Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.

PURPOSE: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials. METHODS: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT. RESULTS: We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry. DISCUSSION: There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects. CONCLUSIONS: The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Plan robustness analysis for threshold determination of SGRT-based intrafraction motion control in 3DCRT breast cancer radiation therapy.

PURPOSE: The goal of this study was to obtain maximum allowed shift deviations from planning position in six degrees of freedom (DOF), that can serve as threshold values in surface guided radiation therapy (SGRT) of breast cancer patients. METHODS: The robustness of conformal treatment plans of 50 breast cancer patients against 6DOF shifts was investigated. For that, new dose distributions were calculated on shifted computed tomography scans and evaluated with respect to target volume and spinal cord dose. Maximum allowed shift values were identified by imposing dose constraints on the target volume dose coverage for 1DOF, and consecutively, for 6DOF shifts using an iterative approach and random sampling. RESULTS: Substantial decreases in target dose coverage and increases of spinal cord dose were observed. Treatment plans showed highly differing robustness for different DOFs or treated area. The sensitivity was particularly high if clavicular lymph nodes were irradiated, for shifts in lateral, vertical, roll or yaw direction, and showed partly pronounced asymmetries. Threshold values showed similar properties with an absolute value range of 0.8 mm to 5 mm and 1.4° to 5°. CONCLUSION: The robustness analysis emphasized the necessity of taking differences between DOFs and asymmetrical sensitivities into account when evaluating the dosimetric impact of position deviations. It also highlighted the importance of rotational shifts, especially if clavicular lymph nodes were irradiated. A practical approach of determining 6DOF shift limits was introduced and a set of threshold values applicable for SGRT based patient motion control was identified.

Development and clinical implementation of a digital system for risk assessments for radiation therapy.

Before introducing new treatment techniques, an investigation of hazards due to unintentional radiation exposures is a reasonable activity for proactively increasing patient safety. As dedicated software is scarce, we developed a tool for risk assessment to design a quality management program based on best practice methods, i.e., process mapping, failure modes and effects analysis and fault tree analysis. Implemented as a web database application, a single dataset was used to describe the treatment process and its failure modes. The design of the system and dataset allowed failure modes to be represented both visually as fault trees and in a tabular form. Following the commissioning of the software for our department, previously conducted risk assessments were migrated to the new system after being fully re-assessed which revealed a shift in risk priorities. Furthermore, a weighting factor was investigated to bring risk levels of the migrated assessments into perspective. The compensation did not affect high priorities but did re-prioritize in the midrange of the ranking. We conclude that the tool is suitable to conduct multiple risk assessments and concomitantly keep track of the overall quality management activities.

Hyperthermia in the treatment of high-risk soft tissue sarcomas: a systematic review.

BACKGROUND: The therapy of high-risk soft tissue sarcomas (STS) remains an interdisciplinary challenge. Regional hyperthermia (RHT) sparked interest as it has been shown to improve overall survival when added to perioperative chemotherapy (CTX). However, questions arise on how RHT should be optimally integrated into current multi-modal therapies. MATERIALS AND METHODS: We performed a systematic literature review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies written in English and focused mainly on radiative RHT and superficial hyperthermia were evaluated and included. Studies including patients below the age of 18, with metastatic disease or review articles, were excluded. RESULTS: We identified 15 clinical reports from 1990 until July 2022. Three articles combined RHT + CTX, and twelve focused on combined RHT + radiotherapy (RT) or neoadjuvant chemoradiotherapy (CRT). Most treatments were based on invasive thermometry, and less on magnetic resonance imaging (MRI)-based, noninvasive thermometry for STS of the extremities. Perioperative chemotherapy was used for the combination of RHT and CTX, mostly Ifosfamide-based. The effectiveness of RT appeared to be increased by RHT, especially with two RHT sessions/week. The trimodal simultaneous approach of neoadjuvant RHT and CRT was also feasible. No significant toxicity of RHT was reported. CONCLUSIONS: The gathered data strengthen the beneficial role of RHT in the multimodal setting. Further expert consensus and clinical trials are required to determine the optimal integration of RHT in treating STS.

External-Beam-Accelerated Partial-Breast Irradiation Reduces Organ-at-Risk Doses Compared to Whole-Breast Irradiation after Breast-Conserving Surgery.

