High-dose Radiation Research Articles

Brachytherapy in Brain Metastasis Treatment: A Scoping Review of Advances in Techniques and Clinical Outcomes.

Brain metastases pose a significant therapeutic challenge in the field of oncology, necessitating treatments that effectively control disease progression while preserving neurological and cognitive functions. Among various interventions, brachytherapy, which involves the direct placement of radioactive sources into or near tumors or into the resected cavity, can play an important role in treatment. Current literature describes brachytherapy's capacity to deliver targeted, high-dose radiation while minimizing damage to adjacent healthy tissues-a crucial consideration in the choice of treatment modality. Furthermore, advancements in implantation techniques as well as in the development of different isotopes have expanded its efficacy and safety profile. This review delineates the contemporary applications of brachytherapy in managing brain metastases, examining its advantages, constraints, and associated clinical outcomes, and provides a comprehensive understanding of advances in the use of brachytherapy for brain metastasis treatment, with implications for improved patient outcomes and enhanced quality of life.

UV-A treatment of phenolic extracts impacts colour, bioactive compounds and antioxidant activity.

The unintended co-extraction of chlorophylls during the recovery of polyphenols from plant sources yields green-coloured phenolic extracts with limited use in colour-sensitive foods. This study aimed at decolourizing the ethanolic extracts of sugar beet leaves using a UV-A treatment (390 nm). Exposure of the phenolic extracts to 30 UV-A LEDs at 8.64 J m-2 radiation dose decreased the total chlorophyll content by 69.23% and reduced the greenness parameter (-a*) significantly (P < 0.05) from 27.33 ± 0.32 to 8.64 ± 0.16. Additionally, UV-A treatment increased the content of most individual phenolic compounds (e.g. gallic acid, ferulic acid, etc.) significantly, resulting in an increase in the overall phenolic content in the extracts from 900.56 ± 14.11 μg g-1 fresh weight (FW) to a maximum of 975.09 ± 9.62 μg g-1 FW at 0.67 J m-2. However, rutin content had a significant decrease at the highest radiation dose (8.64 J m-2). The soluble sugar content (i.e. glucose and fructose) increased simultaneously with phenolic compounds after the UV-A treatment. Although the UV treatment reduced the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, it had no significant effect on the ferrous chelating activity and the extract's ability to delay lipid oxidation in corn oil. The antioxidant activity index of the treated extract was comparable to that of butylated hydroxytoluene, a synthetic antioxidant. Key findings of this study include successful decolourization of the extract, decomposition of bound polyphenols to their free form, and maintaining the antioxidant activity of the extract in the oil system after UV-A exposure. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Scintillating sampling ECAL technology for the LHCb PicoCal

The aim of the LHCb Upgrade II is to operate at a luminosity of up to 1.5×1034 cm2s−1 to collect a data set of 300 fb−1. The required substantial modifications of the current LHCb electromagnetic calorimeter due to high radiation doses in the central region and increased particle densities are referred to as PicoCal. Modification of the ECAL already during Long Shutdown 3 (LS3) will reduce the occupancy and mitigate substantial ageing effects in the central region after Run 3. Several scintillating sampling ECAL technologies are currently being investigated in an ongoing R&D campaign: Spaghetti Calorimeter (SpaCal) with garnet scintillating crystals and tungsten absorber, SpaCal with scintillating plastic fibres and tungsten or lead absorber, and Shashlik with polystyrene tiles, lead absorber and fast WLS-fibres. Timing capabilities with tens of picoseconds precision and increased granularity with denser absorber in the central region are needed for pile-up mitigation. Time resolutions of better than 20 ps at high energy were observed in test beam measurements of SpaCal and Shashlik prototype modules.

