Role of Oxidative Stress Signaling, Nrf2, on Survival and Stemness of Human Adipose-Derived Stem Cells Exposed to X-rays, Protons and Carbon Ions.

Some cancers have a poor prognosis and often lead to local recurrence because they are resistant to available treatments, e.g., glioblastoma.

Proton therapy for adult-type diffuse glioma: A systematic review.

Background: We conducted a systematic review to evaluate outcomes and toxicities associated with proton therapy in the treatment of adult-type diffuse glioma.

Methods: Following PRISMA guidelines, we searched PubMed for both prospective and retrospective studies on proton therapy for adult diffuse gliomas, including IDH-mutated gliomas WHO grade 2-3 and glioblastomas. Survival and toxicity outcomes were reported separately for these glioma types.

Neuro-Oncologic Veterinary Trial for the Clinical Transfer of Microbeam Radiation Therapy: Acute to Subacute Radiotolerance after Brain Tumor Irradiation in Pet Dogs.

Synchrotron Microbeam Radiation Therapy (MRT) has repeatedly proven its superiority compared with conventional radiotherapy for glioma control in preclinical research. The clinical transfer phase of MRT has recently gained momentum; seven dogs with suspected glioma were treated under clinical conditions to determine the feasibility and safety of MRT. We administered a single fraction of 3D-conformal, image-guided MRT.

Simultaneous integrated boost on pathologic lymph nodes safely improves clinical outcomes compared to sequential boost in locally advanced cervical cancer: a multicenter retrospective study.

Objective: This multicenter study aimed to retrospectively evaluate the impact of high boost simultaneous integrated boost (SIB) to pathologic lymph nodes compared to Sequential boost (Seq) in patients with locally advanced cervical cancer (LACC).

Materials And Methods: 97 patients with pelvic and/or para-aortic (PAo) node-positive LACC treated by definitive chemoradiation were included. Two groups were analyzed: Sequential boost group and simultaneous integrated boost (SIB) group.

Neurologic Changes Induced by Whole-Brain Synchrotron Microbeam Irradiation: 10-Month Behavioral and Veterinary Follow-Up.

Purpose: Novel radiation therapy approaches have increased the therapeutic efficacy for malignant brain tumors over the past decades, but the balance between therapeutic gain and radiotoxicity remains a medical hardship. Synchrotron microbeam radiation therapy, an innovative technique, deposes extremely high (peak) doses in micron-wide, parallel microbeam paths, whereas the diffusing interbeam (valley) doses lie in the range of conventional radiation therapy doses. In this study, we evaluated normal tissue toxicity of whole-brain microbeam irradiation (MBI) versus that of a conventional hospital broad beam (hBB).

Radioresistance of Non-Small Cell Lung Cancers and Therapeutic Perspectives.

Survival in unresectable locally advanced stage non-small cell lung cancer (NSCLC) patients remains poor despite chemoradiotherapy. Recently, adjuvant immunotherapy improved survival for these patients but we are still far from curing most of the patients with only a 57% survival remaining at 3 years. This poor survival is due to the resistance to chemoradiotherapy, local relapses, and distant relapses.

A randomized controlled phase III study comparing hadrontherapy with carbon ions versus conventional radiotherapy - including photon and proton therapy - for the treatment of radioresistant tumors: the ETOILE trial.

Background: Some cancers such as sarcomas (bone and soft tissue sarcomas) and adenoid cystic carcinomas are considered as radioresistant to low linear energy transfer radiation (including photons and protons) and may therefore beneficiate from a carbon ion therapy. Despite encouraging results obtained in phase I/II trials compared to historical data with photons, the spread of carbon ions has been limited mainly because of the absence of randomized medical data. The French health authorities stressed the importance of having randomized data for carbon ion therapy.

Toward Neuro-Oncologic Clinical Trials of High-Dose-Rate Synchrotron Microbeam Radiation Therapy: First Treatment of a Spontaneous Canine Brain Tumor.