In order to evaluate organ-at-risk (OAR) doses in external-beam-accelerated partial-breast irradiation (APBI) compared to standard whole-breast irradiation (WBI) after breast-conserving surgery. Between 2011 and 2021, 170 patients with early breast cancer received APBI within a prospective institutional single-arm trial. The prescribed dose to the planning treatment volume was 38 Gy in 10 fractions on 10 consecutive working days. OAR doses for the contralateral breast, the ipsilateral, contralateral, and whole lung, the whole heart, left ventricle (LV), and the left anterior descending coronary artery (LAD), and for the spinal cord and the skin were assessed and compared to a control group with real-world data from 116 patients who underwent WBI. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Compared to WBI, APBI led to reduced OAR doses for the contralateral breast (0.4 ± 0.6 vs. 0.8 ± 0.9 Gy, p = 0.000), the ipsilateral (4.3 ± 1.4 vs. 9.2 ± 2.5 Gy, p = 0.000) and whole mean lung dose (2.5 ± 0.8 vs. 4.9 ± 1.5 Gy, p = 0.000), the mean heart dose (1.6 ± 1.6 vs. 1.7 ± 1.4 Gy, p = 0.007), the LV V23 (0.1 ± 0.4 vs. 1.4 ± 2.6%, p < 0.001), the mean LAD dose (2.5 ± 3.4 vs. 4.8 ± 5.5 Gy, p < 0.001), the maximum spinal cord dose (1.5 ± 1.1 vs. 4.5 ± 5.7 Gy, p = 0.016), and the maximum skin dose (39.6 ± 1.8 vs. 49.1 ± 5.8 Gy, p = 0.000). APBI should be recommended to suitable patients to minimize the risk of secondary tumor induction and the incidence of consecutive major cardiac events.

Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial.

BACKGROUND: Several randomised, phase 3 trials have investigated the value of different techniques of accelerated partial breast irradiation (APBI) for patients with early breast cancer after breast-conserving surgery compared with whole-breast irradiation. In a phase 3 randomised trial, we evaluated whether APBI using multicatheter brachytherapy is non-inferior compared with whole-breast irradiation. Here, we present the 10-year follow-up results. METHODS: We did a randomised, phase 3, non-inferiority trial at 16 hospitals and medical centres in Austria, Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland. Patients aged 40 years or older with early invasive breast cancer or ductal carcinoma in situ treated with breast-conserving surgery were centrally randomly assigned (1:1) to receive either whole-breast irradiation or APBI using multicatheter brachytherapy. Whole-breast irradiation was delivered in 25 daily fractions of 50 Gy over 5 weeks, with a supplemental boost of 10 Gy to the tumour bed, and APBI was delivered as 30·1 Gy (seven fractions) and 32·0 Gy (eight fractions) of high-dose-rate brachytherapy in 5 days or as 50 Gy of pulsed-dose-rate brachytherapy over 5 treatment days. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was ipsilateral local recurrence, analysed in the as-treated population; the non-inferiority margin for the recurrence rate difference (defined for 5-year results) was 3 percentage points. The trial is registered with ClinicalTrials.gov, NCT00402519; the trial is complete. FINDINGS: Between April 20, 2004, and July 30, 2009, 1328 female patients were randomly assigned to whole breast irradiation (n=673) or APBI (n=655), of whom 551 in the whole-breast irradiation group and 633 in the APBI group were eligible for analysis. At a median follow-up of 10·36 years (IQR 9·12-11·28), the 10-year local recurrence rates were 1·58% (95% CI 0·37 to 2·8) in the whole-breast irradiation group and 3·51% (1·99 to 5·03) in the APBI group. The difference in 10-year rates between the groups was 1·93% (95% CI -0·018 to 3·87; p=0·074). Adverse events were mostly grade 1 and 2, in 234 (60%) of 393 participants in the whole-breast irradiation group and 314 (67%) of 470 participants in the APBI group, at 7·5-year or 10-year follow-up, or both. Patients in the APBI group had a significantly lower incidence of treatment-related grade 3 late side-effects than those in the whole-breast irradiation group (17 [4%] of 393 for whole-breast irradiation vs seven [1%] of 470 for APBI; p=0·021; at 7·5-year or 10-year follow-up, or both). At 10 years, the most common type of grade 3 adverse event in both treatment groups was fibrosis (six [2%] of 313 patients for whole-breast irradiation and three [1%] of 375 patients for APBI, p=0·56). No grade 4 adverse events or treatment-related deaths have been observed. INTERPRETATION: Postoperative APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is a valuable alternative to whole-breast irradiation in terms of treatment efficacy and is associated with fewer late side-effects. FUNDING: German Cancer Aid, Germany.

