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BACKGROUND: Inborn errors of immunity (IEI) are rare diseases, which makes diagnosis a challenge. A better description of the initial presenting manifestations should improve awareness and avoid diagnostic delay. Although increased infection susceptibility is a well-known initial IEI manifestation, less is known about the frequency of other presenting manifestations.OBJECTIVE: We sought to analyze age-related initial presenting manifestations of IEI including different IEI disease cohorts.METHODS: We analyzed data on 16,486 patients of the European Society for Immunodeficiencies Registry. Patients with autoinflammatory diseases were excluded because of the limited number registered.RESULTS: Overall, 68% of patients initially presented with infections only, 9% with immune dysregulation only, and 9% with a combination of both. Syndromic features were the presenting feature in 12%, 4% had laboratory abnormalities only, 1.5% were diagnosed because of family history only, and 0.8% presented with malignancy. Two-third of patients with IEI presented before the age of 6 years, but a quarter of patients developed initial symptoms only as adults. Immune dysregulation was most frequently recognized as an initial IEI manifestation between age 6 and 25 years, with male predominance until age 10 years, shifting to female predominance after age 40 years. Infections were most prevalent as a first manifestation in patients presenting after age 30 years.CONCLUSIONS: An exclusive focus on infection-centered warning signs would have missed around 25% of patients with IEI who initially present with other manifestations.

Rationale and Objectives Mobile mammography units provide preventive health care to patients facing barriers to annual screening. This study reviews the outcomes of a mobile mammography service during a recent 5-year period. Materials and Methods This retrospective study analyzed the examinations by mobile mammography during a 5-year period (9327 examinations). The patients recalled, biopsies performed, and cancers detected were tallied. The race, age, breast cancer size, lymph node involvement, and metastases were recorded. The positive predictive value (PPV) and cancer detection rate metrics were calculated as outlined by the American College of Radiology Breast Imaging Reporting and Data System Atlas. Results The program identified cancer in 14 cases (cancer detection rate = 1.5 per 1000 examinations [95% confidence interval [CI], 0.9–2.5]) with 11 being invasive. The majority of these cancers were small and of low stage. Lymph node status was determined in 11 of the 14 cases (1 as N1mi, 5 as N0, 4 as N1,1 as N2a). Abnormalities led to 1686 examinations recalled (Recall Rate = 17.8%; PPV 1 = 0.8% [95% CI, 0.5%–1.4%]). One hundred and one were recommended for biopsy (PPV 2 = 13.9% [95% CI, 8.4%–21.9%]), and 98 pursued biopsy (PPV 3 = 14.3% [95% CI, 8.7%–22.6%]). Patient age ranged from 41 to 67 years with an average of 50.6 years. Conclusion The program detected many cancers in an asymptomatic population facing barriers to breast cancer screening. These findings are underscored by the cancers detected at an early stage with a favorable prognosis and support the need for the development of similar programs.

INTRODUCTION: Endothelial shear stress (ESS) is a local hemodynamic factor that is dependent on vessel geometry and influences the process of atherogenesis. As in vivo measurements of ESS are not possible, it must be calculated using computational fluid dynamics (CFD). In this feasibility study we explore CFD-models generated from coronary CT-angiography (CCTA) using an individualised blood viscosity and a pulsatile flow profile derived from in vivo measurements. MATERIALS AND METHODS: We retrospectively recruited 25 consecutive patients who received a CCTA followed by a coronary angiography including intravascular ultrasound (IVUS) and generated 3D models of the coronary arteries from the CT-datasets. We then performed CFD-simulations on these models. Hemodynamically non-relevant stenosis were identified in IVUS. They were isolated in the CFD-model and separated longitudinally into a half with atherosclerotic lesion (AL) and one without (NAL). ESS was measured and compared for both halves. RESULTS: After excluding vessels with no IVUS data or relevant stenosis we isolated 31 hemodynamically non-relevant excentric AL from a total of 14 vessels. AL segments showed consistently significantly lower ESS when compared to their corresponding NAL segments when regarding minimum (0.9 Pa, CI [0.6, 1.2] vs. 1.3 Pa, CI [0.9, 1.8]; p = 0.004), mean (5.0 Pa, CI [3.4, 6.0] vs. 6.7 Pa, CI [5.5, 8.4]; p = 0.008) and maximum ESS values (12.4 Pa, CI [8.6, 14.6] vs. 19.6 Pa, CI [12.4, 21.0]; p = 0.005). Qualitatively ESS was lower on the inside of bifurcations and curvatures. CONCLUSION: CFD simulations of coronary arteries from CCTA with an individualised flow profile and blood viscosity are feasible and could provide further prognostic information and a better risk stratification in coronary artery disease. Further prospective studies are needed to investigate this claim.

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores.MethodsWe retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis.ResultsWith a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (pConclusionStereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.

Background We recently published 2-year results of the prospective, randomized IMRT-MC2 trial, showing non-inferior local control and cosmesis in breast cancer patients after conventionally fractionated intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB), compared to 3D-conformal radiotherapy with sequential boost (3D-CRT-seqB). Here, we report on 2-year quality of life results. Patients and Methods 502 patients were enrolled and randomized to IMRT-SIB (50.4 Gy in 1.8 Gy fractions with a 64.4 Gy SIB to the tumor bed) or to 3D-CRT-seqB (50.4 Gy in 1.8 Gy fractions, followed by a sequential boost of 16 Gy in 2 Gy fractions). For quality of life (QoL) assessment, patients completed the QLQ-C30 and QLQ-BR23 questionnaires at baseline, 6 weeks and 2 years after radiotherapy. Results Significant differences between treatment arms were seen 6 weeks after radiotherapy for pain (22.3 points for IMRT vs. 27.0 points for 3D-CRT-seqB; p = 0.033) and arm symptoms (18.1 points for IMRT vs. 23.6 points for 3D-CRT-seqB; p = 0.013), both favoring IMRT-SIB. Compared to baseline values, both arms showed significant improvement in global score (IMRT: p = 0.009; 3D-CRT: p = 0.001) after 2 years, with slight deterioration on the role (IMRT: p = 0.008; 3-D-CRT: p = 0.001) and social functioning (IMRT: p = 0.013, 3D-CRT: p = 0.001) as well as the future perspectives scale (IMRT: p = 0.003; 3D-CRT: p = 0.0034). Conclusion This is the first randomized phase III trial demonstrating that IMRT-SIB was associated with slightly superior QoL compared to 3-D-CRT-seqB. These findings further support the clinical implementation of SIB in adjuvant breast cancer treatment.

Purpose Scientific and clinical achievements in radiation, medical, and surgical oncology are changing the landscape of interdisciplinary oncology. The German Society for Radiation Oncology (DEGRO) working group of young clinicians and scientists (yDEGRO) and the DEGRO representation of associate and full professors (AKRO) are aware of the essential role of radiation oncology in multidisciplinary treatment approaches. Together, yDEGRO and AKRO endorsed developing a German radiotherapy & radiation oncology vision 2030 to address future challenges in patient care, research, and education. The vision 2030 aims to identify priorities and goals for the next decade in the field of radiation oncology. Methods The vision development comprised three phases. During the first phase, areas of interest, objectives, and the process of vision development were defined jointly by the yDEGRO, AKRO, and the DEGRO board. In the second phase, a one-day strategy retreat was held to develop AKRO and yDEGRO representatives’ final vision from medicine, biology, and physics. The third phase was dedicated to vision interpretation and program development by yDEGRO representatives. Results The strategy retreat’s development process resulted in conception of the final vision “Innovative radiation oncology Together – Precise, Personalized, Human.” The first term “Innovative radiation oncology” comprises the promotion of preclinical research and clinical trials and highlights the development of a national committee for strategic development in radiation oncology research. The term “together” underpins collaborations within radiation oncology departments as well as with other partners in the clinical and scientific setting. “Precise” mainly covers technological precision in radiotherapy as well as targeted oncologic therapeutics. “Personalized” emphasizes biology-directed individualization of radiation treatment. Finally, “Human” underlines the patient-centered approach and points towards the need for individual longer-term career curricula for clinicians and researchers in the field. Conclusion The vision 2030 balances the ambition of physical, technological, and biological innovation as well as a comprehensive, patient-centered, and collaborative approach towards radiotherapy & radiation oncology in Germany.

