Stereoscopic X-ray image and thermo-optical surface guidance for breast cancer radiotherapy in deep inspiration breath-hold.

PURPOSE: To investigate the feasibility of a thermo-optical surface imaging (SGRT) system combined with room-based stereoscopic X­ray image guidance (IGRT) in a dedicated breast deep inspiration breath-hold (DIBH) irradiation workflow. In this context, benchmarking of portal imaging (EPID) and cone-beam CT (CBCT) against stereoscopic X­rays was performed. METHODS: SGRT + IGRT data of 30 left-sided DIBH breast patients (1 patient with bilateral cancer) treated in 351 fractions using thermo-optical surface imaging and X-ray IGRT were retrospectively analysed. Patients were prepositioned based on a free-breathing surface reference derived from a CT scan. Once the DIBH was reached using visual feedback, two stereoscopic X­ray images were acquired and registered to the digitally reconstructed radiographs derived from the DIBH CT. Based on this registration, a couch correction was performed. Positioning and monitoring by surface and X-ray imaging were verified by protocol-based EPID or CBCT imaging at selected fractions and the calculation of residual geometric deviations. RESULTS: The median X­ray-derived couch correction vector was 4.9 (interquartile range [IQR] 3.3-7.1) mm long. Verification imaging was performed for 134 fractions (216 RT field verifications) with EPID and for 37 fractions with CBCT, respectively. The median 2D/3D deviation vector length over all verification images was 2.5 (IQR 1.6-3.9) mm/3.4 (IQR 2.2-4.8) mm for EPID/CBCT, both being well within the planning target volume (PTV) margins (7 mm). A moderate correlation (0.49-0.65) was observed between the surface signal and X-ray position in DIBH. CONCLUSION: DIBH treatments using thermo-optical SGRT and X-ray IGRT were feasible for breast cancer patients. Stereoscopic X­ray positioning was successfully verified by standard IGRT techniques.

Radiotherapy in localized prostate cancer: a multicenter analysis evaluating tumor control and late toxicity after brachytherapy and external beam radiotherapy in 1293 patients.

BACKGROUND AND PURPOSE: Comparing oncological outcomes and toxicity after primary treatment of localized prostate cancer using HDR- or LDR-mono-brachytherapy (BT), or conventionally (CF) or moderately hypofractionated (HF) external beam radiotherapy. MATERIALS AND METHODS: Retrospectively, patients with low- (LR) or favorable intermediate-risk (IR) prostate cancer treated between 03/2000 and 09/2022 in two centers were included. Treatment was performed using either CF with total doses between 74 and 78 Gy, HF with 2.4-2.6 Gy per fraction in 30 fractions, or LDR- or HDR-BT. Biochemical control (BC) according to the Phoenix criteria, and late gastrointestinal (GI), and genitourinary (GU) toxicity according to RTOG/EORTC criteria were assessed. RESULTS: We identified 1293 patients, 697 with LR and 596 with IR prostate cancer. Of these, 470, 182, 480, and 161 were treated with CF, HF, LDR-BT, and HDR-BT, respectively. For BC, we did not find a significant difference between treatments in LR and IR (p = 0.31 and 0.72). The 5­year BC for LR was between 93 and 95% for all treatment types. For IR, BC was between 88% in the CF and 94% in the HF group. For CF and HF, maximum GI and GU toxicity grade ≥ 2 was between 22 and 27%. For LDR-BT, we observed 67% grade ≥ 2 GU toxicity. Maximum GI grade ≥ 2 toxicity was 9%. For HDR-BT, we observed 1% GI grade ≥ 2 toxicity and 19% GU grade ≥ 2 toxicity. CONCLUSION: All types of therapy were effective and well received. HDR-BT caused the least late toxicities, especially GI.

Biochemical control in intermediate- and high-risk prostate cancer after EBRT with and without brachytherapy boost.

