Fractionated Radiation Therapy Research Articles

Fractionated radiation therapy alters energy metabolism and induces cellular quiescence exit in patient-derived orthotopic xenograft models of high-grade glioma

Radiation is one of the standard therapies for pediatric high-grade glioma (pHGG), of which the prognosis remains poor. To gain an in-depth understanding of biological consequences beyond the classic DNA damage, we treated 9 patient-derived orthotopic xenograft (PDOX) models, including one with DNA mismatch repair (MMR) deficiency, with fractionated radiations (2 Gy/day x 5 days). Extension of survival time was noted in 5 PDOX models (P < 0.05) accompanied by γH2AX positivity in >95 % tumor cells in tumor core and >85 % in the invasive foci as well as ∼30 % apoptotic and mitotic catastrophic cell death. The model with DNA MMR (IC-1406HGG) was the most responsive to radiation with a reduction of Ki-67(+) cells. Altered metabolism, including mitochondria number elevation, COX IV activation and reactive oxygen species accumulation, were detected together with the enrichment of CD133+ tumor cells. The latter was caused by the entry of quiescent G0 cells into cell cycle and the activation of self-renewal (SOX2 and BMI1) and epithelial mesenchymal transition (fibronectin) genes. These novel insights about the cellular and molecular mechanisms of fractionated radiation in vivo should support the development of new radio-sensitizing therapies.

Mini-Beam Spatially Fractionated Radiation Therapy for Whole-Brain Re-Irradiation—A Pilot Toxicity Study in a Healthy Mouse Model

For patients with recurrent brain metastases, there is an urgent need for a more effective and less toxic treatment approach. Accumulating evidence has shown that spatially fractionated radiation therapy (SFRT) is able to provide a significantly higher therapeutic ratio with lower toxicity compared to conventional radiation using a uniform dose. The purpose of this study was to explore the potential low toxicity benefit of mini-beam radiotherapy (MBRT), a form of SFRT, for whole-brain re-irradiation in a healthy mouse model. Animals first received an initial 25 Gy of uniform whole-brain irradiation. Five weeks later, they were randomized into three groups to receive three different re-irradiation treatments as follows: (1) uniform irradiation at 25 Gy; (2) MBRT at a 25 Gy volume-averaged dose (106.1/8.8 Gy for peak/valley dose, 25 Gy-MBRT); and (3) MBRT at a 43 Gy volume-averaged dose (182.5/15.1 Gy for peak/valley dose, 43 Gy-MBRT). Animal survival and changes in body weight were monitored for signs of toxicity. Brains were harvested at 5 weeks after re-irradiation for histologic evaluation and immunostaining. The study showed that 25 Gy-MBRT resulted in significantly less body weight loss than 25 Gy uniform irradiation in whole-brain re-irradiation. Mice in the 25 Gy-MBRT group had a higher level of CD11b-stained microglia but also maintained more Ki67-stained proliferative progenitor cells in the brain compared to mice in the uniform irradiation group. However, the high-dose 43 Gy-MBRT group showed severe radiation toxicity compared to the low-dose 25 Gy-MBRT and uniform irradiation groups, indicating dose-dependent toxicity. Our study demonstrates that MBRT at an appropriate dose level has the potential to provide less toxic whole-brain re-irradiation. Future studies investigating the use of MBRT for brain metastases are warranted.

Accelerated Fractionated Radiation Therapy for Localized Glottic Carcinoma

Background: The aim of this study is to examine the outcomes of an accelerated fractionated irradiation for N0 glottic carcinoma. Methods: In this retrospective analysis, 29 patients with N0 glottic carcinoma treated by radiation therapy were enrolled. Thirteen patients had T1a disease, six had T1b disease, and ten had T2 disease. A fractional dose of 2.1 Gy was administered to seven patients. The total doses were 65.1 and 67.2 Gy in four and three patients, respectively. A fractional dose of 2.25 Gy was administered to 22 patients. The total doses were 63 and 67.5 Gy in 21 patients and 1 patient with T2 disease, respectively. Additionally, 13 patients underwent the use of TS-1 (80–100 mg per day). Results: The median follow-up period was 33 months, and the 3-year local control rate was 95.6%. No patient had a lymph node or distant recurrence. As acute adverse events, grades 2 and 3 dermatitis were observed in 18 patients and 1 patient, and grades 2 and 3 mucositis were observed in 15 patients and 1 patient. As a late adverse event, one patient required tracheotomy because of laryngeal edema occurring. Conclusions: Accelerated fractionated irradiation may be an option in the radiation therapy of N0 glottic carcinoma because of its ability to shorten the treatment time.