Objective Stereotactic body radiotherapy (SBRT) is a noninvasive treatment option for lymph node metastases (LNM). Magnetic resonance (MR)-guidance offers superior tissue contrast and enables treatment of targets in close vicinity to radiosensitive organs at risk (OAR). However, literature on MR-guided SBRT of LNM is scarce with no report on outcome parameters. Materials and methods We report a subgroup analysis of a prospective observational study comprising patients with LNM. Patients received MR-guided SBRT at our MRIdian Linac (ViewRay Inc., Mountain View, CA, USA) between January 2019 and February 2020. Local control (LC), progression-free survival (PFS) and overall survival (OS) analysis were performed using the Kaplan–Meier method with log rank test to test for significance (p Results Twenty-nine patients (72.4% with prostate cancer; 51.7% with no distant metastases) received MR-guided SBRT for in total 39 LNM. Median dose was 27 Gy in three fractions, prescribed to the 80% isodose. At 1‑year, estimated LC, PFS and OS were 92.6, 67.4 and 100.0%. Compared to baseline, six patients (20.7%) developed new grade I toxicities (mainly fatigue). One grade II toxicity occurred (fatigue), with no adverse event grade ≥III. Overall treatment experience was rated particularly positive, while the technically required low room temperature still represents the greatest obstacle in the pursuit of the ideal patient acceptance. Conclusion MR-guided SBRT of LNM was demonstrated to be a well-accepted treatment modality with excellent preliminary results. Future studies should evaluate the clinical superiority to conventional SBRT.

Objectives In the microbiological diagnosis of periprosthetic joint infection (PJI), there is much discussion about the methodology of obtaining proper specimens, the processing technique, and suitable culture media. This retrospective study was conducted to analyse the accuracy of our culture techniques. Methods Tissue samples and components from 258 patients after revision arthroplasty of the hip, knee, and shoulder were investigated, and the results of tissue cultures (TC) were compared to those of sonicate fluid cultures (SFC). Furthermore, an evaluation was performed of the influence of different culture media on the detection rate. Results PJI was confirmed in 186 patients. The overall sensitivity of TC was no different to that of SFC (91.3% vs 90.8%, P = 1). In 153 cases (82.3%), TC and SFC showed concordant positive results. Results were discordant in 33 cases (17.7%). When differentiated according to the type of infection, TC showed significantly better results than SFC in detecting polymicrobial infections (97.0% vs 67.0%, P = 0.004). There were also significant differences between the culture media regarding the yield of microorganisms. Conclusions TC was more effective in detecting co-infections. The best results were obtained using both TC and SFC. The choice of culture media has a significant influence on the quality of results.

Background Metastatic non-small cell lung cancer (NSCLC) often requires a multimodal treatment including chemotherapy, targeted therapy and radiotherapy. In addition to this, many patients take supportive drugs. Since only scarce data on possible interactions between radiotherapy and pharmaceutical or herbal drugs exist, description of clinical cases is of special interest. Case report A patient with stage IV NSCLC was treated with docetaxel/ramucirumab followed by radiotherapy for brain and bone metastases while taking several other over-the-counter drugs (OTCs) including topical St. John’s wort skin oil. Results A 63-year-old female patient with stage IV NSCLC presented with 11 asymptomatic brain metastases and a painful osteolytic bone metastasis in the 12th thoracic vertebral body (T12). Four weeks before the start of palliative whole-brain radiotherapy and bone irradiation of T12, she was administered a combination of docetaxel and ramucirumab. At an administered dose of 24 Gy, the patient presented with severe folliculitis capitis, while skin examination over the thoracolumbar spine was unremarkable although skin dose was similar. After thorough questioning, the patient reported using a herbal skin oil that contained St. John’s wort for scalp care only, but not for skin care of her back during radiotherapy. After stopping the topical application of the skin oil, folliculitis improved with a course of systemic and topical antibiotics within 10 days, though the healing process was prolonged and included desquamation and hyperpigmentation. Conclusion St. John’s wort seems to be a significant radiosensitizer for photon radiotherapy and can cause severe skin toxicity even though the literature lacks data on this interaction. As an OTC, it is easily accessible and often used by oncological patients due to antidepressant and local antimicrobial and pain-relieving effects.

Purpose Hybrid MRI-linear accelerator systems (MR-linacs) allow for the incorporation of MR images with high soft-tissue contrast into the radiation therapy procedure prior to, during, or post irradiation. This allows not only for the optimization of the treatment planning, but also for real-time monitoring of the tumor position using cine MRI, from which intrafractional motion can be compensated. Fast imaging and accurate tumor tracking are crucial for effective compensation. This study investigates the application of cine MRI with a radial acquisition scheme on a low-field MR-linac to accelerate the acquisition rate and evaluates the effect on tracking accuracy. Methods An MR sequence using tiny golden-angle radial k-space sampling was developed and applied to cine imaging on patients with liver tumors on a 0.35 T MR-linac. Tumor tracking was assessed for accuracy and stability from the cine images with increasing k-space undersampling factors. Tracking was achieved using two different auto-segmentation algorithms: a deformable image registration B-spline similar to that implemented on the MR-linac and a convolutional neural network approach known as U-Net. Results Radial imaging allows for increased temporal resolution with reliable tumor tracking, although tracking robustness decreases as temporal resolution increases. Additional acquisition-based artifacts can be avoided by reducing the angle increment using tiny golden-angles. The U-net algorithm was found to have superior auto-segmentation metrics compared to B-spline. U-net was able to track two well-defined tumors, imaged with just 30 spokes per image (10.6 frames per second), with an average Dice coefficient ≥ 83%, Hausdorff distance ≤ 1.4 pixel, and mean contour distance ≤ 0.5 pixel. Conclusions Radial acquisitions are commonplace in dynamic imaging; however, in MR-guided radiotherapy, robust tumor tracking is also required. This study demonstrates the in vivo feasibility of tumor tracking from radially acquired images on a low-field MR-linac. Radial imaging allows for decreased image acquisition times while maintaining robust tracking. The U-net algorithm can track a tumor with higher accuracy in images with undersampling artifacts than a conventional deformable B-spline algorithm and is a promising tool for tracking in MR-guided radiation therapy.

Background and Purpose The clinical introduction of on-table adaptive radiotherapy with Magnetic Resonance (MR)-guided linear accelerators (Linacs) yields new challenges and potential risks. Since the adapted plan is created within a highly interdisciplinary workflow with the patient in treatment position, time pressure or erroneous communication may lead to various possibly hazardous situations. To identify risks and implement a safe workflow, a proactive risk analysis has been conducted. Materials and Methods A process failure mode, effects and criticality analysis (P-FMECA) was performed within a group of radiation therapy technologists, physicians and physicists together with an external moderator. The workflow for on-table adaptive MR-guided treatments was defined and for each step potentially hazardous situations were identified. The risks were evaluated within the team in order to homogenize risk assessment. The team elaborated and discussed possible mitigation strategies and carried out their implementation. Results In total, 89 risks were identified for the entire MR-guided online adaptive workflow. After mitigation, all risks could be minimized to an acceptable level. Overall, the need for a standardized workflow, clear-defined protocols together with the need for checklists to ensure protocol adherence were identified among the most important mitigation measures. Moreover, additional quality assurance processes and automated plan checks were developed. Conclusions Despite additional workload and beyond the fulfilment of legal requirements, execution of the P-FMECA within an interdisciplinary team helped all involved occupational groups to develop and foster an open culture of safety and to ensure a consensus for an efficient and safe online adaptive radiotherapy workflow.

