comparison of four hypoxia-inducible factor prolyl hydroxylase inhibitors on drug potency and cost for treatment in patients with renal anemia.

Five hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been approved for marketing in Japan. However, marked differences exist in terms of drug potency, dose requirement, and pharmacokinetics. The primary evaluation in this study was the changes in hemoglobin levels, dose escalation, drug potency, and cost among HIF-PHIs, 3 months after the initiation of treatment. All patients treated with HIF-PHI between August 2020 and December 2023 were enrolled in this study. In total, 124 patients were administered daprodustat (N = 37), enarodustat (N = 44), molidustat (N = 13), or vadadustat (N = 30). The mean hemoglobin levels of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 11.7g/dL, 11.8g/dL, 12.2g/dL, and 11.3g/dL, respectively. At 3 months, the mean doses of daprodustat, enarodustat, molidustat, and vadadustat increased by 110%, 177%, 125%, and 152%, respectively, from the initial dose. The HIF-PHI potency indices (HPI) of daprodustat, enarodustat, molidustat, and vadadustat at 3 months were 0.168, 0.307, 0.184, and 0.254, respectively. At 3 months, the mean daily costs of daprodustat, enarodustat, molidustat, and vadadustat were JPY 345, JPY 434, JPY 206, and JPY 565, respectively. The difference in dose escalation for anemia treatment among HIF-PHIs is due to differences in drug potency, where the HPI significantly differs among HIF-PHIs. The disparity between the HPI and the cost of the initial dose accounts for the variance in the daily costs of renal anemia treatment among HIF-PHIs.

Minimizing normal tissue low dose bath for left breast Volumetric Modulated Arc Therapy (VMAT) using jaw offset.

With proper beam setup and optimization constraints in the treatment planning system, volumetric modulated arc therapy (VMAT) can improve target dose coverage and conformity while reducing doses to adjacent structures for whole breast radiation therapy. However, the low-dose bath effect on critical structures, especially the heart and the ipsilateral lung, remains a concern. In this study, we present a VMAT technique with the jaw offset VMAT (JO-VMAT) to reduce the leakage and scatter doses to critical structures for whole breast radiation therapy. The data of 10 left breast cancer patients were retrospectively used for this study. CT images were acquired on a CT scanner (GE, Discovery) with the deep-inspiration breath hold (DIBH) technique. The planning target volumes (PTVs) and the normal structures (the lungs, the heart, and the contralateral breast) were contoured on the DIBH scan. A 3D field-in-field plan (3D-FiF), a tangential VMAT (tVMAT) plan, and a JO-VMAT plan were created with the Eclipse treatment planning system. An arc treatment field with the x-jaw closed across the central axis creates a donut-shaped high-dose distribution and a cylinder-shaped low-dose volume along the central axis of gantry rotation. Applying this setup with proper multi-leaf collimator (MLC) modulation, the optimized plan potentially can provide sufficient target coverage and reduce unnecessary irradiation to critical structures. The JO-VMAT plans involve 5-6 tangential arcs (3 clockwise arcs and 2-3 counterclockwise arcs) with jaw offsets. The plans were optimized with objective functions specified to achieve PTV dose coverage and homogeneity; For organs at risk (OARs), objective functions were specified individually for each patient to accomplish the best achievable treatment plan. For tVMAT plans, optimization constraints were kept the same except that the jaw offset was removed from the initial beam setup. The dose volume histogram (DVH) parameters were generated for dosimetric evaluation of PTV and OARs. The D95% to the PTV was greater than the prescription dose of 42.56Gy for all the plans. With both VMAT techniques, the PTV conformity index (CI) was statistically improved from 0.62 (3D-FiF) to 0.83 for tVMAT and 0.84 for JO-VMAT plans. The difference in the homogeneity index (HI) was not significant. The Dmax to the heart was reduced from 12.15Gy for 3D-FiF to 8.26Gy for tVMAT and 7.20Gy for JO-VMAT plans. However, a low-dose bath effect was observed with tVMAT plans to all the critical structures including the lungs, the heart, and the contralateral breast. With JO-VMAT, the V5Gy and V2Gy of the heart were reduced by 32.7% and 15.4% compared to 3D-FiF plans. Significantly, the ipsilateral lung showed a reduction in mean dose (4.65-3.44Gy) and low dose parameters (23.4% reduction for V5Gy and 10.7% reduction for V2Gy) for JO-VMAT plans compared to the 3D-FiF plans. The V2Gy dose to the contralateral lung and breast was minimal with JO-VMAT techniques. A JO-VMAT technique was evaluated in this study and compared with 3D-FiF and tVMAT techniques. Our results showed that the JO-VMAT technique can achieve clinically comparable coverage and homogeneity and significantly improve dose conformity within PTV. Additionally, JO-VMAT eliminated the low-dose bath effect at all OARs evaluation metrics including the ipsilateral/contralateral lung, the heart, and the contralateral breast compared to 3D-FiF and tVMAT. This technique is feasible for the whole breast radiation therapy of left breast cancers.

