Particle Beam Radiobiology Status and Challenges: A PTCOG Radiobiology Subcommittee Report.

Particle therapy (PT) represents a significant advancement in cancer treatment, precisely targeting tumor cells while sparing surrounding healthy tissues thanks to the unique depth-dose profiles of the charged particles. Furthermore, their linear energy transfer and relative biological effectiveness enhance their capability to treat radioresistant tumors, including hypoxic ones. Over the years, extensive research has paved the way for PT's clinical application, and current efforts aim to refine its efficacy and precision, minimizing the toxicities.

High-Dose Ionizing Radiation Impairs Healthy Dendrite Growth in .

Purpose: The nervous system is vulnerable to radiation damage, and further optimization is required to increase the efficacy of radiation therapy while reducing harm to neurons. Given recent developments in heavy ion therapy, experimental models would be valuable to improve these therapies. We used the nematode () to evaluate the effects of high-dose radiation on neuron development.

Correction: Role of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung cancer.

[This corrects the article DOI: 10.1371/journal.pone.

Heavy Ion Minibeam Therapy: Side Effects in Normal Brain.

The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium-7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of planar parallel minibeams having 300-micron width and 1-mm center-to-center spacing within a circular array.

Therapeutic Efficacy of Variable Biological Effectiveness of Proton Therapy in U-CH2 and MUG-Chor1 Human Chordoma Cell Death.

Chordoma is a cancer of spinal cord, skull base, and sacral area. Currently, the standard of care to treat chordoma is resection followed by radiation therapy. Since, chordoma is present in the spinal cord and these are very sensitive structures and often complete removal by surgery is not possible.

Role of caveolin-1 as a biomarker for radiation resistance and tumor aggression in lung cancer.

Radiation therapy plays a major role in the treatment of lung cancer patients. However, cancer cells develop resistance to radiation. Tumor radioresistance is a complex multifactorial mechanism which may be dependent on DNA damage and repair, hypoxic conditions inside tumor microenvironment, and the clonal selection of radioresistant cells from the heterogeneous tumor site, and it is a major cause of treatment failure in non-small cell lung cancer (NSCLC).

Effect of hyperthermia and proton beam radiation as a novel approach in chordoma cells death and its clinical implication to treat chordoma.

Purpose: Chordoma is a locally aggressive tumor that most commonly affects the base of the skull/clivus, cervical, and sacral spine. Conventional radiotherapy (RT), cannot be safely increased further to improve disease control due to the risk of toxicity to the surrounding critical structures. Tumor-targeted hyperthermia (HT) combined with Proton Beam Radiation Therapy (PBRT) is known to act as a potent radiosensitizer in cancer control.

Proton minibeams-a springboard for physics, biology and clinical creativity.

Proton minibeam therapy (PMBT) is a form of spatially fractionated radiotherapy wherein broad beam radiation is replaced with segmented minibeams-either parallel, planar minibeam arrays generated by a multislit collimator or scanned pencil beams that converge laterally at depth to create a uniform dose layer at the tumor. By doing so, the spatial pattern of entrance dose is considerably modified while still maintaining tumor dose and efficacy. Recent studies using computational modeling, phantom experiments, and preclinical models, and early clinical feasibility assessments suggest that unique physical and biological attributes of PMBT can be exploited for future clinical benefit.

BIO 300, a Nanosuspension of Genistein, Mitigates Radiation-Induced Erectile Dysfunction and Sensitizes Human Prostate Cancer Xenografts to Radiation Therapy.

Purpose: To assess whether BIO 300, a synthetic genistein nanosuspension, improves the therapeutic index in prostate cancer treatment by preventing radiation-induced erectile dysfunction (ED) without reducing tumor radiosensitivity.

Methods And Materials: Male Sprague-Dawley rats were exposed to 25 Gy of 220-kV prostate-confined x-rays. Animals were randomized to receive sham radiation therapy (RT), RT alone, RT with daily BIO 300 at 2 experimental dosing regimens, or RT with daily genistein.

Hematological Effects of Non-Homogenous Ionizing Radiation Exposure in a Non-Human Primate Model.

Detonation of a radiological or nuclear device in a major urban area will result in heterogenous radiation exposure, given to the significant shielding of the exposed population due to surrounding structures. Development of biodosimetry assays for triage and treatment requires knowledge of the radiation dose-volume effect for the bone marrow (BM). This proof-of-concept study was designed to quantify BM damage in the non-human primate (NHP) after exposure to one of four radiation patterns likely to occur in a radiological/nuclear attack with varying levels of BM sparing.

Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies.

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body.

Merging Orthovoltage X-Ray Minibeams spare the proximal tissues while producing a solid beam at the target.

Conventional radiation therapy of brain tumors often produces cognitive deficits, particularly in children. We investigated the potential efficacy of merging Orthovoltage X-ray Minibeams (OXM). It segments the beam into an array of parallel, thin (~0.

Spatially fractionated proton minibeams.

Extraordinary normal tissue response to highly spatially fractionated X-ray beams has been explored for over 25 years. More recently, alternative radiation sources have been developed and utilized with the aim to evoke comparable effects. These include protons, which lend themselves well for this endeavour due to their physical depth dose characteristics as well as corresponding variable biological effectiveness.

Secondary Malignancies in the Era of High-Precision Radiation Therapy.

Although modern radiation therapy delivers a localized distribution of ionizing energy that can be used to cure primary cancers for many patients, the inevitable radiation exposure to non-targeted normal tissue leads to a risk of a radiation-related new cancer. Modern therapies often produce a complex spectrum of secondary particles, both charged and uncharged, that must be considered both in their physical radiation transport throughout the patient and their potential to induce biological damage, which depends on the microscopic energy deposition from the cascade of primary, secondary, and downstream particles. This work summarizes the experimental data for relative biological effectiveness for particles associated with modern radiotherapy in light of their capacity to induce secondary malignancies in patients.

Cavernous Nerve Injury by Radiation Therapy May Potentiate Erectile Dysfunction in Rats.

Purpose/objectives: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT lead to RiED; however, the precise role of RT-induced neurogenic injury in RiED has not been fully established.

Efficient Interplay Effect Mitigation for Proton Pencil Beam Scanning by Spot-Adapted Layered Repainting Evenly Spread out Over the Full Breathing Cycle.

Purpose: To develop and implement a practical repainting method for efficient interplay effect mitigation in proton pencil beam scanning (PBS).

Methods And Materials: A new flexible repainting scheme with spot-adapted numbers of repainting evenly spread out over the whole breathing cycle (assumed to be 4 seconds) was developed. Twelve fields from 5 thoracic and upper abdominal PBS plans were delivered 3 times using the new repainting scheme to an ion chamber array on a motion stage.

Comparison of multi-institutional Varian ProBeam pencil beam scanning proton beam commissioning data.

Purpose: Commissioning beam data for proton spot scanning beams are compared for the first two Varian ProBeam sites in the United States, at the Maryland Proton Treatment Center (MPTC) and Scripps Proton Therapy Center (SPTC). In addition, the extent to which beams can be matched between gantry rooms at MPTC is investigated.

Method: Beam data for the two sites were acquired with independent dosimetry systems and compared.

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy.

Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients.

Methods And Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model.

Validation of a track repeating algorithm for intensity modulated proton therapy: clinical cases study.

Monte Carlo (MC) methods are acknowledged as the most accurate technique to calculate dose distributions. However, due its lengthy calculation times, they are difficult to utilize in the clinic or for large retrospective studies. Track-repeating algorithms, based on MC-generated particle track data in water, accelerate dose calculations substantially, while essentially preserving the accuracy of MC.

Charged Particle Therapy with Mini-Segmented Beams.

One of the fundamental attributes of proton therapy and carbon ion therapy is the ability of these charged particles to spare tissue distal to the targeted tumor. This significantly reduces normal tissue toxicity and has the potential to translate to a wider therapeutic index. Although, in general, particle therapy also reduces dose to the proximal tissues, particularly in the vicinity of the target, dose to the skin and to other very superficial tissues tends to be higher than that of megavoltage x-rays.

Risk-optimized proton therapy to minimize radiogenic second cancers.

Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient.

Minibeam therapy with protons and light ions: physical feasibility and potential to reduce radiation side effects and to facilitate hypofractionation.

Purpose: Despite several advantages of proton therapy over megavoltage x-ray therapy, its lack of proximal tissue sparing is a concern. The method presented here adds proximal tissue sparing to protons and light ions by turning their uniform incident beams into arrays of parallel, small, or thin (0.3-mm) pencil or planar minibeams, which are known to spare tissues.