Organ Radiation Doses Research Articles

Diagnostic performance of digital tomosynthesis for postoperative assessment of acetabular fractures and pelvic ring injuries

IntroductionDigital tomosynthesis (DTS) has broad non-orthopaedic applications and has seen limited use within orthopaedics for imaging of the wrist. The utility of DTS for assessing reduction and hardware placement following operative treatment of pelvic ring injuries and acetabular fractures has not previously been investigated.MethodsAll operatively treated acetabular fractures and pelvic ring injuries that underwent surgical fixation within a one-year time span received both a computed tomography (CT) scan and a DTS scan as part of their routine postoperative imaging workup. Three orthopaedic traumatologists independently reviewed the images for face-value clinical utility. Radimetrics and PCXMC software were utilized on a subset of the study population's DTS and CT studies to calculate the effective and organ radiation doses delivered.Results52 patients (22 acetabular fractures, 22 pelvic ring injuries, 7 pelvic ring and acetabular fractures, 2 femoral head & acetabular fractures) were included. DTS was considered adequate to assess reduction 83% of the time, hardware position 83% of the time, and sufficient to replace the CT scan 67% of the time. DTS was associated with an 8.3 times lower effective radiation dose than CT. All organ doses were lower for DTS than CT.DiscussionDTS appears to have face-value clinical utility for assessing reduction and hardware position following surgical treatment of acetabular fractures and pelvic ring injuries. Given that DTS is associated with significantly lower radiation doses to patients, further study utilizing more objective criteria is warranted.

A novel x-Ray and γ-Ray combination strategy for radiotherapy after breast-conserving surgery in patients with right breast cancer.

Radiotherapy is a primary therapeutic approach for breast cancer following breast-conserving surgery. The TaiChiB dual-modality radiotherapy system combining X-ray and focused γ-ray, offers a new approach to reduce the radiation dose of organs at risk (OARs) and has the potential to mitigate the adverse effects of radiotherapy. Currently, there are few studies on the dosimetric characteristics of the TaiChiB dual-modality system for actual treatment plans for specific diseases. The purpose of this work is to study the dosimetric advantages of dual-modal systems for right breast patients after breast-conserving surgery. Treatment plans for 20 patients with right breast cancer were generated for a linear accelerator (LINAC) based system and the TaiChiB dual-modality system, respectively. Volumetric modulated arc therapy plans with simultaneous integrated boost (VMAT-SIB) were made for the LINAC. Focused γ-ray was used to deliver the boost dose with the dual-modality system. The dosimetric parameters of the target and OARs were evaluated and compared between the treatment plans generated for the two systems. The TaiChiB dual-modality plans exhibit a higher conformal index (CI) and lower gradient index (GI) for the PGTV and PTV compared with the LINAC-based VMAT-SIB plans. Compared to VMAT-SIB plans, the PTV Dmax, PTV Dmean, PTV V110, PGTV Dmax, and PGTV Dmean of the TaiChiB dual-modality plans are significantly lower. Meanwhile, the dose to OARs, such as the Dmean of the heart, the V5 of liver, the Dmean of ipsilateral lung, the V30 of ipsilateral lung, the V20 of ipsilateral lung, the V5 of ipsilateral lung, the Dmean of contralateral lung, Dmax of contralateral breast and the Dmean of contralateral breast are significantly reduced. Our study demonstrates the dosimetric advantages of the novel TaiChiB dual-modality radiotherapy system for the treatment of right-sided breast cancer. Overall, for the TaiChiB dual-modality radiotherapy system, the radiation dose outside the target region decreases rapidly, thereby minimizing radiation exposure to neighboring organs and ensuring the conformity of the target area. Our research confirms the potential of the TaiChiB dual-modality system for future radiotherapy.

Dosimetry of lutetium-177-PSMA-I&T radioligand therapy in recurrent/metastatic adenoid cystic carcinoma.

6093 Background: There is a high unmet need for effective systemic therapies for recurrent and/or metastatic (R/M) adenoid cystic carcinoma (AdCC), as no standard-of-care exists. AdCC frequently expresses prostate-specific membrane antigen (PSMA), providing rationale for PSMA-targeted therapies, which have demonstrated significant efficacy in prostate cancer. In our phase 2 pilot trial (EudraCT 2019-003857-27), we assessed the safety, efficacy and feasibility of lutetium-177 (177Lu)-PSMA-I&T in R/M AdCC patients. Despite well-tolerated, the efficacy was limited. To gain further insight into causes of the limited efficacy, we measured absorbed 177Lu-PSMA-I&T radiation doses in tumors and organs at risk. Methods: Dosimetry was feasible and was performed in all 10 enrolled AdCC patients. They received 177Lu-PSMA-I&T with a median activity of 7.40 (range 6.78-7.49) GBq and a median of 4 (range 1-4) cycles. For bone marrow dosimetry, blood samples were collected during cycle 1. Single-photon emission CT/CT (SPECT/CT) was performed at 1, 24, 48, 72 and 168 hours after 177Lu-PSMA-I&T injection at cycle 1. Tumors >1 cm were categorized based on gallium-68 (68Ga)-PSMA PET mean standardized uptake value (SUVmean): above, at (±10%), and below liver SUVmean. Per site, up to 3 index lesions per category were selected. Volumes of interest with ~1 cm margin were drawn on SPECT/CT. Background correction was applied. Salivary gland and bone lesion volume were determined by iterative thresholding on 68Ga-PSMA PET. Other tumor volumes were determined on CT. Hermes dosimetry software and Olinda 2.2 software were used to estimate doses according to the Medical Internal Radiation Dose scheme. Results were reported as the absorbed dose at cycle 1 (Gy). Results: In total, 66 tumor lesions were analyzed. Tumor sites included lung (n=35), pleura (n=16), liver (n=5), bone (n=4), lymph node (n=3), local recurrence (n=2) and thoracic wall (n=1). The median 68Ga-PSMA PET tumor/liver SUVmean ratio was 0.94 (range 0.33-2.62). The median tumor-absorbed dose was 0.47 (range, 0.01-4.66) Gy. Highest median doses by tumor site were 1.84 (range, 0.76-2.92) Gy in local recurrences and 1.35 (range, 0.33-2.62) Gy in bone lesions. Lowest median doses by tumor site were 0.18 (range, 0.14-0.27) Gy in lymph node lesions and 0.21 (range, 0.12-0.79) Gy in liver lesions. In organs at risk, the absorbed dose was highest in the kidneys, followed by the salivary glands, with mean values of 6.29 (standard deviation [SD], 2.32) Gy and 5.07 (SD, 2.47) Gy, respectively. The mean bone marrow absorbed dose was 0.53 (SD, 0.14) Gy. Conclusions: Tumor-absorbed radiation doses in our AdCC patient cohort receiving 177Lu-PSMA-I&T were significantly lower than in prostate cancer (~10-40 Gy per cycle), likely due to lower and heterogeneous PSMA expression. This could explain the limited efficacy. Organ-absorbed doses aligned with studies in prostate cancer. Clinical trial information: NCT04291300 .

