IQGAP3 activates Hedgehog signaling to confer stemness and metastasis via up-regulating GLI1 in lung cancer.

Lung cancer ranks as the most prevalent malignant neoplasm worldwide, contributing significantly to cancer-related mortality. Stemness is a well-recognized factor underlying radiotherapy resistance, recurrence and metastasis in non-small-cell lung cancer (NSCLC) patients. Our prior investigations have established the role of IQ motif containing GTPase-activating protein 3 (IQGAP3) in mediating radiotherapy resistance in lung cancer, but its impact on lung cancer stemness remains unexplored.

Definition of a framework for volumetric modulated arc therapy plan quality assessment with integration of dose-, complexity-, and robustness metrics.

Background And Purpose: Conventionally, the quality of radiotherapy treatment plans is assessed through visual inspection of dose distributions and dose-volume histograms. This study developed a framework to evaluate plan quality using dose, complexity, and robustness metrics. Additionally, a method for predicting plan robustness metrics using dose and complexity metrics was introduced for cases where plan robustness evaluation is unavailable or impractical.

Radioimmunotherapy: a game-changer for advanced non-small cell lung cancer.

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related deaths, with conventional treatments offering limited effectiveness in advanced stages, due to distant metastases and treatment resistance. Recent advancements in immunotherapy, specifically immune checkpoint inhibitors (ICIs), have shown promise, but their efficacy as standalone therapies are often insufficient. This has led to increased interest in combining ICIs with radiotherapy, known as radioimmunotherapy (iRT), to enhance treatment outcomes.

Metastasis-directed stereotactic radiotherapy in patients with breast cancer: results of an international multicenter cohort study.

Metastasis-directed therapy (MDT) for oligometastatic breast cancer (≤ 5 metastases) has shown little effect in specific scenarios of randomized trials. Therefore, we aimed to assess outcomes after metastasis-directed stereotactic radiotherapy (SRT) in various clinical scenarios. We conducted an international retrospective cohort study in thirteen centers including breast cancer patients receiving SRT to any metastatic site.

Mixed- and multi-relative biological effectiveness model simultaneous optimization in carbon ion radiotherapy: A proof-of-concept.

Background And Purpose: In carbon ion radiotherapy (CIRT), different relative biological effectiveness (RBE) models have been used for calculating RBE-weighted dose (D). Conversion between current RBE predictions and introduction of novel approaches remains a challenging task. Our aim is to introduce a framework considering multiple RBE models simultaneously during CIRT plan optimization, easing the translation between D prescriptions.

Hematologic Toxicity Profiles and the Impact of Hemoglobin Nadir and Transfusion on Oncologic Outcome in Definitive Radiochemotherapy for Cervical Cancer.

: Definitive radiochemotherapy with concomitant cisplatin 40 mg/m weekly represents the standard of care for locally advanced cervical cancer. Current studies (KEYNOTE-A18 and INTERLACE) are intensifying this regimen at the cost of increased hematologic toxicity. We aimed to evaluate influencing factors on hematotoxicity to ensure the safe application of radiochemotherapy.

First-line treatments for KRAS-mutant non-small cell lung cancer: current state and future perspectives.

mutations are common in non-small cell lung cancer (NSCLC) and are associated with patient prognosis; however, targeting has faced various difficulties. Currently, immunotherapy, chemotherapy, and chemoimmunotherapy play pivotal roles in the first-line treatment of -mutated NSCLC. Here, we summarize the current evidence on first-line therapies and compare the treatment outcomes and biomarkers for different regimens.

Concomitant ALK Fusion and TP53/EGFR Mutation Lead to Adverse Prognostic Outcome.

Lung cancer treatment has evolved at the molecular level. Detecting the presence of driver genes in lung cancer fundamentally alters the choice of therapeutic regimens and the outcome of this disease. ALK fusion mutation is one of the most important mutations in nonsmall cell lung cancer (NSCLC).

Immunotherapy beyond progression following first‑line chemotherapy plus immunotherapy in advanced non‑small cell lung cancer: A retrospective study.

Immunotherapy has paved the way for new treatment options for advanced non-small cell lung cancer (NSCLC). However, for patients who have progressed following first-line immunotherapy combined with chemotherapy, little is known about the benefits of the continuation of immunotherapy. Thus, the current study aimed to evaluate the efficacy of immunotherapy beyond progression (IBP) in patients with advanced NSCLC.

Long-term outcome in cervical lymph node-positive nasopharyngeal carcinoma following IMRT with one-step cervical nodal CTV delineation by geometric-anatomic expansion from nodal GTV: A double-center experience.

Background: To report long-term results of cervical node-positive (CLN+) nasopharyngeal carcinoma (NPC) patients treated with IMRT with one-step nodal clinical target volume (CTVn) delineation by geometric-anatomic expansion from the nodal gross target volume (GTVn).

Materials: CLN+ NPC treated with the same one-step-CTVn delineation in two Chinese academic centers were pooled for this study. GTVn was prescribed to 70 Gy equivalent, CTVn1 was omitted, CTVn2 was prescribed to 45-55 Gy equivalent and defined as GTVn + 3 mm geometric expansion (5 mm if radiological extranodal extension-positive, rENE+) + elective nodal regions defined by anatomic boundary of cervical nodal levels.

Investigating LETd optimization strategies in carbon ion radiotherapy for pancreatic cancer: a dosimetric study using an anthropomorphic phantom.

Background: Clinical carbon ion beams offer the potential to overcome hypoxia-induced radioresistance in pancreatic tumors, due to their high dose-averaged Linear Energy Transfer (LETd), as previous studies have linked a minimum LETd within the tumor to improved local control. Current clinical practices at the Heidelberg Ion-Beam Therapy Center (HIT), which use two posterior beams, do not fully exploit the LETd advantage of carbon ions, as the high LETd is primarily focused on the beams' distal edges. Different LETd-boosting strategies, such as Spot-scanning Hadron Arc (SHArc), could enhance LETd distribution by concentrating high-LETd values in potential hypoxic tumor cores while sparing organs at risk.

Bimodal intensity-modulated radiotherapy in combination with carbon ion therapy (C12) of mucosal melanomas - data of the last decade from Heidelberg University Hospital.

Introduction: Due to the rarity of mucosal melanomas, few recent studies can be found investigating the success and side effects of therapy for this entity with large numbers of patients. In this retrospective analysis, the efficacy and toxicity of combined intensity-modulated radiotherapy (IMRT) and carbon ion therapy (C12) of mucosal melanomas were analyzed to contribute to a better understanding of this rare disease.

Methods: Twenty-two patients were included from 2013 to 2022 in the Department of Radiation Oncology at Heidelberg University Hospital.

Extracellular vesicles in cancers: mechanisms, biomarkers, and therapeutic strategies.

Extracellular vesicles (EVs) composed of various biologically active constituents, such as proteins, nucleic acids, lipids, and metabolites, have emerged as a noteworthy mode of intercellular communication. There are several categories of EVs, including exosomes, microvesicles, and apoptotic bodies, which largely differ in their mechanisms of formation and secretion. The amount of evidence indicated that changes in the EV quantity and composition play a role in multiple aspects of cancer development, such as the transfer of oncogenic signals, angiogenesis, metabolism remodeling, and immunosuppressive effects.

Spatio-temporal transcriptomics of chromothriptic SHH-medulloblastoma identifies multiple genetic clones that resist treatment and drive relapse.

Paediatric medulloblastomas with chromothripsis are characterised by high genomic instability and are among the tumours with the worst prognosis. However, the molecular makeup and the determinants of the aggressiveness of chromothriptic medulloblastoma are not well understood. Here, we apply spatial transcriptomics to profile a cohort of 13 chromothriptic and non-chromothriptic medulloblastomas from the same molecular subgroup.