Online and offline Radiation-Induced Attenuation measurements on FD-7 radiophotoluminescence dosimeters irradiated at high X-ray doses

Radiophotoluminescence (RPL) FD-7 glass dosimeters find applications in low to high dose radiation environments. This work presents an experimental characterization of RPL glass dosimeter, irradiated with 100 kV X-ray tubes at room temperature at doses ranging from 1.3 kGy to 0.47 MGy, much higher of their common use range. In this study, a customized set-up has been developed, allowing the online investigation of the glass transmission changes with radiation, known as Radiation-Induced Attenuation (RIA), as well as the recovery and post-mortem characterizations up to 2 months after irradiation. Multi-wavelength analysis was performed, focusing on the range between 200 nm and 800 nm. At 700 nm and 800 nm, RIA increases progressively with dose up to about 5 kGy, and tends to approach saturation (2–3 dB/mm) for doses higher than 50 kGy. Higher attenuation is reported at lower wavelengths: 445-nm light transmission reduces to only about 1% of its initial value after 2 kGy. RIA recovery after irradiation was observed, up to 6% at 700 nm wavelength within 3 h from the irradiation conclusion and up to 26% 2 months after, especially at doses in the kGy range. Both online RIA and its recovery are highly dependent on the selected wavelength and on the total absorbed dose. This information is crucial for the extension of the use of these dosimeters up to high doses, complementary to the RPL signal, traditionally used alone for the determination of doses up to the Gy range.

Revitalizing gut health: Liangxue guyuan yishen decoction promotes akkermansia muciniphila -induced intestinal stem cell recovery post-radiation in mice

BackgroundThe efficacy of Liangxue Guyuan Yishen Decoction (LGYD), a traditional Chinese medicine, has been scientifically proven in the treatment of radiation-induced intestinal injury (RIII) and preservation of intestinal integrity and function following high-dose radiation exposure. However, further investigation is required to comprehensively elucidate the precise mechanisms underlying the therapeutic effects of LGYD in order to provide potential pharmaceutical options for radiation protection. PurposeThis study aims to elucidate the potential mechanism through which LGYD exerts its therapeutic effects on RIII by modulating the gut microbiota (GM). Methods16 s rRNA analysis was employed to assess the impact of varying doses of whole body irradiation (WBI) on GM in order to establish an appropriate model for this study. The effects of LGYD on GM and SCFA were evaluated using 16 s rRNA and Quantification of SCFA. UHPLC-QE-MS was utilized to identify the active components in LGYD as well as LGYD drug containing serum (LGYD-DS). Subsequently, immunofluorescence and immunohistochemical staining were conducted to validate the influence of LGYD and/or characteristic microbiota on RIII recovery in vivo. The effects of LGYD-DS, characteristic flora, and SCFA on intestinal stem cell (ISC) were assessed by measuring organoid surface area in intestinal organoid model. ResultsThe species composition and abundance of GM were significantly influenced by whole-body irradiation with a dose of 8.5 Gy, which was used as in vivo model. LGYD significantly improves the survival rate and promotes recovery from RIII. Additionally, LGYD exhibited a notable increase in the abundance of Akkermansia muciniphila (AKK) and levels of SCFA, particularly isobutyric acid. LGYD-DS consisted of seven main components derived from herbs of LGYD. In vivo experiments indicated that both LGYD and AKK substantially enhanced the survival rate after radiation and facilitated the recovery process for intestinal structure and function. In the organoid model, treatment with LGYD-DS, AKK supernatant or isobutyric acid significantly increased organoid surface area. ConclusionsLGYD has the potential to enhance RIII by promoting the restoration of intestinal stem cell, which is closely associated with the upregulation of AKK abundance and production of SCFA, particularly isobutyric acid.

Deep-learning-based Attenuation Correction for 68Ga-DOTATATE Whole-body PET Imaging: A Dual-center Clinical Study.

Attenuation correction is a critical phenomenon in quantitative positron emission tomography (PET) imaging with its own special challenges. However, computed tomography (CT) modality which is used for attenuation correction and anatomical localization increases patient radiation dose. This study was aimed to develop a deep learning model for attenuation correction of whole-body 68Ga-DOTATATE PET images. Non-attenuation-corrected and computed tomography-based attenuation-corrected (CTAC) whole-body 68Ga-DOTATATE PET images of 118 patients from two different imaging centers were used. We implemented a residual deep learning model using the NiftyNet framework. The model was trained four times and evaluated six times using the test data from the centers. The quality of the synthesized PET images was compared with the PET-CTAC images using different evaluation metrics, including the peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), mean square error (MSE), and root mean square error (RMSE). Quantitative analysis of four network training sessions and six evaluations revealed the highest and lowest PSNR values as (52.86±6.6) and (47.96±5.09), respectively. Similarly, the highest and lowest SSIM values were obtained (0.99±0.003) and (0.97±0.01), respectively. Additionally, the highest and lowest RMSE and MSE values fell within the ranges of (0.0117±0.003), (0.0015±0.000103), and (0.01072±0.002), (0.000121±5.07xe-5), respectively. The study found that using datasets from the same center resulted in the highest PSNR, while using datasets from different centers led to lower PSNR and SSIM values. In addition, scenarios involving datasets from both centers achieved the best SSIM and the lowest MSE and RMSE. Acceptable accuracy of attenuation correction on 68Ga-DOTATATE PET images using a deep learning model could potentially eliminate the need for additional X-ray imaging modalities, thereby imposing a high radiation dose on the patient.

Significance of androgen-deprivation therapy for intermediate- and high-risk prostate cancer treated with high-dose radiotherapy: A literature review.

The real-world benefits of adding androgen-deprivation therapy (ADT) and its optimal duration when combined with current standard high-dose radiation therapy (RT) remain unknown. We aimed to assess the efficacy of and toxicities associated with ADT in the setting of combination with high-dose RT for intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). This article is a modified and detailed version of the commentary on Clinical Question 8 described in the Japanese Clinical Practice Guidelines for Prostate Cancer (ver. 2023). A qualitative systematic review was performed according to the Minds Guide. All relevant published studies between September 2010 and August 2020, which assessed the outcomes of IR or HR PCa treated with high-dose RT, were screened using two databases (PubMed and ICHUSHI). A total of 41 studies were included in this systematic review, mostly consisting of retrospective studies (N = 34). The evidence basically supports the benefit of adding ADT to high-dose RT to improve tumor control. Regarding IR populations, many studies suggested the existence of a subgroup for which adding ADT had no impact on either overall survival or the BF-free duration. On the other hand, regarding HR populations, several studies suggested the positive impact of adding ADT for ≥1 year on overall survival. Adding ADT increases not only the risk of sexual dysfunction but also that of cardiovascular toxicities or bone fracture. Although the benefit of adding ADT was basically suggested for both IR and HR populations, further investigations are warranted to identify subgroups of patients for whom ADT has no benefit, as well as the appropriate duration of ADT for those who do derive benefit.

G0-PCC-FISH derived multi-parametric biodosimetry methodology for accidental high dose and partial body exposures

High dose radiation exposures are rare. However, medical management of such incidents is crucial due to mortality and tissue injury risks. Rapid radiation biodosimetry of high dose accidental exposures is highly challenging, considering that they usually involve non uniform fields leading to partial body exposures. The gold standard, dicentric assay and other conventional methods have limited application in such scenarios. As an alternative, we propose Premature Chromosome Condensation combined with Fluorescent In-situ Hybridization (G0-PCC-FISH) as a promising tool for partial body exposure biodosimetry. In the present study, partial body exposures were simulated ex-vivo by mixing of uniformly exposed blood with unexposed blood in varying proportions. After G0-PCC-FISH, Dolphin’s approach with background correction was used to provide partial body exposure dose estimates and these were compared with those obtained from conventional dicentric assay and G0-PCC-Fragment assay (conventional G0-PCC). Dispersion analysis of aberrations from partial body exposures was carried out and compared with that of whole-body exposures. The latter was inferred from a multi-donor, wide dose range calibration curve, a-priori established for whole-body exposures. With the dispersion analysis, novel multi-parametric methodology for discerning the partial body exposure from whole body exposure and accurate dose estimation has been formulated and elucidated with the help of an example. Dose and proportion dependent reduction in sensitivity and dose estimation accuracy was observed for Dicentric assay, but not in the two PCC methods. G0-PCC-FISH was found to be most accurate for the dose estimation. G0-PCC-FISH has potential to overcome the shortcomings of current available methods and can provide rapid, accurate dose estimation of partial body and high dose accidental exposures. Biological dose estimation can be useful to predict progression of disease manifestation and can help in pre-planning of appropriate & timely medical intervention.

Quantitative Digital Subtraction Angiography Measurement of Arterial Velocity at Low Radiation Dose Rates.

Quantitative digital subtraction angiography (qDSA) has been proposed to quantify blood velocity for monitoring treatment progress during blood flow altering interventions. The method requires high frame rate imaging [~ 30 frame per second (fps)] to capture temporal dynamics. This work investigates performance of qDSA in low radiation dose acquisitions to facilitate clinical translation. Velocity quantification accuracy was evaluated at five radiation dose rates in vitro and in vivo. Angiographic technique ranged from 30 fps digital subtraction angiography ( at the interventional reference point) down to a 30 fps protocol at 23% higher radiation dose per frame than fluoroscopy ( ). The in vitro setup consisted of a 3D-printed model of a swine hepatic arterial tree connected to a pulsatile displacement pump. Five different flow rates (3.5-8.8mL/s) were investigated in vitro. Angiography-based fluid velocity measurements were compared across dose rates using ANOVA and Bland-Altman analysis. The experiment was then repeated in a swine study (n = 4). Radiation dose rate reductions for the lowest dose protocol were 99% and 96% for the phantom and swine study, respectively. No significant difference was found between angiography-based velocity measurements at different dose rates in vitro or in vivo. Bland-Altman analysis found little bias for all lower-dose protocols (range: [- 0.1, 0.1]cm/s), with the widest limits of agreement ([- 3.3, 3.5]cm/s) occurring at the lowest dose protocol. This study demonstrates the feasibility of quantitative blood velocity measurements from angiographic images acquired at reduced radiation dose rates.

Evaluation of Radiation Doses Received by Physicians during Permanent 198Au Grain Implant Brachytherapy for Oral Cancer

Brachytherapy is a practical, effective procedure for the local treatment of cancer; it delivers a high radiation dose to a limited tissue volume while sparing the surrounding normal tissues. Although the clinical benefit of brachytherapy is clear, there have been very few studies on the radiation dose received by physicians during the procedure. Furthermore, no study has investigated the eye radiation dose received by physicians performing 198Au grain (seed) brachytherapy, using an eye dosimeter. Recently, the International Commission on Radiological Protection (ICRP) recommended significantly reducing the occupational lens dose limit, from 150 to 20 mSv/yr (100 mSv/5 years). Therefore, it has become essential to evaluate the eye radiation doses of medical workers. We evaluated the eye radiation dose of a brachytherapy physician performing 198Au permanent grain implantation for tongue cancer; this is the first study on this topic. The maximum eye dose was ~0.1 mSv/procedure, suggesting that it is unlikely to exceed the ICRP limit (20 mSv/yr) for the lens, unless many procedures are performed with inappropriate radiation protection. To reduce the dose of radiation received by 198Au grain brachytherapy physicians, it is necessary to use additional lead shielding equipment when preparing the treatment needles, i.e., when loading the grains. This study provides useful information on radiation exposure of physicians conducting 198Au permanent grain brachytherapy.

Exploring predictive molecules of acute adverse events in response to volumetric‑modulated arc therapy for prostate cancer using urinary metabolites.

Volumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples. Urine samples from 11 patients with prostate cancer who were treated with VMAT (76 Gy/38 fractions) were collected. The study found that seven patients (~64%) exhibited genitourinary toxicity (Grade 1) and four patients had no AEs. A total of 630 urinary metabolites were then analyzed using a mass spectrometer (QTRAP6500+; AB SCIEX), and 234 relevant molecules for biological and clinical applications were extracted from the absolute quantified metabolite values using the MetaboINDICATOR tool. In the Grade 1 acute AE group, there was a significant negative correlation (rs=-0.297, P<0.05) between the number of VMAT fractions and total phospholipase A2 activity in the urine. Additionally, patients with Grade 1 AEs exhibited a decrease in PC aa C40:1, a phospholipid. These findings suggested that specific lipids found in urinary metabolites may serve as predictive biomarkers for acute AEs in response to external radiotherapy.

Evidence-based clinical recommendations for hypofractionated radiotherapy: exploring efficacy and safety - Part 3. Genitourinary and gynecological cancers.

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/β ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies.

Ag-Pt@BSA bimetallic nanoparticles for breast cancer radiation treatment dose augmentation

Cancer has traditionally been treated with surgery and chemotherapy. Radiation therapy (RT) is a branch of oncology based on radiation therapy that can be used alone or in combination with surgery and chemotherapy to achieve local control of breast cancer. Radiosensitizers make tumor cells more responsive and sensitive to ionizing radiation, consequently facilitating production of free radicals and hastening DNA damages. Stages I to III of breast cancer is managed with curative intent with multimodality treatment including radiotherapy. The current cancer therapies in particular radiotherapy have a high risk of serious side effects to the healthy tissues and do not guarantee remission. In response to this challenge, the present study developed bovine serum albumin capped platinum and silver nanoparticles (Ag-Pt@BSA NPs), a bimetallic radiosensitizer, which is a remedy to the aforementioned issue. This research makes use of a nanoplatform that contains two high-Z nanoparticles— Pt and Ag. A variety of methods were used to fully characterize the developed Ag-Pt@BSA NPs. Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), dynamic light scattering (DLS), UV–Vis, X-ray diffractometery (XRD) and energy-dispersive X-ray spectroscopy (EDS) techniques were used to investigate the physical and chemical features of designed bimetallic nanoradiosensitizer. The Ag-Pt@BSA naoradiosensitizer was proven to have successfully prepared by FTIR, XRD and EDX. According to the DLS result, the hydrodynamic size of the NPs is 35.42 nm, and the average diameter in the TEM image is around 7.8 ± 2.6 nm. The initial hydrodynamic size Ag-Pt@BSA was around 35 nm and within the storage time its size remained below 40 nm which indicating the unique colloidal stability of fabricated nanoradiosensitizers. The zeta potential of Ag-Pt@BSA radio-enhancement was determined to be approximately −17.9 mV, providing additional support for the nanoparticles’ colloidal stability. The results showed that the utilization of Ag-Pt@BSA NPs in conjunction with X-ray irradiation could substantially enhance the effectiveness of cancer therapy. This is supported by research, examining a series of in vitro tests including reactive oxygen species generation (ROS), cell viability, apoptosis and colony formation assay. Furthermore, the dosage-dependent radiosensitizing ability of the Ag-Pt@BSA NPs was also observed in the apoptosis and MTT assay against 4 T1 cells by increasing the localized radiation dosage. Ag-Pt@BSA NPs could be a potential radio-enhancer agent against breast cancers and, by extension, other cancers, since it multiplies the therapeutic effect of low-dose radiation while reducing the damage to normal tissues compared to high-dose radiation therapy. Increasing the concentration of Ag-Pt@BSA NPs and the dosage of X-ray irradiation boosted the radiosensitizing capacity in a dose-dependent way.

Secretory factors released from high dose radiation-activated osteoclasts increase the expression level of pain-associated neuropeptides in sensory neuronal cultures.

Stereotactic Body Radiation Therapy for lung tumors near the chest wall often causes significant chest wall pain (CWP), negatively impacting patients' quality of life. The mechanisms behind SBRT-induced CWP remain unclear and may involve multiple factors. We investigated the potential crosstalk between radiation-activated osteoclasts and sensory neurons, focusing on osteoclast-derived factors in CWP. Using the murine pre-osteoclast cell line Raw264.7, we induced differentiation with RANKL, followed by 10Gy gamma-irradiation. Conditioned media from these irradiated osteoclasts was used to treat sensory neuronal cultures from mouse dorsal root ganglia. Neuronal cultures were also directly exposed to 10Gy radiation, with and without osteoclast co-culture. Analysis of osteoclast markers and pain-associated neuropeptides was conducted using RT-qPCR and histochemical staining. Osteoclast differentiation and activity were inhibited using Osteoprotegerin and risedronate. Results showed that high-dose radiation significantly increased osteoclast size, resorption pit size, and activity biomarkers. Neurons treated with CM from irradiated osteoclasts showed increased expression of pain-associated neuropeptides CGRP and Substance P, which was mitigated by osteoprotegerin and risedronate. This study suggests that high-dose radiation enhances osteoclast activity, upregulating pain-associated neuropeptides in sensory neurons, and that inhibitors like osteoprotegerin and risedronate may offer therapeutic strategies for managing radiation-induced pain.

X-Ray-Sensitizers: Organic Pharmaceutical Drug Intermediates Activated Directly by X-Rays to Efficiently Populate Triplet Excitons for Cancer Treatment

Radiotherapy is an important treatment for cancer, but it is associated with major side effects due to the high dose of radiation (generally more than 50 Gy). Because radiation’s low acute and late toxicity, many tumors are treated with fractionated radiation in small doses (< 2 Gy). Scintillator X-ray-induced photodynamic therapy is an efficient methodology for cancer management that employs small doses of X-ray irradiation (< 2 Gy) in a complex process. Here we screened pharmaceutical drug intermediates that are derivatives of thioxanthone (TX) and investigated TX-derived organic pharmaceutical molecules that efficiently undergo X-ray-sensitization to populate triplet excitons (singlet oxygen) for cancer therapy when exposed to low-dose X-ray irradiation. By modifying alkoxy side chain substitutions at the 2-position to tune the molecular packing and intermolecular interactions, the fluorescence and room-temperature phosphorescence of a series of TX derivatives were assessed under X-ray irradiation. The ability of these derivatives to generate singlet oxygen and their potential for treating tumors provide new opportunities for developing organic molecules with simple chemical structures, in which large numbers of triplets can be populated directly under ultralow-dose X-ray irradiation.

Pharyngeal Constrictor-Sparing Salvage Stereotactic Body Radiation Therapy With Tongue-Out for In-Field Recurrence After Definitive Radiation Therapy for Head and Neck Cancer: Guide to Tongue-Out Radiation Therapy

This report details a pharyngeal constrictor muscle (PCM)–sparing stereotactic body radiation therapy (SBRT) using our institutional technique of “tongue-out” radiation therapy (TORT) for treating a local recurrent cancer in the uvula (GTVuvula) in a patient with history of a definitive chemotherapy with radiation therapy (70 Gy with weekly cisplatin) for a locally advanced laryngeal cancer 4 years ago. TORT includes optimizing the patients’ reproducible tongue-out position using readily available medicine cup (30 cc) followed by sculping the thermoplastic mask with tongue-out, and real-time visual monitoring of the tongue position during the computed tomography simulation scan, cone beam computed tomography acquisition, and treatment. Between arcs during volumetric modulated arc therapy, time for tongue relaxation and saliva swallowing can be given to the patient. Without TORT, the patient's GTVuvula abutted the medial aspect of superior PCM (medial-sPCM) and a substantial volume of the previously irradiated superior PCM (sPCM) would have received high radiation dose from this salvage SBRT (32.5 Gy in 5 fractions). Comparing without TORT, the shortest distance between medial-sPCM-to-GTVuvula was increased by 13 mm with TORT, which reduced radiation dose to sPCM in the salvage SBRT plan. The mean dose to sPCM was decreased from 20.5 Gy without TORT to 12.7 Gy with TORT. With TORT, minimal sPCM volumes fell within higher isodose line: volume receiving ≥ 60% prescription dose (V60%Rx), V80%Rx, and V100%Rx to sPCM was, 4.8 versus 0.7 cc (without vs with TORT, respectively), 2.9 versus 0.19 cc, and 1.6 versus 0.04 cc, respectively. Maximum dose (Dmax) to medial-sPCM was 34.6 Gy without TORT versus 22.7 Gy with TORT. These high doses to the sPCM and intrafractional swallowing-related geographic misses of GTVuvula were avoided through the application of TORT in this salvage reirradiation setting. The patient successfully finished salvage SBRT with TORT resulting in no dysphagia or mucositis and maintained complete response at 12 months after treatment.

MANAGING LOCALLY ADVANCED CERVICAL CARCINOMA WITH A PELVIC KIDNEY USING VOLUMETRIC MODULATED ARC THERAPY: A CLINICAL CHALLENGE

The coexistence of cervical carcinoma and pelvic kidney is uncommon. Given that the pelvic kidney occupies the traditional radiation field for cervical carcinoma, treating these patients with radiation poses a therapeutic dilemma. We report the case of a 72 years old patient with stage IIIB cervical carcinoma with an incidental diagnosis of pelvic kidney was treated with radical chemoradiotherapy using volumetric-modulated arctherapy with concurrent weekly cisplatin.. At the 12-month follow-up, the patient was disease free and had no deterioration in kidney function. Volumetric-modulated arc therapy (VMAT) allowed for the precise delivery of high radiation doses in this particular case, while effectively sparing the kidney.

Low-Dose Ionizing Radiation Exposure on Human Male Gametes: Damage or Benefit.

With the improvement of medical devices for diagnosis and radiotherapy, concerns about the effects of low doses of ionizing radiation are also growing. There is no consensus among scientists on whether they might have beneficial effects on humans in certain cases or pose more risks, making the exposure unreasonable. While the damaging consequences of high-dose radiation have been known since the discovery of radioactivity, low-dose effects present a much bigger investigative challenge. They are highly specific and include radio-adaptive responses, bystander effects, and genomic instability. Current data regarding the consequences of exposure to low-dose radiation on the quality of male gametes and fertility potential are contradictory. The reports suggest two directions: indirect impact on male gametes-through spermatogenesis-or direct effects at low doses on already mature spermatozoa. Although mature gametes are used for observation in both models, they are fundamentally different, leading to varied results. Due to their unique physiological characteristics, in certain cases, exposure of spermatozoa to low-dose ionizing radiation could have positive effects. Despite the findings indicating no beneficial effects of low-dose exposure on male fertility, it is essential to research its impact on mature spermatozoa, as well.

Cumulative Dose from Recurrent CT Scans: Exploring the DNA Damage Response in Human Non-Transformed Cells.

Recurrent computed tomography (CT) examination has become a common diagnostic procedure for several diseases and injuries. Though each singular CT scan exposes individuals at low doses of low linear energy transfer (LET) radiation, the cumulative dose received from recurrent CT scans poses an increasing concern for potential health risks. Here, we evaluated the biological effects of recurrent CT scans on the DNA damage response (DDR) in human fibroblasts and retinal pigment epithelial cells maintained in culture for five months and subjected to four CT scans, one every four weeks. DDR kinetics and eventual accumulation of persistent-radiation-induced foci (P-RIF) were assessed by combined immunofluorescence for γH2AX and 53BP1, i.e., γH2AX/53BP1 foci. We found that CT scan repetitions significantly increased both the number and size of γH2AX/53BP1 foci. In particular, after the third CT scan, we observed the appearance of giant foci that might result from the overlapping of individual small foci and that do not associate with irreversible growth arrest, as shown by DNA replication in the foci-carrying cells. Whether these giant foci represent coalescence of unrepaired DNA damage as reported following single exposition to high doses of high LET radiation is still unclear. However, morphologically, these giant foci resemble the recently described compartmentalization of damaged DNA that should facilitate the repair of DNA double-strand breaks but also increase the risk of chromosomal translocations. Overall, these results indicate that for a correct evaluation of the damage following recurrent CT examinations, it is necessary to consider the size and composition of the foci in addition to their number.

GCT-26. INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOR WITH MALIGNANT TRANSFORMATION TO EMBRYONAL RHABDOMYSARCOMA

Abstract BACKGROUND Non-germinomatous germ cell tumors (NGGCT) constitute 35%- 45% of intracranial germ cell tumors. Growing teratoma syndrome has been observed in patients with NGGCTs after starting chemotherapy. While growing teratomas are typically benign, this process can rarely involve malignant transformation and result in poor prognosis. We present the case of a patient with pineal NGGCT and growing teratoma syndrome with malignant transformation to embryonal rhabdomyosarcoma. CASE REPORT A 13-year-old male presented with headaches and vision changes. An MRI brain demonstrated a 26 x 25 x 19 mm (AP X TR X CC) mixed solid and cystic pineal mass with no evidence of metastatic disease. Due to elevated alpha fetoprotein levels in the serum and cerebrospinal fluid, he was diagnosed with intracranial NGGCT. Treatment was initiated with alternating cycles of Carboplatin/Etoposide and Ifosfamide/Etoposide. After 2 cycles of chemotherapy, a complete biochemical response was noted but MRI showed increased tumor size (presumed growing teratoma syndrome). The patient underwent complete tumor resection. Histology showed embryonal rhabdomyosarcoma as a somatic malignancy arising in a mature teratoma. Further molecular characterization revealed somatic NF1 and KRAS pathogenic mutations that are consistent with the primary diagnosis. Methylation profiling, however, did not exhibit a match with any known malignancies. Continued complete response was noted following two additional chemotherapy cycles. The patient is planned for six total chemotherapy cycles followed by high-dose craniospinal radiation with boost to the primary tumor. CONCLUSIONS Malignant transformation is a rare phenomenon in NGGCT. There is no standard of care for these patients. Further studies are needed to define ideal therapy for this patient population.