Gy Dose Research Articles

Abstract 5060: Role of molecular driver mutations in recurrence of early stage laryngeal cancer following narrow field definitive radiotherapy

Abstract PURPOSE/OBJECTIVES Recurrent early-stage laryngeal cancer poses profound clinical and prognostic dilemmas. The primary endpoint of this study was to identify patient exome differences between early-stage laryngeal cancer patients who responded or rapidly progressed following definitive, narrow field radiotherapy. Our study offers the first exploration of mutation patterns in early-stage laryngeal head and neck squamous cell carcinoma (HNSCC) patients receiving curative radiation therapy. MATERIALS/METHODS We identified 36 early-stage laryngeal (T1 = 8, T1a = 4, T1b = 2, T1c = 1, T2 = 20, NA =1) HNSCC patients from the University of Kansas Medical Center treated with definitive narrow field radiotherapy to 63-70 Gray (gy) dose. Whole exome sequencing was performed in all patients. Patients were stratified into “responders” (never failed, N=14) and “non-responders” (recurrence <12 months, N=21). Most non-responder patients with local recurrence underwent total salvage laryngectomy (TSL, N=18). All patients underwent whole exome sequencing. The Genome Analysis Toolkit (GATK) was used for pre-processing and functional annotation of variants. Cancer driver genes were detected for each group using the OncodriveCLUST algorithm. Differentially mutated genes were assessed using Fisher’s exact or exact McNemar’s test at P < 0.05. Tumor mutational burden (TMB) comparisons employed the Wilcoxon rank-sum test with the same threshold. For pathway analysis in Reactome and Ingenuity, a P < 0.1 was used for exploratory significance. RESULTS Mutation analysis identified distinct cancer driver genes between responders, (N=3), non-responders (N=36), and post-TSL (N=4). Among 75 genes with significant pre-treatment mutation differences between responders and non-responders, KCNT2 and AGAP6 were exclusively mutated in non-responders (OR=0, P=0.005 and OR=0, P=0.027, respectively), ADAMTS7 was solely mutated in responders (OR=inf, P=0.019), and PLEC showed more mutations in responders (OR=11.6, P=0.006). Pathway analysis showed these genes were involved in the RND2 GTPase cycle, protein O-glycosylation related diseases, and apoptotic pathways. Post-treatment analysis indicated an enrichment of mutations in apoptosis regulation pathways, with genes like PLEC being more frequently mutated in responders than in non-responders or TSL patients. In addition, we observed in non-responders that they trended towards higher median pre-treatment TMB compared to responders (7.98 vs 6.16, P=0.072). There was no significant difference in TMB between TSL patients and responders or non-responders pre-treatment. CONCLUSION Our analysis reveals distinct mutation patterns in early-stage laryngeal cancer patients by response to radiotherapy and the potential role of these mutated genes in apoptosis related pathways. Citation Format: Aaron Segura, Emily Nissen, Chris Lominska, Ryan Morse, Deri Morgan, Prakash Neupane, Dong Pei, Devin Koestler, Randall Kimple, Umamaheswar Duvvuri, Kevin Sykes, Sufi Thomas, Rohit Nallani, Lisa Shnayder, Kiran Kakarala, Emrullah Yilmaz, Andres Bur. Role of molecular driver mutations in recurrence of early stage laryngeal cancer following narrow field definitive radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5060.

Abstract 2879: Spatiotemporal fractionation: An innovative concept of fractionated radiotherapy

