Radiotherapy Strategies Research Articles

Nanozymes as Glucose Scavengers and Oxygenerators for Enhancing Tumor Radiotherapy.

Insufficient accumulation of reactive oxygen species (ROS) due to tumor hypoxia significantly contributes to increased radiation resistance and the failure of radiotherapy (RT). Therefore, developing methods to alleviate hypoxia and boost ROS levels represents a promising strategy for enhanced radiosensitivity. This study introduced a self-cascade catalytic Pt@Au nanozymes as a radiosensitizer, using glucose oxidase (GOx)-, catalase (CAT)-, and peroxidase (POD)-like activities to improve hypoxia and increase ROS accumulation, thereby affecting glucose metabolism and enhancing the effects of RT. Pt@Au nanozymes exhibit GOx-like activity, which not only depletes glucose to induce starvation therapy, but also generates hydrogen peroxide (H2O2) for cascade reactions. Moreover, Pt@Au nanozymes demonstrate CAT-like activity, catalyzing the conversion of H2O2 to O2. This conversion effectively alleviates hypoxia, stabilizes ROS, increases DNA damage, significantly enhancing RT efficacy and sustaining the effects of starvation therapy. As high-Z materials, Pt@Au nanozymes can deposit more X-ray energy. Furthermore, the POD-like activity catalyzes the conversion of H2O2 into highly reactive hydroxyl radicals (·OH), which increases ROS levels and enhances RT. Pt@Au nanozymes serve as X-ray computed tomography (CT) imaging agents, allowing for clear differentiation between tumor and normal tissue boundaries and enhancing the precision of RT. In summary, Pt@Au nanozymes serve as effective radiosensitizers by depleting glucose to induce starvation therapy, enhancing cascade reactions, and inhibiting tumor proliferation. Through their self-cascade reactions, these nanozymes dramatically increase oxygen levels within tumors, reduce hypoxia, and enhance ROS levels. This advancement addresses the radioresistance associated with hypoxic tumors, paving the way for innovative strategies in RT.

Evaluation of the positional reproducibility of sedation versus non-sedation state in pediatric radiotherapy: a retrospective study

ObjectiveTo assess the positional reproducibility of sedated and non-sedated pediatric tumor patients during radiotherapy through a retrospective analysis of cone-beam computed tomography (CBCT) and planned computed tomography (CT) scan data.MethodsThe positional reproducibility of 40 pediatric tumor patients, aged 2 to 17 years with a median age of 4.5 years, who received radiotherapy under sedated and non-sedated states was retrospectively compared. The first CBCT images obtained during CT-based treatment planning were analyzed. The analysis encompassed six-dimensional positional changes, including vertical (Vrt), longitudinal (Lng), lateral (Lat), rotational (Rtn), pitch, and roll directions. Kolmogorov-Smirnov Z nonparametric rank-sum testing was employed to evaluate the positional deviations, considering absolute values regardless of directionality. Data were further stratified based on different fixation methods used during treatment.ResultsSedated patients exhibited significantly smaller positional deviations in Vrt, Lng, Lat, and Rtn directions in the body membrane group compared with their non-sedated counterparts (P<0.05). Similarly, sedated patients demonstrated reduced positional deviations in Vrt, Lng, Lat, Rtn, pitch and Roll directions in the head and neck group compared with non-sedated patients (P<0.05). Meanwhile, compared with vacuum bag plus body membrane fixation, the head and shoulder film fixation technique proved superior in terms of positional reproducibility during sedated treatment, specifically in Vrt, Lng, Lat, Pitch, and Roll directions (P<0.05). Similarly, compared with the alternative fixation method, the head and shoulder film fixation method showed better positional deviations in six-Dimensional directions in non-sedated patients (P<0.05).ConclusionWhile sedated radiotherapy may offer advantages in terms of positional reproducibility, the present study underscores the importance of considering non-sedated radiotherapy as a viable option for pediatric tumor patients. Non-sedated treatment not only provides effective tumor control but also mitigates the psychological trauma and long-term side effects associated with repeated sedative drug use. Future studies should further explore the optimal sedation and fixation strategies for pediatric radiotherapy.

