Quality requirements for MRI simulation in cranial stereotactic radiotherapy: a guideline from the German Taskforce "Imaging in Stereotactic Radiotherapy".

Accurate Magnetic Resonance Imaging (MRI) simulation is fundamental for high-precision stereotactic radiosurgery and fractionated stereotactic radiotherapy, collectively referred to as stereotactic radiotherapy (SRT), to deliver doses of high biological effectiveness to well-defined cranial targets. Multiple MRI hardware related factors as well as scanner configuration and sequence protocol parameters can affect the imaging accuracy and need to be optimized for the special purpose of radiotherapy treatment planning. MRI simulation for SRT is possible for different organizational environments including patient referral for imaging as well as dedicated MRI simulation in the radiotherapy department but require radiotherapy-optimized MRI protocols and defined quality standards to ensure geometrically accurate images that form an impeccable foundation for treatment planning. For this guideline, an interdisciplinary panel including experts from the working group for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology (DEGRO), the working group for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics (DGMP), the German Society of Neurosurgery (DGNC), the German Society of Neuroradiology (DGNR) and the German Chapter of the International Society for Magnetic Resonance in Medicine (DS-ISMRM) have defined minimum MRI quality requirements as well as advanced MRI simulation options for cranial SRT.

Identifying core MRI sequences for reliable automatic brain metastasis segmentation.

BACKGROUND: Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS: We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS: The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS: A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

Development and implementation of a student tumor board as a teaching format for medical students.

PURPOSE: Tumor boards serve as established platforms for interdisciplinary expert discussions and therapeutic recommendations tailored to individual patient characteristics. Despite their significance, medical students often lack exposure to such interdisciplinary discussions as tumor boards are currently not integrated into medical curricula. To address this, we aimed to enhance future physicians' interdisciplinary communication skills and subject-specific knowledge by introducing an interactive series of five linked tumor board seminars within the domain of neuro-oncology. METHODS: We developed a neuro-oncological student tumor board using a flipped-classroom format. The primary objectives of this case-centered approach included fostering an understanding of the tumor board process, active participation in multidisciplinary case discussions, honing appropriate communication strategies, and creating personalized therapy plans that consider inputs from all relevant disciplines, individual patient factors, and ethical considerations. To gauge the effectiveness of the seminar series, we administered structured pre- and post-course questionnaires. RESULTS: Fourteen medical students in third to fifth year participated in the pilot series. Despite its organizational complexity, the interdisciplinary seminars were feasible. Students demonstrated significant growth in competence, aligned with predefined learning objectives. Notably, they appreciated the supportive learning environment and interactive teaching format, which kindled their interest in interdisciplinary oncology. CONCLUSION: Active participation in a student tumor board can empower students to tackle the diverse challenges of caring for cancer patients within an interdisciplinary team during the early stages of their careers. The student tumor board represents an innovative, learner-centered approach to teach interdisciplinary cancer treatment, communication strategies, and ethical aspects of medical practice.

Assessment of dual-energy computed tomography derived virtual monoenergetic imaging for target volume delineation of brain metastases.

BACKGROUND: Objective and subjective assessment of image quality of brain metastases on dual-energy computed tomography (DECT) virtual monoenergetic imaging (VMI) and its impact on target volume delineation. MATERIALS AND METHODS: 26 patients with 37 brain metastases receiving Magnetic Resonance Imaging (MRI) and DECT for stereotactic radiotherapy planning were included in this retrospective analysis. Lesion contrast (LC), contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were assessed for reconstructed VMI at 63 keV and artificial 120 kV Computed Tomography (CT). Image contrast and demarcation of metastases between 120 kV CT, VMI and MRI were subjectively assessed. Brain metastases were delineated by four radiation oncologists on VMI with a fixed or free brain window and contours were compared to solely MRI-based delineation using the Dice similarity coefficient. RESULTS: LC, CNR and SNR were significantly higher in VMI than in 120 kV CT (p < 0.0001). Image contrast and lesion demarcation were significantly better on VMI compared to 120 kV CT (p < 0.0001). Mean gross tumor volume (GTV)/planning target volume (PTV) Dice similarity coefficients were 0.87/0.9 for metastases without imaging uncertainties (no artifacts, calcification or impaired visibility with MRI) but worse for metastases with imaging uncertainties (0.71/0.74). Target volumes delineated on VMI were around 5-10% smaller compared to MRI. CONCLUSION: Image quality of VMI is objectively and subjectively superior to conventional CT. VMI provides significant advantages in stereotactic radiotherapy planning with improved visibility of brain metastases and geometrically distortion-free representation of brain metastases. Beside a plausibility check of MRI-based target volume delineation, VMI might improve reliability and accuracy in target volume definition particularly in cases with imaging uncertainties with MRI.