PURPOSE: External beam radiotherapy (EBRT) with or without brachytherapy boost (BTB) has not been compared in prospective studies using guideline-recommended radiation dose and recommended androgen-deprivation therapy (ADT). In this multicenter retrospective analysis, we compared modern-day EBRT with BTB in terms of biochemical control (BC) for intermediate-risk (IR) and high-risk (HR) prostate cancer. METHODS: Patients were treated for primary IR or HR prostate cancer during 1999-2019 at three high-volume centers. Inclusion criteria were prescribed ≥ 76 Gy EQD2 (α/ß = 1.5 Gy) for IR and ≥ 78 Gy EQD2 (α/ß = 1.5 Gy) for HR as EBRT alone or with BTB. All HR patients received ADT and pelvic irradiation, which were optional in IR cases. BC between therapies was compared in survival analyses. RESULTS: Of 2769 initial patients, 1176 met inclusion criteria: 468 HR (260 EBRT, 208 BTB) and 708 IR (539 EBRT, 169 BTB). Median follow-up was 49 and 51 months for HR and IR, respectively. BTB patients with ≥ 113 Gy EQD2Gy experienced a stable, good BC outcome compared with BTB at lower doses. Patients treated with ≥ 113 Gy EQD2Gy also experienced significantly improved BC compared with EBRT (10-year BC failure rates after ≥ 113 Gy BTB and EBRT: respectively 20.4 and 41.8% for HR and 7.5 and 20.8% for IR). CONCLUSIONS: In patients with IR and HR prostate cancer, BTB with ≥ 113 Gy EQD2Gy offered a BC advantage compared with dose-escalated EBRT and lower BTB doses.

Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: systematic review and consensus recommendations by the EORTC-ESTRO OligoCare consortium.

Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.

Comparative effectiveness of moderate hypofractionation with volumetric modulated arc therapy versus conventional 3D-radiotherapy after radical prostatectomy.

PURPOSE: Hypofractionated radiotherapy for prostate cancer is well established for definitive treatment, but not well defined in the postoperative setting. The purpose of this analysis was to assess oncologic outcomes and toxicity in a large cohort of patients treated with conventionally fractionated three-dimensional (3D) conformal radiotherapy (CF) and hypofractionated volumetric modulated arc therapy (HF) after radical prostatectomy. METHODS: Between 1994 and 2019, a total of 855 patients with prostate carcinoma were treated by postoperative radiotherapy using CF (total dose 65-72 Gy, single fraction 1.8-2 Gy) in 572 patients and HF (total dose 62.5-63.75 Gy, single fraction 2.5-2.55 Gy) in 283 patients. The association of treatment modality with biochemical control, overall survival (OS), and gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using logistic and Cox regression analysis. RESULTS: There was no difference between the two modalities regarding biochemical control rates (77% versus 81%, respectively, for HF and CF at 24 months and 58% and 64% at 60 months; p = 0.20). OS estimates after 5 years: 95% versus 93% (p = 0.72). Patients undergoing HF had less frequent grade 2 or higher acute GI or GU side effects (p = 0.03 and p = 0.005, respectively). There were no differences in late GI side effects between modalities (hazard ratio 0.99). Median follow-up was 23 months for HF and 72 months for CF (p < 0.001). CONCLUSION: For radiation therapy of resected prostate cancer, our analysis of this largest single-centre cohort (n = 283) treated with hypofractionation with advanced treatment techniques compared with conventional fractionation did not yield different outcomes in terms of biochemical control and toxicities. Prospective investigating of HF is merited.

Hybrid TRUS/CT with optical tracking for target delineation in image-guided adaptive brachytherapy for cervical cancer.

