Publications by authors named "Luitpold V Distel"

Background: Promptable foundation auto-segmentation models like Segment Anything (SA, Meta AI, New York, USA) represent a novel class of universal deep learning auto-segmentation models that could be employed for interactive tumor auto-contouring in RT treatment planning.

Methods: Segment Anything was evaluated in an interactive point-to-mask auto-segmentation task for glioma brain tumor auto-contouring in 16,744 transverse slices from 369 MRI datasets (BraTS 2020 dataset). Up to nine interactive point prompts were automatically placed per slice.

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Article Synopsis
  • Patients with tuberous sclerosis complex (TSC) often have benign tumors and show increased sensitivity to ionizing radiation compared to healthy individuals.
  • A study analyzed blood samples from 13 adult TSC patients and found a higher mean number of chromosome breaks per metaphase (B/M) in their cells after radiation exposure.
  • The results indicated that while TSC patients usually have non-cancerous growths, their radiosensitivity is similar to that of patients with malignant tumors, emphasizing potential treatment considerations.
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Background: The Autotaxin (ATX)-lysophosphatidic acid (LPA) axis is involved in decreasing radiation sensitivity of breast tumor cells. This study aims to further elucidate the effect of irradiation on the ATX-LPA axis and cytokine secretion in different breast cancer cell lines to identify suitable breast cancer subtypes for targeted therapies.

Methods: Different breast cancer cell lines (MCF-7 (luminal A), BT-474 (luminal B), SKBR-3 (HER2-positive), MDA-MB-231 and MDA-MB-468 (triple-negative)) and the breast epithelial cell line MCF-10A were irradiated.

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(1) Head and neck squamous cell carcinoma (HNSCC) is common, while treatment is difficult, and mortality is high. Kinase inhibitors are promising to enhance the effects of radiotherapy. We compared the effects of the PARP inhibitors talazoparib and niraparib and that of the DNA-PKcs inhibitor AZD7648, combined with ionizing radiation.

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The prognostic significance of tumor-infiltrating neutrophils in head and neck squamous cell carcinoma (HNSCC) is poorly understood. It is unclear how the presence of neutrophils affects prognosis due to their polarization into cytotoxic N1 or immunosuppressive N2. Therefore, we determined the number of CD66b+ neutrophil granulocytes separately in the stromal and epithelial compartments in cancer tissues from 397 patients with HNSCC.

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Article Synopsis
  • - This study focuses on the role of Flap Endonuclease 1 (FEN1) as a potential therapeutic target in breast cancer, exploring how the FEN1 inhibitor FEN1-IN-4 interacts with ionizing radiation to impact cell death and survival rates in different cell types.
  • - The research shows that FEN1-IN-4 increases cell death and other detrimental effects in breast cancer cells but has a limited impact on healthy skin fibroblasts, indicating varying responses based on cell type and FEN1 expression levels.
  • - Higher levels of FEN1 mRNA in breast cancer patients correlate with worsened prognosis, suggesting that FEN1 could be used as a new marker for tumor progression and that
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Despite substantial advancements in understanding the pathomechanisms of head and neck squamous cell carcinoma (HNSCC), effective therapy remains challenging. The application of kinase inhibitors (KIs) in HNSCC, specifically mTOR and DNA-PK inhibitors, can increase radiosensitivity and therefore presents a promising strategy when used simultaneously with ionizing radiation (IR) in cancer treatment. Our study focused on the selective DNA-PK-inhibitor AZD7648; the selective mTOR-inhibitor Sapanisertib; and CC-115, a dual inhibitor targeting both mTOR and DNA-PK.

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We introduce a deep-learning- and a registration-based method for automatically analyzing the spatial distribution of nodal metastases (LNs) in head and neck (H/N) cancer cohorts to inform radiotherapy (RT) target volume design. The two methods are evaluated in a cohort of 193 H/N patients/planning CTs with a total of 449 LNs. In the deep learning method, a previously developed nnU-Net 3D/2D ensemble model is used to autosegment 20 H/N levels, with each LN subsequently being algorithmically assigned to the closest-level autosegmentation.

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Non-professional phagocytosis in cancer has been increasingly studied in recent decades. In malignant melanoma metastasis, cell-in-cell structures have been described as a sign of cell cannibalism. To date, only low rates of cell-in-cell structures have been described in patients with malignant melanoma.

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Colorectal cancer remains one of the most commonly diagnosed cancers. Advanced rectal cancer patients receive neoadjuvant radiochemotherapy as well as surgery and suffer from reduced health-related quality of life due to various side effects. We were interested in the role of the COVID-19 pandemic and how it affected those patients' quality of life.

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The poor prognosis of HNSCC is partly due to treatment resistance. The SMAC mimetic Xevinapant is a promising new approach to targeted cancer therapy. Xevinapant inhibits cIAP1/2 and XIAP, leading to apoptosis, necroptosis and inhibition of prosurvival signaling.