Purpose Hypofractionated radiotherapy is the standard of care for adjuvant whole breast radiotherapy (RT). However, adoption has been slow. The indication for regional nodal irradiation has been expanded to include patients with 0–3 involved lymph nodes. We investigated the impact of the publication of the updated German S3 guidelines in 2017 on adoption of hypofractionation and enrollment of patients with lymph node involvement within a randomized controlled phase III trial. Methods In the experimental arm of the HYPOSIB trial (NCT02474641), hypofractionated RT with simultaneous integrated boost (SIB) was used. In the standard arm, RT could be given as hypofractionated RT with sequential boost (HFseq), normofractionated RT with sequential boost (NFseq), or normofractionated RT with SIB (NFSIB). The cutoff date for the updated German S3 guidelines was December 17, 2017. Temporal trends were analyzed by generalized linear regression models. Multiple logistic regression models were used to investigate the influence of time (prior to/after guideline) and setting (university hospital/other institutions) on the fractionation patterns. Results Enrollment of patients with involved lymph nodes was low throughout the trial. Adoption of HFseq increased over time and when using the guideline publication date as cutoff. Results of the multiple logistic regressions showed an interaction between time and setting. Furthermore, the use of HFseq was significantly more common in university hospitals. Conclusion The use of HFseq in the standard arm increased over the course of the HYPOSIB trial and after publication of the S3 guideline update. This was primarily driven by patients treated in university hospitals. Enrolment of patients with lymph node involvement was low throughout the trial.

This multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non-small-cell lung cancer (NSCLC).This analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT.The median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed.SBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.

Clinical issue Image-guided radiotherapy (IGRT) using X‑rays and cone-beam computed tomography (CT) has fostered precision radiotherapy. However, inter- and intrafractional variations of target volume position and organs at risk still limit target volume dose and sparing of radiosensitive organs at risk. Methodological innovations Hybrid machines directly combining linear accelerators and magnetic resonance (MR) imaging allow for live imaging during radiotherapy. Performance Besides highly improved soft tissue contrast, MR-linacs enable online, on-table adaptive radiotherapy. Thus, adaptation of the treatment plan to the anatomy of the day, dose escalation and superior sparing of organs at risk become possible. Achievements This article summarizes the underlying intention for the development of MR-guided radiotherapy, technical innovations and challenges as well as the current state-of-the-art. Potential clinical benefits and future developments are discussed. Practical recommendations Increasing availability of MR imaging at linear accelerators calls for the ability to review and interpret MR images. Therefore, close collaborations of diagnostic radiologists and radiation oncologists are mandatory to foster this fascinating technique.

In response to the COVID-19 social distancing guidelines, residency and fellowship programs transitioned to virtual instruction to deliver didactics and continue with medical education. The efficacy of such a fully online learning environment, however, remains unknown. To investigate its impact on medical education, this study surveyed hematology/oncology fellows at The University of Texas MD Anderson Cancer Center on their attitudes regarding the online-based lecture program. Fellows were emailed a 19-question survey with questions on demographics, ease of technical access to the online platform, level of comfort with participation, knowledge acquisition, wellness, and COVID-19-specific coverage. A free-text question soliciting ways to improve upon online learning was also included. The response rate was 71% (30/42). Most respondents reported easy/very easy accessibility to the online environment. Seventy-seven percent of the participants did not experience a technical issue. Seventy percent felt comfortable/very comfortable with participating in the conference. Thirty-seven percent felt comfortable/very comfortable with actively offering an answer to questions during the interactive board review session. Eighty-seven percent would have been more willing to offer an answer during the board review session if an anonymous poll format was utilized. Sixty-three percent felt they learned the same amount as they typically do during an in-person session. Thirty-three percent reported they were less focused as compared with an in-person session. One hundred percent of the participants had their questions answered, either at all times (87%) or sometimes (13%). Sixty percent experienced a change in social interactions as compared with an in-person session. Fifty-four percent reported that it was easy/very to balance online attendance despite personal/family commitments. One hundred percent appreciated the flexibility of the online learning environment. Ninety percent felt safer at home attending these lectures compared with receiving these lectures in-person during the COVID-19 pandemic. Overall, most fellows felt comfortable with the transition to a fully online learning environment. Strategies to encourage active participation, enhance social interaction, and provide additional flexibility are still needed. Electronic supplementary material The online version of this article (10.1007/s13187-020-01863-6) contains supplementary material, which is available to authorized users.

Purpose Combined radioimmunotherapy (RIT) in follicular lymphomas (FL) has shown promising treatment efficacy in the Mabthera® and Involved field Radiation (MIR) study. Aim of this study was to analyze treatment efficacy and recurrence patterns after RIT in early-stage nodal and extranodal FL. Methods We reviewed 107 patients who were treated with combined RIT in two centers. Treatment consisted of 4 × rituximab followed by RIT with 4 × rituximab and involved field (IF) radiotherapy with 30/40 Gy. Median follow-up period was 71 months. In contrast to the MIR study, extranodal involvement and grade 3A histology were included in the analysis. Results Extranodal involvement and grade 3A histology were present in 21.8% and 13.1%, respectively. Overall response rate (ORR) after 4 × rituximab, after completion of RIT, and after 6 months was 78.1%, 98.8%, and 98.8%, respectively, with increasing rates of complete remissions (CR). Predictive factors associated with superior PFS were tumor size, completely excised lymphomas, and response to first 4 × rituximab. 5‑year PFS rate was 87.3%, with mostly outfield recurrences (94.1%). Second-line treatment was effective, with 53.3% CR and 46.7% partial remissions (PR). 5‑year OS was 98.1%. RIT was tolerated well, with mainly grade 1–2 acute side effects. Conclusion The real-world efficacy of RIT is comparable with the results of the MIR study. Additionally, this analysis shows that extranodal involvement and grade 3A histology are not associated with inferior PFS.

Q methodology provides a unique mixed-methods means of examining subjectivity through the use of an activity called a Q sort in which participants must sort a list of given items within a predetermined sorting form. Although Q methodology has a long history as a research tool, its use as an instructional tool has not been extensively explored. This is unfortunate because the Q sort activity—an element of Q methodology—offers instructors with an evidence-based approach to helping individual students understand their own subjective points of view while also helping to reveal distinctive subjective profiles or perspectives held by all students in the class. One reason why Q sorts may not have been embraced by instructors is perhaps the fact that it is difficult to prepare a Q sort in its traditional, paper-based form. A prototype of a Q sort software tool was built to meet this challenge. The purpose of this paper is to present the story of the current design of this tool. Four categories of design iterations developed over a four-year period are presented and discussed.

Purpose Magnetic resonance-guided radiotherapy (MRgRT) has recently been introduced in our institution. As MRgRT requires high patient compliance compared to conventional techniques and can be associated with prolonged treatment times, feasibility and patient tolerance were prospectively assessed using patient-reported outcome questionnaires (PRO-Q). Materials and methods Forty-three patients were enrolled in a prospective observational study and treated with MRgRT on a low-field hybrid Magnetic Resonance Linear Accelerator system (MR-Linac) between April 2018 and April 2019. For assistance in gated breath-hold delivery using cine-MRI, a video feedback system was installed. PRO-Qs consisted of questions on MR-related complaints and also assessed aspects of active patient participation. Results The most commonly treated anatomic sites were nodal metastases and liver lesions. The mean treatment time was 34 min with a mean beam-on time of 2:17 min. Gated stereotactic body radiotherapy (SBRT) was applied in 47% of all patients. Overall, patients scored MRgRT as positive or at least tolerable in the PRO‑Q. Almost two thirds of patients (65%) complained about at least one item of the PRO‑Q (score ≥4), mainly concerning coldness, paresthesia, and uncomfortable positioning. All patients reported high levels of satisfaction with their active role using the video feedback system in breath-hold delivery. Conclusion MRgRT was successfully implemented in our clinic and well tolerated by all patients, despite MR-related complaints and complaints about uncomfortable immobilization. Prospective clinical studies are in development for further evaluation of MRgRT and for quantification of the benefit of MR-guided on-table adaptive radiotherapy.