Glioblastoma multiforme recurrence on skin and subcutaneous tissue: a case report

Glioblastoma multiforme (GBM) is the most common malignant primary central nervous system (CNS) tumor. It presents an aggressive pattern, with a tendency for intracranial progression despite optimal treatment. On the other hand, metastases and manifestations outside the CNS are exceptional, and very few cases have been described. The authors submitted a case of a 48-year-old male diagnosed with a left parietooccipital GBM isocitrate dehydrogenase (IDH) wild-type, non-methylated O6-methylguanine-DNA methyltransferase (MGMT). Six months after surgical treatment, followed by a chemotherapy (CT) and radiotherapy scheme, he developed a few subcutaneous erythematous nodules within the surgical scar. A punch biopsy confirmed the histopathology of GBM. The CT scan showed concomitant intracranial progression. We ruled out systemic metastases. As the performance status was good [Karnofsky Performance Status 90 (KPS 90)] and the subcutaneous implants were growing rapidly, limiting the quality of life, we decided to perform palliative surgery to remove the implants. The result was good. Unfortunately, the patient worsened during the following week, after ruling out medical complications, we attributed the worsening to cerebral tumor swelling, revealed in the CT scan, as unresponsive to steroids. He passed away a few days later. Based on the analysis of our case, we intend to provide useful information for the approach to this peculiar manifestation of GBM.

AOP Report: Development of an adverse outcome pathway for deposition of energy leading to bone loss.

Bone loss, commonly seen in osteoporosis, is a condition that entails a progressive decline of bone mineral density and microarchitecture, often seen in post-menopausal women. Bone loss has also been widely reported in astronauts exposed to a plethora of stressors and in patients with osteoporosis following radiotherapy for cancer. Studies on mechanisms are well documented but the causal connectivity of events to bone loss development remains incompletely understood. Herein, the adverse outcome pathway (AOP) framework was used to organize data and develop a qualitative AOP beginning from deposition of energy (the molecular initiating event) to bone loss (the adverse outcome). This qualitative AOP was developed in collaboration with bone loss research experts to aggregate relevant findings, supporting ongoing efforts to understand and mitigate human system risks associated with radiation exposures. A literature review was conducted to compile and evaluate the state of knowledge based on the modified Bradford Hill criteria. Following review of 2029 studies, an empirically supported AOP was developed, showing the progression to bone loss through many factors affecting the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. The structural, functional, and quantitative basis of each proposed relationship was defined, for inference of causal changes between key events. Current knowledge and its gaps relating to dose-, time- and incidence-concordance across the key events were identified, as well as modulating factors that influence linkages. The new priorities for research informed by the AOP highlight areas for improvement to enable development of a quantitative AOP used to support risk assessment strategies for space travel or cancer radiotherapy.

Inhibition of ATM or ATR in combination with hypo-fractionated radiotherapy leads to a different immunophenotype on transcript and protein level in HNSCC.

The treatment of head and neck tumors remains a challenge due to their reduced radiosensitivity. Small molecule kinase inhibitors (smKI) that inhibit the DNA damage response, may increase the radiosensitivity of tumor cells. However, little is known about how the immunophenotype of the tumor cells is modulated thereby. Therefore, we investigated whether the combination of ATM or ATR inhibitors with hypo-fractionated radiotherapy (RT) has a different impact on the expression of immune checkpoint markers (extrinsic), the release of cytokines or the transcriptome (intrinsic) of head and neck squamous cell carcinoma (HNSCC) cells. The toxic and immunogenic effects of the smKI AZD0156 (ATMi) and VE-822 (ATRi) in combination with a hypo-fractionated scheme of 2x5Gy RT on HPV-negative (HSC4, Cal-33) and HPV-positive (UM-SCC-47, UD-SCC-2) HNSCC cell lines were analyzed as follows: cell death (necrosis, apoptosis; detected by AnxV/PI), expression of immunostimulatory (ICOS-L, OX40-L, TNFSFR9, CD70) and immunosuppressive (PD-L1, PD-L2, HVEM) checkpoint marker using flow cytometry; the release of cytokines using multiplex ELISA and the gene expression of Cal-33 on mRNA level 48h post-RT. Cell death was mainly induced by the combination of RT with both inhibitors, but stronger with ATRi. Further, the immune phenotype of cancer cells, not dying from combination therapy itself, is altered predominantly by RT+ATRi in an immune-stimulatory manner by the up-regulation of ICOS-L. However, the analysis of secreted cytokines after treatment of HNSCC cell lines revealed an ambivalent influence of both inhibitors, as we observed the intensified secretion of IL-6 and IL-8 after RT+ATRi. These findings were confirmed by RNAseq analysis and further the stronger immune-suppressive character of RT+ATMi was enlightened. We detected the down-regulation of a central protein of cytoplasmatic sensing pathways of nucleic acids, RIG-1, and found one immune-suppressive target, EDIL3, strongly up-regulated by RT+ATMi. Independent of a restrictive toxicity, the combination of RT + either ATMi or ATRi leads to comprehensive and immune-modulating alterations in HNSCC. This includes pro-inflammatory signaling induced by RT + ATRi but also anti-inflammatory signals. These findings were confirmed by RNAseq analysis, which further highlighted the immune-suppressive nature of RT + ATMi.