Low-dose radiotherapy of osteoarthritis: from biological findings to clinical effects-challenges for future studies.

Osteoarthritis (OA) is one of the most common and socioeconomically relevant diseases, with rising incidence and prevalence especially with regard to an ageing population in the Western world. Over the decades, the scientific perception of OA has shifted from a simple degeneration of cartilage and bone to a multifactorial disease involving various cell types and immunomodulatory factors. Despite a wide range of conventional treatment modalities available, a significant proportion of patients remain treatment refractory. Low-dose radiotherapy (LDRT) has been used for decades in the treatment of patients with inflammatory and/or degenerative diseases and has proven a viable option even in cohorts of patients with a rather poor prognosis. While its justification mainly derives from a vast body of empirical evidence, prospective randomized trials have until now failed to prove the effectiveness of LDRT. Nevertheless, over the decades, adaptions of LDRT treatment modalities have evolved using lower dosages with establishment of different treatment schedules for which definitive clinical proof is still pending. Preclinical research has revealed that the immune system is modulated by LDRT and very recently osteoimmunological mechanisms have been described. Future studies and investigations further elucidating the underlying mechanisms are an essential key to clarify the optimal patient stratification and treatment procedure, considering the patients' inflammatory status, age, and sex. The present review aims not only to present clinical and preclinical knowledge about the mechanistic and beneficial effects of LDRT, but also to emphasize topics that will need to be addressed in future studies. Further, a concise overview of the current status of the underlying radiobiological knowledge of LDRT for clinicians is given, while seeking to stimulate further translational research.

The Emerging Evidence Supporting Integration of Deep Regional Hyperthermia With Chemoradiation in Bladder Cancer.

For decades, the antineoplastic potential of hyperthermia alone or in combination with radiotherapy and/or chemotherapy has been subject of intensive preclinical and clinical research in various tumor entities. The clinical evidence on the beneficial effects of additional hyperthermia in combination with intravesical Mitomycin C for superficial non-muscle-invasive bladder cancer as well as for deep regional microwave hyperthermia techniques applied during an external beam radiotherapy or chemoradiation treatment for more advanced tumors are summarized. In some series, deep regional hyperthermia in combination with an initial transurethral resection and Cisplatin-based chemoradiation increased the 5-year overall survival rates up to 20%. The presented data justifies a fresh irrespective chance for mild regional hyperthermia in the context of new progressive prospective trials on multimodality treatment for bladder preservation.

Prerequisites for the clinical implementation of a markerless SGRT-only workflow for the treatment of breast cancer patients.

PURPOSE: A markerless workflow for the treatment of breast cancer patients has been introduced and evaluated retrospectively. It includes surface-guided radiation therapy (SGRT)-only positioning for patients with small cone beam CT (CBCT) position corrections during the first five fractions. Prerequisites and the frequency of its clinical application were evaluated, as well as potential benefits in terms of treatment time and dose savings, the frequency of CBCT scans, and the accuracy of the positioning. METHODS: A group of 100 patients treated with the new workflow on two Versa HD linacs has been compared to a matched control group of patients treated with the former workflow, which included prepositioning with skin markings and lasers, SGRT and daily CBCT. The comparison was based on the evaluation of logfiles. RESULTS: Of the patients treated with the new workflow, 40% did not receive daily CBCT scans. This resulted in mean time savings of 97 s, 166 s and 239 s per fraction for the new workflow, for patients treated without daily CBCT and for SGRT-only fractions, respectively, when compared to the old workflow. Dose savings amounted to a weighted computed tomography dose index reduction of CTDIW = 2.56 cGy on average for normofractionated treatment and weekly CBCTs, while for patients not treated with daily CBCT, SGRT-based positioning accuracy was 5.2 mm for the mean translational magnitude, as evaluated by CBCT. CONCLUSION: For 40% of the patients, after five fractions with small CBCT corrections, the workflow could be changed to SGRT-only positioning with weekly CBCT. This leads to imaging dose and time savings and thus also reduced intrafraction motion, potentially increased patient throughput and patient comfort, while assuring appropriate positioning accuracy.