Abstract Impressive outcomes in therapeutic radiation oncology have been achieved in the past decade through the development of advanced computer technology and imaging methods, such as intensity modulated radiotherapy. Ideally, radiotherapy treatment delivers a high dose to the tumor while sparing the surrounding healthy tissues and organs at risk from radiation damage. Spatiotemporal Fractionated Radiotherapy has emerged as an innovative technique that delivers different dose distributions to different parts of the tumor in order to achieve high doses to the target while ensuring a low dose-bath in the surrounding normal tissue. Spatiotemporally fractionated regimens showed in silico up to 10 - 15% sparing of normal tissue from radiation damage, while ensuring isoeffective tumor control compared to conventionally fractionated regimens. However, prior to advancing spatiotemporal fractionation to the clinical level, it is important to probe the validity of the main assumption of spatiotemporal fractionation derived from the Biologically Effective Dose (BED) model: two different fractionation schemes that implement a high and a low dose will lead to equivalent clinical effects, regardless of dose-treatment sequence. A tumor growth delay study was performed in a subcutaneous immunocompetent murine tumor model (MC38-tumor cell derived) receiving two different fractionation regimens. Particularly, tumors belonging to the two treatment groups received the same dose combination - a high (12 Gy) and a low (6 Gy) dose fraction separated by 72 hours - with the doses delivered in opposite order in the two treatment groups. The same experimental outline was performed in a subcutaneous immunodeficient murine tumor model derived from the same tumor cells. Tumors were also characterized by immunophenotyping analysis seven days after first irradiation. Even though the two regimens deliver the same physical dose to the tumor - and would be considered equivalent according to the BED model - different tumor growth delays were observed in a time window of 30 days after first irradiation depending on the treatment group. Such differences were observed in the immunocompetent model but not in the immunodeficient model. The immunophenotyping results showed immunostimulatory vs immunosuppressive phenotypes of the tumor microenvironment depending on the order of the treatment doses. An additional tumor growth delay study including immune checkpoint inhibitors confirmed the fundamental role of the immune system with the differential efficacy outcomes of the two regimens. Overall, these intriguing results suggest that a differential radiotherapy-induced immune response to different doses of ionizing radiation plays an important role in the treatment outcome and asks for re-evaluation of the BED model taking scheduling-dependent parameters into consideration. Citation Format: Irene Vetrugno, Irma Telarovic, Nathan Torelli, Jan Unkelbach, Martin Pruschy. Spatiotemporal fractionation: An innovative concept of fractionated radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2879.

Abstract 387: Ionizing radiation induces lipid metabolism-associated vulnerabilities in glioblastoma multiforme

Abstract Introduction: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. It is highly resistant to its current standard-of-care regimen, which includes surgical resection followed by adjuvant ionizing radiation and temozolomide. Therapy resistance can be attributed to the abundance of genomic alterations in GBM tumors that evolve over time, which contribute to intra-and inter-tumoral heterogeneities that render targeted therapies as inadequate treatment options. Thus, there is an urgent unmet need for effective therapies targeting primary and recurrent GBM. Here, we investigated the impact of ionizing radiation on the transcriptome of patient derived GBM tumor spheres to identify key alterations and biological pathways involved in therapy resistance. Materials and methods: We acquired four independent human GBM tumor sphere cell lines, which were derived from patients and cultured in serum-free media. Tumor spheres were treated with either a sham radiation or a single dose of 10Gy. Using poly-A enrichment whole transcriptome sequencing, we evaluated transcriptional alterations occurring in GBM tumors spheres at 96h post-radiation. To do so, we performed differential expression analysis and gene set enrichment analysis (GSEA) to identify top differentially expressed genes and significant changes in biological phenomena. Additionally, we evaluated the cell viability response of these GBM tumor spheres to radiation. Results and discussion: PCA analysis of the four human GBM tumor sphere cell lines demonstrates that cell type has a substantial impact on variation among samples compared to non-irradiated and irradiated treatment conditions. Upon analysis of genes in common that are either upregulated or downregulated followed by GSEA, we identified enrichment of genes associated with inflammatory responses and ferroptosis repression (e.g., NUPR1, PTGS1, AOX1), and depletion of genes involved in fatty acid metabolism (e.g., INSIG1, PLA2G3, ACAT2). Furthermore, the GBM tumor sphere cell viability responses allowed us to stratify our models into radiosensitive and radioresistant subgroups. Conclusion: Radiosensitive human GBM tumor spheres exhibit transcriptional alterations in genes linked to inflammation and fatty acid metabolism to a greater extent compared to radioresistant tumor spheres. Our study characterizes the radiation response of patient derived GBM models, which is to be leveraged for combating therapeutic resistance. Citation Format: Arianna Richelle Izawa-Ishiguro, Subhiksha Nandakumar, Nicholas Carbone, Annalisa V. Ferrotta, Raashed Raziuddin, Kristen C. Vogt, Daniel A. Heller, Ingo K. Mellinghoff. Ionizing radiation induces lipid metabolism-associated vulnerabilities in glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 387.