The Use of Joint Models in Analysis of Aggregate Endpoints in RERF Cohort Studies.

In radiation risk estimation based on the Radiation Effects Research Foundation (RERF) cohort studies, one common analysis is Poisson regression on radiation dose and background and effect modifying variables of an aggregate endpoint such as all solid cancer incidence or all non-cancer mortality. As currently performed, these analyses require selection of a surrogate radiation organ dose, (e.g., colon dose), which could conceptually be problematic since the aggregate endpoint comprises events arising from a variety of organs. We use maximum likelihood theory to compare inference from the usual aggregate endpoint analysis to analyses based on joint analysis. These two approaches are also compared in a re-analysis of RERF Life Span Study all cancer mortality. We show that, except for a trivial difference, these two analytic approaches yield identical inference with respect to radiation dose response and background and effect modification when based on a single surrogate organ radiation dose. When repeating the analysis with organ-specific doses, an interesting issue of bias in intercept parameters arises when dose estimates are undefined for one sex when sex-specific outcomes are included in the aggregate endpoint, but a simple correction will avoid this issue. Lastly, while the joint analysis formulation allows use of organ-specific doses, the interpretation of such an analysis for inference regarding an aggregate endpoint can be problematic. To the extent that analysis of radiation risk for an aggregate endpoint is of interest, the joint-analysis formulation with a single surrogate dose is an appropriate analytic approach, whereas joint analysis with organ-specific doses may only be interpretable if endpoints are considered separately for estimating dose response. However, for neither approach is inference about dose response well defined.

Analisis Distribusi Dosis Berkas Foton pada Kanker Nasofaring dengan Teknik Intensity Modulated Radiation Therapy (IMRT) menggunakan Pesawat Linear Accelerator di Sub Instalasi Radioterapi RSUP Prof. Dr. I.G.N.G. Ngoerah

Analysis for the distribution of photon beam doses in nasopharyngeal cancer has been carried out with the Intensity Modulated Radiation Therapy (IMRT) technique at the Sub-Installation of RSUP Prof. Dr. I.G.N.G. Ngoerah. Calculations were carried out by analyzing the values of the Homogeneity Index (HI) and Conformity Index (CI) as well as radiation dose in Organs a t Risk (OAR). Data from 20 nasopharyngeal cancer patients were used, and a 6 MV energy photon beam with a total dose of 7000 cGy was used, using seven beams of irradiation direction. The data used are radiation doses of 2%, 50%, and 98%, target volume and 95%, and doses at OAR. These data are obtained from the Dose Volume Histogram (DVH) curve in the Treatment Planning System (TPS) process. The results obtained were the average dose distribution on cancer targets in the form of HI and CI values for 20 patients, namely the average HI value of 0.1231±0.0244, while the average CI value was 0.9856±0.022 which, when compared to ICRU report 83 of 2010 HI and CI values were still within the allowable standard limits. The average dose distribution in OAR for 20 patients was the mean spinal cord (4683.9±216.47) cGy, the average right eye (3909.7±605.45) cGy, the average left eye (3683.885±659.89) cGy, the average right optic nerve (4149.01±1099.68) cGy, the average left optic nerve (4174.355±1219.96) cGy, the average right lens (746.29±149.85) cGy, and the average left lens (753.03±144.32) cGy, all average values obtained by OAR are still within the allowable limits. Keywords: nasopharyngeal cancer, 6 MV, IMRT, homogeneity index, conformity index, organ at risk

High-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT Demonstrated a Dose-Response for Durable Complete Remission in Patients with R/R AML