OBJECTIVE: To prospectively compare the interobserver variability of combined transrectal ultrasound (TRUS)/computed tomography (CT)- vs. CT only- vs. magnetic resonance imaging (MRI) only-based contouring of the high-risk clinical target volume (CTVHR) in image-guided adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC). METHODS: Five patients with LACC (FIGO stages IIb-IVa) treated with radiochemotherapy and IGABT were included. CT, TRUS, and T2-weighted MRI images were performed after brachytherapy applicator insertion. 3D-TRUS image acquisition was performed with a customized ultrasound stepper device and software. Automatic applicator reconstruction using optical tracking was performed in the TRUS dataset and TRUS and CT images were fused with rigid image registration with the applicator as reference structure. The CTVHR (based on the GEC-ESTRO recommendations) was contoured by five investigators on the three modalities (CTVHR_CT, CTVHR_TRUS-CT, and CTVHR_MRI). A consensus reference CTVHR_MRI (MRIref) was defined for each patient. Descriptive statistics and overlap measures were calculated using RTslicer (SlicerRT Community and Percutaneous Surgery Laboratory, Queen's University, Canada), comparing contours of every observer with one another and with the MRIref. RESULTS: The interobserver coefficient of variation was 0.18 ± 0.05 for CT, 0.10 ± 0.04 for TRUS-CT, and 0.07 ± 0.03 for MRI. Interobserver concordance in relation to the MRIref expressed by the generalized conformity index was 0.75 ± 0.04 for MRI, 0.51 ± 0.10 for TRUS-CT, and 0.48 ± 0.06 for CT. The mean CTVHR_CT volume of all observers was 71% larger than the MRIref volume, whereas the mean CTVHR_TRUS-CT volume was 15% larger. CONCLUSION: Hybrid TRUS-CT as an imaging modality for contouring the CTVHR in IGABT for LACC is feasible and reproducible among multiple observers. TRUS-CT substantially reduces overestimation of the CTVHR volume of CT alone while maintaining similar interobserver variability.

Postoperative radiotherapy for prostate cancer : Morbidity of local-only or local-plus-pelvic radiotherapy.

PURPOSE: The aim of this work was to characterise actuarial incidence and prevalence of early and late side effects of local versus pelvic three-dimensional conformal postoperative radiotherapy for prostate cancer. MATERIALS AND METHODS: Based on a risk-adapted protocol, 575 patients received either local (n = 447) or local-plus-pelvic (n = 128) radiotherapy. Gastrointestinal (GI) and genitourinary (GU) side effects (≥grade 2 RTOG/EORTC criteria) were prospectively assessed. Maximum morbidity, actuarial incidence rate, and prevalence rates were compared between the two groups. RESULTS: For local radiotherapy, median follow-up was 68 months, and the mean dose was 66.7 Gy. In pelvic radiotherapy, the median follow-up was 49 months, and the mean local and pelvic doses were 66.9 and 48.3 Gy respectively. Early GI side effects ≥ G2 were detected in 26% and 42% of patients respectively (p < 0.001). Late GI adverse events were detected in 14% in both groups (p = 0.77). The 5­year actuarial incidence rates were 14% and 14%, while the prevalence rates were 2% and 0% respectively. Early GU ≥ G2 side effects were detected in 15% and 16% (p = 0.96), while late GU morbidity was detected in 18% and 24% (p = 0.001). The 5­year actuarial incidence rates were 16% and 35% (p = 0.001), while the respective prevalence rates were 6% and 8%. CONCLUSIONS: Despite the low prevalence of side effects, postoperative pelvic radiotherapy results in significant increases in the actuarial incidence of early GI and late GU morbidity using a conventional 4­field box radiotherapy technique. Advanced treatment techniques like intensity-modulated radiotherapy (IMRT) or volumetric modulated arc radiotherapy (VMAT) should therefore be considered in pelvic radiotherapy to potentially reduce these side effects.

Pulmonary Function Changes After Radiotherapy for Lung or Esophageal Cancer: A Systematic Review Focusing on Dose-Volume Parameters.

BACKGROUND: Despite technical developments in treatment delivery, radiation-induced lung toxicity (RILT) remains a crucial problem in thoracic radiotherapy. Clinically based RILT scores have their limitations, and more objective measures such as pulmonary functions tests (PFTs) might help to improve treatment strategies. PURPOSE: To summarize the available evidence about the effect of dose to the lung in thoracic radiotherapy on forced expiratory volume in one second (FEV1) and diffusion capacity (DLCO) in patients with lung and esophageal cancer treated with curative intent. MATERIAL AND METHODS: A systematic review following the PRISMA guidelines was performed, using MEDLINE and including clinical studies using (chemo)radiotherapy (CRT) or stereotactic ablative radiotherapy (SABR) for lung or CRT for esophageal cancer that reported both lung dose-volume histogram (DVH) parameters and changes in PFT results. Search terms included lung and esophageal neoplasms, respiratory function tests, and radiotherapy. RESULTS: Fifteen studies met the inclusion criteria. Seven out of 13 studies on lung cancer reported significant declines (defined as a p value < .05) in PFT results. Both esophageal studies reported significant DLCO declines. One SABR study found a correlation between low lung-dose parameters and FEV1 decline. Relations between decline of FEV1 (three studies) or decline of DLCO (five studies), respectively, and DVH parameters were found in eight studies analyzing CRT. Furthermore, a heterogeneous range of clinical risk factors for pulmonary function changes were reported in the selected studies. CONCLUSIONS: There is evidence that pulmonary function declines after RT in a dose-dependent manner, but solid data about lung DVH parameters predicting changes in PFT results are scarce. A major disadvantage was the wide variety of methods used, frequently lacking multivariable analyses. Studies using prospective high-quality data, analyzed with appropriate statistical methods, are needed. The Oncologist 2017;22:1257-1264 IMPLICATIONS FOR PRACTICE: Radiation-induced lung toxicity remains crucial in thoracic radiotherapy. To prevent this toxicity in the future and individualize patient treatment, objective measures of pulmonary toxicity are needed. Pulmonary function tests may provide such objective measures. This systematic review, included all available clinical studies using external beam radiotherapy for lung or esophageal cancer reporting pulmonary function combined with dose-volume histogram parameters. There is preliminary evidence that pulmonary function declines post radiotherapy in a dose-dependent manner. Data quality and analyses were generally limited. Analyses of high-quality data are therefore urgently needed to improve individualization of advanced radiation therapy.

Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.

BACKGROUND: The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. METHODS: Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). FINDINGS: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). INTERPRETATION: SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. FUNDING: Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.

Metastases-directed local therapies (MDT) beyond genuine oligometastatic disease (OMD): Indications, endpoints and the role of imaging.

To further personalise treatment in metastatic cancer, the indications for metastases-directed local therapy (MDT) and the biology of oligometastatic disease (OMD) should be kept conceptually apart. Both need to be vigorously investigated. Tumour growth dynamics - growth rate combined with metastatic seeding efficiency - is the single most important biological feature determining the likelihood of success of MDT in an individual patient, which might even be beneficial in slowly developing polymetastatic disease. This can be reasonably well assessed using appropriate clinical imaging. In the context of considering appropriate indications for MDT, detecting metastases at the edge of image resolution should therefore suggest postponing MDT. While three to five lesions are typically used to define OMD, it could be argued that countability throughout the course of metastatic disease, rather than a specific maximum number of lesions, could serve as a better parameter for guiding MDT. Here we argue that the unit of MDT as a treatment option in metastatic cancer might best be defined not as a single procedure at a single point in time, but as a series of treatments that can be delivered in a single or multiple sessions to different lesions over time. Newly emerging lesions that remain amenable to MDT without triggering the start of a new systemic treatment, a change in systemic therapy, or initiation of best supportive care, would thus not constitute a failure of MDT. This would have implications for defining endpoints in clinical trials and registries: Rather than with any disease progression, failure of MDT would only be declared when there is progression to polymetastatic disease, which then precludes further options for MDT.

The interplay between autophagy and cGAS-STING signaling and its implications for cancer.