Abstract PO5-19-10: First oncological outcomes of HypoG-01: a UNICANCER phase III trial comparing loco-regional hypo vs normo fractionated radiation therapy in early breast cancer patients

Abstract Objective Normofractionated (NF) radiation therapy (RT) is still standard for loco-regional early breast cancer (EBC) in many countries. HypoG-01, a UNICANCER, non-inferiority, open-label, multicenter, randomized phase III trial (NCT03127995), conducted in parallel with the DBCG Skagen trial 1 (NCT02384733), evaluated hypofractionated (HF) RT with 40 Gy/15 fr (2.67 Gy/fr) versus NF RT 50 Gy/25 fr (2.0 Gy/fr). This is the first report of oncological outcomes, secondary endpoints of the trial. Methods Patients (pts) ≥18 years old were operated for T1-3, N0-3, M0 breast cancer. All pts received nodal and thoracic wall or breast RT. Tumor-bed boost (sequential or simultaneous) and nodal levels treated were decided according to local guidelines. Target volumes were delineated according to the ESTRO consensus. RT technique was left at the investigator’s discretion. Stratification factors included treating center, type of surgery, number of positive nodes and body mass index. The primary endpoint, reported previously, was time to occurrence of arm lymphedema. Oncological outcomes included locoregional relapse free survival (LRFS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS), breast cancer specific survival (BCSS) and overall survival (OS) as defined per DATECAN guidelines. All time to cancer related endpoints were defined as starting from the date of randomization until the event. The primary statistic test was stratified one-sided logrank test: 5% significance level in per-protocol population (PPP) with a pre-specified non-inferiority margin of 1.545. Stratified Cox model was used for calculating hazard ratios of oncological outcomes. Results In total, 1265 pts were randomized to HF versus NF RT from Sep 2016 to Mar 2020 with 1221 in the PPP (HF group 614 pts (50.3%); NF group 607 (49.7%)), 5 consent withdrawn and 39 major deviations. Median age was 58 years (range 23-91), surgery included mastectomy (501 pts; 45%) and axillary clearance (921 pts; 82.8%). Sequential (67.8%) or simultaneous integrated (32.2%) tumor-bed boost was used in 596 pts (48.8%). With a median follow-up for OS in PP analysis of 3.8 years (95% CI 3.3 to 3.9), HF was non-inferior to NF RT in terms of lymphedema (HR=1.07; 90% CI 0.86-1.34, non-inferiority p=0.003). Table 1 reports the hazard ratio and 3-year survival rates for the oncological endpoints LRFS, IDFS, DDFS, BCCS and OS. There was no sign of disadvantage for any of these endpoints comparing HF to NF. Additional analyses will be presented at the meeting. Conclusion Moderately HF loco-regional RT is non-inferior to NF RT in terms of lymphedema risk in EBC and does not show a disadvantage in terms of LRFS, IDFS, DDFS, BCCS and OS with a median follow-up of 3.8 years. Together with the Skagen 1 trial, this study provides level 1A evidence supporting the use of 40 Gy/15 fr for loco-regional radiation therapy in EBC with respect to arm lymphedema risk; Table 1: Oncological outcomes according to treatment arm in the per protocol analysis HF: Moderately hypofractionated radiation therapy; NF: Normofractionated radiation therapy; n:number of patients; N: number of events Citation Format: Sofia Rivera, Eleni Karamouza, Youlia Kirova, Séverine Racadot, Mohamed Benchalal, Jean-Baptiste Clavier, Claire Charra-Brunaud, Marie-Eve Chand-Fouche, Delphine Argo-Leignel, Karine Peignaux, Ahmed Benyoucef, David Pasquier, Philippe Guilbert, Julien Blanchecotte, Agnès Tallet, Adeline Petit, Guillemette Bernadou, Xavier Zasadny, Claire Lemanski, Jacques Fourquet, Emmanuelle Malaurie, Honorine Kouto, Carole Massabeau, Alexandre Henni, Pauline Regnault, Aurélie Belliere, Yazid Belkacemi, Magali Le Blanc-Onfroy, Julien Geffrelot, Jean-Briac Prevost, Marie Bergeaud, Assia Lamrani-Ghaouti, Amandine Ruffier, Naima Bonnet, Stephanie Wong, Christine Rossier, Thomas Brion, Pierre Maroun, Claire Petit, Guillaume Auzac, Stefan Michiels. First oncological outcomes of HypoG-01: a UNICANCER phase III trial comparing loco-regional hypo vs normo fractionated radiation therapy in early breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-10.