Dysphagia in Head and Neck Radiotherapy: The Influence of Pharyngeal Constrictor Anatomy and Dosimetry.

The goal of this study was to identify which anatomical and dosimetric changes correlated with late patient-reported dysphagia throughout the course of head and neck chemo-radiotherapy treatment. The patient cohort (n = 64) considered oropharyngeal and nasopharyngeal patients treated with curative intent, exhibiting no baseline dysphagia with a follow-up time greater than one year. Patients completed the MD Anderson Dysphagia Inventory during a follow-up visit. A composite score was measured ranging from 20 to 100, with a low score indicating a high symptom burden; a score ≤60 indicated patient-reported dysphagia. The pharyngeal (PCM) and cricopharyngeal constrictor muscles (CPM) were contoured on a planning CT image and adapted to weekly cone-beam CT anatomy using deformable image registration and dose was accumulated using weighted dose-volume histogram curves. The PCM and CPM were examined for volume, thickness, and dosimetric changes across treatment with the results correlated to symptom group. Anatomical evaluation indicated the PCM thickness increased more during treatment for patients with dysphagia, with base of C2 vertebrae (p = 0.04) and superior-inferior middle PCM (p = 0.01) thicknesses indicating a 1.0-1.5mm increase. The planned and delivered mean dose and DVH metrics to PCM and CPM were found to be within random error measured for the dose accumulation, indicating delivered and planned dose are equivalent. The PCM and CPM organs were found to lie approximately 5mm closer to high dose gradients in patients exhibiting dysphagia. The volume, thickness, and high dose gradient metrics may be useful metrics to identify patients at risk of late patient-reported dysphagia.

Tubarial gland sparing with intensity modulated radiation therapy for oropharyngeal cancers: A pilot study of dosimetric feasibility.

Tubarial glands are a new organ at risk for head and neck cancer radiation therapy (RT). We aimed to study the feasibility of sparing them using intensity-modulated radiation therapy (IMRT). Tubarial glands were delineated for 17 patients with oropharyngeal carcinoma receiving definitive RT, and treatment plans were re-optimized to spare dose to the tubarial glands while maintaining target coverage. A paired t test was performed to compare the mean dose of tubarial glands and target coverage. The difference in mean doses was 4.9 and 7.0 Gy for the ipsilateral and contralateral tubarial glands, respectively (p < 0.01). The mean dose to tubarial gland was ≤39 Gy in 35% versus 47% (ipsilateral) and 70% versus 100% (contralateral) in clinical and re-optimized plans, respectively. Re-optimized ipsilateral tubarial gland mean ≤39 Gy was achieved more commonly in patients with base of tongue versus tonsil primaries (86% vs. 20%, p = 0.02). This pilot study demonstrates the dosimetric feasibility of tubarial gland sparing with IMRT. Dosimetric constraints need to be determined with larger studies.