Long-Term Total Neoadjuvant Therapy Leads to Impressive Response Rates in Rectal Cancer: Results of a German Single-Center Cohort.

Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy-TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II-III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials.

Strategic Clinical Trial Design for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) involves infusion of cancer patients with a tumor-seeking, boron-loaded compound and irradiation by a beam of neutrons, with an energy range of 1 eV-10 keV. Neutron capture in the 10B atoms results in an effective lethal radiation dose to the tumor cells, while sparing the healthy tissue. Recently available accelerator-based irradiation facilities facilitate developing BNCT to a treatment modality. However, the binary principle of BNCT, together with other points, is challenging in designing clinical trials that allow a timely and safe introduction of this innovative targeted modality into clinical practice. We propose a methodological framework to work toward a systematic, coordinated, and internationally accepted and evidence-based approach.

Planning adaptive treatment by longitudinal response assessment implementing MR imaging, liquid biopsy and analysis of microenvironment during neoadjuvant treatment of rectal cancer (PRIMO).

INTRODUCTION: Conducting neoadjuvant chemoradiotherapy (CRT) and additional preoperative consolidating chemotherapy (CTx), that is, total neoadjuvant therapy (TNT), improves local control and complete response (CR) rates in locally advanced rectal cancer (LARC), putting the focus on organ preservation concepts. Therefore, assessing response before surgery is crucial. Some LARC patients would either not benefit from intensification by TNT or may reach CR, making resection not mandatory. Treatment of LARC should therefore be based on patient individual risk and response to avoid overtreatment.The "PRIMO" pilot study aims to determine early response assessment to form a basis for development and validation of a noninvasive response prediction model by a subsequent prospective multicenter trial, which is highly needed for individual, response-driven therapy adaptions. METHODS: PRIMO is a prospective observational cohort study including adult patients with LARC receiving neoadjuvant CRT. At least 4 multiparametric magnetic resonance imaging (MRI) scans (diffusion-weighted imaging [DWI] and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyze circulating tumor cells (CTC) and cell-free tumor DNA (ctDNA) are scheduled. Pelvic radiotherapy (RT, 50.4 Gy) will be performed in combination with a 5-fluorouracil/oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional (immuno)histochemical markers, such as tumor-infiltrating lymphocytes (TIL) and programmed death ligand 1 (PD-L1) status will be analyzed before and after CRT. Routine resection is scheduled subsequently, nonoperative management is offered alternatively in case of clinical CR (cCR).The primary endpoint is pathological response; secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TIL. These are evaluated for early response prediction during neoadjuvant therapy, in order to develop a noninvasive response prediction model for subsequent analyses. DISCUSSION: Early response assessment is the key in differentiating "good" and "bad" responders during neoadjuvant CRT, allowing adaption of subsequent therapies (additional consolidating CTx, organ preservation). This study will contribute in this regard, by advancing MR imaging and substantiating new surrogate markers. Adaptive treatment strategies might build on these results in further studies.

Development, implementation, and results of a simulation-based hands-on brachytherapy workshop for medical students.