Background: Breast-conserving therapy including lumpectomy and adjuvant whole breast irradiation (WBI) has become the standard therapy for early-stage breast cancer (EBC). Without WBI, the recurrence rate is significantly increased. However, when selecting patients at a low a priori risk of local recurrence only a small breast-cancer-specific mortality benefit, but no overall survival improvement, was detected for WBI. As most recurrences occur close to the lumpectomy cavity, accelerated partial breast irradiation (APBI) delivered exclusively to a limited volume of tissue around the initial lumpectomy site, has gained increased attention and is now discussed as an alternative to WBI for selected EBC patients. Summary: Numerous techniques for APBI (interstitial brachytherapy, external beam-based APBI, intraoperative radiotherapy, MR-guided radiotherapy) allow treatment delivery in a shorter period of time, and radiation oncologists expect to further reduce side effects by using these new techniques, with improvements in cosmetics and quality of life. In this review, we aim to describe the existing evidence for the feasibility and effectiveness of different APBI techniques used in modern radiotherapy. Key Messages: APBI has provided outcomes similar to WBI combined with potentially reduced toxicity. While appropriate patient selection persists to be crucial for acceptable recurrence rates, the precise definition of patients suitable for APBI remains a matter of discussion. As long-term data are often still lacking, special attention should be paid to late side effects and long-term outcomes. Decision-making on appropriate treatment techniques should take into account not only local control rates, but also the impact on the patient’s quality of life.

Background High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data. Materials and methods We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size. Results A total of 109 local progressions were observed after a median of 17.7 months (range 0.6–76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12–16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy. Conclusions Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12–16 Gy are more probable, consistent with recent meta-regression analyses.

Background: Vaginal cancer is a rare disease for which prospective randomized trials do not exist. We aimed to assess survival outcomes, patterns of recurrence, prognostic factors, and toxicity in the curative treatment using image-guided radiotherapy (RT). Methods: In this retrospective review, we identified 53 patients who were treated at a single center with external beam radiotherapy and brachytherapy with or without concomitant chemotherapy from 2000 to 2021. Results: With a median follow-up of 64.5 months, the Kaplan-Meier 2-, 5-, and 7-year overall survival (OS) was found to be 74.8%, 62.8%, and 58.9%, respectively. Local and distant control were 67.8%, 65.0%, and 65.0% and 74.4%, 62.6%, and 62.6% at 2, 5, and 7 years, respectively. In univariate Cox proportional hazards ratio analysis, OS was significantly correlated to FIGO stage (hazard ratio [HR] 1.78, p = 0.042), postoperative RT (HR 0.41, p = 0.044), and concomitant chemotherapy (HR 0.31, p = 0.009). Local control rates were superior when an equivalent dose in 2-Gy fractions (EQD2) of ⩾65 Gy was delivered (HR 0.216, p = 0.028) and with the use of concurrent chemotherapy (HR 0.248, p = 0.011). Not surprisingly, local control was inferior for patients with a higher TNM stage (HR 3.303, p = 0.027). Minimal toxicity was observed with no patients having documentation of high-grade toxicity (CTCAE grade 3+). Conclusion: In treatment of vaginal cancer, high-dose RT in combination with brachytherapy is well tolerated and results in effective local control rates, which significantly improve with an EQD2(α/β=10) ⩾65 Gy. Multivariate analyses revealed concomitant chemotherapy was a positive prognostic factor for overall and progression-free survival.

Hybrid magnetic resonance (MR)-guided linear accelerators represent a new horizon in the field of radiation oncology. By harnessing the favorable combination of on-board MR-imaging with the possibility to daily recalculate the treatment plan based on real-time anatomy, the accuracy in target and organs-at-risk identification is expected to be improved, with the aim to provide the best tailored treatment. To date, two main MR-linac hybrid machines are available, Elekta Unity and Viewray MRIdian. Of note, compared to conventional linacs, these devices raise practical issues due to the positioning phase for the need to include the coil in the immobilization procedure and in order to perform the best reproducible positioning, also in light of the potentially longer treatment time. Given the relative novelty of this technology, there are few literature data regarding the procedures and the workflows for patient positioning and immobilization for MR-guided daily adaptive radiotherapy. In the present narrative review, we resume the currently available literature and provide an overview of the positioning and setup procedures for all the anatomical districts for hybrid MR-linac systems. Supplementary Information The online version contains supplementary material available at 10.1186/s13014-021-01910-6.

PURPOSE: Opioid misuse during cancer pain management places patients at risk for harm and physicians for legal liability. Identifying and monitoring patients who are at risk is challenging given the lack of validated clinical tools and evidence-based guidelines. In the current study, we aimed to standardize opioid prescribing practices at a community oncology clinic to help ensure patient safety and physician compliance with Texas state regulations. METHODS: We used the Plan-Do-Study-Act methodology. In the planning phase, current practices of assessing opioid efficacy, toxicity, and misuse were determined by surveying clinic physicians and reviewing patients’ charts. We developed a new standardized process that incorporated published literature, the Texas Administrative Code, and expert opinion. Two interactive documentation templates (SmartPhrases) were designed to implement the standardized process. The intervention was studied using repeat physician surveys and chart reviews, which prompted action for refinement and sustainability. RESULTS: At baseline, 9% of providers followed a systematic approach to prescribing opioids and 86% expressed an interest in process standardization. We noted high interprovider variability in the opioid risk stratification and refill process. At 2 months and 6 months postimplementation, provider satisfaction with the intervention was 83% and 75%, whereas compliance with SmartPhrase use was 70% and 54%, respectively. The frequency of state database check improved from 36% to 94% at 6 months. Improvement was also noted in assessment and documentation of baseline risk, chemical coping, and toxicity. CONCLUSION: We implemented a systematic approach for assessing opioid misuse, toxicity, and efficacy during cancer pain management at a community oncology clinic. The approach resulted in notable improvement in provider practices and documentation compliance.

OBJECTIVES Left ventricular (LV) hypertrophy in resistant hypertensive patients is associated with a reduced intramyocardial perfusion. Renal sympathetic denervation (RDN) has been shown to reduce blood pressure (BP) and sympathetic tone. We aimed to prospectively investigate the effect of RDN on functional myocardial parameters and myocardial perfusion reserve (MPR) using cardiac magnetic resonance imaging (cMRI) in patients with resistant hypertension. METHODS A total of 15 resistant hypertensive patients (11 male individuals, mean age 62±13 y) were included. Adenosine stress-induced cMRI was performed at baseline, 3, 6, and 12 months after RDN. RDN was performed using a single soft-tip radiofrequency catheter (Symplicity). cMRI semiquantitative perfusion analysis was performed using the upslope of myocardial signal enhancement to derive the myocardial perfusion reserve index. RESULTS Both systolic-BP and diastolic-BP significantly decreased from 148±14 to 133±14 mm Hg and 87±14 to 80±10 mm Hg, respectively (P

Despite a lack of evidence and low compliance, current guidelines recommend the use of a vaginal dilator (VD) after pelvic radiotherapy (RT). We analyzed the effect of VD on vaginal stenosis (VS) and its influence on sexual quality of life (QoL) in women treated with adjuvant RT for endometrial cancer (EC). Between 2014 and 2015, 56 consecutive patients were instructed to use a VD after completion of treatment. The maximum diameter of the comfortably introducible VD was measured before and at 1 year after treatment. The degree of VS was evaluated clinically, and sexual QoL was assessed with the European Organisation for Research and Treatment of Cancer (EORTC) sexual functioning items before RT, during RT, at 6 weeks, and at 1 year after RT. One year after RT, mean VD diameter had decreased by 2.7 ± 3.2 mm (p

Objectives We aimed to present the first clinical results for adenoid cystic carcinoma (ACC) of the nasopharynx after primary radiotherapy (RT) with the focus on local control (LC) and patterns of recurrence. Materials and methods We retrospectively analyzed 59 patients with ACC of the nasopharynx, who were treated with bimodal radiotherapy (RT) consisting of intensity modulated radiotherapy and carbon ion boost at the Heidelberg Ion-Beam Therapy Center between 2009 and 2018. The patients had predominantly inoperable (n = 42, 72%) or incompletely resected (n = 17, 29%) tumors. Kaplan-Meier estimates and the log-rank (Mantel-Cox) test were used for univariate and multivariate analyses. Results The median follow-up was 32 months. At last follow-up, 67% of the patients were still alive (n = 39/58), of whom 74% were free of progression (n = 29/39). The 2-year LC, distant progression-free survival (DPFS) and overall survival (OS) were 83%, 81%, 87% and the estimated 5-year LC, DPFS and OS were 49%, 54%, 69%, respectively. LC was significantly inferior in patients with large tumor volumes (gross tumor volume, GTV > 100 cc, p = 0.020) and T4 tumors (p = 0.021). The majority of the recurrences occurred at the margin, where critical structures were spared (n = 11/19, 58%). Overall, grade 3 toxicity was moderate with 12% acute and 8% late side effects. Conclusion Bimodal RT including active raster-scanning carbon ion boost for nasopharyngeal ACC resulted in adequate LC and OS rates with moderate toxicity. T4 stage, large tumor volume and the necessary dose sparing in critical structures, i.e. optic nerves, brain stem and orbit, negatively affected LC.

Lung cancer remains one of the tumour diagnoses with high lethality, although innovative treatment approaches have yielded improvements in local control and survival rates. There is still no consensus on how to treat local relapse in patients after first-line treatments. Radiotherapy may be considered in this situation; however, data supporting its effectiveness are rare. The purpose of this retrospective analysis was to evaluate outcomes of patients re-irradiated for thoracic tumours in terms of overall survival (OS), local progression-free survival (LPFS), toxicity and dose–volume parameters. Sixty-two patients with locally recurrent previously irradiated lung cancer were analysed retrospectively (NSCLC n = 52, SCLC n = 10). Target volumes both in lung and mediastinum were re-irradiated with conventional three-dimensional or intensity-modulated radiotherapy techniques. Median overall dose of re-irradiation was 38.5 Gy (range 20–60 Gy) with a median single dose per fraction of 2 Gy (1.8–3.0 Gy). Clinical documents and treatment plans were evaluated. Median follow-up was 8.2 months (range 0–27 months). OS following re-irradiation was 9.3 months (range: 0–27 months) and LPFS was 6.5 months (range: 0–24 months). OS and LPFS were not affected by histology, total dose or patient age and gender. OS was improved in patients whose re-irradiation volumes included less than two mediastinal lymph node stations (p = 0.016). Twelve patients suffered from pneumonitis ≥grade II (19%) and two from pneumonitis grade III. One patient presumably died from pneumonitis grade V. A slight decline in forced expiratory volume (FEV1) was detected in post-re-irradiation lung function testing. Re-irradiation is an option for patients with tumour recurrence to control local progression and lower the symptom burden. Oncological outcome appears to be affected by size, location of mediastinal target volumes and lung function. Prospective clinical trials are warranted to substantiate the role of re-irradiation in recurrent lung cancer.

Purpose: To examine change in gross motor function in children with cerebral palsy (CP) following repeated periods of intensive physiotherapy in real-life group-settings, with expected motor develo...

Background Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10-15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. Patients and methods Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45-59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0-2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival. Results Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3-34.0, 95% CI: 11.0-32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein

A white blood cell (WBC) count with partial differential is an important clinical laboratory test. However, current methods to perform a WBC count and differential are difficult to use at the point of care or too expensive for use in low-resource settings. To meet this need, we developed the LeukoScope: a low-cost system to measure a WBC and neutrophil count from a single drop of blood at the point of care. The LeukoScope is battery powered and has a sample-to-answer time of

The original version of this article unfortunately contained mistakes. The name of the author Hess was corrected. Fig. 1 contained orthographic errors. Additionally, to ensure that the hyperlinks embedded in Fig. 1 can be accessed, Fig. 1 was added as Supplement 3. A reference to Supplement 3 has been added in the description of Fig. 1 in the article. The original article has been corrected. Korrektur zu 10.1007/s00066-021-01843-9

ObjectiveApproximately 3.4% of adults aged >75 years suffer from aortic stenosis (AS). Guideline indications for aortic valve replacement (AVR) distinguish between patients with symptomatic and asymptomatic severe AS. The present analysis aims to assess contemporary practice in the treatment of severe AS across Europe and identify characteristics associated with treatment decisions, namely denial of AVR in symptomatic patients and assignment of asymptomatic patients to AVR.MethodsParticipants of the prospective, multinational IMPULSE database of patients with severe AS were grouped according to AS symptoms, and stratified into subgroups based on assignment to/denial of AVR.ResultsOf 1608 symptomatic patients, 23.8% did not undergo AVR and underwent medical treatment. Denial was independently associated with multiple factors, including severe frailty (p=0.024); mitral (p=0.002) or tricuspid (p=0.004) regurgitation grade III/IV, and the presence of renal impairment (p=0.017). Of 392 asymptomatic patients, 86.5% had no prespecified indication for AVR. Regardless, 36.3% were assigned to valve replacement. Those with an indexed aortic valve area (AVA; p=0.045) or left ventricular ejection fraction (LVEF; pConclusionsThere may be considerable discrepancies between guideline-based recommendations and clinical practice decision-making in the treatment of AS. It appears that guidelines may not fully capture the complete clinical spectrum of patients with AS. Thus, there is a need to find ways to increase their acceptance and the rate of adoption.

Competitions often serve to identify the most capable individual or increase overall effort in corporations and sports. Whether to provide individuals with (ranking) information in such a context is an intriguing question. We investigate individuals' competitive behavior under different degrees of ex-ante information regarding their competitors’ ability. A natural experiment in table tennis, particularly, the introduction of table tennis rankings in 2010, allows us to study the effect of (standardized) information on individual behavior, based on more than 1.5 million matches for over 34,000 individuals. Our results suggest that favorites benefit most from additional information as their winning probability increases, whereas underdogs are discouraged by such (standardized) information. These findings are stronger for more heterogeneous matches and hold even if players possess private information. Consistently, competition intensity declines after the release of information regarding competitors' ability. Our results imply that corporations should strategically provide information based on their specific aim.

Aim: to report clinical outcome in patients with acinic cell carcinoma of the salivary glands treated with intensity-modulated radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) boost. Materials and Methods: all patients with acinic cell carcinoma of the salivary glands treated at the Heidelberg Ion-Beam Therapy Center were considered for this retrospective analysis. All patients received a CIRT boost with 18&ndash, 24 Gy radiobiologic effectiveness (RBE)-weighted dose in 3 Gy RBE-weighted dose per fraction followed by IMRT, with 50&ndash, 54 Gy in 2 Gy per fraction. Disease outcome was evaluated for local (LR), nodal (NR), distant recurrence (DR), and disease-free (DFS) and overall survival (OS). Morbidity was scored based on Common Terminology Criteria for Adverse Events (CTCAE) version 5. Descriptive statistics and the Kaplan-Meier method were used for analysis. Results: fifteen patients were available for analysis. Median follow-up after radiotherapy was 43 months. Six patients were treated for primary disease and nine for recurrent disease. Eight patients were treated with radiotherapy for macroscopic disease. Disease recurrence was observed in four patients: 1 LR, 2 NR, and 2 DR, 5-year local control, DFS, and OS were 80%, 52%, and 80%, respectively. No radiotherapy-related G3-5 morbidity was observed. Conclusion: In acinic cell carcinoma, IMRT with carbon ion radiotherapy boost leads to excellent results after R1-resection and is a promising treatment modality for definitive treatment in inoperable patients.