Lymphopenia Induced by Different Neoadjuvant Chemo-Radiotherapy Schedules in Patients with Rectal Cancer: Bone Marrow as an Organ at Risk.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

Impact of motion management strategies on abdominal organ at risk delineation for magnetic resonance-guided radiotherapy

Background and purposeThe impact of respiratory motion management strategies for abdominal radiotherapy, such as abdominal compression (AC) and breath hold (BH), on abdominal organ at risk (OAR) delineation on magnetic resonance imaging (MRI) is unknown. This feasibility study compared the inter- and intra- observer delineation variation on MRI acquired with AC, BH for three critical abdominal OAR. Materials and methodsT2-weighted (W) 3D MRI in free-breathing (FB) and with AC, and T1W 3D mDixon exhale BH were acquired. Four observers blinded to motion management strategy used, delineated stomach, liver, and duodenum on all MRI. One case per strategy was repeated over 6 weeks later to quantify intra-observer variation. Simultaneous truth and performance level estimation (STAPLE) contours for each OAR were generated, median and IQR mean distance to agreement (mDTA) and maximum Hausdorff distance (HD) between observer and STAPLE contours were calculated. Observers scored organ visibility on each MRI using a four-point Likert scale. ResultsA total of 27 scans including repeats were delineated. Pooled mDTA for all OARs was 1.3 mm (0.5 mm) with AC, 1.4 mm (1.0 mm) with BH, and 1.3 mm (0.5 mm) in FB. Intra-observer mDTA was highest for all organs in FB with 10.8 mm for duodenum, 1.8 mm for liver, and 2.7 mm for stomach. The pooled mean perceptual quality score value was highest for AC across organs. ConclusionsNo motion management strategy demonstrated superior similarity across OAR, emphasizing the need for personalised approaches based on individual clinical and patient factors.

The m6A modification of ACSL4 mRNA sensitized esophageal squamous cell carcinoma to irradiation via accelerating ferroptosis.

Radioresistance is a major obstacle for the therapy of esophageal squamous cell carcinoma (ESCC) and lead to a poor prognosis. Ferroptosis is supposed to be responsible for radioresistance. However, the ferroptosis-induced radioresistance in ESCC and its related regulatory mechanisms are not yet fully understood. In this study, human ESCC cell line and the corresponding radioresistance cells were irradiated with 6 megavolts (MV) X-ray. It was showed that irradiation led to less ferroptosis in radioresistant ESCC cells as compared to the parental cells, as depicted by transmission electron microscopy, intracellular Fe2+ iron contents, lipid peroxidation, and expression of COX2. The increase of ASCL4 expression levels in radioresistant cells after radiotherapy was smaller than that in the parental cells. ACSL4 overexpression significantly enhanced ferroptosis. The fold increase in ACSL4 m6A modification in the radioresistant cells was significantly smaller than that in the parental cells as detected by methylated RNA immunoprecipitation with qRT-PCR. METTL14 overexpression accelerated ferroptosis induced by irradiation via upregulating m6A modification of ACSL4 mRNA. In conclusions, ferroptosis ablation was responsible for the radioresistant of ESCC. The METTL14-mediated m6A modification of ACSL4 mRNA sensitized ESCC to irradiation via accelerating ferroptosis. This study sheds new light on our understanding of radioresistant in ESCC, and provides potential strategies for ESCC radiotherapy.

The Current use of Adaptive Strategies for External Beam Radiotherapy in Cervical Cancer: A Systematic Review

AimsVariability in the target and organs at risk (OARs) in cervical cancer treatment presents challenges for precise radiotherapy. Adaptive radiotherapy (ART) offers the potential to enhance treatment precision and outcomes. However, the increased workload and a lack of consensus on the most suitable ART approach hinder its clinical adoption. This systematic review aims to assess the current use of adaptive strategies for cervical cancer and define the optimal approach. Materials and methodsA systematic review of current literature published between January 2012 and May 2023 was conducted. Searches used PubMed/Medline, Cochrane Library, and Web of Science databases, supplemented with the University of Manchester, Google Scholar, and papers retrieved from reference lists. The review assessed workflows, compared dosimetric benefits, and examined resources for each identified strategy. Excluded were abstracts, conference abstracts, reviews, articles unrelated to ART management, proton therapy, brachytherapy, or qualitative studies. A narrative synthesis involved data tabulation, summarizing selected studies detailing workflow for cervical cancer and dosimetric outcomes for targets and OARs. ResultsSixteen articles met the inclusion criteria; these were mostly retrospective simulation planning studies, except four studies that had been clinically implemented. We identified five approaches for ART radiotherapy for cervical cancer: reactive and scheduled adaptation, internal target volume (ITV)-based approach using library of plans (LOP), fixed-margin approach using LOP, and real-time adaptation, with each approach reducing irradiated volumes without compromising target coverage compared to the non-ART approach. The LOP-based ITV approach is the most used and clinically assessed. ConclusionIdentifying the optimal strategy is challenging due to dosimetric assessment limitations. Implementing cervical cancer ART necessitates strategic optimization of clinical benefits and resources through research, including studies to identify the optimal frequency, and prospective evaluations of toxicity.

846: Adaptive strategies for external beam radiotherapy in cervical cancer: a systematic review.

846: Adaptive strategies for external beam radiotherapy in cervical cancer: a systematic review.

Current state, challenges, and future perspective of adaptive radiotherapy: A narrative review of nasopharyngeal carcinoma

Patients with nasopharyngeal carcinoma often experience weight loss and tumor regression during the course of radiotherapy that lasts for up to 6–7 weeks. Adaptive radiotherapy is a systematic feedback control approach based on image-guided technology that adjusts these changes and optimizes the radiotherapy plans according to new imaging findings during treatment. There is growing evidence that adaptive radiotherapy can reduce side effects, improve the quality of life, and enhance disease control. However, the routine application of adaptive radiotherapy for nasopharyngeal remains relatively limited. This review discusses the necessity, clinical benefits, and limitations of adaptive radiotherapy, and presents the current state, challenges, and future perspective of adaptive radiotherapy strategies for nasopharyngeal carcinoma.

A novel x-Ray and γ-Ray combination strategy for radiotherapy after breast-conserving surgery in patients with right breast cancer.