Background: Most older patients (pts) with relapsed or refractory (R/R) AML cannot tolerate intensive treatment and are not eligible for curative allogeneic hematopoietic cell transplant (alloHCT). 131I-apamistamab, an anti-CD45 radioimmunoconjugate, delivers high dose targeted radiation to hematopoietic cells, allowing for myeloablation and eradication of leukemic cells. 131I-apamistamab led induction and conditioning can provide these pts with access to alloHCT. Methods: SIERRA (NCT02665065) was a multi-center, randomized, controlled phase 3 study comparing the efficacy of 131I-apamistamab led induction and conditioning versus physician's choice of conventional care (CC) in pts ≥55 years of age with active, R/R AML. Pts were randomized (1:1, n=153) to CC or 131I-apamistamab with fludarabine and total body irradiation (2 Gy) followed by alloHCT. Primary endpoint was durable complete remission (dCR), defined as CR ≥6 mos with or without platelet recovery (CRp). Pts not achieving CR in CC could crossover (CO) to receive 131I-apamistamab. Treatment with 131I-apamistamab was prescribed as an individualized dose for each pt following a dosimetric infusion and biodistribution analysis, with the prescribed activity of 131I set to deliver a maximum estimated radiation dose to the liver as the dose limiting organ of 24 Gy (determined as the maximum tolerable dose (MTD)) in earlier studies), thereby providing the highest dose to the diseased bone marrow and circulating leukemic cells without exceeding individual organ radiation dose tolerances. Here, we performed an analysis to determine whether a radiation dose-response relationship could be established based on either 1) administered radiation dose to liver and the rate of achieving the primary endpoint of dCR (with 95% binomial confidence intervals) or 2) dCR rate and the ratio of bone marrow/liver absorbed radiation dose as an indicator of favorable biodistribution between target/risk organ. Results: All pts receiving the therapeutic dose of 131I-apamistamab (n=66) were able to receive an alloHCT, and the primary endpoint (dCR) was achieved in 13 pts receiving 131I-apamistamab vs 0 pts in CC (p<0.0001). The median absorbed liver dose was 21.6 Gy (IQR: 21.0 - 22.8 Gy), median absorbed dose to bone marrow was 16.0 Gy (IQR: 11.5 - 22.3 Gy), and median ratio between marrow/liver dose was 0.79 (IQR: 0.52 - 1.02). Table 1 shows the distribution and rate of dCR for pts who received above or below 22 Gy administered dose to liver (24 Gy to liver was the established MTD from earlier studies, in which doses were escalated in 2 Gy increment and thus, 22 Gy represented MTD-1), and for pts stratified by marrow/liver dose ratio (higher ratio representing more favorable biodistribution). Pts with ≤22 Gy liver dose had a dCR rate of 13.5% vs. 27.6% for pts with >22 Gy liver dose, and pts with <median dose to bone marrow had a dCR rate of 12.1% vs. 27.3% for pts with ≥median estimated marrow dose. Importantly, pts with increasingly favorable biodistribution had nominally higher dCR rates of 10.0%, 20.0% and 26.9% for a marrow/liver ratio <0.6, 0.6-0.9 and >0.9, respectively, as illustrated in Figure 1. Taken together this demonstrates a radiation dose-response for the primary endpoint in this study. Overall, safety was similar across doses to the liver. Conclusion: 131I-apamistamab led induction and conditioning followed by alloHCT resulted in statistically significant improvement in dCR at 6 mos vs conventional care. A dose-response was demonstrated for pts receiving 131I-apamistamab with those receiving a liver dose closer to the MTD of 24 Gy having about twice the dCR rate compared to pts 22 Gy (MTD-1) or less. We also found pts with higher marrow/liver ratio experienced considerably higher rates of dCR which highlights the importance of maximizing the dose to target tissues, within the limits of established risk organ dose tolerances.

The application of 3D-printed oral stents in intensity-modulated radiotherapy for oropharyngeal cancer and their dosimetric effect on organs at risk

BackgroundThis study investigates the accuracy of 3D-printed dental stents in intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) and their dosimetric effects on normal tissues.MethodsWe selected 60 patients with OPC who underwent IMRT in the Department of Oncology, Special Medical Center of Army Medical University. These patients were randomly assigned into 3D-printed oral stent, simple glass bottle, and nonstent groups (20 patients/group). The positioning error was analyzed with the onboard imaging system once a week after 5 fractions of IMRT. The conformity index (CI), homogeneity index (HI), radiation dose of organs at risk (OARs), and oral mucosal reaction were compared among the three groups.ResultsNo significant difference was observed in the conformity and uniformity of the target dose and the dose received by the spinal cord, larynx, and bilateral parotid glands among the three groups (P > 0.05). Meanwhile, the dose received by the upper cheek, hard palate, and soft palate of patients was significantly lower in the 3D-printed oral stent group than in the nonstent group (P < 0.05) but insignificantly different between the 3D-printed oral stent and simple glass bottle groups (P > 0.05). When compared with the nonstent group, the simple glass bottle group showed a markedly lower dose received by the upper cheek (P < 0.05) and an insignificantly different dose received by the hard palate and soft palate (P > 0.05). According to Common Terminology Criteria for Adverse Events v.5.0, the adverse response rate of the hard palate mucosa was lower in the 3D-printed oral stent group than in the simple glass bottle and nonstent groups (P < 0.05).ConclusionsFor OPC patients undergoing IMRT, the application of 3D-printed oral stents can significantly reduce the exposure dose of the upper cheek and hard palate and decrease the occurrence of adverse events such as oral mucositis although it cannot affect the positioning error.

The impact of iodine contrast agent on radiation dose of heart and blood: a comparison between coronary CT angiography and cardiac calcium scoring CT.

Iodine contrast agent (CA) is widely used in cardiac computed tomography (CT). The CA can increase the organ radiation doses due to the photoelectric effect. To investigate the impact of CA on radiation dose in cardiac CT by comparing the radiation dose between contrast coronary CT angiography (CCTA) and non-contrast calcium scoring CT (CSCT). Radiation doses were computationally calculated for 30 individual patients who received CSCT and CCTA in the same exam session. The geometry and acquisition parameters were modeled in the simulations based on individual patient CT images and acquisitions. Doses in the presence and absence of CA were obtained in the aorta, left ventricle (LV), right ventricle (RV), and myocardial tissue (MT). The dose values were normalized by size-specific dose estimate (SSDE). The dose enhancement factors (DEFSSDE) were calculated as the ratio of doses in CCTA over doses in CSCT. Compared to the CSCT scans, doses increase in the CCTA scans in the aorta (DEFSSDE = 2.14 ± 0.20), LV (DEFSSDE = 1.78 ± 0.26), and RV (DEFSSDE = 1.31 ± 0.22). A linear relation is observed between the local CA concentrations and the dose increase in the heart; DEFSSDE = 0.07*I(mg/mL) + 0.80 (R2 = 0.8; p < 0.01). The DEFSSDE in the MT (DEFSSDE = 0.96 ± 0.08) showed no noticeable impact of CA on the dose in this tissue. In addition, patient variability in the dose distributions was observed. A linear causal relation exists between local CA concentration and increase in radiation dose in cardiac CT. For the same CT exposure, dose to the heart is on average 55% higher in contrast cardiac CT.

In Vivo evaluation of newly synthesized 213Bi-conjugated alpha-melanocyte stimulating hormone (α-MSH) peptide analogues in melanocortin-1 receptor (MC1-R) positive experimental melanoma model

Given the rising pervasiveness of melanocortin-1 receptor (MC1-R) positive melanoma malignum (MM) and pertinent metastases, radiolabelled receptor-affine alpha-melanocyte stimulating hormone-analogue (α-MSH analogue) imaging probes would be of crucial importance in timely tumor diagnostic assessment. Herein we aimed at investigating the biodistribution and the MM targeting potential of newly synthesized 213Bi-conjugated MC1-R specific peptide-based radioligands with the establishment of MC1-R overexpressing MM preclinical model. DOTA-conjugated NAP, -HOLD, -FOLD, -and MARSamide were labelled with 213Bi. Ex vivo biodistribution studies were conducted post-administration of 3.81 ± 0.32 MBq [213Bi]Bi-DOTA conjugated deriva-tives into twenty B16-F10 tumor-bearing C57BL/6 J and healthy mice. Organ Level Internal Dose Assessment (OLINDA) and IDAC-Dose were used to calculate translational data-based absorbed radiation dose in human organs. Moderate or low %ID/g uptake of [213Bi]Bi-DOTA conjugated NAP, -HOLD, -and MARSamide and significantly increased [213Bi]Bi-DOTA-FOLDamide accumulation was observed in the thoracic and abdominal organs (p ≤ 0.01). High [213Bi]Bi-DOTA-NAP (%ID/g:3.76 ± 0.96), -and FOLDamide (%ID/g:3.28 ± 0.95) tumor tracer activity confirmed their MC1-R-affinity. The bladder wall received the highest radiation absorbed dose followed by the kidneys (bladder wall: 1.95·10-2 and 8.97·10-2 mSv/MBq; kidneys: 7.47·10-3 vs. 5.88·10-2 mSv/MBq measured by IDAC and OLINDA; respectively) indicating the suitability of the NAPamide derivative for clinical use. These novel [213Bi]Bi-DOTA-linked peptide probes displaying meaningful MC1-R affinity could be promising molecular probes in MM imaging.

Персонализированная дозиметрия внутреннего облучения опухолевых образований и органов риска пациентов: разработка и реализация методического базиса для дозиметрического обеспечения клинических исследований терапевтических радиофармпрепаратов

The cluster of calculational and instrumental methods for estimation of personalized internal radiation doses to foci and organs at risk among patients undergoing to therapy by radiopharmaceuticals has been developed. The developed set of methods was used for dosimetrical support of clinical trials of therapeutic radiopharmaceuticals: a) Lu-177-DOTA-PSMA (or "Lutaprost") targeted for radioligand therapy of metastatic castrate-resistant prostate cancer; b) Re-188 albumin microspheres 5-10 μm (or "Artroren") targeted for radiosynovectomy in the local treatment of chronic inflammatory diseases of the joints and c) 188Re albumin microspheres 20-40 μm (or "Gepatoren") targeted for intra-arterial radionuclide embolization in the treatment of inoperable liver cancer. The results of estimations absolute activities of radiopharmaceuticals and their dynamics during SPECT/CT scanning of radiopharmaceuticals in the body of patients were verified by measurements using physical phantoms of humans with different body weights and various standard activities of radionuclides distributed inside the phantoms. The developed cluster of programs (for calculating the absorbed fraction of energy in biostructures), relevant databases and instrumental methods were used as the basis for estimations personalized internal radiation doses in foci and organs at risk among patients included in clinical trials of the studied radiopharmaceuticals. Individual internal radiation doses in foci among 39 patients, included in the first phase of clinical trials of the three studied radiopharmaceuticals, were estimated. The analysis of the distribution of estimated doses shows that absorbed doses in foci are very differing not only in different patients, but also in different foci in the same patient. Irradiation doses in foci increase with an increasing in the administered activities of radiopharmaceuticals and, depending on the volume of foci, are within the following ranges: 1) in a case of “Lutaprost” – from 1.4 to 32 Gy (planned administered activity – 5 GBq), from 5.1 to 59 Gy (planned activity – 7.5 GBq), from 13 to 94 Gy (planned activity – 10 GBq); 2) in a case of "Arthroren" – from 17.5 to 74 Gy (planned administered activities – from 0.37 to 0.925 GBq); 3) in a case of “Gepatoren” – from 10.7 to 43 Gy (planned administered activities – from 1 to 3 GBq). Individual absorbed doses in organs at risk were estimated as well. Dose values in organs at risk also vary greatly between different patients and between different critical organs. These doses ranged from 0.01 to 7.4 Gy (39 patients), which is many times less than “commonly applied dose constraints” in radiotherapy.

