Marco Durante

• Ph.D.
• Managing Director at GSI Helmholtz Centre for Heavy Ion Research

FOOT (FragmentatiOn Of Target) is a nuclear physics experiment currently under construction that will measure differential cross sections for the production of secondary fragments induced by the interactions of proton and ion beams, up to 400 MeV/u, with human tissues. By extending the energy range to about 800 MeV/u, FOOT will also provide data us...

Objective. To identify suitable combination strategies for treatment planning and beam delivery in scanned carbon ion therapy of moving tumors. Approach. Carbon ion treatment plans for five abdominal tumors were optimized on four-dimensional (4D) computed tomography (CT) data using the following approaches. 4DITV across all phases and within a gati...

Purpose This work presents a proof-of-concept study of HyperSHArc, spot-scanning hadron arc (SHArc) therapy for single-isocenter stereotactic radiosurgery of multiple brain metastases (MBMs). HyperSHArc plans using proton, helium, and carbon ions were compared with state-of-the-art volumetric modulated photon arc therapy. Methods and Materials Tre...

Tumor motion is a major challenge for scanned ion-beam therapy. In the case of lung tumors, strong under- and overdosage can be induced due to the high density gradients between the tumor- and bone tissues compared to lung tissues. This work proposes a non-invasive concept for 4D monitoring of high density gradients in carbon ion beam therapy, by d...

Brain tumors are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity to the normal tissue including post-irradiation contrast enhanced lesions often linked to necrosis. The poorly understood mechanisms behind such brain lesions were studied using cerebral organoids. Here we show that irradiation of such...

Galactic cosmic rays (GCR) are among the biggest hindrances to crewed space exploration. The ions contributing the most to fluence and absorbed dose in free space are 1H and 4He. In addition, their contribution to dose equivalent increases behind thick shields. In this work, the results of depth-dose measurements performed with high-energy 1H and 4...

Among the most investigated hypotheses for a radiobiological explanation of the mechanism behind the FLASH effect in ultra-high dose rate radiotherapy, intertrack recombination between particle tracks arriving at a close spatiotemporal distance has been suggested. In the present work, we examine these conditions for different beam qualities and ene...

The fragmentation cross sections of carbon ion beams with kinetic energies of $115 - 353~\text{MeV/u}$ impinging on thin targets of graphite (C), polyvinyl-toluene (C$_9$H$_{10}$) and PMMA (C$_2$O$_5$H$_8$) have been measured at 90$^{\text{o}}$ and 60$^{\text{o}}$ at the CNAO particle therapy center (Pavia, Italy). The presented measurements are a...

We perform Single Event Effects (SEE) tests with well-characterized fully fragmented (i.e., beyond Bragg peak) high-energy heavy-ion beams and compare the results with those expected from conventional, mono-Linear Energy Transfer (LET) measurements, showing a satisfactory level of agreement between the two. This compliance paves the way to the expl...

This paper presents the measurements of the angular differential cross sections for the forward production of He, Li, Be, B, C and N nuclei in the fragmentation process of a 400$\text{MeV/nucleon}$ $^{16}\text{O}$ beam interacting with a graphite target. Due to the limited data available in this energy regime, these measurements of nuclear fragment...

This report describes the general framework, research goals, preliminary technical design, and resources required for a novel accelerator-based research infrastructure for cancer therapy and biomedical sciences with ion beams. The information presented is the result of five years of research and design activities conducted by a wide multinational c...

Purpose To describe the role of hadrontherapy (HT) in treating radioresistant, rare, recurrent, and radio-induced tumors, which can be defined, in assonance with the 4Rs of radiobiology, the “4Rs” of HT indications. Materials and Methods This is a narrative review written by a multidisciplinary team consisting of radiation oncologists, radiobiolog...

Objective. Real-time adaptive particle therapy is being investigated as a means to maximize the treatment delivery accuracy. To react to dosimetric errors, a system for fast and reliable verification of the agreement between planned and delivered doses is essential. This study presents a clinically feasible, real-time 4D-dose reconstruction system,...

Radioactive ion beams (RIB) are a key focus of current research in nuclear physics. Already long ago it was proposed that they could have applications in cancer therapy. In fact, while charged particle therapy is potentially the most effective radiotherapy technique available, it is highly susceptible to uncertainties in the beam range. RIB are wel...