Beta irradiation-induced thermoluminescence: Glow curve analysis and kinetic parameters in combustion-synthesized undoped Ca4YO(BO3)3

This study examines the thermoluminescent (TL) properties of undoped Ca4YO(BO3)3 phosphor, focusing on how it behaves under a variety of experimental conditions. The IRSL-TL 565 nm was chosen as the appropriate detection filter among various optical detection filter combinations. During the preheating trials conducted at a rate of 2 °C/s, the TL peak exhibited increased intensity, particularly around 200 °C. The experimental outcomes demonstrated a reliable linear relationship (R2 = 0.996 and b = 1.015) in the dose response of undoped preheated Ca4YO(BO3)3 within the range of 1–200 Gy. The investigation encompasses a range of techniques, including the TM-Tstop method, computerized glow curve deconvolution (CGCD) analysis, and theoretical modelling. The application of the TM-Tstop method to samples irradiated with a 5 Gy dose revealed distinct zones on the TM versus Tstop diagram, signifying the presence of at least two discernible components within the TL glow curve, specifically, a single general order kinetics peak and a continuous distribution. The analysis of activation energy versus preheated temperature exhibited a stepwise curve, indicating five trap levels with depths ranging between 1.13 eV and 1.40 eV. The CGCD method also revealed the superposition of at least five distinct TL glow peaks. It was observed that their activation energies were consistent with the Tm-Tstop experiment. Furthermore, the low Figure of Merit (FOM) value of 1.18% indicates high reliability in the goodness-of-fit measure. These findings affirm the reliability and effectiveness of the employed methods in characterizing the TL properties of the Ca4YO(BO3)3 phosphor under investigation. Theoretical models, including the semi-localized transition model, were introduced to explain anomalous observations in TL glow peak intensities and heating rate patterns. While providing a conceptual framework, these models may require adjustments to accurately capture the specific characteristics uncovered through CGCD analysis. As a potential application, the study suggests that the characterized TL properties of Ca4YO(BO3)3 phosphor could be utilized in dosimetric applications, such as radiation dose measurements, owing to its reliable linear response within a broad dose range.

Effect of Gamma Irradiation on Embryogenic Calli of Rice and Subsequent Shoot and Regeneration

This study was carried out during May 2021 to January 2022 at the Tissue Culture Laboratory of Biotechnology Division, Bangladesh Institute of Nuclear Agriculture (BINA), Mymensingh, Bangladesh for callus induction and regeneration ability of plantlet from low doses irradiated embryogenic calli of Binadhan-13 and BR5 (Dulabhog). The effect of low gamma rays such as 4, 6 and 8 Gy were observed in vitro shoot, root and plantlet formation. Two different incubation conditions such as light and dark incubation were maintained. Between two varieties, Binadhan-13 showed the highest ability of callus induction in both conditions. Callus induction was significantly higher under dark condition (77.14%) than light condition (67.14%) ‍at 21 days. Data revealed that gamma rays affect both shoot and root regeneration ability of embryogenic callus. Shoot regeneration ability was the highest at 4 Gy in Binadhan-13 (60%) and gradually decreased with the increased doses of gamma rays. Among the treatments, shoot regeneration ability (60% in Binadhan-13 and 50% in BR5) was higher at 4 Gy dose of gamma ray followed by 6 Gy where shoot regeneration ability was 55% and 45% in Binadhan-13 and BR5 respectively. In root induction, the highest root induction ability (80%) was observed in the cultivar Binadhan-13 at control condition. Like shoot regeneration, 4 Gy gamma ray showed better root induction in both the varieties (70% in Binadhan-13, 60% in BR5). The in vitro regenerated plantlets from irradiated embryogenic calli were successfully transferred to soil in pots. The regeneration protocol could be further used for varietal improvement of rice varieties using nuclear technique (60Co gamma ray). Bangladesh J. Nuclear Agric, 37(2): 29-42, 2023

Dose Evaluation in 2-Phase Method for Advanced Esophageal Cancer by Hybrid Irradiation Techniques

PurposeIn concurrent chemoradiotherapy for advanced esophageal cancer, a 2-phase method consisting of initial irradiation of a wide elective nodal region and boost irradiation of the primary lesion is commonly employed. Although dose escalation to the primary lesion may be required to achieve higher local control rates, the radiation dose to critical organs must not exceed dose constraints. To achieve an optimum balance of dose prescription and dose reduction to surrounding organs, such as the lungs and heart, we compared hybrid dose distributions and investigated the best combination of the following recent irradiation techniques: volumetric modulation arc therapy (VMAT), proton broad-beam irradiation, and intensity-modulated proton beam therapy (IMPT). Materials and MethodsForty-five patients with advanced esophageal cancer whose primary lesions were located in the middle- or lower-thoracic region were studied. Radiotherapy plans for the initial and boost irradiation in the 2-phase method were calculated using VMAT, proton broad-beam irradiation, and IMPT calculation codes, and the dose-volume histogram indices of the lungs and heart for the accumulated plans were compared. ResultsIn plans using boost proton irradiation with a prescribed dose of 60 Gy(RBE), all dose-volume histogram indices were significantly below the tolerance limits. Initial and boost irradiation with VMAT resulted in the median dose of V30 Gy(RBE)(heart) of 27.4% and an achievement rate below the tolerance limit of 57.8% (26 cases). In simulations of dose escalation up to 70 Gy(RBE), initial and boost IMPT resulted in the highest achievement rate, satisfying all dose constraints in 95.6% (43 cases). ConclusionApplying VMAT to both initial and boost irradiation is not recommended because of the increased risk of the cardiac dose exceeding the tolerance limit. IMPT may allow dose escalation of up to 70 Gy(RBE) without radiation risks to the lungs and heart in the treatment of advanced esophageal cancer.