Radiotherapy Effects on Airway Management in Patients with Nasopharyngeal Cancer.

: At present, there is a paucity of data in the literature pertaining to the impact of radiotherapy (RT) on the success of tracheal intubation in patients with nasopharyngeal cancer (NPC). The aim of this study is to investigate the frequency of difficult tracheal intubation in patients with NPC following RT. : Patients with NPC who underwent RT followed by surgery between 2012 and April 2024 at the University Hospital Heidelberg were retrospectively analyzed.

ADAR1 enhances tumor proliferation and radioresistance in non-small cell lung cancer by interacting with Rad18.

Purpose: Posttranslational modification significantly contributes to the transcriptional diversity of tumors. Adenosine deaminase acting on RNA 1 (ADAR1) and its mediated adenosine-to-inosine (A-to-I) editing have been reported to influence tumorigenesis across various cancer types. Nevertheless, the relationship between ADAR1 and radioresistence remains to be elucidated.

Triggering immunogenic death of cancer cells by nanoparticles overcomes immunotherapy resistance.

Immunotherapy resistance poses a significant challenge in oncology, necessitating novel strategies to enhance the therapeutic efficacy. Immunogenic cell death (ICD), including necroptosis, pyroptosis and ferroptosis, triggers the release of tumor-associated antigens and numerous bioactive molecules. This release can potentiate a host immune response, thereby overcoming resistance to immunotherapy.

Gliosarcoma: A Multi-Institutional Analysis on Clinical Outcomes and Prognostic Factors.

Purpose: This study describes oncological outcomes and investigates prognostic factors for patients with gliosarcomas (GSM).

Methods: Histopathologically confirmed GSM patients who underwent treatment at five European institutions were retrospectively analyzed.

Results: We analyzed 170 patients with a median clinical follow-up time of 9.

The interplay between microbiome and host factors in pathogenesis and therapy of head and neck cancer.

Heterogeneous cancers that lack strong driver mutations with high penetrance, such as head and neck squamous cell carcinoma (HNSCC), present unique challenges to understanding their aetiology due to the complex interactions between genetics and environmental factors. The interplay between lifestyle factors (such as poor oral hygiene, smoking, or alcohol consumption), the oral and gut microbiome, and host genetics appears particularly important in the context of HNSCC. The complex interplay between the gut microbiota and cancer treatment outcomes has also received increasing attention in recent years.

Efficacy of palliative hemostatic radiotherapy for tumor bleeding and pain relief in locally advanced pelvic gynecological malignancies.

Purpose: The appearance of symptomatic tumor-related vaginal bleeding and pain in advanced incurable cancer patients with pelvic gynecological malignancies remains a therapeutic challenge in oncological treatment. The aim of our analysis was to evaluate the efficacy and safety of palliative hemostatic radiotherapy.

Methods: We retrospectively identified patients who had received palliative hemostatic radiotherapy (RT) at our institution between 2011 and 2023 and evaluated acute toxicity, local control, cessation of bleeding, and pain relief.

Oxygen consumption measurements at ultra-high dose rate over a wide LET range.

Background: The role of radiolytic oxygen consumption for the in-vitro "Ultra-High Dose Rate" (UHDR) sparing and in-vivo FLASH effect is subject to active debate, but data on key dependencies such as the radiation quality are lacking.

Purpose: The influence of "dose-averaged Linear Energy Transfer" (LETd) and dose rate on radiolytic oxygen consumption was investigated by monitoring the oxygen concentration during irradiation with electrons, protons, helium, carbon, and oxygen ions at UHDR and "Standard Dose Rates" (SDR).

Methods: Sealed "Bovine Serum Albumin" (BSA) 5% samples were exposed to 15 Gy of electrons and protons, and for the first time helium, carbon, and oxygen ions with LETd values of 1, 5.