Radioactive ion beams (RIB) are essential instruments in contemporary nuclear physics research. Already long ago it was proposed that they could have applications in cancer therapy. In fact, while charged particle therapy is potentially the most effective radiotherapy technique available, it is highly susceptible to uncertainties in the beam range....

Objective. Upright positioning has seen a surge in interest as a means to reduce radiotherapy (RT) cost, improve patient comfort, and, in selected cases, benefit treatment quality. In particle therapy (PT) in particular, eliminating the need for a gantry can present massive cost and facility footprint reduction. This review discusses the opportunit...

Very-high-energy (VHE), heavy ions are of particular interest for single event effects testing due to their combination of high linear energy transfer (LET) and high penetration within electronics components. The dosimetry of such beams poses an important challenge for facilities aiming to provide VHE ions for radiation effects testing. In this pap...

Radiotherapy can trigger activation of the cGAS-STING axis via cytoplasmic dsDNA fragment induction. The activation of cGAS–STING initiates innate immune signaling mediated by interferon type-I that can contribute to eradicate the malignancy. The effect was shown to depend on the fractionation scheme employed. We hypothesized that the innate immune...

Objective. Scanned particle therapy often requires complex treatment plans, robust optimization, as well as treatment adaptation. Plan optimization is especially complicated for heavy ions due to the variable relative biological effectiveness. We present a novel deep-learning model to select a subset of voxels in the planning process thus reducing...

Background and purpose In recent years, ultra-high dose rate (UHDR) irradiation has emerged as a promising innovative approach to cancer treatment. Characteristic feature of this regimen, commonly referred to as FLASH effect, demonstrated primarily for electrons, photons or protons, is the improved normal tissue sparing, while the tumor control is...

A renewed interest in upright therapy is currently driven by the availability of upright positioning and imaging systems. Aside from reduced cost, upright positioning possibly provides clinical advantages. The comparison between upright and supine particle therapy treatments can be biased through multiple variables, such as differences in the targe...

Due to the advantageous depth dose profile of carbon ion beams, carbon ion therapy is commonly applied in the form of intensity modulated particle therapy (IMPT) with few treatment fields. Carbon ion arc therapy (C-Arc) has recently been proposed to improve dose conformity and increase the dose-averaged linear energy transfer (LETd) inside the targ...

Without the protective shielding of Earth’s atmosphere, astronauts face higher doses of ionizing radiation in space, causing serious health concerns. Highly charged and high energy (HZE) particles are particularly effective in causing complex and difficult-to-repair DNA double-strand breaks compared to low linear energy transfer. Additionally, chro...

To provide an introduction to the special issue containing the proceedings of the workshop on cancer therapy using hadrons (proton, carbon ions or boron neutron capture therapy) that was held in Pavia in October 2023 and organized by CNAO and IAEA. Papers contained in the issue are briefly summarized. This issue contains a collection of papers from...

The COVID-19 pandemic has made clear the need for effective and rapid vaccine development methods. Conventional inactivated virus vaccines, together with new technologies like vector and mRNA vaccines, were the first to be rolled out. However, the traditional methods used for virus inactivation can affect surface-exposed antigen, thereby reducing v...

We present an extension of the Local Effect Model (LEM) to include time-dose relationships for predicting effects of protracted and split-dose ion irradiation at arbitrary LET. With this kinetic extension, the spatial and temporal induction and processing of DNA double strand breaks (DSB) in cellular nuclei can be simulated for a wide range of ion...

Purpose: Lymphopenia is now generally recognized as a negative prognostic factor in radiotherapy. Already at the beginning of the century we demonstrated that high-energy carbon ions induce less damage to the lymphocytes of radiotherapy patients than X-rays, even if heavy ions are more effective per unit dose in the induction of chromosomal aberra...

Background Mechanistic modelling of normal tissue toxicities is unfolding as an alternative to the phenomenological normal tissue complication probability models. The latter, currently used in the clinics, rely exclusively on limited patient data and neglect spatial dose distribution information. Among the various approaches, agent-based models are...

Introduction: Charged Particle Therapy plays a key role in the treatment of deep-seated tumours, because of the advantageous energy deposition culminating in the Bragg peak. However, knowledge of the dose delivered in the entrance channel is limited by the lack of data on the beam and fragmentation of the target. Methods: The FOOT experiment has be...

Background The remarkable resistance to ionizing radiation found in anhydrobiotic organisms, such as some bacteria, tardigrades, and bdelloid rotifers has been hypothesized to be incidental to their desiccation resistance. Both stresses produce reactive oxygen species and cause damage to DNA and other macromolecules. However, this hypothesis has on...

Knowledge of the characteristics of secondary neutrons produced by the interaction of Galactic Cosmic Radiation with spacecraft shielding materials is becoming increasingly important for predicting and mitigating biological risks of space explorers during deep-space travel. Hadron accelerators for medical applications are well suited to reproduce p...

Objective. We demonstrate a novel focus stacking technique to improve spatial resolution of single-event particle radiography (pRad), and exploit its potential for 3D feature detection. Approach. Focus stacking, used typically in optical photography and microscopy, is a technique to combine multiple images with different focal depths into a single...

Nuclear reaction cross-sections are an essential ingredient to reliable deterministic and stochastic radiation transport codes used for radiation protection in space and heavy-ion therapy applications. A recent study compared the existing literature data compiled within the open-access GSI-ESA-NASA cross-section database to the models implemented i...

The next years will see the completion of several new facilities at Istituto Nazionale di Fisica Nucleare – Laboratori Nazionali del Sud (LNS) opening up new possibilities in the fields of nuclear structure, nuclear dynamics, nuclear astrophysics and applications. These include a new line for high-intensity cyclotron beams, a new facility for in-fl...

Introduction: Cancer treatment has evolved significantly, yet concerns about tumor recurrence and metastasis persist. Within the dynamic tumor microenvironment, a subpopulation of mesenchymal tumor cells, known as Circulating Cancer Stem Cells (CCSCs), express markers like CD133, TrkB, and CD47, making them radioresistant and pivotal to metastasis....

The generation of space radiation on Earth is essential to study and predict the effects of radiation on space travelers, electronics, or materials during future long-term space missions. Next to the heavy ions of the galactic cosmic rays, solar particle events play a major role concerning the radiation risk in space, which consist of intermediate-...

A fast and reliable range monitoring method is required to take full advantage of the high linear energy transfer provided by therapeutic ion beams like carbon and oxygen while minimizing damage to healthy tissue due to range uncertainties. Quasi-real-time range monitoring using in-beam positron emission tomography (PET) with therapeutic beams of p...

Brain tumor patients are commonly treated with radiotherapy, but the efficacy of the treatment is limited by its toxicity, particularly the risk of radionecrosis. We used human cerebral organoids to investigate the mechanisms and nature of postirradiation brain image changes commonly linked to necrosis. Irradiation of cerebral organoids lead to inc...

Simple Summary Carbon-ion radiotherapy is a potential elective treatment option for hypoxic tumors. Its high linear energy transfer enables enhanced cell killing in radiation-resistant tumors, while the Bragg peak ensures precise targeting. Clinical evidence in pancreatic and cervical cancers supports positive outcomes of carbon treatments. However...

Hypoxia, associated with abnormal vessel growth, is a characteristic feature of many solid tumors that increases their metastatic potential and resistance to radiotherapy. Carbon ion radiation therapy, alone or in combination with other treatments, is one of the most promising treatments for hypoxic tumors because the oxygen enhancement ratio decre...

Mechanistic modelling of normal tissue toxicities is unfolding as an alternative to the phenomenological Normal Tissue Complication Probability models currently used in the clinics that rely exclusively on limited patient data. Among the various approaches, Agent-Based Models (ABMs) are appealing as they provide the means to include patient-specifi...

Simple Summary It is paramount to preserve the genetic material of endangered wildlife species for future generations, including that of the African savanna elephant (Loxodonta africana). By analyzing their genetic information, it is possible to decipher how endangered species such as elephants adapted to live on our planet and how they are related...

Purpose: To investigate the accuracy of the treatment planning system (TPS) TRiP4D in reproducing doses computed by the clinically used TPS SyngoRT. Methods: Proton and carbon ion beam models in TRiP4D were converted from SyngoRT. Cubic plans with different depths in a water-tank phantom (WP) and previously treated and experimentally verified pa...

fast and reliable range monitoring method is required to take full advantage of the high linear energy transfer (LET) provided by therapeutic ion beams like carbon and oxygen while minimizing damage to healthy tissue due to range uncertainties. Quasi-real-time range monitoring using in-beam positron emission tomography (PET) with positron-emitting...

Background The remarkable resistance to ionizing radiation found in anhydrobiotic organisms, such as some bacteria, tardigrades, and bdelloid rotifers has been hypothesized to be incidental to the desiccation resistance. Both stresses produce reactive oxygen species and cause damage to DNA and other macromolecules, including DNA. However, this hypo...

Particle minibeam therapy has demonstrated the potential for better healthy tissue sparing due to spatial fractionation of the delivered dose. Especially for heavy ions, the spatial fractionation could enhance the already favorable differential biological effectiveness at the target and the entrance region. Moreover, spatial fractionation could eve...

The indirect effect of radiation plays an important role in radio-induced biological damages. Monte Carlo codes have been widely used in recent years to study the chemical evolution of particle tracks. However, due to the large computational efforts required, their applicability is typically limited to simulations in pure water targets and to tempo...

The FRagment Separator FRS at GSI is a versatile spectrometer and separator for experiments with relativistic in-flight separated short-lived exotic beams. One branch of the FRS is connected to the target hall where the bio-medical cave (Cave M) is located. Recently a joint activity between the experimental groups of the FRS and the biophysics at t...

Cancer therapy with accelerated charged particles is one of the most valuable biomedical applications of nuclear physics. The technology has vastly evolved in the past 50 years, the number of clinical centers is exponentially growing, and recent clinical results support the physics and radiobiology rationale that particles should be less toxic and...

ICONIC is a multicenter, open-label, nonrandomized phase II clinical trial aiming to assess the feasibility and clinical activity of the addition of carbon ion radiotherapy to immune checkpoint inhibitors in cancer patients who have obtained disease stability with pembrolizumab administered as per standard-of-care. The primary end point is objectiv...

Charged particle radiotherapy, mainly using protons and carbon ions, provides physical characteristics allowing for a volume conformal irradiation and a reduction of the integral dose to normal tissue. Carbon ion therapy additionally features an increased biological effectiveness resulting in peculiar molecular effects. Immunotherapy, mostly perfor...

•Improvement of therapeutic ratio by novel unconventional radiotherapy approaches.•Immunomodulation using high-dose spatially fractionated radiotherapy.•Boosting radiation anti-tumor effects by adding an immune-mediated cell killing.

Human spaceflight is entering a new era of sustainable human space exploration. By 2030 humans will regularly fly to the Moon’s orbit, return to the Moon’s surface and preparations for crewed Mars missions will intensify. In planning these undertakings, several challenges will need to be addressed in order to ensure the safety of astronauts during...

Purpose Treatment of locally advanced lung cancer is limited by toxicity and insufficient local control. Particle therapy could enable more conformal treatment than intensity modulated photon therapy but is challenged by irregular tumor motion, associated range changes, and tumor deformations. We propose a new strategy for robust, online adaptive p...

Human spaceflight is associated with several health-related issues as a result of long-term exposure to microgravity, ionizing radiation, and higher levels of psychological stress. Frequent reported skin problems in space include rashes, itches, and a delayed wound healing. Access to space is restricted by financial and logistical issues; as a cons...

The 3D range-modulator is a device used in particle delivery systems that can create a highly conformal and homogeneous dose distribution in the target volume with mono-energetic beams, providing an option for high dose-rate FLASH therapy. In the normal case, the modulators are positioned at a typical distance of 30-50 cm in front of the target in...

Stopping power predictions in radiation transport codes are based on the Bethe-Bloch formula and different corrections. For very heavy ions at relativistic energies the available experimental data are scarce and therefore verification of stopping power predictions is only possible to a limited extent. In this work, a full experimental Bragg curve f...

\textit{Objective}. Beams of stable ions have been a well-established tool for radiotherapy for many decades. In the case of ion beam therapy with stable $^{12}$C ions, the positron emitters $^{10,11}$C are produced via projectile and target fragmentation, and their decays enable visualization of the beam via positron emission tomography (PET). How...

Sharp dose gradients and high biological effectiveness make ions such as ¹²C an ideal tool to treat deep-seated tumors, however, at the same time, sensitive to errors in the range prediction. Tumor safety margins mitigate these uncertainties, but during the irradiation they lead to unavoidable damage to the surrounding healthy tissue. To fully expl...