Adjuvant proton beam therapy in patients with grade 2 meningiomas.

The World Health Organization (WHO) grade 2 meningiomas behave aggressively with a high proclivity toward recurrence despite maximal surgical resection. Our institution, a pioneer of proton therapy, uses exclusively proton beam radiation, and thus, we present a retrospective cohort analysis of patients with WHO grade 2 meningiomas treated with adjuvant proton beam therapy (PBT) at our institution between 2007 and 2019. The effects of adjuvant PBT were evaluated. Data collected include diagnosis, gender, histological subtype, WHO grade, the extent of surgical resection, adjuvant PBT radiation, details of the PBT radiation, recurrence, any additional PBT radiation, systemic medical therapy, and disease-specific survival. Among the WHO grade 2 meningiomas (n = 50) recommended PBT, 80% and 78% of patients with gross-total resection (GTR) and subtotal resection (STR), respectively, followed through with PBT. The median radiation dose of PBT was 59.5 Gy and 59.92 Gy for patients with GTR and STR, respectively, with a median of 33 fractions delivered in 1.8 Gy doses for both groups. Combined 3-year progression-free survival (PFS) was 96%, and 5-year PFS was 92%. Combined overall survival was 95% at five years. Minimal radiation side effects were reported with no grade 3 or higher toxicities. Our results suggest that adjuvant PBT is well tolerated with minimal radiation toxicity. Alternative to photon radiation, PBT may be considered at least as safe and effective for adjuvant treatment of WHO grade 2 meningiomas when it is available.

Exploring sterile pollen technique as a novel tool for management of Palmer amaranth (Amaranthus palmeri)

AbstractThe success of the insect sterile technique (IST) in managing insect pests raised the hypothesis that a similar approach could be employed to control weed populations. Here, we investigated the feasibility of employing irradiated sterile pollen as a means to disrupt seed production in dioecious weeds, specifically focusing on Palmer amaranth (Amaranthus palmeri S. Watson). Our goal was to determine the optimal irradiation dose that strikes a balance between inducing sterility and preserving competitiveness, as excessive doses could result in pollen mortality, while low doses may retain fertility. Plants were grown in a greenhouse during the summer of 2020 and spring of 2021. Once they reached the flowering stage, male and female individuals were isolated. Mature pollen samples were collected and exposed to varying dosages (0, 100, 200, 300, 400, and 500 Gy) of gamma rays. These irradiated and non-irradiated pollen samples were used in pollen viability assessments and hand-pollination experiments. In the hand-pollination study conducted in 2020, we employed six pollination treatments using different irradiation doses. The results showed that 300 Gy was the most effective dose, resulting in a maximum reduction of 30% in seed set compared with open pollination when irradiated pollen had prior access to the stigma through artificial pollination before open pollination. In 2021, to simulate real field conditions, three additional treatments were introduced into the study, further confirming the effectiveness of the optimal 300 Gy dose. Our findings indicate that the sterile pollen technique (SPT) using irradiated pollen can be a valuable approach for reducing weed seed production. SPT also holds potential for broad-spectrum weed control by mixing sterile pollen from multiple weed species in a single application. Additionally, it could aid in managing herbicide-resistant weeds that have survived in-season control efforts. This research contributes to the development of novel and sustainable weed management strategies.