Radiometal-theranostics: the first 20 years*

This review describes the basic principles of radiometal-theranostics and its dawn based on the development of the positron-emitting 86Y and 86Y-labeled radiopharmaceuticals to quantify biodistribution and dosimetry of 90Y-labeled analogue therapeutics. The nuclear and inorganic development of 86Y (including nuclear and cross section data, irradiation, radiochemical separation and recovery) led to preclinical and clinical evaluation of 86Y-labeled citrate and EDTMP complexes and yielded organ radiation doses in terms of mGy/MBq 90Y. The approach was extended to [86/90Y]Y-DOTA-TOC, yielding again yielded organ radiation doses in terms of mGy/MBq 90Y. The review further discusses the consequences of this early development in terms of further radiometals that were used (68Ga, 177Lu etc.), more chelators that were developed, new biological targets that were addressed (SSTR, PSMA, FAP, etc.) and subsequent generations of radiometal-theranostics that resulted out of that.

Low Toxicity and Disease Responses in Systemic AL-Amyloidosis Using an Yttrium-90 Labelled Anti-CD66 Monoclonal Antibody TLX66 As the Only Conditioning Prior to Autologous Stem Cell Transplantation

Despite the introduction of new therapies Systemic AL-amyloidosis (AL) remains incurable and the majority of patients will relapse. Autologous stem cell transplantation (ASCT) remains an important treatment option with improvement of organ function and survival in responding patients, however the toxicity of ASCT using conventional chemotherapy results in high morbidity and mortality limiting the application in this vulnerable patient group. We tested the use of a monoclonal anti-CD66 radiolabelled with yttrium-90, TLX66 (90Y-besilesomab) as the sole conditioning agent prior to ASCT in a phase I study in patients with AL. The study had full ethical and regulatory approvals (EudraCT 2015-002231-18; ISRCTN 13400668). The study consisted of three radiation activity levels, 30, 40 and 45 Mega Becquerels (MBq) per kg body weight with 3 patients treated at each activity level. Patients entered the study after fulfilling entry requirements and with informed consent. Prior to receiving the 90Y-besilesomab organ dosimetry and biodistribution were determined using the same anti-CD66 radiolabelled with indium-111 (111In-anti-CD66) with sequential gamma camera imaging. Estimated absorbed radiation to critical organs was determined from an established dosimetry model, organ radiation dose expressed in Gray (Gy). Radiation dose limits of 45Gy for the bone marrow and 15Gy for the liver were used as safety measures. Table 1 summarises patient details. The median previous lines of treatment were 2 (range 1-5) including three who had previous ASCT using high dose melphalan. The primary end-point was treatment related toxicity as determined using CTCAE v4.0. Haematological toxicities (cytopenia) were excluded as adverse events (AEs) unless considered life-threatening. Secondary end-points: Disease response determined by changes in clonal free light chain assay (FLCa), malignant plasma cell percentage in BM as determined by multi-colour flow cytometry; cardiac toxicity from NT-proBNP assay; overall survival and time to disease progression; biodistribution and dosimetry SPECT-CT imaging; engraftment using the European Blood and Marrow Transplant (EBMT) criteria for neutrophil and platelet engraftment. Results: Ten patients underwent dosimetry with 111In-anti-CD66, 9 received the 90Y-besilesomabwith infused activity determined by study cohort and patient body weight; one patient failed dosimetry with excessive hepatic uptake, two received reduced activity to keep the marrow dose within the 45Gy limit. There were no serious adverse events (SAE's) in the trial. There were 3 grade 4 AE's (mainly cytopenias during transplantation) and no SUSAR's were reported. A total of 41 grade 1-4 AE's were recorded. There were no transplant related deaths. All patients became profoundly cytopenic consistent with bone marrow suppression due to the targeted radiation. All patients engrafted with median neutrophils recovery by D+13 and platelets by D+11. Importantly, no patients experienced any mucositis or therapy related diarrhoea. All maintained oral nutrition. Only two patients experienced a fever post-transplant, neither were life-threatening. Table 2 summarises the estimated absorbed radiation dose to critical organs and disease responses. Of the 9 patients treated with 90Y-besilesomaband ASCT 7 had haematologic responses with 2 complete responses (CR), 5 partial responses (PR), 1 stable disease (SD) and 1 progressive disease (PD) as determined. Six of 8 evaluable patients showed a reduction in percentage of malignant plasma cells in the BM. The study collected data up to D+100 post-transplant but 2 patients showed continuing slow reduction in clonal FLCa beyond D+100 with 1 achieving a CR 5 months post-transplant. No radiation dose limiting toxicity was seen. No consistent changes were seen in NT-proBNP. Importantly no cardiac AEs were recorded. All patients are alive. The long term follow up data will be presented. Acknowledgement: The native anti CD66 MAb (Besilesomab) was provided by Telix Pharmaceuticals. TLX66 (90Y-besilesomab) was acquired by Telix Pharmaceuticals in 2021. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

RADT-34. ANALYSIS OF A METHYLATION CLASS-GUIDED RADIOTHERAPY IN MENINGIOMA PATIENTS - AND THE PROSPECTIVE PHASE II MARCIE TRIAL WITH CARBON-ION BOOST RADIOTHERAPY

Abstract Meningiomas represent the most common primary brain tumor type, with a recurrence rate of approximately 20% following resection. Classification by molecular classes was demonstrated to be more accurate in identifying patients at high risk of disease progression in meningiomas, compared to WHO grading only. Novel radiotherapeutic modalities using protons or carbon ions provide an increased relative biological effectiveness (RBE) compared to photons, enabling a higher local dose deposition while reducing the radiation dose for organs of risks. The prospective single-arm phase II - MARCIE trial investigated a bimodal radiotherapy using photons (50 Gy in 25 fractions) and a carbon-ions boost with 18 Gy (RBE) in 6 fractions. Local progression-free survival after 3 years was defined as primary endpoint. In total, 33 patients were recruited before termination of the trial. After 3 years, local progression free survival was estimated at 94.7% and overall survival at 89.8%. Serious adverse events in the form of radiation necrosis were observed in 3 cases, requiring a subsequent treatment with bevacizumab. Post-hoc DNA methylation profiling revealed that relapses occur more frequently in high-risk meningiomas following radiotherapy, compared to the intermediate risk-group, confirming the prognostic relevance of the methylation-based meningioma classifier.Subsequently, a retrospective matched-pair analysis was performed to compare irradiated (n &amp;gt; 100) and non-irradiated meningiomas, stratified into the molecular risk groups (ben, int, high). The clinical benefit of postoperative radiotherapy and dose escalation with regard to the local control are currently being assessed for the respective molecular meningioma classes. Postoperative, bimodal radiotherapy with carbon-ion boost represent an auspicious treatment modality with an excellent local tumor control following resection. Molecular risk stratification is crucial in identifying patients who might benefit from postoperative radiotherapy.

Dosimetric assessment and secondary cancer risk in breast radiotherapy: a Monte Carlo approach

To calculate the risk of secondary cancer induction resulting from this dose through a Monte Carlo simulation code and voxel-based anthropomorphic phantom to determine the radiation dose in organs and/or tissues with dosimetric importance and the effect of using static MLC in the 3D-CRT technique. In this work, a radiotherapy treatment of breast cancer was simulated using the radiation transport code MCNPX 2.7.0 and the adult anthropomorphic simulator FSTA_H50_M50. The absorbed doses for a set of organs with dosimetric importance were determined. A LINAC Varian 2100C device operated with two techniques was simulated: 2D with open field (OF) and 3D-conformational (3D-CRT), the latter with the use of a multilayer collimator (MLC) of the breast, both acting with 6 MV energy. The highest values of absorbed dose were obtained for the ipsilateral lung (7.22 Gy (3D-CRT) and 8.49 Gy (OF)) and the contralateral breast (6.29 Gy (3D-CRT) and 6.56 Gy (OF)), generating for these organs the greatest risks of secondary cancer induction. With the OF technique, due to the non-collimation of the beam, there was an increase in the absorbed dose in all organs compared to 3D-CRT, thus evidencing a more effective treatment with the 3D-CRT technique, improving both homogeneity and conformity with the dose absorbed in the target organ.

Sol Meme Kanseri Radyoterapisi Simülasyonunda Pron pozisyon mu Supin pozisyon mu ?

Aim: The aim of this study was to compare radiation doses of target volumes and critical organs among prone and supine positions for left-sided breast cancer patients who were treated with breast-conserving surgery and adjuvant radiotherapy. &#x0D; Materials and Methods: The doses of critical organs and target volumes were evaluated by using dose-volume histograms on the new radiotherapy plans of twenty patients.&#x0D; Results: The mean heart dose was lower in the prone position (mean heart doses 656cGy and 933cGy respectively p = 0.01). Mean lung doses for prone and supine positions were 396 cGy and 1032 cGy (p =0.01); lung V5 13% and 33% (p =0.01); lung V10 8% and 25% (p =0.01); lung V20 5% and 17% (p =0.01). &#x0D; Conclusion: Considering that lower doses of normal structures may reduce side effects, prone position may be preferred in patients with left breast cancer.

Effect of Body Size Change on Off-Center Cervical Point and Face Doses in Patients Undergoing Nasopharyngeal Carcinoma Radiotherapy.

Nasopharyngeal carcinoma (NPC) is a clinically multiple malignant tumor. At present, with the increase in the infection rate of Epstein-Barr virus, the incidence of nasopharyngeal carcinoma is also increasing day by day. To explore the effect of body size change on off-center cervical point and face doses in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy, in total, 100 patients with NPC from January 2019 to May 2020 in our hospital were selected for retrospective analysis, and they all received intensity-modulated radiation therapy. Bodyweight, horizontal longitudinal diameter of the odontoid process, longitudinal diameter of the third cervical spine, maximum radiation dose, and average radiation dose of normal organs in the first and last treatments were assessed, and the correlation between normal organ irradiation dose and body size was analyzed. Bodyweight, horizontal longitudinal diameter of the odontoid process, and longitudinal diameter of the third cervical spine in the last treatment were lower than those in the first treatment, with a statistically significant difference. There was no statistically significant difference in the maximum normal organ irradiation dose to the left eyeball, right eyeball, left crystalline lens, right crystalline lens, and maximum irradiation dose to optic nerve between the last treatment and the first treatment. In the last treatment, the maximum dose to the left parotid gland, right parotid gland, spinal cord, and brain stem was higher than that in the first treatment. The average irradiation dose to the left eye bulb, right eye bulb, left lens, right lens, optic nerve in the last treatment, and that in the first treatment showed no significant difference. The average dose to the left parotid gland, right parotid gland, spinal cord, and brain stem in the last treatment was higher than that in the first treatment. The irradiation dose to the left parotid gland, right parotid gland, spinal cord, and brain stem was significantly negatively correlated with body weight, horizontal longitudinal diameter of the odontoid process, and longitudinal diameter of the third cervical spine. After NPC radiotherapy, the body size of patients can change, which can have different effects on irradiation doses. Therefore, the target area and dose should be corrected during treatment to ensure the efficacy and safety of the treatment.

Autologous Stem Cell Transplantation in AL-Amyloidosis Following Yttrium-90 Labelled Anti-CD66 Monoclonal Antibody As Sole Conditioning Is Associated with Low Toxicity and Demonstrable Disease Responses

▪Delayed diagnosis and lack of effective therapies results in the death of approximately 30% of patients with AL-amyloidosis (AL-A) within the first year of diagnosis. Autologous stem cell transplantation (ASCT) remains an important treatment option, resulting in improved organ function and survival in responders, however its utility is restricted due to the substantial toxicity of conventional ASCT conditioning in the vulnerable AL-A population. We report here the use of a monoclonal anti-CD66 monoclonal antibody (Besilesomab)radiolabelled with yttrium-90 (90Y-anti-CD66) as the sole conditioning agent prior to ASCT in a phase I study in AL-A patients. The study had full ethical and regulatory approvals (EudraCT 2015-002231-18; ISRCTN 13400668) and comprised 3 ascending radiation activity levels, 30, 40 and 45 MBq per kg body weight, each with 3 patients. Patients entered the study after fulfilling entry requirements and with informed consent. Prior to receiving 90Y-anti-CD66, organ dosimetry and biodistribution were determined using anti-CD66 labelled with indium-111 (111In-anti-CD66) with sequential gamma camera imaging. Estimated absorbed radiation to critical organs was determined from an established dosimetry model, organ radiation dose expressed in Gray (Gy). Radiation dose limits of 45Gy for the bone marrow, 15Gy for the liver were used as safety measures.Table 1 summarises patient characteristics, the majority of whom had received multiple lines of treatment including three who had previously undergone ASCT using high dose melphalan (HDM) conditioning. The primary end-point was treatment related toxicity as determined using CTCAE v4.0. Haematological toxicities (cytopenia) were excluded as adverse events (AEs) unless considered life-threatening. Secondary end-points were: clonal disease response determined by changes in serum free light chain assay (FLCa) and malignant plasma cell percentage in bone marrow (BM) as determined by multi-colour flow cytometry; cardiac toxicity using NT-proBNP measurements; overall survival and time to disease progression; biodistribution and dosimetry using SPECT-CT imaging; neutrophil and platelet engraftment (European Blood and Marrow Transplant criteria).Results: Ten patients were studied with 111In-anti-CD66, of whom 9 proceeded to 90Y-anti-CD66 conditioning with infused activity determined by study cohort and body weight; one patient failed dosimetry with excessive hepatic uptake and 2 received reduced activity to keep the BM dose within the 45Gy limit. In total 47 AEs were recorded the majority (41) grades 1-2 with no Serious Adverse Events (SAEs); 3 AEs recorded as grade 4; no transplant related deaths and all patients engrafted with median neutrophil recovery by D+13, platelets by D+11. Importantly no patients experienced mucositis or therapy related diarrhoea maintaining oral nutrition. All patients became profoundly cytopenic consistent with bone marrow suppression due to the targeted radiation. Only two patients experienced a fever post-transplant, neither life-threatening. Table 2 summarises the estimated absorbed radiation dose to critical organs and disease responses. Of the 9 patients treated with 90Y-anti-CD66 and ASCT, 2 had complete responses (CR) and 5 had partial responses (PR); 1 stable disease and 1 progressive disease determined by FLCa. Six of 8 evaluable patients showed a reduction in percentage of malignant plasma cells in the BM. The study collected data to D+100 post-transplant but 4 patients showed continuing reduction in clonal FLCa beyond D+100 with one achieving a near CR 9 months post-transplant. No dose limiting toxicity was seen. No cardiac AEs were recorded. All patients are alive with median follow-up of 32.8 months (15.3 - 58.4).Summary: We have demonstrated that 90Y-anti-CD66 therapy can be used safely as sole conditioning agent prior to ASCT in pre-treated AL patients, associated with low toxicity and promising disease response rates, including patients who previously had undergone ASCT using HDM. BM radiation doses of up to 45Gy were achieved using this targeted approach with acceptably low doses delivered to other critical organs. Further trials are required to determine the full potential of this agent in the context of stem cell transplantation for AL amyloidosis and other haematological diseases. This research was funded by the charity Blood Cancer UK. [Display omitted] DisclosuresOrchard: GSK: Current holder of individual stocks in a privately-held company; Pfizer: Speakers Bureau. Cook: BMS: Current Employment, Honoraria; Celegene: Honoraria, Other: Travel support, Research Funding; Jansen: Honoraria; Takeda: Honoraria, Other: Travel support. Jackson: amgen: Consultancy, Honoraria, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; J and J: Consultancy, Honoraria, Speakers Bureau; oncopeptides: Consultancy; Sanofi: Honoraria, Speakers Bureau.

A Phase III Prospective Randomized Controlled Clinical Trial for the Efficacy and Safety of Neoadjuvant Chemotherapy Combined With Concurrent Chemoradiotherapy and Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer (Lump ≥4 cm)

The standard treatment for locally advanced cervical cancer was concurrent chemoradiotherapy. The effect of concurrent chemoradiotherapy was poor in locally advanced cervical cancer (lump ≥4 cm) (LACC) (lump ≥4 cm). We conduct this research in order to explore the role of neoadjuvant chemotherapy combined with concurrent radiotherapy in LACC (lump ≥4 cm).A phase III, prospective, randomized controlled clinical trial was conducted at Guizhou Cancer Hospital. LACC (lump ≥4 cm) (FIGO 2018) were randomly divided into two groups, neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (NACT+CCRT) group and concurrent chemoradiotherapy (CCRT) group. In NACT+CCRT group, patients were treated with paclitaxel cisplatin (TP) for 2 cycles, then they received concurrent chemoradiotherapy with TP for 2 cycles. In CCRT group, the patients were treated concurrent chemoradiotherapy with TP for 2 cycles. Tumor volume shrinkage, response rate and toxicity were the primary endpoints. Progression-free survival (PFS) and overall survival (OS) were the second endpoints.Between March 2019 and December 2020, 97 patients randomly assigned (52 patients in the NACT+CCRT group and 45 patients in the CCRT group). In the NACT+CCRT group, after NACT, of evaluable 52, 52 responded: complete response (CR) 1(1.92%) and partial response (PR) 24(46.15%), stable disease (SD) 27(51.92%) and progressive disease (PD) 0(0%). 52 patients have completed CCRT, after NACT+CCRT, of evaluable 52, 52 responded: CR17(32.69%) and PR 35(67.31%), SD 0 and PD 0. In the CCRT group, 5 patients have not completed CCRT (because of the large tumor and concurrent radiotherapy not be tolerated), of evaluable 40, 40 responded: CR 8(20.00%) and PR 32(80.00%), SD 0 and PD 0. The immediate CR rate was better in NACT+CCRT than in the CCRT (P = 0.001). Treatment completion status: in the NACT+CRT group, all the patients (100%) have completed the NACT+CCRT, there were 40 (88.89%) patients have completed treatment (P = 0.013). In the tumor shrinkage, the median tumor volume after NACT was 33.91cm3 and 79.74cm3 in the CCRT group. There was significant difference between two groups (P = 0.000). Adverse event Hematological and gastrointestinal toxicity were most common. The Acute toxicities were hematological toxicity, gastrointestinal toxicity, there was no significant difference between two groups in the NACT+CCRT group versus the CCRT group (P>0.05).NACT can minify the tumor volume of LACC (lump≥4cm) before CCRT and reduce the radiation dose of normal organs around the target area, thereby improved the completion rate of concurrent radiotherapy treatment. After NACT+CRT, the immediate response rate was improved significantly, especially the CR. However, there were more significant adverse events during NACT+CRT but it was well tolerated by patients. The high efficiency can be transformed into the advantage of prolonging survival or not, longer follow up and further research is needed.F. Li: None. J. Li: None. S. Yin: None. F. Mei: None. Y. Du: None. L. Hu: None. X. Tian: None. W. Hong: None. L. Shan: None. M. Liu: None. Y. Chen: None. W. Mao: None. J. Mu: None. B. Lu: None.

Organs dosimetry in targeted radionuclide therapy

The objective of this study is to assess the patients' effective and organ dose during theranostic applications in Kuwait. In total, eighteen adults' patients were conducted nuclear medicine procedures with 177Lu Dotatate for theranostic purpose in Kuwait Cancer control center (KCCC), Kuwait. Medium energy collimator (MEC) (208 keV Scatter 26% better than 113 keV Scatter 60%) was utilized to obtain scans in definite time intervals ranged from one to 2 h (before voiding), 6:00, 24:00, 48:00, 72:00 h. Patients, tissue and organ radiation doses were computed utilizing OLINDA/EXM Software. The average radiation effective dose (in mSv/MBq) for bladder, liver, and both kidneys (left & right), were 0.36, 0.08, 0.61 & 0.60. The range of the effective dose was from 0.55 mSv to 7.7 mSv. The acquired scans using 177Lu were delivered diagnostic findings. The patients’ effective dose is lower compared to the previous studies. Variation is attributed to the departmental protocol and administered activity. The values of the mean organ dose were comparable and lower than previously published studies. Different organs have different level of doses, which may affected by the presence of the metastatic tumors in the entire organ.

Assessment of hysterosalpingography radiation doses in Taif city, Saudi Arabia

The main purpose of this study was to determine the entrance surface air kerma (ESAK), effective dose (E), and organ radiation dose to patients during hysterosalpingography performed in three major hospitals in Taif city, KSA [King Abdul Aziz Hospital (A), King Faisal Hospital (B), and a private hospital (C)]. The study involved 100 female patients (22–44 years of age) for approximately 6 months. Dosecalc software was used to determine the ESAKs. This software needs to record the exposure factors and X-ray tube output (OP), as well as the backscatter factor (BSF). The mean ESAK was 21.7 mGy for all hospitals and 20, 28, and 17 mGy for hospitals A, B, and C, respectively. There were wide ranges in the ESAKs among the hospitals in the current and previous studies. The mean organ radiation dose estimated for the urinary bladder, gonads, bone marrow, and colon was 0.87, 1.7, 2.6, and 1.7 mSv, respectively. The average ESAK results for all patients was higher than most previous studies. Due to the exposure factors, filtration, and skill of the operator, the dose values varied. Additionally, organs (e.g., ovaries and bone marrow) reported high doses, which increased the probability of cancer and hereditary effects, and necessitate radiation dose optimization. The results indicated the need to standardize the technology and introduce the diagnostic reference level throughout hospitals.