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Radiation resistance represents a major challenge in the treatment of breast cancer. As heparan sulfate (HS) chains are known to contribute to tumorigenesis, we aimed to investigate the interplay between HS degradation and radiation response in triple-negative breast cancer (TNBC) cells.HS chains were degraded in vitro as TNBC cells MDA-MB-231 and HCC1806 were treated with heparinase I and III. Subsequently, radioresistance was determined via colony formation assay after doses of 2, 4 and 6 Gy. Cell cycle profile, stem cell characteristics, expression of HS, activation of beta integrins, and apoptosis were determined by flow cytometry. Additionally, cell motility was analyzed via wound-healing assays, and expression and activation of FAK, CDK-6, Src, and Erk1/2 were quantified by western blot pre- and post-irradiation. Finally, the expression of cytokines was analyzed using a cytokine array.Radiation promoted cell cycle changes, while heparinase treatment induced apoptosis in both cell lines. Colony formation assays showed significantly increased radio-resistance for both cell lines after degradation of HS. Cell migration was similarly upregulated after degradation of HS compared to controls. This effect was even more prominent after irradiation. Interestingly, FAK, a marker of radioresistance, was significantly activated in the heparinase-treated group. Additionally, we found Src to be dysregulated in MDA-MB-231 cells. Finally, we observed differential secretion of GRO, CXCL1, IGFBP1, IL8, Angiogenin, and Osteoprotegerin after HS degradation and radiotherapy.Our results suggest an influence of HS chains on the development of radioresistance in TNBC.

Introduction Glioblastoma multiforme (GBM) carries a strongly unfavorable prognosis despite intensive multidisciplinary therapy. Physical exercise is rarely offered to patients for fear of adverse events such as falls, epileptic seizures, or bleeding, despite little supporting evidence. Here, we report a study of high-level and long-term exercise in a GBM patient. Methods A 33-yr-old male, diagnosed with a large cystic GBM, was included in our institution's Personal Training Program after initial tumor resection and adjuvant radiochemotherapy. The program was designed to facilitate individual long-term high-intensity exercise. Supervised by a certified personal trainer, it consisted of at least four weekly training sessions and intermittent performance diagnostics. An activity tracker quantified training intensity. Results In this setting, the patient exercised at high intensity without adverse events for 87 continuous weeks (21 months). He averaged 43.7 metabolic equivalent of task hours per week (MET·h·wk), well above the 75th percentile of healthy males the same age, while undergoing multiple surgeries, chemotherapy, and radiation therapy regimens. The patient completed two marathons averaging less than 5 min·km both times, despite tumor progression. Performance diagnostics indicated a gain of fitness even during continuous GBM treatment. Due to multiple intraventricular lesions and increasing intracranial pressure, training was stopped 6 wk before the patient passed away 2 yr after initial diagnosis. Conclusions This study demonstrates that high-intensity, long-term physical training regimens are feasible in GBM patients during full multidisciplinary therapy. In this patient, the exercise was pursued without adverse events and led to a gain of fitness despite tumor progression and intensive multiple therapies. We conclude that, in GBM patients, exercise regimens require further study instead of general discouragement.

Purpose While the stem cell marker Musashi-1 (MSI-1) has been identified as a key player in a wide array of malignancies, few findings exist on its prognostic relevance and relevance for cancer cell death and therapy resistance in breast cancer. Methods First, we determined prognostic relevance of MSI-1 in database analyses regarding multiple survival outcomes. To substantiate findings, MSI-1 was artificially downregulated in MCF-7 breast cancer cells and implications for cancer stem cell markers, cell apoptosis and apoptosis regulator p21, proliferation and radiation response were analyzed via flow cytometry and colony formation. Radiation-induced p21 expression changes were investigated using a dataset containing patient samples obtained before and after irradiation and own in vitro experiments. Results MSI-1 is a negative prognostic marker for disease-free and distant metastasis-free survival in breast cancer and tends to negatively influence overall survival. MSI-1 knockdown downregulated stem cell gene expression and proliferation, but increased p21 levels and apoptosis. Similar to the MSI-1 knockdown effect, p21 expression was strongly increased after irradiation and was expressed at even higher levels in MSI-1 knockdown cells after irradiation. Finally, combined use of MSI-1 silencing and irradiation reduced cancer cell survival. Conclusion MSI-1 is a prognostic marker in breast cancer. MSI-1 silencing downregulates proliferation while increasing apoptosis. The anti-proliferation mediator p21 was upregulated independently after both MSI-1 knockdown and irradiation and even more after both treatments combined, suggesting synergistic potential. Radio-sensitization effects after combining radiation and MSI-1 knockdown underline the potential of MSI-1 as a therapeutic target. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03743-y.

Background Assessment of risk associated with lung cancer resection is primarily based on evaluation of cardiopulmonary function and remains imprecise. We investigated the relationship between thoracic muscle and early outcomes after lobectomy. Methods Cross-sectional area of skeletal muscle was measured at the level of the fifth thoracic vertebra on computed tomography in 135 consecutive patients before lobectomy for lung cancer. Patients were stratified into low and high muscle groups using the sex-specific muscle median. Primary outcome was a composite of any postoperative complication as per The Society of Thoracic Surgeons General Thoracic Surgical Database. Secondary outcomes included postoperative respiratory complications, postoperative intensive care unit admission, hospital length of stay, and hospital readmission within 30 days of hospital discharge. The χ2 test, adjusted multivariable regression analysis, and likelihood ratio test were performed. Results Patients with low muscle were significantly more likely to have any postoperative complication and respiratory postoperative complications. Although postoperative intensive care unit admission was similar for low muscle and high muscle groups, low muscle patients had longer hospital length of stay and a higher rate of hospital readmission. Adjusted multivariable regression revealed the independent association of thoracic muscle with all outcomes. The likelihood ratio test suggested that thoracic muscle adds predictive capability to information captured by preoperative pulmonary function testing. Conclusions Low thoracic muscle is independently associated with increased postoperative complications and health care utilization among patients undergoing lobectomy for lung cancer. Evaluation of thoracic muscle may enhance risk prediction models.

The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p < 0.001). Despite over-representation of these unfavorable characteristics, there was no survival difference between groups (p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials.

Pretreatment risk stratification is key for personalized medicine. While many physicians rely on an "eyeball test" to assess whether patients will tolerate major surgery or chemotherapy, "eyeballing" is inherently subjective and difficult to quantify. The concept of morphometric age derived from cross-sectional imaging has been found to correlate well with outcomes such as length of stay, morbidity, and mortality. However, the determination of the morphometric age is time intensive and requires highly trained experts. In this study, we propose a fully automated deep learning system for the segmentation of skeletal muscle cross-sectional area (CSA) on an axial computed tomography image taken at the third lumbar vertebra. We utilized a fully automated deep segmentation model derived from an extended implementation of a fully convolutional network with weight initialization of an ImageNet pre-trained model, followed by post processing to eliminate intramuscular fat for a more accurate analysis. This experiment was conducted by varying window level (WL), window width (WW), and bit resolutions in order to better understand the effects of the parameters on the model performance. Our best model, fine-tuned on 250 training images and ground truth labels, achieves 0.93 ± 0.02 Dice similarity coefficient (DSC) and 3.68 ± 2.29% difference between predicted and ground truth muscle CSA on 150 held-out test cases. Ultimately, the fully automated segmentation system can be embedded into the clinical environment to accelerate the quantification of muscle and expanded to volume analysis of 3D datasets.

A brain tumor diagnosis poses a significant psychological burden and it severely impacts quality of life (QOL), both in patients and relatives. However, comprehensive strategies addressing QOL in this setting remain rare. Here, we aim to share our findings of a one-week ski exercise intervention, with emphasis on feasibility, safety, QOL, and physical exercise. The intervention consisted of week-long daily ski sessions with professional ski guides as well as dedicated physicians present. The participants were handed questionnaires, including distress and QOL items before, during, and after the intervention. Using fitness watches, exercise intensity was also tracked at these timepoints. During the intervention, patients were checked for adverse events daily. Fifteen participants, nine patients after multidisciplinary treatment, and six relatives were included in the study. Additionally, 13 children participated in the exercise, but not in the study. All of the participants completed the entire program. No severe adverse events were documented during daily checks. There was a strong increase in quantified activity and QOL with a corresponding decrease in distress during the intervention, and, partly, afterwards. This prospective brain tumor rehabilitation study demonstrates the feasibility and safety of challenging ski exercise in brain tumor patients. The findings also underline the exercise-mediated QOL benefits, emphasizing the need for more comprehensive brain tumor rehabilitation programs.