Purpose: The high potential of microbeam radiation therapy (MRT) in improving tumor control while reducing side effects has been shown by numerous preclinical studies. MRT offers a widened therapeutic window by using the periodical spatial fractionation of synchrotron generated x-rays into an array of intense parallel microbeams. MRT now enters a clinical transfer phase.

Individual Response to Radiation of Individuals with Neurofibromatosis Type I: Role of the ATM Protein and Influence of Statins and Bisphosphonates.

Neurofibromatosis type 1 (NF1) is a disease characterized by high occurrence of benign and malignant brain tumours and caused by mutations of the neurofibromin protein. While there is an increasing evidence that NF1 is associated with radiosensitivity and radiosusceptibility, few studies have dealt with the molecular and cellular radiation response of cells from individuals with NF1. Here, we examined the ATM-dependent signalling and repair pathways of the DNA double-strand breaks (DSB), the key-damage induced by ionizing radiation, in skin fibroblast cell lines from 43 individuals with NF1.

Morbidity following image-guided brachytherapy for cervical cancer: Patient and treatment related factors.

Purpose: This retrospective study aims to assess factors associated with the occurrence of toxicity after brachytherapy (BT), as boost after external beam radiotherapy (EBRT) for treatment of invasive cervix carcinoma.

Methods And Materials: All consecutive patients diagnosed with cervical carcinoma, and treated with concurrent radiochemotherapy from August 2017 to January 2020 were retrospectively included. An isodose conformation index (ICI) was developed to assess the percentage of the prescription isodose contained within the intermediate risk clinical target volume (IR-CTV).

Doses delivered by portal imaging quality assurance in routine practice of adjuvant breast radiotherapy worth to by monitored and compensated in some cases.

Background: Imaging, in radiotherapy, has become a routine tool for repositioning of the target volume at each session. The repositioning precision, currently infracentimetric, evolves along with the irradiation techniques. This retrospective study aimed to identify practices and doses resulting from the use of high energy planar imaging (portal imaging) in daily practice.

Prospective Assessment of Early Proton Therapy-Induced Optic Neuropathy in Patients With Intracranial, Orbital or Sinonasal Tumors: Impact of A Standardized Ophthalmological Follow Up.

Purpose: Proton therapy (PT) can be a good option to achieve tumor control while reducing the probability of radiation induced toxicities compared to X-ray-based radiotherapy. However, there are still uncertainties about the effects of PT on the organs in direct contact with the irradiated volume. The aim of this prospective series was to report 6-month follow-up of clinical and functional optic neuropathy rates of patients treated by proton therapy using a standardized comprehensive optic examination.

[New indications of protontherapy for adults intracranial tumours].

Considering intracranial tumours, only few indications of protontherapy, such as chordoma, chondrosarcoma or uveal melanoma, are uniformly approved in the world. Other indications, excluding paediatric pathologies, are still debated. The aim of this article is to describe the rationale for the use of protonbeam irradiation for meningioma, pituitary adenoma, craniopharyngioma, paraganglioma, glioma, and schwannoma, and to inform the radiation oncologists if prospective studies or randomized studies are opened for inclusions.

Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial).

Background And Purpose: Brain metastasis impacts greatly on patients' quality of life and survival. The phase I NANO-RAD trial assessed the safety and maximum tolerated dose of systemic administration of a novel gadolinium-based nanoparticle, AGuIX, in combination with whole brain radiotherapy in patients with multiple brain metastases not suitable for stereotactic radiotherapy.

Materials And Methods: Patients with measurable brain metastases received escalating doses of AGuIX nanoparticles (15, 30, 50, 75, or 100 mg/kg intravenously) on the day of initiation of WBRT (30 Gy in 10 fractions) in 5 cohorts of 3 patients each.

Unexpected Benefits of Multiport Synchrotron Microbeam Radiation Therapy for Brain Tumors.

Delivery of high-radiation doses to brain tumors via multiple arrays of synchrotron X-ray microbeams permits huge therapeutic advantages. Brain tumor (9LGS)-bearing and normal rats were irradiated using a conventional, homogeneous Broad Beam (BB), or Microbeam Radiation Therapy (MRT), then studied by behavioral tests, MRI, and histopathology. A valley dose of 10 Gy deposited between microbeams, delivered by a single port, improved tumor control and median survival time of tumor-bearing rats better than a BB isodose.

Sphincter-saving surgery for ultra-low rectal carcinoma initially indicated for abdominoperineal resection: Is it safe on a long-term follow-up?

Background: Rate of abdominoperineal resection (APR) varies from countries and surgeons. Surgical impact of preoperative treatment for ultra-low rectal carcinoma (ULRC) initially indicated for APR is debated. We report the 10-year oncological results from a prospective controlled trial (GRECCAR 1) which evaluate the sphincter saving surgery (SSR).

Targeting brain metastases with ultrasmall theranostic nanoparticles, a first-in-human trial from an MRI perspective.

The use of radiosensitizing nanoparticles with both imaging and therapeutic properties on the same nano-object is regarded as a major and promising approach to improve the effectiveness of radiotherapy. Here, we report the MRI findings of a phase 1 clinical trial with a single intravenous administration of Gd-based AGuIX nanoparticles, conducted in 15 patients with four types of brain metastases (melanoma, lung, colon, and breast). The nanoparticles were found to accumulate and to increase image contrast in all types of brain metastases with MRI enhancements equivalent to that of a clinically used contrast agent.

Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma.

Background: The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.

Synchrotron X-Ray Boost Delivered by Microbeam Radiation Therapy After Conventional X-Ray Therapy Fractionated in Time Improves F98 Glioma Control.

Purpose: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly collimated synchrotron beam into arrays of parallel microbeams depositing several hundred grays. It appears relevant to combine MRT with a conventional treatment course, preparing a treatment scheme for future patients in clinical trials. The efficiency of MRT delivered after several broad-beam (BB) fractions to palliate F98 brain tumors in rats in comparison with BB fractions alone was evaluated in this study.

Hadrontherapy Interactions in Molecular and Cellular Biology.

The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues.

Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus.

The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation.

Film dosimetry studies for patient specific quality assurance in microbeam radiation therapy.

Microbeam radiation therapy (MRT) uses synchrotron arrays of X-ray microbeams to take advantage of the spatial fractionation effect for normal tissue sparing. In this study, radiochromic film dosimetry was performed for a treatment where MRT is introduced as a dose boost in a hypofractionated stereotactic radiotherapy (SRT) scheme. The isocenter dose was measured using an ionization chamber and two dimensional dose distributions were determined using radiochromic films.

Efficacy and Safety of Two Neoadjuvant Strategies With Bevacizumab in MRI-Defined Locally Advanced T3 Resectable Rectal Cancer: Final Results of a Randomized, Noncomparative Phase 2 INOVA Study.

Background: Recurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials.

Patients And Methods: Patients with mid/low magnetic resonance imaging-defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab-5-fluorouracil [5-FU]-radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU-RT then TME).

Ultra high dose rate Synchrotron Microbeam Radiation Therapy. Preclinical evidence in view of a clinical transfer.

This paper reviews the current state of the art of an emerging form of radiosurgery dedicated to brain tumour treatment and which operates at very high dose rate (kGy·s). Microbeam Radiation Therapy uses synchrotron-generated X-rays which triggered normal tissue sparing partially mediated by FLASH effect.

Treatment of multiple brain metastases using gadolinium nanoparticles and radiotherapy: NANO-RAD, a phase I study protocol.

Introduction: Occurrence of multiple brain metastases is a critical evolution of many cancers with significant neurological and overall survival consequences, despite new targeted therapy and standard whole brain radiotherapy (WBRT). A gadolinium-based nanoparticle, AGuIX, has recently demonstrated its effectiveness as theranostic and radiosensitiser agent in preclinical studies. The favourable toxicity profile in animals and its administration as a simple intravenous injection has motivated its use in patients with this first in human study.