Ultrasound-guided Pectoral Nerve Block in Combination with Interpleural Block for Surgical Anesthesia during Breast Cancer Surgery: A Prospective Feasibility Study

Abstract Background: The aim of this study was to evaluate the feasibility of ultrasound-guided pectoral nerve block combined with interpleural block for surgical anesthesia during the modified radical mastectomy (MRM). Methods: Thirty-six female patients scheduled to undergo MRM were included in this study. After taking all aseptic precautions, an ultrasound-guided pectoral nerve block and interpleural block were performed with 20 ml of 0.25% bupivacaine for each block. We started all patients on dexmedetomidine infusion to achieve conscious sedation and used injection ketamine as rescue analgesia. We recorded hemodynamic parameters throughout the surgery and visual analog scale scores of pain at baseline and after providing rescue analgesia. Postoperatively, we assessed surgeon and patient satisfaction scores. Results: MRM was completed in 31 (86%) out of the 36 recruited patients. Among these 31 patients, 5 (16%) did not require a rescue dose of ketamine, 14 (45%) required one rescue dose, and 12 (39%) patients required two rescue doses of ketamine. Postoperatively, the median patient and surgeon satisfaction scores were 85 (75–90) and 85 (80–90), respectively. The mean dose of dexmedetomidine was 175 (±27) μg, and the mean dose of ketamine was 32.8 (±6) mg. No serious adverse events were reported. Conclusion: MRM can be feasibly performed under ultrasound-guided pectoral nerve block and interpleural block, along with conscious sedation, without any significant adverse events.

A Prospective Study on the Use of Deep Inspiration Breath-Hold Technique in External Beam Radiotherapy for Breast Cancer

Background Breast cancer is the most common cancer and the leading cause of death in women. The deep inspiration breath-hold (DIBH) technique helps reduce the dose received by the heart and lungs in breast cancers during adjuvant radiotherapy (RT). We present the dosimetry of heart and lungs with DIBH technique, reproducibility, and ease of execution. Materials and Methods This is a prospective study among breast cancer patients planned for adjuvant RT following either breast conservation or mastectomy. Patients received adjuvant RT to a dose of 42.5 Gy/16 Fr to the chest wall/whole breast followed by a boost of 10 Gy/5 Fr for breast conservation surgery patients with either three-dimensional conformal RT or volumetric modulated arc therapy technique. The dosimetric parameters such as lung mean dose, heart mean dose, and V25 Gy were compared between DIBH and free-breathing (FB) scans. Data were analyzed using SPSS software, and p-value &lt;0.05 was considered statistically significant. Results The study was conducted from September 2018 to August 2020, and 32 patients were included. The compliance to the DIBH technique was good. The dose received by ipsilateral lung V20 (17 vs. 25%) and mean dose (9 vs. 12 Gy) were significantly lower in DIBH compared with FB (p &lt; 0.001). The V5 (31 vs. 15%), V25 (9 vs. 2%), and mean dose (7 vs. 3.3 Gy) to the heart were much higher in FB compared with DIBH (p &lt; 0.001). Conclusion DIBH-based RT treatment delivery for breast cancer patients requiring adjuvant RT showed good compliance and offers a significant reduction in radiation dose to the heart and lung.

Clinical and Radiological Response following Single-Session Gamma Knife Radiosurgery in Cavernous Sinus Hemangiomas.