Dosimetric comparison of 3D-Conformal and IMRT techniques used in radiotherapy of gastric cancer: A retrospective study

This study aimed to compare three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) planning techniques commonly used in gastric cancer radiotherapy with dose volume histograms. Computed tomography (CT) images of 20 gastric cancer patients were retrospectively analyzed. 3D-CRT, 5F- IMRT and 7F- IMRT treatment plans were created for each patient. The 3 plans were compared on dose volume histogram (DVH). 3D-CRT, 5F-IMRT and 7F-IMRT plans achieved a prescribed dose of 45 Gy for 95% of PTV volume. D95 values were 45.06±0.47 Gy for 3DCRT, 46.39±0.38 Gy for 5F-IMRT and 45.20±0.11 Gy for 7F-IMRT. In 3D-CRT, 5F-IMRT and 7F-IMRT techniques, the 13 Gy receiving volumes of the right kidney were found to be 35.08+9.59, 36.25+7.97 and 37.03+9.03 respectively. Moreover, the volume of the right kidney receiving a 20 Gy and 30 Gy dose received less dose with 5F-IMRT than with 7F-IMRT. Since each patient's critical organs are at different distances from the target and each technique has its own advantages in terms of critical organs, we suggest that the useful technique should be decided by clinical consensus.

Pencil Beam Scanning Proton Bragg Peak Conformal FLASH in Prostate Cancer Stereotactic Body Radiotherapy.

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT.

FLASH Proton Radiation Therapy Mitigates Inflammatory and Fibrotic Pathways and Preserves Cardiac Function in a Preclinical Mouse Model of Radiation-Induced Heart Disease

PurposeStudies during the past 9 years suggest that delivering radiation at dose rates exceeding 40 Gy/s, known as “FLASH” radiotherapy, enhances the therapeutic index of radiation therapy (RT) by decreasing normal tissue damage while maintaining tumor response compared to conventional (or standard) RT. This study demonstrates the cardioprotective benefits of FLASH proton RT (F-PRT) compared to standard (conventional) proton RT (S-PRT), as evidenced by reduced acute and chronic cardiac toxicities. Methods and MaterialsMice were imaged using cone beam computed tomography to precisely determine the heart's apex as the beam isocenter. Irradiation was conducted utilizing a shoot-through technique with a 5mm diameter circular collimator. Bulk RNA-sequencing was performed on non-irradiated (NR) samples, as well as apexes treated with F-PRT or S-PRT, at 2 weeks following a single 40 Gy dose. Inflammatory responses were assessed through multiplex cytokine/chemokine microbead assay and immunofluorescence analyses. Levels of perivascular fibrosis were quantified using Masson's Trichrome and Picrosirius red staining. Additionally, cardiac tissue functionality was evaluated by 2D echocardiograms at 8 and 30 weeks post-PRT. ResultsRadiation damage was specifically localized to the heart's apex. RNA profiling of cardiac tissues treated with PRT revealed that S-PRT uniquely upregulated pathways associated with DNA damage response, induction of tumor necrosis factor superfamily and inflammatory response, while F-PRT primarily affected cytoplasmic translation, mitochondrion organization and ATP synthesis. Notably, F-PRT led to a milder inflammatory response, accompanied by significantly attenuated changes in TGF-β1 and αSMA levels. Critically, F-PRT decreased collagen deposition, and better preserved cardiac functionality compared to S-PRT. ConclusionsThis study demonstrated that F-PRT reduces the induction of an inflammatory environment with lower expression of inflammatory cytokines and profibrotic factors. Importantly, the results indicate that F-PRT better preserves cardiac functionality, as confirmed by echocardiography analysis, while also mitigating the development of long-term fibrosis.

Efficacy of Immediate Postoperative Single Fractional 10Gy Radiotherapy for Earlobe Keloids.

The ear is a common site for keloid formation, typically due to ear piercing or trauma. Auricular keloids are always difficult to treat and pose a challenging situation. The purpose of this study is to present our experience treating earlobe keloids through complete surgical excision followed by immediate postoperative single fraction 10Gy radiation therapy either on the same day or the next day. The authors retrospectively evaluated 48 patients with 71 earlobe keloids treated with complete surgical excision followed by single-fractional 10Gy radiotherapy within 24 hours from May 2021 to December 2022. The outcome was reported with a recurrence-free rate and side effects. The mean follow-up period was 20.8 months. All patients tolerated the treatments well. The overall recurrence-free rate was 100%. There were only 2 grade III radiation dermatitis. There were no reports of second malignancies or severe complications. The authors have obtained excellent outcomes from treating earlobe keloids through complete excision followed by postoperative radiotherapy with a single fractional dose of 10Gy on the same day or the next day.

Response of gamma irradiation on germination and seedling growth of green gram var. GAM 8

Being a pulse crop, green gram has huge scope in crop improvement in terms of productivity and other yield related parameters. Genetic variability is a preferable option for breeders in breeding programme for varietal development programme and others crop improvement aspect. The present investigation was framed to create the variability in mung bean var. GAM 8 during the seedling period through gamma (γ) irradiation. The significant variation was observed in germination percentage and it was found that dose dependent relationship between the germination rate and dose. Significantly minimum germination percentage (22.38 %) was observed in 700 Gy but optimal lethal dose (LD50) calculated through Probit analysis based on germination percentage was revealed at 540.26 Gy. Data revealed that γ irradiation had significantly reduced the seedling growth parameters such as shoot length (10.05 cm), shoot dry weight (19.68 mg), seedling length (13.90 cm), vigour index I (311.01) and II (509.01) was registered in 700 Gy while minimum root length (3.83 cm) was occurred in 600 Gy γ irradiation. Growth reduction (GR) 50 and 30 with respect to the seedling length was occurred respectively at 1093.79 and 1469.74 Gy. Therefore, this finding as the source of genetic variability would be used in future breeding and crop improvement programme like enhancement of yield potentiality and stress management in mung bean var. GAM 8.

Comparison of photon energies and field techniques for ovarian dose reduction in volumetric modulated arc therapy

For fertility preservation in young female patients undergoing pelvic radiotherapy for cervical cancer, lateral ovarian transposition (LOT) is a procedure that moves the ovaries away from the radiation field. However, it is still challenging to fully protect the ovaries from radiation damage in volumetric modulated arc therapy (VMAT). In this study, we optimized VMAT techniques and simulated the effect of the LOT position on the ovarian dose. Ten cervical cancer patients who received pelvic radiotherapy after LOT were retrospectively analyzed. A restricted arc plus split field technique, which incorporated beam avoidance sectors, split field, fixed jaw, and orthogonal collimator orientation with 10 MV energy (rasf-10MV-VMAT), was designed to minimize the dose to the ovaries. This technique was compared with dual-arc conventional VMAT (dac-6MV-VMAT) and restricted arc and field VMAT (raf-6MV-VMAT) techniques with 6 MV energy. Ovarian dose, target coverage, and organs at risk (OAR) sparing were compared. The location of the ovaries in the anterior-posterior and superior-inferior directions was changed to simulate the effect of the LOT position on the ovarian dose. Compared to dac-6MV-VMAT and raf-6MV-VMAT, rasf-10MV-VMAT decreased the ovarian dose significantly more, especially for a low-dose volume. Both ovaries, received a 44.0–52.1 % lower volume of >3 Gy dose, and (0.5–1.9 Gy) lower maximum and mean doses with rasf-10MV-VMAT (p < 0.05). Rasf-10MV-VMAT also improved target conformity and coverage more than raf-6MV-VMAT (p < 0.05) and reduced the bladder mean dose more than dac-6MV-VMAT (p < 0.05). The ovarian dose decreased with the distance from the target contour, and placing the ovaries near the mid-frontal plane or as high as possible after the LOT lowered ovarian exposure. This technique, using 10 MV photon energy combined with field technique optimization, reduced the ovarian dose, particularly by decreasing the low-dose exposure of ovarian tissue and improving the target conformity simultaneously. The ovarian dose could be minimized by a proper LOT position. This optimized technique could enhance ovarian protection and fertility preservation for young female survivors of cervical cancer.

Alterations of Sexual and Erectile Functions after Brachytherapy for Prostate Cancer Based on Patient-Reported Questionnaires.

The aim of the study was to compare the side effects of high-dose-rate brachytherapy (HDRBT) and low-dose-rate brachytherapy (LDRBT), with a particular focus on the effects on sexual functions and sexual well-being (PROMOBRA study, NCT02258087). Localized low-risk and low-intermediate-risk prostate cancer patients were treated with mono LDR (N = 123, 145 Gy dose) or mono HDR brachytherapy (N = 117, 19/21 Gy). Prior to the treatment and during follow-up (at 3, 6, 9, 12, 18, and 24 months after treatment, and then annually after two years), patients completed patient-reported outcome measurement (PROM) questionnaires EORTC QLQ-PR-25, International Index of Erectile Function (IIEF), and IIEF-5 (SHIM). We compared the patients in different group breakdowns (HDR vs. LDR, hormone naïve and hormone-receiving HDR vs. LDR, hormone naïve and hormone-receiving patients in general, and 19 Gy HDR vs. 21 Gy HDR). In the hormone-naive LDR group, erectile function, orgasm function, sexual desire, satisfaction with intercourse, and overall satisfaction functions significantly decreased compared to baseline throughout the whole follow-up period. However, there were significant decreases in function at a maximum of three time points after HDR therapy without hormone therapy. In hormone-receiving patients, the orgasm function was significantly better in the HDR group at multiple time points compared to the baseline, and sexual desire improved at four time points. According to our results, both LDRBT and HDRBT can be safely administered to patients with localized prostate cancer. In hormone-naive patients, the HDR group showed only recovering decreases in sexual functions, while the LDR group showed a lasting decline in multiple areas. Thus, HDR appears to be more advantageous to hormone-naive patients.

Development of Two Tossa Jute Mutants for Higher Fiber Yield Through Mutation Breeding

The demand for jute fiber is increasing instead of synthetic fiber nowadays. Developing an early and high fiber-yielding tossa jute line is the main breeding objective of jute growing areas including Bangladesh. To fulfill that objective, the existing cultivar JRO-524 was irradiated with five (700, 800, 900, and 1000 gy) doses of gamma-ray. A total of 25 M3 plants were first selected from bulked M2 plants. Two years of replicated yield trial experiments were conducted in different locations in Bangladesh. Among them, two mutants BJM-10-1-3 and BJM-10-1-5 were selected for higher fiber and stick yield. The selected mutants BJM-10-1-3 and BJM-10-1-5 showed 4% to 6% higher yield than their parent JRO-524. The mutant line BJM-10-1-5 showed higher fiber percentage (34.04%), fiber fitness (2.65%), and fiber brightness (44.15%). These two mutants have been under participatory varietal trial (PVT) for evaluation to release a tossa jute variety. These lines will play a vital role in reducing the seed import of variety JRO-524 from India. Vol. 10, No. 3, December 2023: 259-268

Effects of applying lime and phosphogypsum in soybean and wheat nutrition

This study aimed to assess the nutritional status of soybean and wheat and the relationship with grain yield and biometric components after lime and phosphogypsum (GY) reapplication. Treatments consisted of two lime application methods, surface liming and incorporated liming, to different levels of base saturation (BS) (44, 70, and 90%), in addition to surface liming to 70% BS associated with a standard dose (70GY1) or double dose (70GY2) of GY. Treatments were applied in 2012 and reapplied in 2016. The results refer to the 2018/2019 soybean season and the 2019 wheat season. Lime + GY treatment increased leaf area, plant height, leaf dry matter, and stem dry matter in soybean but had no effect on specific leaf area (235.4 cm2 g−1), stem diameter (6.08 mm), number of pods per plant (71.7), grain number per plant (165), or thousand grain weight (117 g). Liming to 90% BS reduced leaf manganese contents in both crops and leaf iron content in soybean. GY application improved the calcium status of both crops and the sulfur status of soybean. However, 70GY2 reduced leaf magnesium contents in soybean and wheat. Soil tillage without lime reduced wheat yield by 12% compared with no-till. Soybean yield correlated positively with leaf nitrogen (0.79), leaf phosphorus (0.91), leaf area (0.62), and thousand grain weight (0.65), whereas wheat yield correlated with leaf phosphorus (0.83), calcium (0.75), and sulfur (0.74). For improved soybean and wheat performance, it is preferable to apply lime and GY to the soil surface (70GY1), permanently maintaining no-till practices.

Enhanced RBE of Particle Radiation Depends on Beam Size in the Micrometer Range.

High-linear energy transfer (LET) radiation, such as heavy ions is associated with a higher relative biological effectiveness (RBE) than low-LET radiation, such as photons. Irradiation with low- and high-LET particles differ in the interaction with the cellular matter and therefore in the spatial dose distribution. When a single high-LET particle interacts with matter, it results in doses of up to thousands of gray (Gy) locally concentrated around the ion trajectory, whereas the mean dose averaged over the target, such as a cell nucleus is only in the range of a Gy. DNA damage therefore accumulates in this small volume. In contrast, up to hundreds of low-LET particle hits are required to achieve the same mean dose, resulting in a quasi-homogeneous damage distribution throughout the cell nucleus. In this study, we investigated the dependence of RBE from different spatial dose depositions using different focused beam spot sizes of proton radiation with respect to the induction of chromosome aberrations and clonogenic cell survival. Human-hamster hybrid (AL) as well as Chinese hamster ovary cells (CHO-K1) were irradiated with focused low LET protons of 20 MeV (LET = 2.6 keV/µm) beam energy with a mean dose of 1.7 Gy in a quadratic matrix pattern with point spacing of 5.4 × 5.4 µm2 and 117 protons per matrix point at the ion microbeam SNAKE using different beam spot sizes between 0.8 µm and 2.8 µm (full width at half maximum). The dose-response curves of X-ray reference radiation were used to determine the RBE after a 1.7 Gy dose of radiation. The RBE for the induction of dicentric chromosomes and cell inactivation was increased after irradiation with the smallest beam spot diameter (0.8 µm for chromosome aberration experiments and 1.0 µm for cell survival experiments) compared to homogeneous proton radiation but was still below the RBE of a corresponding high LET single ion hit. By increasing the spot size to 1.6-1.8 µm, the RBE decreased but was still higher than for homogeneously distributed protons. By further increasing the spot size to 2.7-2.8 µm, the RBE was no longer different from the homogeneous radiation. Our experiments demonstrate that varying spot size of low-LET radiation gradually modifies the RBE. This underlines that a substantial fraction of enhanced RBE originates from inhomogeneous energy concentrations on the µm scale (mean intertrack distances of low-LET particles below 0.1 µm) and quantifies the link between such energy concentration and RBE. The missing fraction of RBE enhancement when comparing with high-LET ions is attributed to the high inner track energy deposition on the nanometer scale. The results are compared with model results of PARTRAC and LEM for chromosomal aberration and cell survival, respectively, which suggest mechanistic interpretations of the observed radiation effects.

Low-Dose Radiation Yields Lower Rates of Pathologic Response in Esophageal Cancer Patients

BackgroundAlthough neoadjuvant chemoradiation (nCRT) followed by surgery is standard treatment for locally advanced esophageal or gastroesophageal junction (E/GEJ) cancer, the optimal radiation dose is still under debate.ObjectiveThe aim of this study was to assess the impact of different preoperative radiation doses (41.4 Gy, 45 Gy or 50.4 Gy) on pathologic response and survival in E/GEJ cancer patients.MethodsAll consecutive patients with E/GEJ tumors, treated with curative intent between January 2009 and December 2016 in two referral centers were divided into three groups (41.4 Gy, 45 Gy and 50.4 Gy) according to the dose of preoperative radiotherapy. Pathologic complete response (pCR) rates, postoperative morbidity, overall survival (OS) and disease-free survival (DFS) were compared among the three groups, with separate analyses for adenocarcinoma (AC) and squamous cell carcinoma (SCC).ResultsFrom the 326 patients analyzed, 48 were included in the 41.4 Gy group (14.7%), 171 in the 45 Gy group (52.5%) and 107 in the 50.4 Gy group (32.8%). Postoperative complication rates were comparable (p = 0.399). A pCR was observed in 15%, 30%, and 34% of patients in the 41.4 Gy, 45 Gy and 50.4 Gy groups, respectively (p = 0.047). A 50.4 Gy dose was independently associated with pCR (odds ratio 2.78, 95% confidence interval 1.10–7.99) in multivariate analysis. Within AC patients, pCR was observed in 6.2% of patients in the 41.4 Gy group, 29.2% of patients in the 45 Gy group, and 22.7% of patients in the 50.4 Gy group (p = 0.035). No OS or DFS differences were observed.ConclusionsA pCR was less common after a preoperative radiation dose of 41.4 Gy in AC patients. Radiation dose had no impact on postoperative morbidity, long-term survival, and recurrence.

Acute Large Dose Irradiation Sensitizes Surviving Cells to Subsequent Irradiation; Implications for Stereotactic Body Radiation Therapy.

To determine if the radiation sensitivity of cells that survive acute high-dose radiation exposure used in stereotactic body radiation therapy (SBRT), differs from the sensitivity of non-irradiated cells and cells that survive multiple 2 Gy doses of radiation. Isogenic rodent and two human tumor cell lines were exposed to 14 × 2 Gy of radiation, or a single acute dose of 12 Gy. The most resistant cell line was also exposed to an acute dose of 15 Gy. One week after 12 Gy, and 4 days after 14 × 2 Gy, surviving cells were exposed to 0-8 Gy in 2 Gy doses and cell survival was assessed by colony formation. In addition, the colony forming efficiency of 12 Gy survivors was evaluated for 1 month postirradiation. For cells exposed to 15 Gy, the response of surviving cells to 6 Gy was determined for up to 35 days postirradiation and compared to the 6 Gy surviving fraction of control cells. The radiation sensitivity of cells that survived 12 Gy exposure, and cells that survived 14 fractions of 2 Gy irradiation did not differ from the response of unirradiated control cells. However, the growth rate and colony forming efficiency of 12 Gy survivors was transiently reduced for greater than 2 weeks postirradiation. In contrast to the unchanged sensitivity of 12 Gy surviving cells at day 7 postirradiation, 15 Gy survivors exhibited enhanced sensitivity to radiation for up to 21 days postirradiation and suggests a biological basis for SBRT.