A patterns of care analysis of hyperthermia in combination with radio(chemo)therapy or chemotherapy in European clinical centers.

PURPOSE: The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. METHODS: A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. RESULTS: The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3-100%) of patients are treated in clinical study protocols. Temperature readings and the time interval between HT and radio(chemo)therapy or CT are recorded in 13 (81%) and 9 (56%) centers, respectively. The thermal dose quality parameter "cumulative equivalent minutes at 43 °C" (CEM43°C) is only evaluated in five (31%) centers for each HT session. With regard to treatment sequence, 8 (50%) centers administer HT before radio(chemo)therapy and the other 8 in the reverse order. CONCLUSION: There is a significant heterogeneity among European HT centers as to the indications treated and the recording of thermometric parameters. More evidence from clinical studies is necessary to achieve standardization of HT practice.

External Beam Accelerated Partial Breast Irradiation in Early Breast Cancer and the Risk for Radiogenic Pneumonitis.

In order to evaluate the risk for radiation-associated symptomatic pneumonitis in a prospective external beam accelerated partial breast irradiation (APBI) trial, between 2011 and 2021, 170 patients with early stage breast cancer were enclosed in the trial. Patients were eligible for study participation if they had a histologically confirmed breast cancer or an exclusive ductal carcinoma in situ (DCIS), a tumor size ≤3 cm, free safety margins ≥2 mm, no involved axillary lymph nodes, tumor bed clips, and were ≥50 years old. Patients received APBI with 38 Gy with 10 fractions in 10 consecutive working days. The trial was registered at the German Clinical Trials Registry, DRKS-ID: DRKS00004417. Median follow-up was 56 (1−129) months. Ipsilateral lung MLD, V20, and V30 were 4.3 ± 1.4 Gy, 3.0 ± 2.0%, and 1.0 ± 1.0%, respectively. Radiogenic pneumonitis grade 2 appeared in 1/170 (0.6%) patients two months after radiotherapy. Ipsilateral MLD, V20, and V30 were 6.1 Gy, 7, and 3% in this patient. Additionally, individual radiosensitivity was increased in this specific patient. Compared to WBI, APBI leads to lower lung doses. Using APBI, the risk of symptomatic radiogenic pneumonitis is very low and may be limited, with an ipsilateral V20 < 3% to very exceptional cases associated with innate risk factors with an increased radiation susceptibility.

The Effect of Hyperthermia and Radiotherapy Sequence on Cancer Cell Death and the Immune Phenotype of Breast Cancer Cells.

Hyperthermia (HT) is an accepted treatment for recurrent breast cancer which locally heats the tumor to 39-44 °C, and it is a very potent sensitizer for radiotherapy (RT) and chemotherapy. However, currently little is known about how HT with a distinct temperature, and particularly, how the sequence of HT and RT changes the immune phenotype of breast cancer cells. Therefore, human MDA-MB-231 and MCF-7 breast cancer cells were treated with HT of different temperatures (39, 41 and 44 °C), alone and in combination with RT (2 × 5 Gy) in different sequences, with either RT or HT first, followed by the other. Tumor cell death forms and the expression of immune checkpoint molecules (ICMs) were analyzed by multicolor flow cytometry. Human monocyte-derived dendritic cells (moDCs) were differentiated and co-cultured with the treated cancer cells. In both cell lines, RT was the main stressor for cell death induction, with apoptosis being the prominent cell death form in MCF-7 cells and both apoptosis and necrosis in MDA-MB-231 cells. Here, the sequence of the combined treatments, either RT or HT, did not have a significant impact on the final outcome. The expression of all of the three examined immune suppressive ICMs, namely PD-L1, PD-L2 and HVEM, was significantly increased on MCF-7 cells 120 h after the treatment of RT with HT of any temperature. Of special interest for MDA-MB-231 cells is that only combinations of RT with HT of both 41 and 44 °C induced a significantly increased expression of PD-L2 at all examined time points (24, 48, 72, and 120 h). Generally, high dynamics of ICM expression can be observed after combined RT and HT treatments. There was no significant difference between the different sequences of treatments (either HT + RT or RT + HT) in case of the upregulation of ICMs. Furthermore, the co-culture of moDCs with tumor cells of any treatment had no impact on the expression of activation markers. We conclude that the sequence of HT and RT does not strongly affect the immune phenotype of breast cancer cells. However, when HT is combined with RT, it results in an increased expression of distinct immune suppressive ICMs that should be considered by including immune checkpoint inhibitors in multimodal tumor treatments with RT and HT. Further, combined RT and HT affects the immune system in the effector phase rather than in the priming phase.