To report outcome (freedom from local progression: FFLP, overall survival: OS, and toxicity) after stereotactic, palliative, or highly conformal fractionated (> 12) radiotherapy (SBRT, Pall-RT, 3DCRT/IMRT) for adrenal metastases in a retrospective multicenter cohort within the framework of the German Society for Radiation Oncology (DEGRO). Adrenal metastases treated with SBRT (≤ 12 fractions, biologically effective dose, (BED10) ≥ 50 Gy), 3DCRT/IMRT (> 12 fractions, BED10 ≥ 50 Gy) or Pall-RT (BED10 < 50 Gy) were eligible for this analysis. In addition to unadjusted FFLP (Kaplan-Meier/Log-rank), we calculated the competing-risk-adjusted local recurrence rate (CRA-LRR). 326 patients with 366 metastases were included by 21 centers (median follow-up: 11.7 months). Treatment was SBRT, 3DCRT/IMRT, and Pall-RT in 260, 27, and 79 cases, respectively. Most frequent primary tumors were non-small-cell lung cancer (NSCLC; 52.5%), SCLC (16.3%), and melanoma (6.7%). Unadjusted FFLP was higher after SBRT v. Pall-RT (p = 0.026) while numerical differences in CRA-LRR between groups did not reach statistical significance (1-year CRA-LRR: 13.8%, 17.4%, and 27.7%). OS was longer after SBRT v. other groups (p < 0.05) and increased in patients with locally-controlled metastases in a landmark analysis (p < 0.0001). Toxicity was mostly mild; notably, 4 cases of adrenal insufficiency occurred, 2 of which were likely caused by immunotherapy or tumor progression. RT for adrenal metastases was associated with a mild toxicity profile in all groups and a favorable 1-year CRA-LRR after SBRT or 3DCRT/IMRT. 1-year FFLP was associated with longer OS. Dose-response analyses for the dataset are underway. This article is protected by copyright. All rights reserved.

Due to its rarity, there are no randomized trials investigating the outcome of adjuvant radiotherapy in MBC. This study reports on patient and tumor characteristics of 41 consecutive MBC patients treated between 1990 and 2018 and on clinical outcomes after surgical resection of tumors and adjuvant radiotherapy of the chest wall or breast. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS), and toxicity were evaluated. After a median follow-up of 80 months (95% CI: 14.6&ndash, 213.8 months) there was only one recurrence, in a patient&rsquo, s locoregional lymph nodes 17 months after start of radiotherapy, resulting in an LC rate of 100% at 5 years and a 5-year LRC rate of 97.4% (standard deviation (SD): 0.025). Five-year DFS and OS rates were 64.6% (SD: 0.085) and 57.2% (SD: 0.082), respectively. Adjuvant radiotherapy was tolerated well without high-grade (CTCAE grade &gt, II) adverse events. After tumor resection and adjuvant radiotherapy, LC and LRC rates in MBC patients are excellent and comparable to results found for female breast cancer (FBC) patients. However, as patients are often diagnosed with locally advanced, higher-risk tumors, distant recurrences remain the major failure pattern.

BackgroundContemporary data regarding the impact of comorbidities on the clinical presentation and management of patients with severe aortic stenosis (AS) are scarce.MethodsProspective registry of severe patients with AS across 23 centres in nine European countries.ResultsOf the 2171 patients, chronic kidney disease (CKD 27.3%), left ventricular ejection fraction (LVEF) ConclusionsComorbidities in severe patients with AS affect the presentation and management of patients with severe AS. TAVI was offered more often than SAVR and performed within a shorter time period.

Hybrid magnetic resonance (MR) linear accelerators (MR-Linacs) for radiotherapy allow for the visualization and tracking of moving target volumes during the entire treatment. This makes gated treatments possible, decreasing the irradiated volumes and thus sparing healthy tissue from unnecessary radiation dose. Conventionally, tumors that are subject to respiration motion are treated by irradiating the entire area of potential target presence (internal target volume, ITV). This study presents three patient cases (lung, adrenal gland, and liver tumors) treated with gated MR-guided radiotherapy and compares the treatment plans retrospectively with conventional ITV plans.The gross tumor volume was delineated on MR and computed tomography (CT) images of the patients, and MR-Linac treatment plans were generated using additional clinical and planning target volume margins. The motion of the gross tumor volume was evaluated on two-dimensional cine-MRI images during the entire MR-Linac treatment. Based on the motion analysis, standard ITV-based plans were retrospectively created and compared by means of irradiated target volumes and dose-volume parameters.For the MR-Linac plans, the irradiated treatment volumes were reduced by an average of 62% across the three cases, and for one case the ITV-based target volume would have overlapped with a critical organ. Target volume coverage was much better and the lung and adrenal MR-Linac plans revealed superior sparing of the organs at risks thanks to gated treatments.Dosimetrically beneficial treatment plans with promising clinical outcomes can be applied when using gated MR-guided radiotherapy. Future studies will reveal which patients will benefit most from this technique. To utilize the full potential of online adaptive, individualized MR-guided therapy, the close collaboration of radio-oncology and radiology is needed.HINTERGRUND: Hybrid-Magnetresonanz(MR)-Linearakzeleratoren (MR-Linacs) für die Strahlentherapie ermöglichen die Visualisierung und Verfolgung beweglicher Zielvolumina während der gesamten Behandlung. Das erlaubt atemgesteuerte Therapien, vermindert die bestrahlten Volumina und schont somit gesundes Gewebe vor unnötiger Strahlendosis. Konventionell werden Tumoren, die der Atembewegung ausgesetzt sind, durch Bestrahlung des gesamten Bereichs behandelt, in dem sich das Ziel befinden kann („internal target volume“, ITV). In der vorliegenden Studie werden 3 Fälle vorgestellt (Lungen‑, Nebennieren- und Lebertumor), die mittels atemgesteuerter MR-geführter Strahlentherapie behandelt wurden, dabei werden die Behandlungsplanungen retrospektiv mit konventionellen ITV-Planungen verglichen.Das makroskopische Tumorvolumen wurde auf MRT- und Computertomographie(CT)-Aufnahmen der Patienten abgegrenzt, und die jeweilige MR-Linac-Behandlungsplanung wurde unter Berücksichtigung zusätzlicher klinischer und Planungszielvolumenmargen erstellt. Die Bewegung des makroskopischen Tumorvolumens wurde auf zweidimensionalen CINE-MRT-Bildern während der gesamten MR-Linac-Behandlung beurteilt. Auf Grundlage der Bewegungsanalyse wurden retrospektiv Standard-ITV-Planungen erstellt und anhand von bestrahlten Zielvolumina und Dosis-Volumen-Parametern verglichen.Für die jeweilige MR-Linac-Planung wurde in den 3 Fällen das bestrahlte Behandlungsvolumen um durchschnittlich 62% reduziert, und in einem Fall hätte das ITV-basierte Zielvolumen sich mit einem kritischen Organ überschnitten. Die Zielvolumenabdeckung war viel besser und die MR-Linac-Planung für die Lunge und die Nebenniere wiesen eine deutlichere Schonung der gefährdeten Organe durch die atemgesteuerte Behandlung auf.Eine dosimetrisch vorteilhafte Behandlungsplanung mit vielversprechenden klinischen Ergebnissen kann eingesetzt werden, wenn die atemgesteuerte MR-geführte Strahlentherapie angewandt wird. Zukünftige Studien werden zeigen, welche Patienten den größten Vorteil durch diese Technik haben. Um das ganze Potenzial der online adaptiven, individualisierten MR-geführten Therapie zu nutzen, ist eine enge Zusammenarbeit zwischen der Radioonkologie und der Radiologie erforderlich.

Purpose In the modern era, improvements in radiation therapy techniques have paved the way for simultaneous integrated boost irradiation in adjuvant breast radiation therapy after breast conservation surgery. Nevertheless, randomized trials supporting the noninferiority of this treatment to historical standards of care approach are lacking. Methods A prospective, multicenter, randomized phase 3 trial (NCT01322854) was performed to analyze noninferiority of conventional fractionated intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) to 3-D conformal radiation therapy with sequential boost (3-D-CRT-seqB) for breast cancer patients. Primary outcomes were local control (LC) rates at 2 and 5 years (noninferiority margin at hazard ratio [HR] of 3.5) as well as cosmetic results 6 weeks and 2 years after radiation therapy (evaluated via photo documentation calculating the relative breast retraction assessment [pBRA] score [noninferiority margin of 1.25]). Results A total of 502 patients were randomly assigned from 2011 to 2015. After a median follow-up of 5.1 years, the 2-year LC for the IMRT-SIB arm was noninferior to the 3-D-CRT-seqB arm (99.6% vs 99.6%, respectively; HR, 0.602; 95% CI, 0.123-2.452; P = .487). In addition, noninferiority was also shown for cosmesis after IMRT-SIB and 3-D-CRT-seqB at both 6 weeks (median pBRA, 9.1% vs 9.1%) and 2 years (median pBRA, 10.4% vs 9.8%) after radiation therapy (95% CI, –0.317 to 0.107 %; P = .332). Cosmetic assessment according to the Harvard scale by both the patient and the treating physician as well as late-toxicity evaluation with the late effects normal tissues- subjective, objective, management, analytic criteria, a score for the evaluation of long-term adverse effects in normal tissue, revealed no significant differences between treatment arms. In addition, there was no difference in overall survival rates (99.6% vs 99.6%; HR, 3.281; 95% CI: –0.748 to 22.585; P = .148) for IMRT-SIB and 3-D-CRT-seqB, respectively. Conclusions To our knowledge, this is the first prospective trial reporting the noninferiority of IMRT-SIB versus 3-D-CRT-seqB with respect to cosmesis and LC at 2 years of follow-up. This treatment regimen considerably shortens adjuvant radiation therapy times without compromising clinical outcomes.

Stereotactic body radiotherapy (SBRT) to central and ultracentral lung tumors carries a risk of excessive toxicity. This study analyzed changes in pulmonary function tests (PFT) and their correlation with overall survival (OS) in 107 patients following central (n = 62) or ultracentral (n = 45) lung SBRT. Ultracentral location was defined as planning target volume overlap with the proximal bronchial tree (PBT). Vital capacity (VC) (&minus, 0.3 l, absolute &minus, 9.4% of predicted, both p &lt, 0.001) and forced expiratory volume in the first second (FEV1s) (&minus, 0.2 l, absolute &minus, 7.7% of predicted, both p &lt, 0.001) significantly decreased following SBRT. Higher maximum dose to the PBT significantly correlated with a steeper decline in VC (p = 0.005) and FEV1s (p = 0.03) over time. Pronounced decline in FEV1s between 6 and 12 months (HR = 0.90, p = 0.006) and pronounced decline in VC between baseline and 12 months (HR = 0.95, p = 0.004) independently correlated with worse OS. Consequently, PFT presented a statistically significant albeit clinically mild decrease in lung volumes following central and ultracentral SBRT that correlated moderately with maximum dose to the PBT. Stronger decline in pulmonary function was associated with constrained survival, advocating consequent performance of PFT during follow-up.

IntroductionThe PACIFC trial demonstrated a significant benefit of durvalumab consolidation immunotherapy (CIT) after definitive platinum-based chemoradiotherapy (P-CRT) for survival in stage III non-small cell lung cancer (NSCLC). It is unknown how many patients are eligible in clinical practice to receive CIT according to PACIFIC criteria compared to real administration rates and what influencing factors are.Patients and MethodsWe analyzed 442 patients with unresectable stage III NSCLC who received P-CRT between 2009 and 2019 regarding CIT eligibility rates according to PACIFIC criteria and administration rates since drug approval.ResultsSixty-four percent of 437 patients were male, median age was 63 years [interquartile range (IQR): 57–69]. The most common histologic subtypes were adenocarcinoma (42.8%) and squamous cell carcinoma (41.1%), most tumors were in stage IIIB (56.8%). Mean PD-L1 tumor proportion score (TPS) was 29.8% (IQR: 1–60). The median total RT dose was 60 Gy (IQR: 60–66). Platinum component of P-CRT was evenly distributed between cisplatin (51.4%) and carboplatin (48.6%). 50.3% of patients were eligible for CIT according to PACIFIC criteria. Observed contraindications were progressive disease according to RECIST (32.4%), followed by a PD-L1 TPS < 1% (22.3%), pneumonitis CTCAE ≥ 2 (12.6%) and others (4.9%). One year after drug approval, 85.6% of patients who were eligible according to PACIFIC criteria actually received CIT. Time interval between chemotherapy start and radiation therapy start (OR 0.9, 95% CI: [0.9; 1.0] p = 0.009) and probably cisplatin as platinum-component of P-CRT (OR 1.5, 95% CI: [1.0; 2.4] p < 0.061) influence CIT eligibility. Highly positive PD-L1 TPS (≥50%; (OR 2.4, 95% CI: [1.3; 4.5] p = 0.004) was associated to a better chance for CIT eligibility.ConclusionEighty-five percent of potentially eligible patients received CIT one year after drug approval. Fifty percent of patients did not meet PACIFIC criteria for durvalumab eligibility, this was mainly caused by disease progression during platinum-based CRT, followed by therapy-related pneumonitis and PD-L1 TPS < 1% (in view of the EMA drug approval).

Purpose: Proton radiotherapy (PRT) is potentially associated with a lower risk for secondary malignancies due to a decreased integral dose to the surrounding organs at risk (OARs). Prospective trials confirming this are lacking due to the need for long-term follow-up and the ethical complexities of randomizing patients between modalities. The objective of the current study is to calculate the risk for secondary malignancies following PRT and photon-based intensity-modulated radiotherapy (IMRT). Materials and Methods: Twenty-three patients (16 female and seven male), previously treated with active scanning PRT for malignant mediastinal lymphoma at Heidelberg Ion Beam Therapy Center, were retrospectively re-planned using helical photon IMRT. The risk for radiation-induced secondary malignancies was estimated and evaluated using two distinct prediction models (1–4). Results: According to the Dasu model, the median absolute total risk for tumor induction following IMRT was 4.4% (range, 3.3–5.8%), 9.9% (range, 2.0–27.6%), and 1.0% (range, 0.5–1.5%) for lung, breast, and esophageal cancer, respectively. For PRT, it was significantly lower for the aforementioned organs at 1.6% (range, 0.7–2.1%), 4.5% (range, 0.0–15.5), and 0.8% (range, 0.0–1.6%), respectively (p ≤ 0.01). The mortality risk from secondary malignancies was also significantly reduced for PRT relative to IMRT at 1.1 vs. 3.1% (p ≤ 0.001), 0.9 vs. 1.9% (p ≤ 0.001), and 0.7 vs. 1.0% (p ≤ 0.001) for lung, breast, and esophageal tumors, respectively. Using the Schneider model, a significant risk reduction of 54.4% (range, 32.2–84.0%), 56.4% (range, 16.0–99.4%), and 24.4% (range, 0.0–99.0%) was seen for secondary lung, breast, and esophageal malignancies, favoring PRT vs. X-ray-based IMRT (p ≤ 0.01). Conclusion: Based on the two prediction models, PRT for malignant mediastinal lymphoma is expected to reduce the risk for radiation-induced secondary malignancies compared with the X-ray-based IMRT. The young age and the long natural history of patients diagnosed with mediastinal lymphoma predisposes them to a high risk of secondary malignancies following curative radiotherapy treatment and, as a consequence, potentially reducing this risk by utilizing advanced radiation therapy techniques such as PRT should be considered.

Background Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription. Methods and Materials We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BEDmin); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BEDmax); and (3) the average between near-minimum and near-maximum doses (yielding BEDave). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion. Results There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BEDave was the best predictor of risk of local recurrence, and a model based on BEDmin had substantially less evidential support. In univariable logistic regression, the model based on BEDave also performed best. Multivariable classification using fast and frugal trees revealed BEDmax to be the most important predictor, followed by BEDave. Conclusions BEDave was generally better correlated with tumor control probability than either BEDmax or BEDmin. Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation.

We aimed to gain more evidence regarding the feasibility, toxicity, and oncological outcome of primary brachytherapy in patients with medically inoperable endometrial cancer. Thirteen patients receiving primary brachytherapy &plusmn, external beam radiotherapy (EBRT) for endometrial cancer due to medical inoperability were identified. The Kaplan&ndash, Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local failure-free survival (LFFS). Univariate outcome analyses were performed using the log-rank test. Peri-interventional complications, acute and chronic toxicities were evaluated. Additionally, we performed a Pubmed search and review of the literature of the last 10 years. Mean age at time of diagnosis was 73.9 years (60.4&ndash, 87.1 years). Eleven patients were staged FIGO IA/B and one patient each with FIGO IIIA and IIIC. Kaplan&ndash, Meier-estimated 2-/5-year LFFS were 76.2%/56.4%, respectively. High grading correlated with a worse LFFS (p = 0.069). Kaplan&ndash, Meier-estimated 2-/5-year PFS were 76.9%/53.8% and 2-/5-year-OS were 76.9%/69.2%, respectively. No acute toxicities &gt, grade II and only two late toxicities grade II/III occurred. We observed three peri-interventional complications. The available evidence suggests high rates of local control after definitive brachytherapy for inoperable endometrial cancer with a favorable toxicity profile. Definitive brachytherapy +/- EBRT should be considered as the preferred approach for this patient group.

Background Fatigue is one of the most common and distressing side-effects of breast cancer radiotherapy. According to current guidelines, accelerated partial breast irradiation (APBI) may be considered as an alternative treatment option for women with early-stage low-risk breast cancer. One method for APBI is single-dose intraoperative radiotherapy (IORT) applied directly to the tumor bed during breast conserving surgery (BCS). The COSMOPOLITAN trial therefore aims to analyze the intensity of fatigue following single-shot IORT with electrons (IOERT) compared to conventional hypofractionated whole breast irradiation (WBI) in low risk early breast cancer patients. Methods This trial is conducted as a multicenter, prospective, randomized, two-arm phase II study comparing the intensity of fatigue in early-stage breast cancer (cT1cN0cM0, tumor size 50 years) treated either with WBI or APBI after BCS. Secondary outcomes investigated are tumor control, overall survival (OS), disease-free survival (DFS), acute and chronic toxicity, quality of life (QoL) and cosmesis. A total of 202 patients will be randomized into two arms: Patients in arm A will receive WBI (40.05 Gy, 15 fractions) after surgical resection, while patients in arm B will receive IOERT (21 Gy to the 90%-isodose) during BCS. Fatigue will be assessed 12 weeks post surgery with the help of the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale. Discussion The present trial aims to evaluate treatment response to compare single-shot intraoperative electron APBI to conventional WBI following BCS in early-stage low risk breast cancer patients. Fatigue is selected as the primary, patient-reported endpoint due its major clinical relevance. Trial registration The study is prospectively registered on February 12th, 2019: Clinicaltrials.gov, NCT03838419. “Intraoperative Electron Radiotherapy for Low-risk Early Breast Cancer (COSMOPOLITAN)”. Study status Ongoing study. Start of recruitment was December 2019.

Purpose/Objective: Oligometastatic disease (OMD) and oligoprogressive disease (OPD) describe tumor states with a limited metastasization. In contrast to other disease states, treatment of OMD or OPD has not yet become common for breast cancer. We sought to understand the outcomes and toxicities of this treatment paradigm. Material/Methods: We retrospectively analyzed female breast cancer patients with OMD (≤3 metastases) or OPD (1 progressive lesion) who received stereotactic body radiotherapy (SBRT) for their respective extracranial metastatic lesions between 01/2002 and 07/2019. Survival analysis was performed using the Kaplan-Meier method with log-rank test being used for evaluation of significance. Cox regression was used to detect prognostic outcome factors. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Results: Forty-six patients (70% OMD; 30% OPD) with 58 lesions met criteria for inclusion. The majority of treatments (34 out of 58; 58.6%) were delivered from 2017 to 2018. Treatment sites were bone, liver, lung [n = 19 (33%) for each site], and adrenal gland [n = 1 (1%)]. Median biologically effective dose (BED at α/β = 10) was 81.6 Gy (range: 45–112.5 Gy) and median planning target volume was 36.60 mL (range: 3.76–311.00 mL). At 2 years, local control (LC) was 89%, distant control (DC) was 44%, progression free survival (PFS) was 17% and overall survival (OS) was 62%. Multivariate analysis identified the diagnosis of a solitary metastasis as an independent prognostic factor for superior DC (HR = 0.186, CI [0.055; 0.626], p = 0.007) and PFS (HR = 0.363, CI [0.152; 0.863], p = 0.022). OS was independently inferior for patients treated at a higher age (HR = 5.788, CI [1.077; 31.119] p = 0.041). Nine (15.5%) grade I° and one (1.7%) grade II° toxicities were recorded, with no grade III° or higher toxicities. Conclusion: Extracranial SBRT in breast cancer patients with OMD or OPD was well-tolerated with excellent LC. SBRT should especially be offered to younger OMD and OPD breast cancer patients with only one metastasis. The increase in utilization since 2017 points toward a growing acceptance of SBRT for OMD and OPD in breast cancer.

Purpose: Several prognostic indexes for overall survival (OS) after radiotherapy of brain metastases in breast cancer patients exist but are mainly validated for whole-brain radiotherapy or not specifically for breast cancer patients. To date, no such index provides information beyond mere OS. Methods: We retrospectively analyzed 95 breast cancer patients treated with stereotactic radiosurgery for 203 brain metastases. The Kaplan-Meier method with log-rank test was used to assess OS, local control (LC), distant cranial control (DCC), and extracranial control (EC). Cox regression was applied to detect prognostic outcome factors. A point scoring system was designed to stratify patients based on outcome. Nine established prognostic indexes were analyzed using the concordance index (c-index). Results: Two out of nine analyzed prognostic indexes for OS showed a significant c-index, the breast graded prognostic assessment (bGPA; 0.631; 95% CI, 0.514-0.748; p = 0.037) and the modified bGPA (mod-bGPA; 0.662; 95% CI, 0.547-0.777; p = 0.010). Significant results from multivariate analysis (Karnofsky Performance Score, Her2/neu receptor status, extracranial control) were used to generate a new point system: the breast cancer stereotactic radiotherapy score (bSRS), which discriminated three significantly different prognostic groups, for LC, DCC, EC, and OS, respectively. However, the c-index was only significant for OS (0.689; 95% CI, 0.577-0.802; p = 0.003). Conclusions: The new bSRS score was superior to the bGPA and mod-bGPA scores for prognosis of OS. The bSRS is easy to use and the first tool, which might also provide outcome assessment beyond mere OS. Future studies need to validate these findings.