Radiotherapy is a primary therapeutic approach for breast cancer following breast-conserving surgery. The TaiChiB dual-modality radiotherapy system combining X-ray and focused γ-ray, offers a new approach to reduce the radiation dose of organs at risk (OARs) and has the potential to mitigate the adverse effects of radiotherapy. Currently, there are few studies on the dosimetric characteristics of the TaiChiB dual-modality system for actual treatment plans for specific diseases. The purpose of this work is to study the dosimetric advantages of dual-modal systems for right breast patients after breast-conserving surgery. Treatment plans for 20 patients with right breast cancer were generated for a linear accelerator (LINAC) based system and the TaiChiB dual-modality system, respectively. Volumetric modulated arc therapy plans with simultaneous integrated boost (VMAT-SIB) were made for the LINAC. Focused γ-ray was used to deliver the boost dose with the dual-modality system. The dosimetric parameters of the target and OARs were evaluated and compared between the treatment plans generated for the two systems. The TaiChiB dual-modality plans exhibit a higher conformal index (CI) and lower gradient index (GI) for the PGTV and PTV compared with the LINAC-based VMAT-SIB plans. Compared to VMAT-SIB plans, the PTV Dmax, PTV Dmean, PTV V110, PGTV Dmax, and PGTV Dmean of the TaiChiB dual-modality plans are significantly lower. Meanwhile, the dose to OARs, such as the Dmean of the heart, the V5 of liver, the Dmean of ipsilateral lung, the V30 of ipsilateral lung, the V20 of ipsilateral lung, the V5 of ipsilateral lung, the Dmean of contralateral lung, Dmax of contralateral breast and the Dmean of contralateral breast are significantly reduced. Our study demonstrates the dosimetric advantages of the novel TaiChiB dual-modality radiotherapy system for the treatment of right-sided breast cancer. Overall, for the TaiChiB dual-modality radiotherapy system, the radiation dose outside the target region decreases rapidly, thereby minimizing radiation exposure to neighboring organs and ensuring the conformity of the target area. Our research confirms the potential of the TaiChiB dual-modality system for future radiotherapy.

Advancements of prodrug technologies for enhanced drug selectivity in pharmacotherapies.

The therapeutic effects of many pharmacotherapies have been explored, but disadvantages such as low drug specificity, drug resistance and side effects makes their effective delivery to target sites a great challenge. Consequently, a distinctive prodrug-based technology have emerged as an effective treatments because of their distinctive advantages, such as high drug loading capacity, precise targeting, reduced side effects and spatial and temporal controllability. In particular, the use of gamma/X-ray-mediated strategies in radiotherapy is a new strategy that could enable the precise drug release from implanted devices. This review presents readers with the current state of prodrug therapy and reports the design protocols of rational and effective prodrugs for clinical use.

Effects of brain radiotherapy strategies on survival in the era of MRI for patients with limited stage small cell lung cancer

Background and purposeIn the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC).MethodsThis real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI.Results120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group.ConclusionThe results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.

35 Exploration of radiotherapy strategy for brain metastasis with driver gene positivity in lung cancer

35 Exploration of radiotherapy strategy for brain metastasis with driver gene positivity in lung cancer

278 Radiotherapy Strategies for Germinoma: Comparing Regional to Local Rt vs. Vice Versa- Our Experience

278 Radiotherapy Strategies for Germinoma: Comparing Regional to Local Rt vs. Vice Versa- Our Experience

Pelvic lymph node mapping in prostate cancer: examining the impact of PSMA PET/CT on radiotherapy decision-making in patients with node-positive disease

IntroductionProstate Specific Membrane Antigen (PSMA) imaging with Positron Emission Tomography (PET) plays a crucial role in prostate cancer management. However, there is a lack of comprehensive data on how PSMA PET/CT (Computed Tomography) influences radiotherapeutic decisions, particularly in node-positive prostate cancer cases. This study aims to address this gap by evaluating two primary objectives: (1) Mapping the regional and non-regional lymph nodes (LNs) up to the aortic bifurcation and their distribution using conventional methods with CT compared to PSMA PET/CT, and (2) assessing the impact of PSMA PET/CT findings on radiotherapeutic decisions.MethodsA retrospective analysis of 95 node-positive prostate cancer patients who underwent both CT and PSMA PET/CT imaging prior to primary radiotherapy and androgen deprivation therapy (ADT) was conducted. The analysis focused on identifying LNs in various regions including the common iliac, external iliac, internal iliac, obturator, presacral, mesorectal, inguinal, and other stations. Treatment plans were reviewed for modifications based on PSMA PET/CT findings, and statistical analysis was performed to identify predictors for exclusive nodal positivity on PSMA PET/CT scans.ResultsPSMA PET/CT identified additional positive nodes in 48% of cases, resulting in a staging shift from N0 to N1 in 29% of patients. The most frequent metastatic LNs were located in the external iliac (76 LNs; 34%), internal iliac (43 LNs; 19%), and common iliac (35 LNs; 15%) stations. In patients with nodes only detected on PSMA PET the most common nodes were in the external iliac (27, 40%), internal iliac (13, 19%), obturator (11, 15%) stations. Within the subgroup of 28 patients exclusively demonstrating PSMA PET-detected nodes, changes in radiotherapy treatment fields were implemented in 5 cases (18%), and a dose boost was applied for 23 patients (83%). However, no discernible predictors for exclusive nodal positivity on PSMA PET/CT scans emerged from the analysis.DiscussionThe study underscores the pivotal role of PSMA PET/CT compared to CT alone in accurately staging node-positive prostate cancer and guiding personalized radiotherapy strategies. The routine integration of PSMA PET/CT into diagnostic protocols is advocated to optimize treatment precision and improve patient outcomes.

