Editorial: Innovations, advances, and challenges in precision radiation oncology physics

With the continuous advancement of all components contributing to the therapeutic delivery of radiation within the oncology clinic, modern radiotherapy is becoming more precise than ever due to technological innovations and their widespread dissemination and rapid translation into clinical applications. New challenges are organically intertwined with the development of new technologies, which impede fully realizing their potential to improve clinical treatment outcomes. Radiation physics is the foundation of all treatment-related activities within radiotherapy. As such, this Special Issue in the journal of Precision Radiation Oncology aims to provide an up-to-date overview of innovations, advances, and challenges in medical radiation physics. This editorial briefly summarizes the eight manuscripts that are published in this physics Special Issue.

The first manuscript is an original article by Chatzipapas et al. ¹ presenting a Geant4-DNA example application, named “molecularDNA”, publicly released in the Geant4 version 11.1 (December 2022). Geant4 is a general-purpose Monte Carlo simulation toolkit for particle transport with a broad application in the field of radiation physics.² With the increasing interest in DNA damage induction and repair following radiation therapy, including the subsequent biological effects on cellular systems, many different Monte Carlo simulation methods have been proposed to examine the underlying physical, chemical, and biological mechanisms between ionizing radiation and DNA. The Geant4-DNA project was established with these goals in mind.³ This package is an extension of Geant4 to the scale of relevant biological molecules such as DNA and reactive oxygen species. However, the base C++ programming language of Geant4 has presented a somewhat substantial barrier to entry. To help alleviate this obstacle, the Geant4-DNA project members recently developed an example “molecular DNA” for novice Geant4 users. The methods and validation results of this example are described within this manuscript. molecularDNA is a prototype tool that can be applied in various radiobiology studies, providing the scientific community with an open-access base reference case for DNA damage calculations.

The second manuscript is an original article by Guan et al. ⁴ introducing the dosimetric response of GafChromic^TM EBT-XD film to proton radiation. The EBT-XD model has a broader optimal dynamic dose range, up to 40 Gy, compared with its predecessor film models. The authors characterized the dependence of EBT-XD film response to linear energy transfer (LET) and dose rate of therapeutic protons produced from a synchrotron. The responses of dose-averaged LET values of 1.0, 3.6, and 7.6 keV/μm were tested. For the dose rate dependence, films were irradiated at 150 Gy/s in the ultra-high dose rate FLASH mode and 0.3 Gy/s in the conventional dose rate mode.⁵ Their experimental results demonstrate that the response of EBT-XD film is dependent on proton LET but independent of dose rate within this tested range.

The third manuscript is an original article by Ferrone et al. ⁶ where the authors sought to evaluate bone marrow dosimetry with the addition of bone marrow structures to the medical internal radiation dose (MIRD) phantom. The authors integrated new bone marrow structures into the MIRD phantom which was built with the Geant4 framework to offer improved geometric representation. Dose equivalent was calculated to the bone marrow across medical, occupational, and space radiation exposure scenarios. These findings were compared with results using prior indirect estimation methods. Their results showed that the accuracy of bone marrow dose predictions may be improved by up to a factor of three when using the improved fidelity MIRD method compared with traditional methods performed without modeling bone marrow structures, specifically at clinical x-ray energies.

The fourth manuscript is an original article by Chen et al. ⁷ investigating the impact of dose calculation accuracy on inverse LET optimization for intensity-modulated proton therapy (IMPT). Two sets of IMPT plans comprised of two, four, six, or nine beams were created for ten prostate cancer patients. One plan set optimized with dose constraints using the pencil beam algorithm, and the other set optimized with additional LET constraints using a Monte Carlo algorithm. Their results demonstrate that LET-optimized IMPT plans demand high calculation accuracy in inverse optimization and that the addition of more beams did not improve plan robustness to dose calculation error. The authors recommend using the same dose calculation algorithm in LET optimization as the final dose calculation engine.

The fifth manuscript is a brief report by Guan et al.⁸ proffered to introduce their original work adding the X-ray Bragg reflection process originating within a crystal to the Geant4 Monte Carlo simulation toolkit. This work describes their initial efforts to demonstrate the Bragg reflection phenomenon from a crystal slab. X-ray diffraction from a solid crystal shows the wave nature of photons. Bragg diffraction, often called Bragg reflection, is a special case of general X-ray diffraction, known as Laue diffraction. When Bragg's law is met, the incident photon beam is reflected from the crystal plane behaving as a specular reflection at the Bragg angle. However, as of yet, the physical process of Bragg reflection has not been integrated into the public release of Geant4. The authors developed a new electromagnetic (EM) physical process class “G4CrystalBraggReflection” and a new EM physical model class “G4DarwinDynamicalModel” for modeling the Bragg reflection process within a crystal. These models are essential to perform Monte Carlo simulations for a novel radiation delivery modality, convergent x-ray radiotherapy such as the x-ray beam focusing apparatus reported by Bartkoski et al. ⁹

The sixth manuscript is an original article by Waheed et al. ¹⁰ reporting clinical outcomes after salvage external beam radiotherapy (EBRT) combined with interstitial brachytherapy for locally advanced, recurrent endometrial cancer. In this retrospective study, 12 patients with locally advanced, biopsy-proven vaginal recurrence following surgical resection of endometrial cancer received salvage EBRT (45 Gy in 25 daily fractions to microscopic disease and 55–57.5 Gy to gross nodal disease) with magnetic resonance-guided interstitial brachytherapy (20–21 Gy in 3 fractions over 2 days). The investigators found on follow-up, no patient developed local recurrence, one patient developed nodal recurrence outside of the radiotherapy treatment volume and then distant metastases, and one patient developed distant metastasis 2.5 years post-treatment and subsequently died from the disease, no other deaths were reported, and no patients developed grade ≥4 bowel or bladder toxicity. These findings demonstrate the potential of this salvage combination therapy to aid in the survival of patients suffering from recurrent endometrial cancer with minimal side effects.

The seventh manuscript is an original article by Kiladze et al.¹¹ to report their study on definitive chemoradiotherapy (dCRT) in elderly (≥65 years old) patients with unresectable esophageal cancer. The authors retrospectively analyzed 44 elderly patients with esophageal cancer to evaluate the outcome (overall survival) and toxicity (using CTCAE 5.0 criteria). Their results support the feasibility and efficacy of dCRT for unresectable esophageal cancer in carefully selected elderly patients. Their study showed that chronological age alone does not reflect a patient's ability to tolerate dCRT.

The eighth manuscript is a review article by Yu ¹² on the topic of radiotherapy for early-stage breast cancer. The author summarizes influential clinical studies with a focus on technical advancement in radiation therapy for early-stage breast cancer. The author discusses three major radiotherapy strategies including whole-breast irradiation, partial breast irradiation, and stereotactic body radiotherapy. The rationale, techniques, and clinical trials of each modality are systematically summarized and compared. Although the role of radiation therapy in managing early-stage breast cancer has changed in recent years with the introduction of targeted biologic therapies such as tamoxifen, trastuzumab, aromatase inhibitors, and other agents, the author demonstrates radiotherapy is a critical driving factor of the progression in the management of breast cancer. The author also offers a prospective discussion on the potential of the stereotactic technique in replacing both surgery and postoperative irradiation in the next decade to improve the quality of life of breast cancer patients.

In conclusion, the success of this physics Special Issue has strengthened the confidence of the guest editorial team for the continued publication of high-quality medical physics manuscripts and physics-driven clinical and preclinical studies in the journal of Precision Radiation Oncology. The guest editorial team would like to conclude this physics Special Issue as a new start for exploring innovations, advances, and challenges in precision radiation oncology physics.

CONFLICT OF INTEREST

All authors declare no conflicts of interest.