PURPOSE: The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) require the development of competence-oriented teaching formats. In addition, there is a great need for high-quality teaching in the field of radiation oncology, which manifests itself already during medical school. For this reason, we developed a simulation-based, hands-on medical education format to teach competency in performing accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy for early breast cancer. In addition, we designed realistic breast models suitable for teaching both palpation of the female breast and implantation of brachytherapy catheters. METHODS: From June 2021 to July 2022, 70 medical students took part in the hands-on brachytherapy workshop. After a propaedeutic introduction, the participants simulated the implantation of single-lead catheters under supervision using the silicone-based breast models. Correct catheter placement was subsequently assessed by CT scans. Participants rated their skills before and after the workshop on a six-point Likert scale in a standardized questionnaire. RESULTS: Participants significantly improved their knowledge-based and practical skills on APBI in all items as assessed by a standardized questionnaire (mean sum score 42.4 before and 16.0 after the course, p < 0.001). The majority of respondents fully agreed that the workshop increased their interest in brachytherapy (mean 1.15, standard deviation [SD] 0.40 on the six-point Likert scale). The silicone-based breast model was found to be suitable for achieving the previously defined learning objectives (1.19, SD 0.47). The learning atmosphere and didactic quality were rated particularly well (mean 1.07, SD 0.26 and 1.13, SD 0.3 on the six-point Likert scale). CONCLUSION: The simulation-based medical education course for multicatheter brachytherapy can improve self-assessed technical competence. Residency programs should provide resources for this essential component of radiation oncology. This course is exemplary for the development of innovative practical and competence-based teaching formats to meet the current reforms in medical education.

Development and external validation of an MRI-based neural network for brain metastasis segmentation in the AURORA multicenter study.

BACKGROUND: Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability. METHODS: We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers. RESULTS: Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07). CONCLUSION: Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions.

Early Mortality among Patients with Head and Neck Cancer Diagnosed in Thuringia, Germany, between 1996 and 2016-A Population-Based Study.

Population-based studies on early mortality in head and neck cancer (HNC) are sparse. This retrospective population-based study investigated early mortality of HNC and the influence of patients' tumor and treatment characteristics. All 8288 patients with primary HNC of the German federal state Thuringia from 1996 to 2016 were included. Univariate and multivariate analysis were performed to identify independent factors for 30-day, 90-day, and 180-day mortality. The 30-, 90-, and 180-day mortality risks were 1.8%, 5.1%, and 9.6%, respectively. In multivariable analysis, male sex (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.08-1.84), increasing age (OR 1.81; CI 1.49-2.19), higher T (T4: OR 3.09; CI 1.96-4.88) and M1 classification (OR 1.97; CI 1.43-2.73), advanced stage (IV: OR 3.97; CI 1.97-8.00), tumors of the cavity of mouth (OR 3.47; CI 1.23-9.75), oropharynx (OR 3.01; CI 1.06-8.51), and hypopharynx (OR 3.27; CI 1.14-9.40) had a significantly greater 180-day mortality. Surgery (OR 0.51; CI 0.36-0.73), radiotherapy (OR 0.37; CI 0.25-0.53), and multimodal therapy (OR 0.10; CI 0.07-0.13) were associated with decreased 180-day mortality. Typical factors associated with worse overall survival had the most important impact on early mortality in a population-based setting.

Role of Intraparotid and Neck Lymph Node Metastasis in Primary Parotid Cancer Surgery: A Population-Based Analysis.

This population-based study investigated the prognostic role of intraparotid (PAR) and cervical lymph node (LN) metastasis on overall survival (OS) of primary parotid cancer. All 345 patients (median age: 66 years; 43% female, 49% N+, 31% stage IV) of the Thuringian cancer registries with parotid cancer from 1996 to 2016 were included. OS was assessed in relation to the total number of removed PAR and cervical LN, number of positive intraparotid (PAR+), positive cervical LN, LN ratio, log odds of positive LN (LODDS), as well as including the PAR as LODDS-PAR. PAR was assessed in 42% of the patients (22% of these PAR+). T and N classification were not independent predictors of OS. When combining T with LODDS instead of N, higher T (T3/T4) became a prognosticator (hazard ratio (HR) = 2.588; CI = 1.329−5.040; p = 0.005) but not LODDS (p > 0.05). When combining T classification with LODDS-PAR, both higher T classification (HR = 2.256; CI = 1.288−3.950; p = 0.004) and the alternative classification with LODDS-PAR (≥median −1.11; HR 2.078; CI = 1.155−3.739; p = 0.015) became independent predictors of worse OS. LODDS-PAR was the only independent prognosticator out of the LN assessment for primary parotid cancer.