Response-Adapted Ultralow-Dose Radiation Therapy for Orbital Indolent B-Cell Lymphoma

Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common. To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity. This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023. Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment. The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate. The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%). In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes. ClinicalTrials.gov Identifier: NCT02494700.

Tumor Redox‐Responsive Minimalist B/Fe Nano‐Chains for Chemodynamically Enhanced Ferroptosis and Synergistic Boron Neutron Capture Therapy

AbstractBoron neutron capture therapy (BNCT) as a binary targeted particle radiotherapy strategy has shown potent anti‐cancer potential. However, biological barriers and restricted blood supply pose challenges in achieving adequate boron concentration within deep‐seated tumor lesions. BNCT with other anti‐cancer therapies, such as X‐ray radiotherapy and photothermal therapy, is devised to address the limitations of BNCT efficiency. However, the potential risk of organ‐accumulating toxicity and treatment complexity of dual exogenous activation hinders its development. To address this problem, newly redox‐responsive boron nano‐chains (RBNC) are reported that combine BNCT and endogenous chemodynamic therapy (CDT)‐enhanced ferroptosis. RBNC specifically activates nanoparticle size conversion (large‐to‐small) in response to GSH/H2O2 in the tumor microenvironment, releasing boron delivery agents boron quantum dots (BQD) and Fe3+. RBNC exhibits negligible systemic toxicity while demonstrating high boron accumulation at tumor. Meanwhile, the introduction of Fe3+ not only produces ·OH through reaction with H2O2, but also depletes GSH and reduces GPX4 activity in tumors, resulting in amplified intracellular oxidative stress and chemodynamically enhanced ferroptosis. Thus, the work provides a strategy to solve the problem of insufficient boron concentration and poor targeting of boron delivery agents and fill the gaps of BNCT combined with CDT and ferroptosis.

Analysis of KLRB1-Mediated Immunosuppressive Regulation in Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is the most common type of craniopharyngioma (CP). Under the current surgery and/or radiotherapy strategies, the survival rate is high, but the long-term quality of life is poor because of the relationship between the hypothalamic-pituitary axis and the tumor. Many studies had shown that endocrine deficiencies caused by craniopharyngiomas of the hypothalamic-pituitary axis persist throughout almost the entire life of the patients after surgery, requiring them to receive hormone replacement therapy. Thus, we need to explore new treatments to improve the prognosis of patients. In recent years, there are more and more studies on the immunotherapy of various tumors. However, due to the rarity of the disease, immunotherapy for ACP is rarely researched. The discovery of the tumor immune-suppressive checkpoint KLRB1 (killer cell lectinlike receptor B1), which encodes CD161, may provide a novel target for the treatment of ACP. Data analysis of retrospective RNA sequencing was conducted in a cohort of 51 pediatric samples in the GSE94349 dataset, and the results were well validated in the GSE68015 dataset including 31 pediatric samples. We used R language as the main tool for statistical analysis and graphical work. Our research showed that KLRB1 was enriched in ACP. Additionally, the expression of KLRB1 was positively related to immune functions and most inflammatory responses of ACP. We found that most of the T lineage-related immune responses were positively correlated with KLRB1 expression, and KLRB1 played an important role in the activation of inflammatory processes. KLRB1 is a promising target for immunotherapeutic strategies.