Abstract PO5-18-05: Assessment of the Potential of Photon mini-GRID Therapy for Pre-operative Partial Breast Cancer Treatment

Abstract Purpose We propose a new spatially fractionated radiation therapy (SFRT) technique, called mini-GRID therapy, to reduce normal tissue toxicities in pre-operative partial breast cancer radiotherapy. Mini-GRID therapy, an optimized implementation of GRID therapy, utilizes very narrow beams (widths ~ 1-2 mm) which significantly increase normal tissue tolerances. The concept, proposed by our team in 2017 [1], has been successfully implemented at Hospital de Santiago de Compostela (Spain) showing excellent results in terms of brain toxicity reduction [2]. Profiting from this remarkable increase in tolerance, this study aims to evaluate the feasibility and efficacy of photon mini-GRID therapy for pre-operative partial breast cancer treatment. Methods Ten unbiased clinical cases were selected for the study, comparing photon mini-GRID therapy with conventional broad beam radiotherapy. Monte Carlo simulations (TOPAS v.3.6) were performed based on the mini-GRID therapy implementation (megavoltage X-rays, Varian flattening-filter-free LINAC) realized at the University Hospital in Santiago de Compostela. A mean dose of 24 Gy was delivered in the PTV using three photon mini-GRID arrays with mini beams of approximately 1.8x1.8 mm² at the isocenter. The study aimed to achieve better tumor coverage than conventional pre-operative radiotherapy while ensuring comparable skin toxicity. Valley doses, determining tissue-sparing effects, were compared against organs-at-risk (OARs) tolerance limits. Results The mini-GRID therapy treatments ensured partial tumor coverage and met the dose tolerance limits for all the considered OARs, the most challenging of all being the skin [3]. Peak-to-valley dose ratio (PVDR) in the skin was higher than 3.5 for all the considered patients. Compared to standard radiotherapy (SRT) plans, mini-GRID therapy significantly reduced mean doses to the lungs, heart, and chest wall in the studied cases. Conclusion In this proof-of-concept study, we evaluated photon mini-GRID therapy with megavoltage X-rays as an alternative treatment approach for pre-operative partial breast cancer irradiation, demonstrating its feasibility and straightforward implementation. Because of its high skin and normal tissue-sparing capacities, photon mini-GRID therapy has great potential to improve pre-operative treatment outcomes. Complementary studies and clinical validation are needed to fully establish the optimal protocols and assess long-term effects, but the results encourage the integration of photon mini-GRID therapy as a promising modality for breast cancer therapy.

Long-term Outcomes of Surgery and Radiation Treatment for Adult Patients with Craniopharyngioma

Treatment of craniopharyngioma typically entails gross total resection (GTR) or subtotal resection with adjuvant radiation (STR-RT). We analyzed outcomes in the adult population undergoing GTR versus STR-RT. A total of 115 patients in 5 institutions were enrolled in this retrospective study on adult craniopharyngiomas. Patients with STR received postoperative RT with stereotactic radiosurgery (SRS) or fractionated radiation therapy (FRT) per institutional preference and ability to spare optic structures. Median age was 44 years (19 - 79 years). GTR was achieved in 34 patients and STR-RT in 81 patients with median follow up of 78.9 months (1 - 268 months). For GTR, local control was 90.5% at 2 years, 87.2% at 3 years, and 71.9% at 5 years. For STR-RT local control was 93.6% at 2 years, 90.3% at 3 years, and 88.4% at 5 years. At 5 years following resection there was no difference in local control (p = 0.08). Differences in rates of visual deterioration or panhypopituitarism were not observed between GTR and STR-RT. There was no difference in local control in adamantinomatous and papillary craniopharyngioma regardless of treatment. Additionally, worse local control was found in STR-RT patients that were underdosed with FRT (p = 0.03) or SRS (p = 0.04). There is good long-term control for adult craniopharyngioma that underwent STR-RT or GTR with no significant difference in local control. First-line treatment for craniopharyngioma should continue to be maximal safe resection followed by RT as needed to balance optimal local control with long term morbidity.

An Update on H3K27M-altered Diffuse Midline Glioma: Diagnostic and Therapeutic Challenges in Clinical Practice

H3K27-altered diffuse midline glioma (DMG H3K27-altered) is a relatively newly-designated WHO entity which primarily affects the midline structures of the central nervous system (CNS), including the brainstem (predominantly pontine region), thalamus, midbrain, or spinal cord, and primarily affects children and young adults. Despite the proximity of these tumors to eloquent areas in the CNS, novel stereotactic approaches have facilitated the ability to obtain tissue diagnoses without significant morbidity, providing molecular diagnostic information in more than half of patients. Conventionally fractionated radiation therapy to a total dose of 54-60 Gy in 27-30 fractions and 24 Gy in 12 fractions play a crucial role in the definitive treatment of these tumors in the primary and salvage settings, respectively. Hypofractionated regimens may allow for accelerated treatment courses in selected patients without jeopardizing disease control or survival. The decision to add concurrent or adjuvant systemic therapy mainly relies on the physicians’ experience without solid evidence in the literature in favor of any particular regimen. Recently, novel agents, such as ONC201 have demonstrated promising response rates in progressive/recurrent tumors and are currently under investigation in ongoing randomized trials. Given the scarcity of data and well-established guidelines due to the rare nature of the disease, we provide a contemporary overview the molecular underpinnings of this disease entity, describe the role of radiotherapy and systemic therapy, and provide practice management principles based on the published literature.

Dosimetric evaluation of light ion beams for spatially fractionated radiation therapy: a Geant4 Monte Carlo study

Dosimetric evaluation of light ion beams for spatially fractionated radiation therapy: a Geant4 Monte Carlo study

β-delayed multiple-particle emitters minibeam radiation therapy: first dosimetric evaluation with Monte Carlo simulations

Radiation therapy, one of the most effective methods for cancer treatment, is still limited by the tolerances of normal tissues surrounding the tumor. Innovative techniques like spatially fractionated radiation therapy (SFRT) have been shown to increase normal tissue dose resistance. Heavy ions also offer high-dose conformity and increased relative biological effectiveness (RBE) when compared to protons and X-rays. The alliance of heavy ions and spatial fractionation of the dose has the potential to further increase the therapeutic index for difficult-to-treat cases today. In particular, the use of β-delayed multiple-particle emitters might further improve treatment response, as it holds the potential to increase high linear energy transfer (LET) decay products in the valleys of SFRT (low-dose regions) at the end of the range. To verify this hypothesis, this study compares β-delayed multiple-particle emitters (8Li, 9C, 31Ar) with their respective stable isotopes (7Li, 12C, 40Ar) to determine possible benefits of β-delayed multiple-particle emitters minibeam radiation therapy (β-MBRT). Monte Carlo simulations were performed using the GATE toolkit to assess the dose distributions of each ion. RBE-weighted dose distributions were calculated and used for the aforementioned comparison. No significant differences were found among carbon isotopes. In contrast, 8Li and 31Ar exhibited improved RBE-weighted dose distributions with an approximately 12–20% increase in the Bragg-peak-to-entrance dose ratio (BEDR) for both peaks and valleys, which favors tissue sparing. Additionally, 8Li and 31Ar exhibited a lower peak-to-valley dose ratio (PVDR) in normal tissues and higher PVDR in the tumor than 7Li and 40Ar. Biological experiments are needed to conclude whether the differences observed make β-delayed multiple-particle emitters advantageous for MBRT.

Stereotactic Radiosurgery for Patients with Brain Metastases from Hepatopancreaticobiliary Cancers.

The role of stereotactic radiosurgery (SRS) for patients with brain metastases from hepatopancreaticobiliary (HPB) cancers has yet to be established. The authors present a single-institution experience of patients with HPB cancers who underwent SRS when their cancer spread to the brain. We surveyed our Gamma Knife SRS data base of 18,000 patients for the years 1987-2022. In total, 19 metastatic HPB cancer patients (13 male) with 76 brain metastases were identified. The median age at SRS was 61 years (range: 48-83). The primary cancer sites were hepatocellular carcinoma (HCC, 11 patients), cholangiocarcinoma (CCC, 2 patients), and pancreatic carcinoma (PCC, 6 patients). The median Karnofsky Performance Score (KPS) was 80 (range: 50-90). Two patients underwent pre-SRS whole-brain fractionated radiation therapy (WBRT) and eight patients underwent pre-SRS surgical resection. All SRS was delivered in single session. The median margin dose was 18 Gy (range: 15-20). The median cumulative tumor volume was 8.1 cc (range: 1.0-44.2). The median patient overall survival (OS) after SRS was 7 months (range 1-79 months). Four patients had documented local tumor progression after SRS at a median time of 8.5 months (range: 2-15) between SRS and progression. Out of 76 treated tumors, 72 tumors exhibited local control. The local tumor control rate per patient was 78.9%. The local tumor control per tumor was 94.7%. Four patients developed new brain metastases at a median of 6.5 months (range: 2-17) after SRS. No patient experienced adverse radiation effects (AREs). At the last follow-up, 18 patients had died, all from systemic disease progression. Metastatic spread to the brain from HPB cancers occurs late in the course of the primary disease. In this study, all deceased patients ultimately died from primary disease progression. SRS is a non-invasive strategy that maximally preserves quality of life, and our results reported favorable outcomes compared to the existing literature. SRS should be considered as one of the primary management strategies for patients with brain metastatic spread from HPB cancer.

Computational Approach for Spatially Fractionated Radiation Therapy (SFRT) and Immunological Response in Precision Radiation Therapy.

The field of precision radiation therapy has seen remarkable advancements in both experimental and computational methods. Recent literature has introduced various approaches such as Spatially Fractionated Radiation Therapy (SFRT). This unconventional treatment, demanding high-precision radiotherapy, has shown promising clinical outcomes. A comprehensive computational scheme for SFRT, extrapolated from a case report, is proposed. This framework exhibits exceptional flexibility, accommodating diverse initial conditions (shape, inhomogeneity, etc.) and enabling specific choices for sub-volume selection with administrated higher radiation doses. The approach integrates the standard linear quadratic model and, significantly, considers the activation of the immune system due to radiotherapy. This activation enhances the immune response in comparison to the untreated case. We delve into the distinct roles of the native immune system, immune activation by radiation, and post-radiotherapy immunotherapy, discussing their implications for either complete recovery or disease regrowth.

Intracranial malignant peripheral nerve sheath tumor: A case report and comprehensive literature review.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare malignant soft-tissue sarcomas arising from peripheral nerves. Little data exist regarding MPNST originating intracranially. Here, we present a 7th/8th nerve complex MPNST, discuss the treatment strategy and patient outcome, and provide a comprehensive review of existing literature. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed and crossed references were queried, yielding 37 publications from 1952 to the present. Fifty-three cases of primary intracranial and extra-axial MPNST were identified. We additionally report a 40-year-old female presented with acute onset dizziness and subsequent hearing loss with associated right-sided facial numbness. Magnetic resonance imaging revealed a 0.5 cm × 1.7 cm enhancing lesion within the right internal auditory canal extending into the cerebellopontine angle. The patient was initially treated with retro sigmoid craniotomy for tumor resection followed by a trans labyrinth approach for residual tumor resection. She completed adjuvant fractionated radiation therapy and underwent facial nerve transfer to restore complete hemifacial paralysis. The most common cranial nerves involved were V and VIII (43.4% each), with 66% of patients male and 34% female. The average age was 43.4 ± 17.4 years. The mean survival time for reported non-survivors after tissue diagnosis was 15 ± 4 months. Two-year survival for patients receiving gross total resection was 33.3% versus 22.8% with subtotal resection. MPNSTs comprise a group of highly aggressive neoplasms that rarely arise intracranially. Gross total surgical resection should be pursued when feasible.

Abstract 5113: Fractionated radiation therapy alters energy metabolism and induces cellular quiescence exit in patient-derived orthotopic xenograft models of high-grade glioma

Abstract Radiation is one of the standard therapies for pediatric high-grade glioma (pHGG), of which the prognosis remains poor. To gain an in-depth understanding of the biological activities beyond the classic DNA damage, we treated 6 patient-derived orthotopic xenograft (PDOX) models, including one with DNA mismatch repair (MMR) deficiency, with fractionated radiations (2 Gy/day x 5 days). Extension of survival time was noted in 4/6 PDOX models (P&amp;lt;0.05) and widespread γH2AX positivity in &amp;gt;95% tumor cells in tumor core and &amp;gt;85% in the invasive foci, accompanied by ~30% apoptotic and mitotic catastrophic cell death. The model with DNA MMR (IC-1406HGG) was the most responsive to radiation with a reduction of Ki-67(+) cells. Altered metabolism, including mitochondria number elevation, COX IV activation and reactive oxygen species buildup, were detected together with the accumulation of CD133+ tumor cells. The latter was caused by the entry of quiescent G0 cells into cell cycle and the activation of self-renewal (SOX2 and BMI1) and epithelial mesenchymal transition (fibronectin) genes. These novel insights about the cellular and molecular mechanisms of fractionated radiation in vivo should support the development of new radio-sensitizing therapies. Citation Format: Zi-Lu Huang, Zhi-Gang Liu, Qi Lin, Ya-Lan Tao, Xinzhuoyun Li, Patricia Baxter, Jack MF Su, Adekunle M. Adesina, Chris Man, Murali Chintagumpala, Wan Yee Teo, Yu-Chen Du, Yun-Fei Xia, Xiao-Nan Li. Fractionated radiation therapy alters energy metabolism and induces cellular quiescence exit in patient-derived orthotopic xenograft models of high-grade glioma [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 5113.

Beam quality and the mystery behind the lower percentage depth dose in grid radiation therapy

Grid therapy recently has been picking momentum due to favorable outcomes in bulky tumors. This is being termed as Spatially Fractionated Radiation Therapy (SFRT) and lattice therapy. SFRT can be performed with specially designed blocks made with brass or cerrobend with repeated holes or using multi-leaf collimators where dosimetry is uncertain. The dosimetric challenge in grid therapy is the mystery behind the lower percentage depth dose (PDD) in grid fields. The knowledge about the beam quality, indexed by TPR20/10 (Tissue Phantom Ratio), is also necessary for absolute dosimetry of grid fields. Since the grid may change the quality of the primary photons, a new kq,q0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbf{k}}_{\\mathbf{q},{\\mathbf{q}}_{0}}$$\\end{document} should be evaluated for absolute dosimetry of grid fields. A Monte Carlo (MC) approach is provided to resolving the dosimetric issues. Using 6 MV beam from a linear accelerator, MC simulation was performed using MCNPX code. Additionally, a commercial grid therapy device was used to simulate the grid fields. Beam parameters were validated with MC model for output factor, depth of maximum dose, PDDs, dose profiles, and TPR20/10. The electron and photon spectra were also compared between open and grid fields. The dmax is the same for open and grid fields. The PDD with grid is lower (~ 10%) than the open field. The difference in TPR20/10 of open and grid fields is observable (~ 5%). Accordingly, TPR20/10 is still a good index for the beam quality in grid fields and consequently choose the correct kq,q0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbf{k}}_{\\mathbf{q},{\\mathbf{q}}_{0}}$$\\end{document} in measurements. The output factors for grid fields are 0.2 lower compared to open fields. The lower depth dose with grid therapy is due to lower depth fluence with scatter radiation but it does not impact the dosimetry as the calibration parameters are insensitive to the effective beam energies. Thus, standard dosimetry in open beam based on international protocol could be used.

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.

Alleviation of Splenic Injury by CB001 after Low-Dose Irradiation Mediated by NLRP3/Caspase-1-BAX/Caspase-3 Axis.

Low-dose radiation has been extensively employed in clinical practice, including tumor immunotherapy, chronic inflammation treatment and nidus screening. However, the damage on the spleen caused by low-dose radiation significantly increases the risk of late infection-related mortality, and there is currently no corresponding protective strategy. In the present study, a novel compound preparation named CB001 mainly constituted of Acanthopanax senticosus (AS) and Oldenlandia diffusa (OD) was developed to alleviate splenic injury caused by fractionated low-dose exposures. As our results show that, white pulp atrophy and the excessive apoptosis in spleen tissue induced by radiation exposure were significantly ameliorated by CB001. Mechanistically, BAX-caspase-3 signaling and nucleotide-binding domain and leucine-rich-repeat-containing family pyrin 3 (NLRP3) inflammasome signaling were demonstrated to be involved in the radio-protective activity of CB001 with the selective activators. Furthermore, the crosstalk between apoptosis signaling and NLRP3 inflammasome signaling in mediating the radio-protective activity of CB001 was clarified, in which the pro-apoptotic protein BAX but not the anti-apoptotic protein Bcl2 was found to be downstream of NLRP3. Our study demonstrated that the use of a novel drug product CB001 can potentially facilitate the alleviation of radiation-induced splenic injury for patients receiving medical imaging diagnosis or fractionated radiation therapy.

Matrix metal collimators studies for the spatially fractionated radiation therapy

Traditional radiation therapy is hindered by limitations in dose delivery and the risk of over-irradiation, which can harm healthy tissues surrounding tumors. Spatially fractionated and intensity-modulated radiation therapies have emerged as promising techniques to mitigate these issues by reducing damage to healthy tissues. This study explores the potential of enhancing radiation therapy's therapeutic efficacy through spatial fractionation of X-ray beams, a technique that can significantly increase radiation efficiency by reducing the dose load on healthy tissues. This research hypothesizes that microscopic lesions within the paths of micro/mini-beams can be repaired by minimally irradiated cells adjacent to the irradiated tissue slices, based on observations with high-energy (MV) photons. Spatial fractionation is particularly valuable for X-ray and electron radiation therapy, which is more widespread and cost-effective than proton therapy. The study introduces a new type of cost-effective metal matrix collimators designed for beam fractionation. These collimators are constructed using lead plates for thickness variation implementation and employ a 5x5 hole matrix with 1 mm diameter and 3 mm pitch, covering an area of 14x14 mm². To visualize beam distribution, a Timepix detector, capable of providing real-time 2D beam profiles, was employed. Experiments were conducted using a medical LINAC with typical therapeutic energy ranging from 6 to 18 MeV. Results indicate that spatial fractionation can be achieved for X-ray radiation, with a PVDR of approximately 3 for a 3 cm lead collimator. However, issues with hole uniformity and blurring in the peak area prompted a shift to using copper collimators due to their superior manufacturing properties. This study presents a novel matrix collimator design made from various materials for shaping mini beams, aimed at improving the efficiency of spatial dose fractionation for different ionizing radiation types. Geant4 simulations have been instrumental in optimizing collimator features. The findings suggest that high levels of dose fractionization can be achieved for X-rays, electrons, and proton beams. These results warrant further biological studies to evaluate the effects of fractionation on normal and tumoral tissues, supporting the practical implementation of collimation in radiation therapy.

Obtaining organ-specific radiobiological parameters from clinical data for radiation therapy planning of head and neck cancers

Objective. Different radiation therapy (RT) strategies, e.g. conventional fractionation RT (CFRT), hypofractionation RT (HFRT), stereotactic body RT (SBRT), adaptive RT, and re-irradiation are often used to treat head and neck (HN) cancers. Combining and/or comparing these strategies requires calculating biological effective dose (BED). The purpose of this study is to develop a practical process to estimate organ-specific radiobiologic model parameters that may be used for BED calculations in individualized RT planning for HN cancers. Approach. Clinical dose constraint data for CFRT, HFRT and SBRT for 5 organs at risk (OARs) namely spinal cord, brainstem, brachial plexus, optic pathway, and esophagus obtained from literature were analyzed. These clinical data correspond to a particular endpoint. The linear-quadratic (LQ) and linear-quadratic-linear (LQ-L) models were used to fit these clinical data and extract relevant model parameters (alpha/beta ratio, gamma/alpha, d T and BED) from the iso-effective curve. The dose constraints in terms of equivalent physical dose in 2 Gy-fraction (EQD2) were calculated using the obtained parameters. Main results. The LQ-L and LQ models fitted clinical data well from the CFRT to SBRT with the LQ-L representing a better fit for most of the OARs. The alpha/beta values for LQ-L (LQ) were found to be 2.72 (2.11) Gy, 0.55 (0.30) Gy, 2.82 (2.90) Gy, 6.57 (3.86) Gy, 5.38 (4.71) Gy, and the dose constraint EQD2 were 55.91 (54.90) Gy, 57.35 (56.79) Gy, 57.54 (56.35) Gy, 60.13 (59.72) Gy and 65.66 (64.50) Gy for spinal cord, optic pathway, brainstem, brachial plexus, and esophagus, respectively. Additional two LQ-L parameters d T were 5.24 Gy, 5.09 Gy, 7.00 Gy, 5.23 Gy, and 6.16 Gy, and gamma/alpha were 7.91, 34.02, 8.67, 5.62 and 4.95.Significance. A practical process was developed to extract organ-specific radiobiological model parameters from clinical data. The obtained parameters can be used for biologically based radiation planning such as calculating dose constraints of different fractionation regimens.

A Dose Accumulation Assessment of Alignment Errors During Spatially Fractionated Radiation Therapy

IntroductionSpatially fractionated radiotherapy (SFRT) techniques produce high-dose peaks and low-dose valleys within a tumor. Lattice stereotactic body radiation therapy (SBRT) is a form a SFRT delivered across five fractions. Due to the high spatial dose gradients associated with SFRT, it is critical for fractionated SFRT patients to be aligned correctly for treatment. Here we investigate the dosimetric impact of daily alignment uncertainty through a dose accumulation study. MethodsDose accumulation was retrospectively performed for ten patients enrolled on a Phase I trial. Lattice SBRT was completed in 5 fractions with 20Gy prescribed to the entire tumor and a simultaneous integrated boost of 66.7Gy prescribed to a set of regularly spaced high-dose spheres. Daily alignment error was quantified through manually selected landmarks in both the planning computed tomography (CT) scan and daily cone-beam CT. The dosimetric impact of alignment errors was quantified by translating the isocenter in the treatment planning system by the daily average alignment error. Large errors were simulated by translating isocenter 5mm and 10mm for one and two fractions, independently assessing errors in the superior-inferior and axial directions. The reduction of dose gradients was quantified using the dose ratio (DR) of the mean dose in the high-dose and low-dose spheres. ResultsThe average alignment error was 1.8mm across the patient population resulting in minor smoothing of the high- and low-dose distributions in the dose accumulation. Quantitatively, the DR decreased from 3.42 to 3.32 (p=0.093) in the dose accumulation study. The simulated worst case was an inferior-superior shift of 10mm for two fractions where the average DR decreased to 2.72 (p=0.0001). ConclusionsThe dose accumulation study revealed on average DR only decreased from 3.42 to 3.32. However, setup errors >5mm resulted in larger dosimetric degradation, reflecting a larger impact for individual high dose spheres within regions exhibiting larger displacements.

Quality assurance in a phase III, multicenter, randomized trial of POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL): a planning benchmark case

PurposeTo report the planning benchmark case results of the POTENTIAL trial—a multicenter, randomized, phase 3 trial—to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer.MethodsAll participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission.ResultsThe plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively.ConclusionThe major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials.