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Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer.

X‐ray induced photodynamic therapy (X‐PDT) circumvents the poor penetration depth of conventional PDT with minimal radio‐resistance generation. However, conventional X‐PDT typically requires inorganic scintillators as energy transducers to excite neighboring photosensitizers (PSs) to generate reactive oxygen species (ROS). Herein, a pure organic aggregation‐induced emission (AIE) nanoscintillator ( TBDCR NPs ) that can massively generate both type I and type II ROS under direct X‐ray irradiation is reported for hypoxia‐tolerant X‐PDT. Heteroatoms are introduced to enhance X‐ray harvesting and ROS generation ability, and AIE‐active TBDCR exhibits aggregation‐enhanced ROS especially less oxygen‐dependent hydroxyl radical (HO •− , type I) generation ability. TBDCR NPs with a distinctive PEG crystalline shell to provide a rigid intraparticle microenvironment show further enhanced ROS generation. Intriguingly, TBDCR NPs show bright near‐infrared fluorescence and massive singlet oxygen and HO •− generation under direct X‐ray irradiation, which demonstrate excellent antitumor X‐PDT performance both in vitro and in vivo. To the best of knowledge, this is the first pure organic PS capable of generating both 1 O 2 and radicals (HO •− ) in response to direct X‐ray irradiation, which shall provide new insights for designing organic scintillators with excellent X‐ray harvesting and predominant free radical generation for efficient X‐PDT.

Recent reports have suggested that 5-aminolevulinic acid (5-ALA), which is a precursor to protoporphyrin IX (PpIX), leads to selective accumulation of PpIX in tumor cells and acts as a radiation sensitizer in vitro and in vivo in mouse models of melanoma, glioma, and colon cancer. In this study, we investigated the effect of PpIX under X-ray irradiation through ROS generation and DNA damage. ROS generation by the interaction between PpIX and X-ray was evaluated by two kinds of probes, 3′-(p-aminophenyl) fluorescein (APF) for hydroxyl radical (•OH) detection and dihydroethidium (DHE) for superoxide (O2•-). •OH showed an increase, regardless of the dissolved oxygen. Meanwhile, the increase in O2•- was proportional to the dissolved oxygen. Strand breaks (SBs) of DNA molecule were evaluated by gel electrophoresis, and the enhancement of SBs was observed by PpIX treatment. We also studied the effect of PpIX for DNA damage in cells by X-ray irradiation using a B16 melanoma culture. X-ray irradiation induced γH2AX, DNA double-strand breaks (DSBs) in the context of chromatin, and affected cell survival. Since PpIX can enhance ROS generation even in a hypoxic state and induce DNA damage, combined radiotherapy treatment with 5-ALA is expected to improve therapeutic efficacy for radioresistant tumors.

Carbon ion radiotherapy (CIRT) has garnered interest for the treatment of locoregional rectal cancer recurrence. No study has compared CIRT and X-ray radiotherapy (XRT) for reirradiation (reRT) in such cases. We analyzed and compared the clinical outcomes such as local control, overall survival, and late toxicity rate between CIRT and XRT, for treating locoregional rectal cancer recurrence. Patients with rectal cancer who received reRT to the pelvis by CIRT or XRT from March 2005 to July 2019 were included. The CIRT treatment schedule was 70.4 Gy (relative biological effectiveness) in 16 fractions. For the XRT group, the median reRT dose was 50 Gy (range 25–62.5 Gy) with a median of 25 fractions (range 3–33). Thirty-five and 31 patients received CIRT and XRT, respectively. Tumour and treatment characteristics such as recurrence location and chemotherapy treatment differed between the two groups. CIRT showed better control of local recurrence (adjusted hazard ratio [HR] 0.17; p = 0.002), better overall survival (HR 0.30; p = 0.004), and lower severe late toxicity rate (HR 0.15; p = 0.015) than XRT. CIRT was effective for treating locoregional rectal cancer recurrence, with high rates of local control and survival, and a low late severe toxicity rate.

This case study discusses the use of superficial radiotherapy (SXRT) in the treatment of recurrent conjunctival squamous cell carcinoma (SCC). Conjunctival SCC is often an aggressive cancer, with surgery the current standard of care. There is currently limited literature on alternative treatment options to treat conjunctival SCC recurrences that enable ocular function preservation. Furthermore, the use of SXRT in this setting is not well‐reported. Technical feasibility, practical limitations and potential side effects of SXRT (in comparison to other treatment options) are discussed in this case study. This case describes a 62 years old male with limited treatment options following multiple recurrences of conjunctival SCC. He was prescribed a therapeutic SXRT dose of 48.4 Gy in 22 fractions (5 fractions/week). At 6‐month follow‐up, there was no evidence of residual or recurrent disease, or any significant objective or patient reported treatment induced side effects. This case study provides preliminary evidence for the potential application of SXRT for conjunctival SCC. The benefits reported in this case study warrant further investigation of the applicability of SXRT in a larger patient cohort, with the potential to provide patients with a less invasive treatment alternative for recurrent conjunctival SCC. This case study presents an alternative approach to traditional treatments for recurrent conjunctival squamous cell carcinoma. There is currently little consensus in the literature as the optimal care pathway for patients presenting with this condition. In this case, superficial radiotherapy provided an efficient, less invasive, less morbid and cosmetically improved patient alternative.

Microbeam radiation therapy (MRT), a form of experimental radiosurgery of tumours using multiple parallel, planar, micrometres‐wide, synchrotron‐generated X‐ray beams (‘microbeams’), can safely deliver radiation doses to contiguous normal animal tissues that are much higher than the maximum doses tolerated by the same normal tissues of animals or patients from any standard millimetres‐wide radiosurgical beam. An array of parallel microbeams, even in doses that cause little damage to radiosensitive developing tissues, for example, the chick chorioallantoic membrane, can inhibit growth or ablate some transplanted malignant tumours in rodents. The cerebella of 100 normal 20 to 38g suckling Sprague‐Dawley rat pups and of 13 normal 5 to 12kg weanling Yorkshire piglets were irradiated with an array of parallel, synchrotron‐wiggler‐generated X‐ray microbeams in doses overlapping the MRT‐relevant range (about 50‐600Gy) using the ID17 wiggler beamline tangential to the 6GeV electron synchrotron ring at the European Synchrotron Radiation Facility in Grenoble, France. Subsequent favourable development of most animals over at least 1 year suggests that MRT might be used to treat children's brain tumours with less risk to the development of the central nervous system than is presently the case when using wider beams.

This article assesses the therapeutic efficacy of ionizing radiation for the treatment of shoulder tendonitis/bursitis in the USA over the period of its use (human 1936–1961; veterinary 1954–1974). Results from ~3,500 human cases were reported in the clinical case studies over 30 articles, and indicated a high treatment efficacy (>90 %) for patients. Radiotherapy was effective with a single treatment. The duration of treatment effectiveness was prolonged, usually lasting until the duration of the follow-up period (i.e., 1–5 years). Therapeutic effectiveness was reduced for conditions characterized as chronic. Similar findings were reported with race horses in the veterinary literature. These historical findings are consistent with clinical studies over the past several decades in Germany, which have used more rigorous study designs and a broader range of clinical evaluation parameters. Radiotherapy treatment was widely used in the mid twentieth century in the USA, but was abandoned following the discovery of anti-inflammatory drugs and the fear of radiation-induced cancer. That X-ray treatment could be an effective means of treating shoulder tendonitis/bursitis, as a treatment option, and is essentially unknown by the current medical community. This paper is the first comprehensive synthesis of the historical use of X-rays to treat shoulder tendonitis/bursitis and its efficacy in the USA.

PurposeSurgery, chemo- and/or external radiation therapy are the standard therapy options for the treatment of laryngeal cancer. Trans-oral access for the surgery reduces traumata and hospitalization time. A new trend in treatment is organ-preserving surgery. To avoid regrowth of cancer, this type of surgery can be combined with radiation therapy. Since external radiation includes healthy tissue surrounding the cancerous zone, a local and direct intraoral radiation delivery would be beneficial.MethodsA general concept for a trans-oral radiation system was designed, based on clinical need identification with a medical user. A miniaturized X-ray tube was used as the radiation source for the intraoperative radiation delivery. To reduce dose distribution on healthy areas, the X-ray source was collimated by a newly designed adjustable shielding system as part of the housing. For direct optical visualization of the radiation zone, a miniature flexible endoscope was integrated into the system. The endoscopic light cone and the field of view were aligned with the zone of the collimated radiation. The intraoperative radiation system was mounted on a semi-automatic medical holder that was combined with a frontal actuator for rotational and translational movement using piezoelectric motors to provide precise placement.ResultsThe entire technical set-up was tested in a simulated environment. The shielding of the X-ray source was verified by performing conventional detector-based dose measurements. The delivered dose was estimated by an ionization chamber. The adjustment of the radiation zone was performed by a manual controlling mechanism integrated into the hand piece of the device. An endoscopic fibre was also added to offer visualization and illumination of the radiation zone. The combination of the radiation system with the semi-automatic holder and actuator offered precise and stable positioning of the device in range of micrometres and will allow for future combination with a radiation planning system.ConclusionsThe presented system was designed for radiation therapy of the oral cavity and the larynx. This first set-up tried to cover all clinical aspects that are necessary for a later use in surgery. The miniaturized X-ray tube offers the size and the power for intraoperative radiation therapy. The adjustable shielding system in combination with the holder and actuator provides a precise placement. The visualization of radiation zone allows a targeting and observation of the radiation zone.

This study evaluated the dosimetric impact of surface dose reduction due to the loss of backscatter from the bone interface in kilovoltage (kV) X‐ray radiation therapy. Monte Carlo simulation was carried out using the EGSnrc code. An inhomogeneous phantom containing a thin water layer (0.5–5 mm) on top of a bone (thickness=1 cm) was irradiated by a clinical 105 kVp photon beam produced by a Gulmay D3225 X‐ray machine. Field sizes of 2, 5, and 10 cm diameter and source‐to‐surface distance of 20 cm were used. Surface doses for different phantom configurations were calculated using the DOSXYZnrc code. Photon energy spectra at the phantom surface and bone were determined according to the phase‐space files at the particle scoring planes which included the multiple crossers. For comparison, all Monte Carlo simulations were repeated in a phantom with the bone replaced by water. Surface dose reduction was found when a bone was underneath the water layer. When the water thickness was equal to 1 mm for the circular field of 5 cm diameter, a surface dose reduction of 6.3% was found. The dose reduction decreased to 4.7% and 3.4% when the water thickness increased to 3 and 5 mm, respectively. This shows that the impact of the surface dose uncertainty decreased while the water thickness over the bone increased. This result was supported by the decrease in relative intensity of the lower energy photons in the energy spectrum when the water layer was with and over the bone, compared to without the bone. We concluded that surface dose reduction of 7.8%–1.1% was found when the water thickness increased from 0.5–5 mm for circular fields with diameters ranging from 2–10 cm. This decrease of surface dose results in an overestimation of prescribed dose at the patient's surface, and might be a concern when using kV photon beam to treat skin tumors in sites such as forehead, chest wall, and kneecap. PACS number: 87.55.K‐; 87.55.ne; 87.57.uq

To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down‐convert X‐rays into photons with energies ranging from UV to near‐infrared. During radiotherapy, these scintillating properties amplify radiation‐induced damage by UV‐C emission or photodynamic effects. Additionally, nanoscintillators that contain high‐Z elements are likely to induce another, currently unexplored effect: radiation dose‐enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X‐rays by high‐Z elements compared to tissues, resulting in increased production of tissue‐damaging photo‐ and Auger electrons. In this study, Geant4 simulations reveal that rare‐earth composite LaF3:Ce nanoscintillators effectively generate photo‐ and Auger‐electrons upon orthovoltage X‐rays. 3D spatially resolved X‐ray fluorescence microtomography shows that LaF3:Ce highly concentrates in microtumors and enhances radiotherapy in an X‐ray energy‐dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF3:Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose‐enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers. Radiation dose‐enhancement induced by rare‐earth composite nanoscintillators is predicted by in silico simulations and unequivocally demonstrates in vitro in microtumor models of glioblastoma, using tunable monochromatic synchrotron radiation. Radiation dose‐enhancement ultimately elicitsa prominent radiotherapeutic effect in a syngeneic orthotopic model of aggressive glioblastoma. These results prove the strong ability of rare‐earth composite nanoscintillators to enhance the focal damage of radiotherapy.