Clinical Evidence for Thermometric Parameters to Guide Hyperthermia Treatment.

Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40-43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parameters when chosen optimally are associated with increased antitumor efficacy. This review summarizes the existing clinical evidence for the prognostic and predictive role of the most important thermometric parameters to guide the combined treatment of RT and CT with HT. In conclusion, we call for the standardization of thermometric parameters and stress the importance for their validation in future prospective clinical studies.

Corrigendum: Low Dose Radiation Therapy Induces Long-Lasting Reduction of Pain and Immune Modulations in the Peripheral Blood - Interim Analysis of the IMMO-LDRT01 Trial.

[This corrects the article DOI: 10.3389/fimmu.2021.740742.].

Risk analysis for radiotherapy at the Universitätsklinikum Erlangen.

PURPOSE: Risk analysis is required by various laws and regulations in Germany and has an impact on each department of a large clinic. We provide an overview of the relevant laws and regulations in Germany and present the technical and organizational experience of introducing risk analysis in the Department of Radiation Oncology at the Universitätsklinikum Erlangen. METHODS: Risk analysis was performed with an in-house developed extension of our intranet platform and ticketing system. Risks were classified according to occurrence and severity, each on a 5-level scale resulting into a risk matrix. An interdisciplinary team of six experienced members formed the core meeting weekly. RESULTS: A total of 38 risks and 50 measures have been identified in 41 1h-meetings corresponding to approx. 260 working hours. Risk was distributed 8/20/13 to the categories critical (n=8), monitoring (n=20), and conditionally acceptable (n=13). Risk analysis has been evaluated before and after introducing measures. CONCLUSION: The risk analysis method introduced has been successfully used in routine operations for over a year. Risk analysis takes time and effort. However, because experts from different disciplines meet each other every week, the overall workflow of the radiation oncology department can be improved efficiently and continuously.

Cell-In-Cell Structures in Early Breast Cancer Are Prognostically Valuable.

Cell-in-cell (CIC) structures in breast cancer have so far been studied in a small inhomogeneous patient population, suggesting the prognostic importance of CIC. In the present study, we focused on CIC in early hormone-sensitive breast cancer. With in vitro co-culture experiments, we compared the homotypic phagocytic capacity of two breast cancer cell lines to that of primary human fibroblasts. Afterward, we studied 601 tissue specimens from 147 patients participating in an institutional accelerated partial breast irradiation (APBI) phase II trial. Both breast cancer cell lines performed non-professional phagocytosis at a higher rate than primary human fibroblasts. In this study cohort, 93.2% of the patients had T1 tumours, and 6.8% had T2 tumours. CIC was found in 61.2% of the patients, with a CIC rate ranging from <1/mm2 to 556.5/mm2 with a mean of 30.9/mm2 ± 68.4/mm2. CIC structures were prognostically favourable for local recurrence-free survival and disease-free survival. Regarding metastasis-free survival, CIC-positive patients had an unfavourable prognosis. Subgroup analysis indicated a correlation between a high proliferation index and high CIC rates. CIC had the highest prognostic value in young breast cancer patients (p = 0.004). With this study, we provide further evidence of CIC as a prognostic marker in breast cancer.

First clinical evaluation of breathing controlled four-dimensional computed tomography imaging.

BACKGROUND AND PURPOSE: Four-dimensional computed tomography (4DCT) has become an essential part of radiotherapy planning but is often affected by artifacts. A new breathing controlled 4DCT (i4DCT) algorithm has been introduced. This study aims to present the first clinical data and to evaluate the achieved image quality, projection data coverage and beam-on time. MATERIAL & METHODS: The analysis included i4DCT data for 129 scans of patients with thoracic tumors. Projection data coverage and beam-on time were evaluated. Additionally, image quality was exemplarily discussed and rated by ten clinical experts with a 5-score-scale for 30 patients with large variations in their breathing pattern ('challenging subgroup'). Rated images were reconstructed amplitude- and phase-based. RESULTS: Expert scoring revealed that 78% (amplitude-based) and 63% (phase-based) of the challenging subgroup were artifact-free (rating ≥4). For the entire cohort, average beam-on time per couch position was 4.9 ± 1.6 s. For the challenging subgroup, time increased slightly but not significantly compared to the remaining patients (5.1 s vs. 4.9 s; p = 0.64). Median projection data coverage was 93% and 94% for inhalation and exhalation, respectively, for the entire cohort. The comparison for the subgroup and the remaining patients revealed a small but significant decrease of the median coverage values for the challenging cases (inhalation: 90% vs. 94%, p = 0.02; exhalation: 93% vs. 94%, p = 0.02). CONCLUSIONS: This first clinical evaluation of i4DCT shows very promising results in terms of image quality and projection data coverage. The results agree with and support the results of previous i4DCT phantom studies.

Low Dose Radiation Therapy Induces Long-Lasting Reduction of Pain and Immune Modulations in the Peripheral Blood - Interim Analysis of the IMMO-LDRT01 Trial.

The treatment of chronic inflammatory and degenerative diseases by low dose radiation therapy (LDRT) is promising especially for patients who were refractory for classical therapies. LDRT aims to reduce pain of patients and to increase their mobility. Although LDRT has been applied since the late 19th century, the immunological mechanisms remain elusive. Within the prospective IMMO-LDRT01 trial (NCT02653079) the effects of LDRT on the peripheral blood immune status, as well as on pain and life quality of patients have been analyzed. Blood is taken before and after every serial irradiation with a single dose per fraction of 0.5Gy, as well as during follow-up appointments in order to determine a detailed longitudinal immune status by multicolor flow cytometry. Here, we report the results of an interim analysis of 125 patients, representing half the number of patients to be recruited. LDRT significantly improved patients' pain levels and induced distinct systemic immune modulations. While the total number of leukocytes remained unchanged in the peripheral blood, LDRT induced a slight reduction of eosinophils, basophils and plasmacytoid dendritic cells and an increase of B cells. Furthermore, activated immune cells were decreased following LDRT. Especially cells of the monocytic lineage correlated to LDRT-induced improvements of clinical symptoms, qualifying these immune cells as predictive biomarkers for the therapeutic success. We conclude that LDRT improves pain of the patients by inducing systemic immune modulations and that immune biomarkers could be defined for prediction by improved patient stratification in the future.

Region of interest optimization for radiation therapy of breast cancer.

PURPOSE: The goal of this study was to investigate how the choice of the region of interest (ROI) affects the registration results of surface imaging for daily positioning of breast cancer patients. METHODS: The AlignRT system (VisionRT, London) and the XVI Cone beam CT (CBCT; Elekta, Stockholm) installed on two Versa HD linacs (Elekta) were used in this study, which included 28 patients (160 fractions). In the clinical workflow, patients were prepositioned with AlignRT and then shifted in 6 degrees of freedom (DOF) according to the CBCT. A new reference capture was taken immediately afterward. Retrospectively, the surface capture resulting from prepositioning was registered to the latest reference capture. By varying the ROI used for registration, the surface-based results were optimized in terms of minimizing the deviation to the clinically applied CBCT shifts. Two sets of ROIs were used: one obtained by applying a variable margin to the breast surface, another by combining ROIs of anatomical structures, including the sternum and contralateral breast. RESULTS: Registration results showed significant differences from one ROI to another. Generally, the results improved with increasing ROI size, especially for rotational DOFs. ROIs, including the axilla or supraclavicular lymph drainage region, did not yield an improved registration result. On the other hand, an ROI comprising the breast surface, sternum, and a belt caudal to the breasts decreased the average magnitude of the translational and rotational deviations by 6.6% and 30.8% (p < 0.01), respectively, compared to the breast surface only results. CONCLUSION: The influence of the ROI choice on surface imaging registration results was analyzed and the surface-based shifts were compared to clinically applied CBCT shifts. An optimal ROI for the treatment of breast cancer patients, consisting of the breast surface, sternum, and a belt, was identified.