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Phelan-McDermid syndrome is an inherited global developmental disorder commonly associated with autism spectrum disorder. Due to a significantly increased radiosensitivity, measured before the start of radiotherapy of a rhabdoid tumor in a child with Phelan-McDermid syndrome, the question arose whether other patients with this syndrome also have increased radiosensitivity. For this purpose, the radiation sensitivity of blood lymphocytes after irradiation with 2Gray was examined using the G0 three-color fluorescence in situ hybridization assay in a cohort of 20 patients with Phelan-McDermid syndrome from blood samples.

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Article Synopsis
  • The study explores the use of deep learning for autodelineation of head and neck lymph nodes to improve radiotherapy planning, highlighting the lack of existing public resources for this purpose.
  • A trained nnU-net model was evaluated using a cohort of CT images, with clinical experts comparing its segmentation against manually drawn contours.
  • Results showed no significant difference in quality ratings between deep learning and expert contours, but the inclusion of a CT slice plane adjustment improved the ratings for the deep learning segments.
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This study aimed to evaluate the benefit of additional administration of oxaliplatin during fluorouracil-based neoadjuvant radiochemotherapy (nRCT) in terms of pathologic complete remission (pCR), disease-free survival (DFS), and overall survival (OS) in patients with advanced rectal cancer. Between 2006 and 2021, 669 patients (pts) were diagnosed with locally advanced rectal cancer, of whom a total of 414 pts with nRCT were identified and included in the study. A total of 283 pts were treated by nRCT using concurrent chemotherapy with fluorouracil or capecitabine; 131 pts were treated using a combination of fluorouracil or capecitabine and oxaliplatin.

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Superparamagnetic iron oxide nanoparticles (SPION) are being investigated for many purposes, e.g., for the amplification of ionizing radiation and for the targeted application of therapeutics.

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. They are associated with alcohol and tobacco consumption, as well as infection with human papillomaviruses (HPV). Therapeutic options include radiochemotherapy, surgery or chemotherapy.

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Purpose: Despite new treatment options, melanoma continues to have an unfavorable prognosis. DNA damage response (DDR) inhibitors are a promising drug class, especially in combination with chemotherapy (CT) or radiotherapy (RT). Manipulating DNA damage repair during RT is an opportunity to exploit the genomic instability of cancer cells and may lead to radiosensitizing effects in tumors that could improve cancer therapy.

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The application of lipotransfer after breast-conserving therapy (BCT) and irradiation in breast cancer patients is an already widespread procedure for reconstructing volume deficits of the diseased breast. Nevertheless, the safety of lipotransfer has still not been clarified yet due to contradictory data. The goal of this in vitro study was to further elucidate the potential effects of lipotransfer on the irradiated remaining breast tissue.

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The aim of this study was to analyze the quality of life of patients with advanced rectal cancer before and during the COVID-19 pandemic and to determine whether the pandemic affected patients’ quality of life. The study included 389 patients and was performed from May 2010 to June 2021. The fifteen months from March 2020 to June 2021 were categorized as the COVID-19 period.

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Background: Triple-negative breast cancer (TNBC) is associated with aggressiveness and a poor prognosis. Besides surgery, radiotherapy serves as the major treatment modality for TNBC. However, response to radiotherapy is limited in many patients, most likely because of DNA damage response (DDR) signaling mediated radioresistance.

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Purpose: Brain metastases (BM) occur frequently in patients with metastatic cancer. Early and accurate detection of BM is essential for treatment planning and prognosis in radiation therapy. Due to their tiny sizes and relatively low contrast, small BM are very difficult to detect manually.

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Purpose: Kinase inhibitors (KI) are known to increase radiosensitivity, which can lead to increased risk of side effects. Data about interactions of commonly used KI with ionizing radiation on healthy tissue are rare.

Patients And Methods: Freshly drawn blood samples were analyzed using three-color FISH (fluorescence in situ hybridization) to measure individual radiosensitivity via chromosomal aberrations after irradiation (2 Gy).

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(1) Background: Just little is known about the interaction of ALK/ROS1-targeting kinase inhibitors with ionizing radiation (IR), particularly regarding side effects. We investigated the toxicity in two different lung cell lines both ALK/ROS1 wildtype (healthy and tumor origin) as representatives for normal lung tissue; (2) Methods: Human lung cell line BEAS-2B and malignant A549 lung cancer cells (ALK/ROS1 wt) were treated with alectinib or crizotinib, 2 Gy irradiation or a combination of KI and IR. Cell toxicity was analyzed by cell death (Annexin, 7AAD), colony forming, migration assay and live-cell imaging (TMRM, DRAQ7, Caspase3/7).

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In advanced rectal cancer, neoadjuvant radiochemotherapy and total mesorectal excision lead to long overall survival. The quality of life (QOL) of the patients is clearly related to the prognosis. Our question was whether the prognosis can be represented with only one question or one score from the QOL questionnaires.

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Gender is increasingly recognized as an important factor in medicine, although it has long been neglected in medical research in many areas. We have studied the influence of gender in advanced rectal cancer with a special focus on radiosensitivity. For this purpose, we studied a cohort of 495 men (84.

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