Lessons learned after one year of COVID-19 from a urologist and radiotherapist view: A German survey on prostate cancer diagnosis and treatment.

INTRODUCTION: Since the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines. MATERIALS AND METHODS: To longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses. RESULTS: A total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate. CONCLUSION: While the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

No impact of time to treatment initiation for head and neck cancer in a tertiary university center in 2003, 2008 and 2013.

BACKGROUND: This retrospective study investigated factors influencing time to treatment initiation (TTI) and the influence of TTI on overall survival (OS) of primary head and neck cancer (HNC) patients in cohorts from 2003, 2008 and 2013. METHODS: Two hundred and ninenty seven patients (78.8% men; median age: 62 years) were included. Kaplan-Meier analyses and multivariate Cox regression were performed to investigate OS. RESULTS: Mean times to treatment initiation (TTI) of 2003, 2008 and 2013 were 17.11 ± 18.00, 30.26 ± 30.08 and 17.30 ± 37.04 days, respectively. TTI for patients with T3/T4 tumors was higher than for T1/T2 (p = 0.010). In univariable analysis on OS, TTI > 5 days showed lower OS (p = 0.047). In multivariate analysis, longer TTI had no influence on lower OS [hazard ratio (HR) 1.236; 95% CI 0.852-1.791; p = 0.264], but male gender [HR 2.342; 95% CI 1.229-4.466; p = 0.010], increased age [HR 1.026; 95% CI 1.008-1.045; p = 0.005], M1 [HR 5.823; 95% CI 2.252-15.058; p = 0.003], hypopharynx tumor [HR 2.508; 95% CI 1.571-4.003; p < 0.001] and oral cavity tumor [HR 1.712; CI 1.101-2.661; p = 0.017]. The year of treatment showed no significant effect on OS. CONCLUSION: Median TTI seemed to be very short compared to other studies. There was no clear trend in the impact of TTI on OS from 2003 to 2013.

Stereotactic body radiotherapy of adrenal metastases-A dose-finding study.

Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n = 101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P = .003), GTV-D50% (BED10: 74.2 Gy; P = .006), GTV-mean (BED10: 73.0 Gy; P = .007), and PTV-D2% (BED10: 78.0 Gy; P = .02) but not for the PTV-D98% (P = .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (<2% difference). Associations of cut-points with overall survival (OS) and progression-free survival were not significant but durable freedom from local recurrence was associated with OS in a landmark model (P < .001). To achieve a significant improvement of LRR for adrenal SBRT, a moderate escalation of PTV-D50% BED10 >73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.

Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer.

BACKGROUND: Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients. METHODS: Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0-6 weeks prior to and 0-6 weeks after RT using the maintrac® method, and patients were followed over a median period of 8.97 (1.16-19.09) years. RESULTS: Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886). CONCLUSIONS: Using the maintrac® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment. CLINICAL TRIAL REGISTRATION: The trial is registered (2 May 2019) at trials.gov under NCT03935802.

Breast clinical target volume: HU-based glandular CTVs and ESTRO CTVs in modern and historical radiotherapy treatment planning.