Autophagy is an intracellular process that targets various cargos for degradation, including members of the cGAS-STING signaling cascade. cGAS-STING senses cytosolic double-stranded DNA and triggers an innate immune response through type I interferons. Emerging evidence suggests that autophagy plays a crucial role in regulating and fine-tuning cGAS-STING signaling. Reciprocally, cGAS-STING pathway members can actively induce canonical as well as various non-canonical forms of autophagy, establishing a regulatory network of feedback mechanisms that alter both the cGAS-STING and the autophagic pathway. The crosstalk between autophagy and the cGAS-STING pathway impacts a wide variety of cellular processes such as protection against pathogenic infections as well as signaling in neurodegenerative disease, autoinflammatory disease and cancer. Here we provide a comprehensive overview of the mechanisms involved in autophagy and cGAS-STING signaling, with a specific focus on the interactions between the two pathways and their importance for cancer.

Explicitly encoding the cyclic nature of breathing signal allows for accurate breathing motion prediction in radiotherapy with minimal training data.

Background and purpose: Active breathing motion management in radiotherapy consists of motion monitoring, quantification and mitigation. It is impacted by associated latencies of a few 100 ms. Artificial neural networks can successfully predict breathing motion and eliminate latencies. However, they require usually a large dataset for training. The objective of this work was to demonstrate that explicitly encoding the cyclic nature of the breathing signal into the training data enables significant reduction of training datasets which can be obtained from healthy volunteers. Material and methods: Seventy surface scanner breathing signals from 25 healthy volunteers in anterior-posterior direction were used for training and validation (ratio 4:1) of long short-term memory models. The model performance was compared to a model using decomposition into phase, amplitude and a time-dependent baseline. Testing of the models was performed on 55 independent breathing signals in anterior-posterior direction from surface scanner (35 lung, 20 liver) of 30 patients with a mean breathing amplitude of (5.9 ± 6.7) mm. Results: Using the decomposed breathing signal allowed for a reduction of the absolute root-mean square error (RMSE) from 0.34 mm to 0.12 mm during validation. Testing using patient data yielded an average absolute RMSE of the breathing signal of (0.16 ± 0.11) mm with a prediction horizon of 500 ms. Conclusion: It was demonstrated that a motion prediction model can be trained with less than 100 datasets of healthy volunteers if breathing cycle parameters are considered. Applied to 55 patients, the model predicted breathing motion with a high accuracy.

Clinical outcomes of pelvic bone marrow sparing radiotherapy for cervical cancer: A systematic review and meta-analysis of randomised controlled trials.

Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer. We investigated how additional bone marrow sparing (BMS) affects the clinical outcomes. Methods: We queried MEDLINE, Embase, Web of Science Core Collection, Google Scholar, Sinomed, CNKI, and Wanfang databases for articles published in English or Chinese between 2010/01/01 and 2023/10/31. Full-text manuscripts of prospective, randomised trials on BMS in cervical cancer patients treated with definitive or postoperative CRT were included. Risk of bias (RoB) was assessed using Cochrane Collaboration's RoB tool. Random-effects models were used for the meta-analysis. Results: A total of 17 trials encompassing 1297 patients were included. The majority were single-centre trials (n = 1268) performed in China (n = 1128). Most trials used CT-based anatomical BMS (n = 1076). There was a comparable representation of trials in the definitive (n = 655) and postoperative (n = 582) settings, and the remaining trials included both.Twelve studies reported data on G ≥ 3 (n = 782) and G ≥ 2 (n = 754) haematologic adverse events. Both G ≥ 3 (OR 0.39; 95 % CI 0.28-0.55; p < 0.001) and G ≥ 2 (OR 0.29; 95 % CI 0.18-0.46; p < 0.001) toxicity were significantly lowered, favouring BMS. Seven studies (n = 635) reported data on chemotherapy interruptions, defined as receiving less than five cycles of cisplatin, which were significantly less frequent in patients treated with BMS (OR 0.44; 95 % CI 0.24-0.81; p = 0.016). There was no evidence of increased gastrointestinal or genitourinary toxicity.There were no signs of significant heterogeneity. Four studies were assessed as high RoB; sensitivity analyses excluding these provided comparable results for main outcomes. The main limitations include heterogeneity in BMS methodology between studies, low representation of populations most affected by cervical cancer, and insufficient data to assess survival outcomes. Conclusions: The addition of BMS to definitive CRT in cervical cancer patients decreases hematologic toxicity and the frequency of interruptions in concurrent chemotherapy. However, data are insufficient to verify the impact on survival and disease control.

Cancer-specific dose and fractionation schedules in stereotactic body radiotherapy for oligometastatic disease: An interim analysis of the EORTC-ESTRO E2-RADIatE OligoCare study.

BACKGROUND AND INTRODUCTION: Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. MATERIALS AND METHODS: Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/ß of 10 Gy for all primaries, and cancer-specific α/ß of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). RESULTS: Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. CONCLUSION: This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).

Increasing Quality and Efficiency of the Radiotherapy Treatment Planning Process by Constructing and Implementing a Workflow-Monitoring Application.

PURPOSE: To demonstrate how the efficiency of the treatment planning processes of a university radiation oncology department (2,500 new patients/year) could be improved by constructing and implementing a workflow-monitoring application. METHODS: A web-based application was developed in house, which enhanced the process management tools of the clinic's oncology information system. The application calculates the days left for the next task in the treatment planning process and visualizes the information on a browser-based whiteboard. Workflow monitoring considers tumor types (breast, prostate, lung, etc) and treatment techniques and is backward planned from the planned start of treatment. The effect of introducing this application was analyzed over four phases: (1) baseline data without the workflow-monitoring application, (2) after introducing workflow visualization via a browser-based whiteboard, (3) after upgrading the whiteboard and introducing backend rules, and (4) after updating these rules on the basis of data from the previous phase. RESULTS: Implementing the workflow-monitoring application and the introduced measures significantly reduced delays and, consequently, stress and a negative working atmosphere in the treatment planning process. Most notably, the amount of last-minute physics checks (on the day of the treatment start) could be reduced by 50%. CONCLUSION: The study showed what measures can help organize and prioritize the treatment planning workflow. The increased efficiency is believed to improve the quality and reduce the risk of human error.

On the sensitivity of PROMs during breast radiotherapy.

Purpose: To investigate the sensitivity of patient-reported outcome measures (PROMs) to detect treatment-related side effects in patients with breast cancer undergoing external beam photon radiotherapy. Methods: As part of daily clinical care, an in-house developed PROM tool was used to assess side effects in patients during a) whole-breast irradiation (WBI) to 40 Gy, b) WBI with a sequential boost of 10 Gy, and c) partial-breast irradiation (PBI) to 40 Gy. Results: 414 patients participated in this prospective study between October 2020 and January 2022, with 128 patients (31 %) receiving WBI, 241 (58 %) receiving WBI followed by a sequential boost, and 50 patients (12 %) receiving PBI. Significant differences in the reported toxicities (itching, radiation skin reaction, skin darkening, and tenderness and swelling) were reported between the WBI cohorts with and without boost (p < 0.001, p < 0.001, p < 0.001, and p = 0.002, respectively). The comparison of PBI with WBI (no-boost) yielded significant differences for radiation skin reaction (p < 0.001). Conclusion: The results highlight the high sensitivity of PROMs to detect treatment-related side effects in patients with breast cancer. Thus, PROMs may be a valuable tool for quality control and may support evidence-based learning from real-world data originating from daily routine care.

Effect of mannitol-based reduced-volume hydration on kidney function in concomitant cisplatin-based chemoradiation for head-and-neck squamous cell carcinoma.

OBJECTIVE: Nephrotoxicity is frequent in cisplatin-based chemoradiation of head and neck squamous cell carcinoma (HNSCC). Toxicity outcomes and achieved cisplatin-doses after change of departmental hydration policy are presented. METHODS: We performed a retrospective time-series analysis of HNSCC patients undergoing chemoradiation with conventional hydration (CH) between 01/2017 and 09/2018 versus shorter hydration with mannitol (SHM) between 09/2018 and 08/2019 to compare the rate of acute kidney injury (AKI) and cumulative cisplatin dose. RESULTS: Among 113 HNSCC patients, SHM (n = 35) in comparison to CH (n = 78) correlated with less AKI (54.3% vs. 74.4%; p = 0.034) and higher cisplatin doses (82.9% vs. 61.5% ≥200 mg/m2 ; p = 0.025). AKI ≥grade 2 was lower with SHM (2.9% vs. CH: 22.8%; p = 0.01). AKI occurred more frequently in females (92.6% vs. males: 60.5%, p = 0.002). Females received lower cumulative cisplatin doses (51.9% vs. males: 73.3%; p = 0.037). CONCLUSIONS: We observed less AKI and higher cumulative chemotherapy doses with SHM. Female patients were at higher risk of AKI.

Micro- and Nanoplastics Breach the Blood-Brain Barrier (BBB): Biomolecular Corona's Role Revealed.

Humans are continuously exposed to polymeric materials such as in textiles, car tires and packaging. Unfortunately, their break down products pollute our environment, leading to widespread contamination with micro- and nanoplastics (MNPs). The blood-brain barrier (BBB) is an important biological barrier that protects the brain from harmful substances. In our study we performed short term uptake studies in mice with orally administered polystyrene micro-/nanoparticles (9.55 µm, 1.14 µm, 0.293 µm). We show that nanometer sized particles-but not bigger particles-reach the brain within only 2 h after gavage. To understand the transport mechanism, we performed coarse-grained molecular dynamics simulations on the interaction of DOPC bilayers with a polystyrene nanoparticle in the presence and absence of various coronae. We found that the composition of the biomolecular corona surrounding the plastic particles was critical for passage through the BBB. Cholesterol molecules enhanced the uptake of these contaminants into the membrane of the BBB, whereas the protein model inhibited it. These opposing effects could explain the passive transport of the particles into the brain.

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

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

Clinical Implementation and Evaluation of Auto-Segmentation Tools for Multi-Site Contouring in Radiotherapy.

Background and purpose: Tools for auto-segmentation in radiotherapy are widely available, but guidelines for clinical implementation are missing. The goal was to develop a workflow for performance evaluation of three commercial auto-segmentation tools to select one candidate for clinical implementation. Materials and Methods: One hundred patients with six treatment sites (brain, head-and-neck, thorax, abdomen, and pelvis) were included. Three sets of AI-based contours for organs-at-risk (OAR) generated by three software tools and manually drawn expert contours were blindly rated for contouring accuracy. The dice similarity coefficient (DSC), the Hausdorff distance, and a dose/volume evaluation based on the recalculation of the original treatment plan were assessed. Statistically significant differences were tested using the Kruskal-Wallis test and the post-hoc Dunn Test with Bonferroni correction. Results: The mean DSC scores compared to expert contours for all OARs combined were 0.80 ± 0.10, 0.75 ± 0.10, and 0.74 ± 0.11 for the three software tools. Physicians' rating identified equivalent or superior performance of some AI-based contours in head (eye, lens, optic nerve, brain, chiasm), thorax (e.g., heart and lungs), and pelvis and abdomen (e.g., kidney, femoral head) compared to manual contours. For some OARs, the AI models provided results requiring only minor corrections. Bowel-bag and stomach were not fit for direct use. During the interdisciplinary discussion, the physicians' rating was considered the most relevant. Conclusion: A comprehensive method for evaluation and clinical implementation of commercially available auto-segmentation software was developed. The in-depth analysis yielded clear instructions for clinical use within the radiotherapy department.