Purpose: Cavernous sinus hemangiomas (CSH) represent 2-3% of lesions occupying the cavernous sinus. The optimal management strategy for CSH in not established, with microsurgical resection and radiosurgery employed alone or in combination. Therefore, we aimed to analyse the efficacy and safety of Gamma Knife Radiosurgery(GKRS) for CSH in a cohort of primary and residual CSH. Methods: A retrospective analysis of 33 patients(26 primary and 7 residual CSH) that underwent single-session GKRS between 2012 and 2021 for CSH was performed. Demographic, clinical, radiological and follow-up data were acquired, and clinicoradiological response following GKRS was assessed. Results: The mean age of the cohort was 4313.5 years(range 10–77). There were 9 males (27.3%) and 24 females(72.7%). The median lesion volume was 6.9cc, ranging 1.46 to 19.06cc. The mean dose administered to the tumor margin was 13.501.5Gy(Range 12 to 15Gy). The median duration of clinical follow-up was 41 months, over which period the mean reduction in tumor volume was 87.6%. Complete response, defined as absence of tumor on follow-up imaging occurred in 23 patients(69.7%). Twenty-three patients(69.7%) showed clinical improvement following GKRS. There were no radiation-induced complications. Conclusions: CSH have a distinct radiological appearance and a predictable response to radiosurgery. When used primarily in radiologically diagnosed CSH and as adjunctive therapy supplementing a subtotal excision, GKRS produces a high rate of volume reduction with improvement of neurological function and minimal cranial nerve morbidity. Therefore, GKRS presents a viable alternative to surgery without the morbidity associated with surgical resection.

Optimising craniospinal irradiation for medulloblastoma: a dosimetric comparison of two VMAT planning methods.

Craniospinal irradiation (CSI) poses a challenging planning process because of the complex target volume. Traditional 3D conformal CSI does not spare any critical organs, resulting in toxicity in patients. Here the dosimetric advantages of volumetric-modulated arc therapy (VMAT) using partial arc and avoidance sectors are compared with each other in planning in adult patients undergoing CSI to develop a clinically feasible technique that is both effective and efficient. Eight adult patients treated with CSI were retrospectively identified. In total 16 plans were made. We generated two plans for each patient: 1. VMAT plan using partial arc, namely VMAT_pa. 2. VMAT plan using avoidance sectors, namely VMAT_as. The dose prescribed was 36 Gy in 20 fractions. The dose-volume histogram for planning target volume (PTV) and organs at risk (OAR) (lens, eye, heart, thyroid, lungs, liver, gonads and kidneys) were analysed and compared. Dose parameters of mean dose, V95%, and V107% for the PTV were evaluated. The median length of PTV is 65.58 cm (45.8-79.5). The volume of PTV receiving 95% of the dose (V95%) in both the plans are 97.51% (VMAT_as) and 97.99% (VMAT_pa) (p = 0.121) while V107% are 0.733 and 0.742 for VMAT_as and VMAT_pa, respectively (p = 0.969). The doses of OARs such as lens, eye, liver and gonads were comparable. The mean heart dose was 10.4 and 9.0 Gy in VMAT_as and VMAT_pa plans, respectively (p = 0.005). Significant lower doses to the thyroid, kidneys and lungs were seen in VMAT plans using avoidance sectors. This study provides a practically useful VMAT planning method for the treatment of CSI and illustrates the ability of VMAT using avoidance sectors to generate highly conformal and homogeneous treatment plans for CSI, while limiting the dose to the relevant OARs.

Characterizing the voxel-based approaches in radioembolization dosimetry with reDoseMC.

Yttrium-90 ( ) represents the primary radioisotope used in radioembolization procedures, while holmium-166 ( ) is hypothesized to serve as a viable substitute for due to its comparable therapeutic potential and improved quantitative imaging. Voxel-based dosimetry for these radioisotopes relies on activity images obtained through PET or SPECT and dosimetry methods, including the voxel S-value (VSV) and the local deposition method (LDM). However, the evaluation of the accuracy of absorbed dose calculations has been limited by the use of non-ideal reference standards and investigations restricted to the liver. The objective of this study was to expand upon these dosimetry characterizations by investigating the impact of image resolutions, voxel sizes, target volumes, and tissue materials on the accuracy of and dosimetry techniques. A specialized radiopharmaceutical dosimetry software called reDoseMC was developed using the Geant4 Monte Carlo toolkit and validated by benchmarking the generated kernels with published data. The decay spectra of both and were also compared. Multiple VSV kernels were generated for the liver, lungs, soft tissue, and bone for isotropic voxel sizes of 1 mm, 2 mm, and 4 mm. Three theoretical phantom setups were created with 20 or 40mm activity and mass density inserts for the same three voxel sizes. To replicate the limited spatial resolutions present in PET and SPECT images, image resolutions were modeled using a 3D Gaussian kernel with a Full Width at Half Maximum (FWHM) ranging from 0 to 16mm and with no added noise. The VSV and LDM dosimetry methods were evaluated by characterizing their respective kernels and analyzing their absorbed dose estimates calculated on theoretical phantoms. The ground truth for these estimations was calculated usingreDoseMC. The decay spectra obtained through reDoseMC showed less than a 1% difference when compared to previously published experimental data for energies below 1.9MeV in the case of and less than 1% for energies below 1.5MeV for . Additionally, the validation kernels for VSV exhibited results similar to those found in published Monte Carlo codes, with source dose depositions having less than a 3% error margin. Resolution thresholds ( ), defined as resolutions that resulted in similar dose estimates between the LDM and VSV methods, were observed for . They were 1.5mm for bone, 2.5 mm for soft tissue and liver, and 8.5 mm for lungs. For , the accuracy of absorbed dose deposition was found to be dependent on the contributions of absorbed dose from photons. Volume errors due to variations in voxel size impacted the final dose estimates. Larger target volumes yielded more accurate mean doses than smaller volumes. For both radioisotopes, the radial dose profiles for the VSV and LDM approximated but never matched the referencestandard. reDoseMC was developed and validated for radiopharmaceutical dosimetry. The accuracy of voxel-based dosimetry was found to vary widely with changes in image resolutions, voxel sizes, chosen target volumes, and tissue material; hence, the standardization of dosimetry protocols was found to be of great importance for comparable dosimetryanalysis.

Abstract PO5-18-05: Assessment of the Potential of Photon mini-GRID Therapy for Pre-operative Partial Breast Cancer Treatment

Abstract Purpose We propose a new spatially fractionated radiation therapy (SFRT) technique, called mini-GRID therapy, to reduce normal tissue toxicities in pre-operative partial breast cancer radiotherapy. Mini-GRID therapy, an optimized implementation of GRID therapy, utilizes very narrow beams (widths ~ 1-2 mm) which significantly increase normal tissue tolerances. The concept, proposed by our team in 2017 [1], has been successfully implemented at Hospital de Santiago de Compostela (Spain) showing excellent results in terms of brain toxicity reduction [2]. Profiting from this remarkable increase in tolerance, this study aims to evaluate the feasibility and efficacy of photon mini-GRID therapy for pre-operative partial breast cancer treatment. Methods Ten unbiased clinical cases were selected for the study, comparing photon mini-GRID therapy with conventional broad beam radiotherapy. Monte Carlo simulations (TOPAS v.3.6) were performed based on the mini-GRID therapy implementation (megavoltage X-rays, Varian flattening-filter-free LINAC) realized at the University Hospital in Santiago de Compostela. A mean dose of 24 Gy was delivered in the PTV using three photon mini-GRID arrays with mini beams of approximately 1.8x1.8 mm² at the isocenter. The study aimed to achieve better tumor coverage than conventional pre-operative radiotherapy while ensuring comparable skin toxicity. Valley doses, determining tissue-sparing effects, were compared against organs-at-risk (OARs) tolerance limits. Results The mini-GRID therapy treatments ensured partial tumor coverage and met the dose tolerance limits for all the considered OARs, the most challenging of all being the skin [3]. Peak-to-valley dose ratio (PVDR) in the skin was higher than 3.5 for all the considered patients. Compared to standard radiotherapy (SRT) plans, mini-GRID therapy significantly reduced mean doses to the lungs, heart, and chest wall in the studied cases. Conclusion In this proof-of-concept study, we evaluated photon mini-GRID therapy with megavoltage X-rays as an alternative treatment approach for pre-operative partial breast cancer irradiation, demonstrating its feasibility and straightforward implementation. Because of its high skin and normal tissue-sparing capacities, photon mini-GRID therapy has great potential to improve pre-operative treatment outcomes. Complementary studies and clinical validation are needed to fully establish the optimal protocols and assess long-term effects, but the results encourage the integration of photon mini-GRID therapy as a promising modality for breast cancer therapy.

Abstract PO5-22-02: Evaluation of a surface-guided and tattoo-less approach to setup for whole breast radiotherapy

Abstract Background: In preparation for adjuvant breast radiation therapy (RT), several small but permanent skin tattoo marks are often placed to assist with surface alignment for treatment setup and delivery. With advancements in surface-guided technologies, it may be possible to achieve setup accuracy with a “tattoo-less” approach, which can improve cosmetic and quality of life outcomes. This study evaluates the feasibility, accuracy, and potential dosimetric implications of a tattoo-less setup technique. Method: A retrospective analysis of 10 patients diagnosed with right-sided breast cancer who received adjuvant whole breast RT using a tattoo-less approach were included in this study. All patients received an initial whole breast dose of 42.56 Gray (Gy) in 16 daily fractions using a tangential three-dimensional conformal planning technique. This was followed by a 10Gy boost to the lumpectomy site delivered in 4 daily fractions. Daily setup for whole breast treatment was performed by aligning each patient to their individual reference breast surface generated from the planning computed tomography (CT) images via the Vision RT system. Bony landmarks were then verified via daily kV imaging, and translational shifts were recorded for each fraction. The kV imaging was performed to confirm the treatment positioning since the tattoo-less approach was new to the department. For 5 patients, dosimetric differences between initial surface alignment and shifts performed based on bony landmarks were evaluated by recalculating the original clinical plan with a new isocenter position using kV image shifts for each of their 16 treatment fractions. A plan sum of the 16 recalculated plans for each patient was used in further dosimetric analysis. Boost fractions were not included in this study, as setup was verified using surgical clips instead of bony anatomy. Results: Translational shifts for 158 fractions were reviewed as no kV imaging was performed for the other 2 fractions. The mean absolute kV imaging shift was 0.29 cm (CI (95%): 0.25, 0.32; range: 0 to 1.25) in the vertical axis, 0.28 cm (0.23, 0.32; 0 to 1.27) in the longitudinal axis, and 0.24 cm (0.20, 0.28; 0 to 1.98) in the lateral axis. Clinical plans for 5 patients were evaluated with a mean absolute kV shift of 0.27 cm (range: 0.15 to 0.39) in the vertical, 0.32 cm (0.13 to 0.77) in the longitudinal, and 0.29 cm (0.18 to 0.38) in the lateral directions. Dosimetric analysis revealed a slight increase in mean heart dose from the original clinical plan, with an average difference of 4.12 cGy (range: 0.7 to 10.5 cGy). The maximum increase in V20Gy of the ipsilateral lung was 2.7%. Less than 1% of change was observed in the maximum plan dose, as well as in the V95% coverage, expect for one patient, whose V95% was decreased from 99.6% to 94.6%. This difference was caused by a large longitudinal shift which could be attributed to possible patient movement. Conclusions: These findings demonstrate the feasibility and accuracy of a tattoo-less treatment approach in a small cohort of breast cancer patients receiving whole breast RT. Further investigation with larger cohorts is warranted. Citation Format: Xinxin Zhang, Swati Mamidanna, Yin Zhang, Xiao Wang, Ning Yue, Shicha Kumar, Lindsay Potdevin, Maria Kowzun, Mridula George, Lara Hathout, Bruce Haffty, Nisha Ohri. Evaluation of a surface-guided and tattoo-less approach to setup for whole breast radiotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-02.