PURPOSE: The current study aimed to compare contouring of glandular tissue only (gCTV) with the clinical target volume (CTV) as defined according to European Society for Radiotherapy and Oncology (ESTRO) guidelines (eCTV) and historically treated volumes (marked by wire and determined by palpation and anatomic landmarks) in breast cancer radiotherapy. METHODS: A total of 56 consecutive breast cancer patients underwent treatment planning based solely on anatomic landmarks/wire markings ("wire based"). From these treatment plans, the 50% and 95% isodoses were transferred as structures and compared to the following CT-based volumes: eCTV; a Hounsfield unit (HU)-based automatic contouring of the gCTV; and standardized planning target volumes (PTVs) generated with 1­cm safety margins (resulting in the ePTVs and gPTVs, respectively). RESULTS: The 95% isodose volume of the wire-based plan was larger than the eCTV by 352.39 ± 176.06 cm3 but smaller than the ePTV by 157.58 ± 189.32 cm3. The 95% isodose was larger than the gCTV by 921.20 ± 419.78 cm3 and larger than the gPTV by 190.91 ± 233.49 cm3. Patients with larger breasts had significantly less glandular tissue than those with small breasts. There was a trend toward a lower percentage of glandular tissue in older patients. CONCLUSION: Historical wire and anatomic landmarks-based treatment planning sufficiently covers the glandular tissue and the theoretical gPTV generated for the glandular tissue. Modern CT-based CTV and PTV definition according to ESTRO results in a larger treated volume than the historical wire-based techniques. HU-standardized glandular tissue contouring results in a significantly smaller CTV and might be an option for reducing the treatment volume and improving reproducibility of contouring between institutions.

Prospective Monitoring of Circulating Epithelial Tumor Cells (CETC) Reveals Changes in Gene Expression during Adjuvant Radiotherapy of Breast Cancer Patients.

Circulating epithelial tumor cells (CETC) are considered to be responsible for the formation of metastases. Therefore, their importance as prognostic and/or predictive markers in breast cancer is being intensively investigated. Here, the reliability of single cell expression analyses in isolated and collected CETC from whole blood samples of patients with early-stage breast cancer before and after radiotherapy (RT) using the maintrac® method was investigated. Single-cell expression analyses were performed with qRT-PCR on a panel of selected genes: GAPDH, EpCAM, NANOG, Bcl-2, TLR 4, COX-2, PIK3CA, Her-2/neu, Vimentin, c-Met, Ki-67. In all patients, viable CETC were detected prior to and at the end of radiotherapy. In 7 of the 9 (77.8%) subjects examined, the CETC number at the end of the radiotherapy series was higher than before. The majority of genes analyzed showed increased expression after completion of radiotherapy compared to baseline. Procedures and methods used in this pilot study proved to be feasible. The method is suitable for further investigation of the underlying molecular biological mechanisms occurring in cells surviving radiotherapy and possibly the development of radiation resistance.

Long-Term Facial Nerve Outcome in Primary Parotid Cancer Surgery: A Population-Based Analysis.

OBJECTIVES/HYPOTHESIS: To determine immediate postoperative and long-term facial nerve dysfunction after parotid cancer surgery, risk factors, and the role of facial reanimation surgery. STUDY DESIGN: Population-based long-term analysis for all new primary parotid carcinoma cases in Thuringia from 1996 to 2019. METHODS: Data of the cancer registries of Thuringia, a federal state in Germany, were analyzed in combination with hospital-based data on facial function. RESULTS: About 477 patients (42.3% women; median age: 68 years) were included. It was observed that 6.7% had a preoperative facial nerve dysfunction, 11.7% received a radical parotidectomy, that is, that 5% had a normal preoperative facial function but needed radical surgery because of intraoperative detection of tumor infiltration into the facial nerve. About 10.2% received facial nerve reconstruction surgery. Immediate postoperative facial nerve dysfunction in the other patients was observed in 34.4% of the patients. Advanced T classification (odds ratio [OR] = 2.140; confidence interval [CI] = 1.268-3.611; P = .004) and neck dissection (OR = 2.012; CI = 1.027-3.940; P = .041) were independent risk factors for immediate postoperative facial nerve dysfunction. In addition, 22.0% showed no recovery during follow-up. Advanced T classification (OR = 2.177; CI = 1.147-4.133; P = .017) and postoperative radiotherapy (OR = 2.695; CI = 1.244-5.841; P = .012) were independent risk factors for permanent postoperative facial nerve dysfunction. CONCLUSION: Patients with primary parotid cancer are at high risk for long-term facial nerve dysfunction. It seems that the possibilities of facial reanimation surgery needs to be utilized even more effectively. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:2694-2700, 2021.

Theranostics in Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of 10B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the 10B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach.