Radiotherapy For Cancer Research Articles

Potential of non-Western medicines in chemoradiotherapy for cervical cancer

This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical cancer. While radiotherapy remains a radical treatment for cervical cancer, its associated toxicity and decline in quality of life can significantly impact patients’ lives. Currently, most treatments are supportive, with no specific treatment options available in Western medicine. Non-Western medicine, often less toxic and easier to administer, has shown promising results when used alongside radiotherapy for cervical cancer. Despite these potential benefits, challenges such as limited evidence and restricted application areas persist. While non-Western medicines may offer potential improvements in chemoradiotherapy outcomes for cervical cancer, further research is necessary to substantiate these benefits.

Biomarker-Directed Radiotherapy in Breast Cancer

ImportanceIntegration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates. This narrative review explored the potential of biomarker-directed personalized RT approaches, which may optimize treatment strategies and be associated with improved patient outcomes and experiences.ObservationsDistinctions between prognostic and predictive biomarkers were highlighted, emphasizing the importance of analytical and clinical validity in biomarker-based studies. Findings from studies investigating the prognostic and predictive value of various genomic signatures and immunohistochemical markers for guiding breast RT were presented. These included the Adjuvant Radiotherapy Intensification Classifier and the Profile for the Omission of Local Adjuvant Radiation, which have shown potential in predicting RT benefits. The genomic-adjusted radiation dose and role of tumor-infiltrating lymphocytes were also discussed. Ongoing clinical trials exploring the use of biomarkers in ductal carcinoma in situ and invasive breast cancer to refine RT decision-making were illustrated.Conclusions and RelevanceThe results of this narrative review suggest that evidence-based shared decision-making is crucial to optimize treatment according to the individual’s predicted benefits and risks along with their personal preferences. Incorporation of biomarker-directed approaches in RT for breast cancer may hold promise for personalized treatment, potentially facilitating omission of RT for patients at low risk of recurrence, while identifying those who may benefit from intensified therapy. This personalized RT approach may be associated with improved clinical outcomes and quality of life and facilitate decision-making for people with breast cancer. However, there remains a need for robust clinical and analytical validation of biomarkers to ensure reliability and clinical utility for RT optimization.

Computational insights into Sitahe (Leuconotis eugenifolia) bioactive compounds: A promising approach for radioprotection through p53 inhibition

The radioprotective potential of Sitahe (Leuconotis eugenifolia) phytochemicals in cancer radiotherapy remains largely unexplored. In this study, in silico docking simulations were conducted to systematically assess the ability of key phytochemicals from Sitahe to modulate p53 activity, a critical gene in DNA repair and cancer therapy. SwissADME analysis revealed favorable physicochemical properties for compounds such as baurenol, alpha amyrin, and beta amyrin, although high lipophilicity may pose challenges for bioavailability. Molecular docking studies identified strong binding affinities between these compounds and the p53 DNA binding domain, with baurenol demonstrating the highest binding affinity at −6.75 kcal/mol, which is better compared to rhazinilam (−4.55 kcal/mol), leuconolam (−4.36 kcal/mol), leuconoxine (−4.26 kcal/mol), and dehydroleuconoxine (−4.76 kcal/mol). Hydrogen bonding with key residues such as Thr123 further enhanced the stability of these complexes. The low inhibition constants (Ki) suggest significant inhibitory potential, particularly for baurenol (11.31 μM). To evaluate the stability and reliability of these interactions, molecular dynamics (MD) simulations were performed over a duration of 500 ns. The results demonstrated that the selected compounds maintained stable molecular dynamics profiles, showing consistent interactions with the target protein throughout the simulation period. Among the compounds tested, baurenol exhibited the best performance with a MM/PBSA binding energy of −68.568 kJ/mol, which is better than rhazinilam (−63.538 kJ/mol). These findings suggest that baurenol, along with other Sitahe phytochemicals, could serve as dual-function agents, offering protection to healthy tissues from radiation-induced damage while targeting cancer cells through p53 modulation. Although these in silico and MD results are promising, further validation through in vitro and in vivo studies is essential to confirm their therapeutic potential and optimize their pharmacokinetic properties. This study positions Sitahe phytochemicals, particularly baurenol, as promising candidates for the development of novel radioprotective agents in cancer treatment.

Real-world comparative outcomes and toxicities after definitive radiotherapy using proton beam therapy versus intensity-modulated radiation therapy for prostate cancer: a retrospective, single-institutional analysis.

This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A total of 606 patients diagnosed with prostate cancer between January 2008 and December 2018 were included. Of these patients, 510 received PBT up to a dose of 70-78Gy (relative biological effectiveness) and 96 patients received IMRT up to a dose of 70-78Gy. The median follow-up period was 82months (range: 32-140months). Patients in the PBT group had significantly higher 7-year rates of biochemical relapse-free survival (bRFS) and disease-free survival (DFS) rates: 95.1% for PBT vs 89.9% for IMRT (P = 0.0271) and 93.1% for PBT vs 85.0% for IMRT (P = 0.0019). After matching analysis, 94 patients were assigned to both groups, and the PBT group showed significantly higher 7-year bRFS and DFS rates: 98.9% for PBT vs 89.7% for IMRT (P = 0.023) and 93.4% for PBT vs 84.6% for IMRT (P = 0.022), respectively. In the subgroup analysis of intermediate-risk patients, the PBT group showed a significantly higher 7-year bRFS rate (98.3% for PBT vs 90.5% for IMRT; P = 0.007). The V60 of the bladder in the PBT group (18.1% ± 10.1%) was higher than that in the IMRT group (14.4% ± 7.6%) (P = 0.024). This study found that the treatment outcomes of PBT potentially surpassed those of IMRT specifically concerning bRFS and DFS in real-world settings. However, it should be noted that attention is warranted for late bladder complication of PBT.

Professional improbity: How Hermann J. Muller's ethics affected his science.

The present paper provides an assessment of how the scientific and national policy achievements/goals of Hermann J. Muller were impacted by his ethics and provides several documented episodes in which Muller acted unethically to promote his personal gain-at the expense of others-within the scientific community. Muller manipulated the scientific community in self-serving ways to suppress perspectives that challenged his own views on radiation-induced gene mutation, and hereditary and cancer risk assessment in ways that influenced his significant awards (e.g., Nobel Prize in Medicine or Physiology), continued grant funding, and manifest effect on public health policy. Muller acted irresponsibly toward students and directed them to violate University of Texas policies that incurred severe student disciplinary actions (e.g., University suspension). Muller avoided responsibility by resigning from the University of Texas, avoiding a trial that could have led to his dismissal, and impacted his career achievements during the period of his nomination for the Nobel Prize. Muller was also a member of a US National Academy of Sciences Committee that committed scientific misconduct by misrepresenting the research record in ways that enhanced his continued funding support and fortified his influence on US health policy. The case of Muller is presented as a morality and object lesson worthy of consideration for current and future ethical conduct of scientific research.

An Efficient 3D Convolutional Neural Network for Dose Prediction in Cancer Radiotherapy from CT Images

Introduction: Cancer is a highly lethal disease with a significantly high mortality rate. One of the most commonly used methods for treatment is radiation therapy. However, cancer treatment using radiotherapy is a time-consuming process that requires significant manual work from planners and doctors. In radiation therapy treatment planning, determining the dose distribution for each of the regions of the patient’s body is one of the most difficult and important tasks. Nowadays, artificial intelligence has shown promising results in improving the quality of disease treatment, particularly in cancer radiation therapy. Objectives: The main objective of this study is to build a high-performance deep learning model for predicting radiation therapy doses for cancer and to develop software to easily manipulate and use this model. Materials and Methods: In this paper, we propose a custom 3D convolutional neural network model with a U-Net-based architecture to automatically predict radiation doses during cancer radiation therapy from CT images. To ensure that the predicted doses do not have negative values, which are not valid for radiation doses, a rectified linear unit (ReLU) function is applied to the output to convert negative values to zero. Additionally, a proposed loss function based on a dose–volume histogram is used to train the model, ensuring that the predicted dose concentrations are highly meaningful in terms of radiation therapy. The model is developed using the OpenKBP challenge dataset, which consists of 200, 100, and 40 head and neck cancer patients for training, testing, and validation, respectively. Before the training phase, preprocessing and augmentation techniques, such as standardization, translation, and flipping, are applied to the training set. During the training phase, a cosine annealing scheduler is applied to update the learning rate. Results and Conclusions: Our model achieved strong performance, with a good DVH score (1.444 Gy) on the test dataset, compared to previous studies and state-of-the-art models. In addition, we developed software to display the dose maps predicted by the proposed model for each 2D slice in order to facilitate usage and observation. These results may help doctors in treating cancer with radiation therapy in terms of both time and effectiveness.

Efficacy and safety of topical cream containing aminoacryl tRNA synthetase complex interacting 1-derived peptide in mitigating radiation dermatitis after adjuvant radiotherapy for breast cancer

PurposeAcute radiation dermatitis (ARD) is a frequent side effect experienced by breast cancer patients undergoing radiotherapy. This study aimed to assess the efficacy and safety of a topical cream containing aminoacryl tRNA synthetase complex interacting 1 (AIMP1)-derived peptide (AdP) in mitigating radiation dermatitis (RD) in breast cancer patients undergoing radiotherapy.MethodsAn 8-week single-center, prospective pilot study was conducted to compare the clinical efficacy and safety of an AdP-containing cream with a control cream lacking AdP for the mitigation of RD. Fifteen patients undergoing radiotherapy applied the test cream to the right side and the control cream to the left side of the radiation exposure site, bisected by the nipple line. RD was evaluated at baseline and at weeks 2, 4, 6, and 8, employing the 5-point grading system advocated by the Radiation Oncology Group (RTOG).ResultsThe average RTOG score was lower on the test side in comparison to the control side, and a less pronounced increase in melanin index was observed on the test side. However, these differences were not statistically significant. Both sides exhibited increased skin hydration and decreased transepidermal water loss. Analyzing the maximum RTOG scores throughout the study, RD of maximum grades 1 and 2 was noted in 54.5% and 45.5% of patients on the test side. On the control side, the maximum grades 1 and 2 were observed in 45.5% and 54.5% of patients respectively.ConclusionThe AdP-containing cream did not prove to be more effective than the control cream without AdP in mitigating RD. However, the total incidence of RD in our study was notably lower than previously documented, illustrating the protective effects of both the test and control creams.

Efficacy of Neoadjuvant Radiotherapy After Chemotherapy and the Optimal Interval from Radiotherapy to Surgery for Borderline Resectable and Resectable Pancreatic Cancer.

Benefits of neoadjuvant treatment for pancreatic cancer with major vessel invasion has been demonstrated through randomized controlled trials; however, the optimal neoadjuvant treatment strategy remains controversial, especially for radiotherapy. Therefore, we aimed to evaluate the efficacy and safety of neoadjuvant radiotherapy followed by chemotherapy and the optimal time interval to undergo surgery after radiotherapy in (borderline) resectable pancreatic cancer. Between 2013 and 2022, patients with (borderline) resectable pancreatic cancer with vessel contact who received 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan or gemcitabine and nanoparticle albumin-bound paclitaxel as initial treatment following surgery were included. Patients who received radiotherapy after chemotherapy and those who did not were matched using 1:1 nearest-neighbor propensity scores. Propensity scores were measured using the tumor size at initial image, duration of neoadjuvant chemotherapy, and responsiveness to neoadjuvant chemotherapy. Of 212 patients, 166 patients were retrieved for the matched cohort. Patients who received radiotherapy had significantly better postoperative survival, local control, and R0 resection rates than those who did not. Furthermore, patients who underwent surgery within 4 weeks after completing radiotherapy had lower intraoperative blood loss and a clinically relevant postoperative pancreatic fistula rate than those who underwent surgery after more than 4 weeks. In patients with (borderline) resectable pancreatic cancer with vessel contact who were scheduled for curative-intent surgery after neoadjuvant chemotherapy, additional radiotherapy was associated with better postoperative survival and local control. Furthermore, our findings suggested that scheduling surgery within 4 weeks following radiation therapy might enhance the perioperative outcomes.

Transoral Laser Microsurgery Versus Radiotherapy for T1-T2 Glottic Cancer with Anterior Commissure Involvement: A Systematic Review and Meta-Analysis.

To identify the most effective treatment modality for achieving favorable outcomes in early glottic tumors with anterior commissure involvement (ACI). PubMed, Embase, Web of Science, and ScienceDirect. Random-effects proportional meta-analysis model is used to evaluate the oncological and functional outcomes of transoral laser microsurgery (TLM) versus radiation therapy (RT) in early glottic (T1-T2) cancer with ACI. From a total of 736 studies, 40 studies were included, comprising 2666 early glottic tumor patients with ACI. TLM (52%) and upfront RT (48%) were the primary treatment groups. TLM had better 5-year overall survival (OS) (84.5% [80.3%-88.0%] vs. 79.4% [75.7%-82.7%]). Similarly, TLM-treated patients had better 3-year pooled disease-free survival (DFS) compared with RT-treated patients (82.7% [77.1%-87.1%] vs. 73.3% [23.8%-96.0%]). TLM exhibited a better 5-year local control rate (LCR) than RT (77.2% vs. 71.6%). In our temporal analysis, TLM had a higher 5-year LCR than RT (78.2% vs. 63.5%) in 2001-2012, with similar rates in 2013-2024 (76.8% vs. 78.4%). TLM-treated patients had higher laryngeal preservation rates compared with RT patients (93% [90.6%-94.8%] vs. 87.6% [82.8%-91.2%]). Our meta-analysis is the first in the literature to compare the outcomes between TLM and RT-treated patients with ACI in early glottic tumors. TLM-treated patients appear to have superior 5-year OS and laryngeal preservation compared with upfront RT-treated patients. However, both TLM and RT exhibited comparable oncological outcomes in early glottic tumor patients with ACI during the recent period from 2013 to 2024. Laryngoscope, 2025.

Patient- and clinician-based evaluation of large language models for patient education in prostate cancer radiotherapy.

This study aims to evaluate the capabilities and limitations of large language models (LLMs) for providing patient education for men undergoing radiotherapy for localized prostate cancer, incorporating assessments from both clinicians and patients. Six questions about definitive radiotherapy for prostate cancer were designed based on common patient inquiries. These questions were presented to different LLMs [ChatGPT‑4, ChatGPT-4o (both OpenAI Inc., San Francisco, CA, USA), Gemini (Google LLC, Mountain View, CA, USA), Copilot (Microsoft Corp., Redmond, WA, USA), and Claude (Anthropic PBC, San Francisco, CA, USA)] via the respective web interfaces. Responses were evaluated for readability using the Flesch Reading Ease Index. Five radiation oncologists assessed the responses for relevance, correctness, and completeness using afive-point Likert scale. Additionally, 35prostate cancer patients evaluated the responses from ChatGPT‑4 for comprehensibility, accuracy, relevance, trustworthiness, and overall informativeness. The Flesch Reading Ease Index indicated that the responses from all LLMs were relatively difficult to understand. All LLMs provided answers that clinicians found to be generally relevant and correct. The answers from ChatGPT‑4, ChatGPT-4o, and Claude AI were also found to be complete. However, we found significant differences between the performance of different LLMs regarding relevance and completeness. Some answers lacked detail or contained inaccuracies. Patients perceived the information as easy to understand and relevant, with most expressing confidence in the information and awillingness to use ChatGPT‑4 for future medical questions. ChatGPT-4's responses helped patients feel better informed, despite the initially standardized information provided. Overall, LLMs show promise as atool for patient education in prostate cancer radiotherapy. While improvements are needed in terms of accuracy and readability, positive feedback from clinicians and patients suggests that LLMs can enhance patient understanding and engagement. Further research is essential to fully realize the potential of artificial intelligence in patient education.

A comparative analysis of toxicity and treatment outcomes of adaptive radiotherapy and intensity-modulated radiotherapy in cervical cancer

Adaptive radiotherapy (ART) provides greater benefits than intensity-modulated radiotherapy (IMRT) regarding dosimetric outcomes in patients with cervical cancer. To investigate the clinical benefits of ART, we have collected data from 115 cervical cancer patients who underwent radical radiotherapy at our institution. Fifty-nine patients received a single course of IMRT. Fifty-six patients underwent offline ART, defined as the reduction of the gross tumor volume (GTV) by at least 30% after 30 Gy of radiotherapy, followed by a modified treatment plan for the second-stage. After treatment, 53 patients of ART group achieved a partial response (PR) or completement response (CR), resulting in an objective response rate (ORR) of 94.6% for the ART group, compared to 93.2% for the IMRT group. Patients in both groups exhibited no significant differences in acute toxicities. However, the incidence of chronic constipation was significantly higher in the IMRT group compared to the ART group (p = 0.021). With a median follow-up time of 27 months, the ART group experienced a higher mortality (10/56) than the IMRT group (6/59). However, the difference between the two groups was not statistically significant. In summary, ART may be advantageous in reducing the incidence of chronic constipation among patients with locally advanced cervical cancer, and both clinical prognosis and near-term survival are satisfactory.

Linear regression analysis for complete blood count parameters during radiotherapy.

This study aimed to evaluate the correlations between complete blood count (CBC) during radiotherapy and patient and treatment factors. Data of cancer patients, including age, sex, concurrent chemotherapy (CCRT), radiotherapy dose (equivalent dose in 2‑Gy fractions with an alpha/beta value of 10 Gy, EQD2Gy10), radiotherapy location, and baseline CBC were collected. Linear regression was used to determine results during radiation. Validation data comprised 20% of the whole cohort. Atotal of 496 radiotherapy courses and 1884 weekly CBC results during treatment were analyzed. Baseline hemoglobin (Hb) was positively associated with subsequent Hb. Each 1 g/dL increase in baseline Hb predicted a0.73 g/dL increase in Hb during treatment (95% confidence interval [CI] 0.7-0.76). Male sex was associated with a0.16 g/dL higher Hb (95% CI 0.04-0.29), while female sex showed the opposite trend. CCRT was associated with a0.18 g/dL reduction in Hb (95% CI -0.33 to -0.03). Radiotherapy to the pelvis, bone, and head and neck regions resulted in Hb reductions of 0.18, 0.34, and 0.94 g/dL, respectively (95% CI -0.33 to -0.03, -0.53 to -0.15, and -1.26 to -0.62, respectively), while brain irradiation increased Hb by 0.22 g/dL (95% CI 0.05-0.38). Age, cumulative dose, and thoracic irradiation did not show asignificant correlation with Hb changes. Adjusted R‑squared for the development and validation data were 0.6 and 0.71 for Hb, 0.42 and 0.11 for white blood cell count, 0.36 and 0.32 for neutrophils, 0.42 and 0.06 for absolute neutrophil count, and 0.43 and 0.36 for platelets, respectively. Hb levels during radiotherapy could be explained using linear regression, although they did not negatively correlate with cumulative dose.

Implant-based reconstruction and adjuvant radiotherapy in breast cancer patients-current status and DEGRO recommendations.

The aim of this review is to give an overview of the results of prospective and retrospective studies using allogenic reconstruction and postmastectomy radiotherapy (PMRT) in breast cancer and to make recommendations regarding this interdisciplinary approach. APubMed search was conducted to extract relevant articles from 2000 to 2024. The search was performed using the following terms: (breast cancer) AND (reconstruction OR implant OR expander) AND (radiotherapy OR radiation). Data from the literature on allogenic breast reconstruction and radiation are presented and discussed in relation to toxicity and cosmesis. Breast reconstruction is also feasible if PMRT is necessary. Patients need to be informed about the relevant risk of capsular fibrosis and implant failure. Aplanned reconstruction is no reason to forgo PMRT nor is an indication for PMRT areason to forego implant-based breast reconstruction if desired by the patient. It is important to provide detailed information here to enable shared decision-making. There is still no clear consensus regarding implant-based reconstruction (IBR) and PMRT. However, in clinical practice, both aone-stage (immediate "implant-direct" IBR) procedure with PMRT up to the final implant and atwo-stage (immediate-delayed IBR) procedure with PMRT up to the tissue expander (TE) and later exchange of the TE are used; both approaches have their specific advantages and disadvantages. Depending on patient-specific factors and the surgeon's experience and estimates, both IBR procedures are also possible in combination with PMRT. When using aTE/implant approach, completing skin stretching by adequately filling the expander before PMRT may be favorable. This approach is particularly practical when adjuvant chemotherapy is planned but may lead to postponement of radiotherapy when primary systemic therapy is given. According to the latest data, moderate hypofractionation also appears to be safe in the context of the IBR approach. It is important to have aclosely coordinated interdisciplinary approach and to fully inform patients about the increased rate of potential side effects.

Photodynamic therapy as a strategic ally in radiotherapy for triple-negative breast cancer: the importance of treatment order.

Triple-negative breast cancer (TNBC) accounts for 20% of all breast cancer cases and is notably resistant to radiotherapy (RT). Photodynamic therapy (PDT) using porphyrins or their derivatives has shown promise as a potential cancer treatment and immune activator. This study evaluated the effects of combining PDT and RT in sublethal conditions for TNBC using in vitro and in vivo models. In vitro, PDT was combined with RT (2.5Gy) using a porphyrin (TMPyP, 32 μmolL-1) and red light (660 ± 15nm) with a dose of 50 Jcm-2. We assessed cell viability, survival, apoptosis, ROS, singlet oxygen, and GSH/GSSG ratio. In vivo, we used a TNBC-bearing mouse model and combined PDT with RT in four sessions, comparing treatment sequences. We evaluated tumor volume, clinical manifestations, survival, metastasis in the lungs, ROS, singlet oxygen, and glutathione levels. Cells treated with PDT + RT had a lower survival fraction, although PDT alone showed higher apoptosis and singlet oxygen levels than RT-treated groups. In vivo, the treatment sequence plays a crucial role: PDT after RT resulted in better clinical outcomes, prolonged survival, and fewer lung nodules compared to RT, with higher singlet oxygen levels likely stimulating an immune response. Our results show that PDT can be a valuable adjunct in the RT of TNBC, with the treatment sequence playing a crucial role in enhancing efficacy.

Stereotactic body radiotherapy and poly (ADP-ribose) polymerase inhibitors in ovarian cancer: a knowledge and attitudes survey in collaboration with the Italian Association of Radiation Oncology (AIRO) and Multicenter Italian Trials in Ovarian Cancer (MITO) groups.

The aim of this study was to present a nationwide survey on the specialist's attitudes towards stereotactic body radiotherapy (SBRT) combined with poly (ADP-ribose) polymerase inhibitors (PARPi) with oligometastatic/oligoprogressive/oligorecurrent ovarian cancer (oMPR-OC) patients. The 19-item questionnaire was developed by specialists and distributed online. Replies were stratified by categories and analyzed using descriptive statistics. Respondents (N = 100) were radiation oncologists (57%), medical oncologists (32%), and gynecologic oncologists (11%). Fifty-four percent of respondents considered medical oncologists as the primary oncologists for oMPR-OC, while 23% preferred radiation oncologists and 15% favored gynecologic oncologists. Seventy-three percent discuss these cases in the Multidisciplinary Tumor Board, while 15, 6, and 2% send the patients straight to SBRT, surgery, or chemotherapy, respectively. Seventy-four percent of the experts interviewed were treated with SBRT less than 10 oMPR-OC patients. Concomitant treatment was highly heterogeneous, but it had little to no reported side effects. A significant variation in how PARPi is managed during SBRT was found: 34% do not interrupt the administration, while 52% pause and restart it later. Forty-three percent of respondents believe that the PARPi dosage should not be reduced when administered concurrently with SBRT. Sixty-nine percent of respondents believe that the SBRT dose should not be decreased while receiving PARPi if the constraints are met. The majority of respondents (40%) favored expert consensus for enhancing the clinical management of oMPR-OC, while 34% preferred clinical guidelines. A lack of or low toxicity with the combination of PARPi and SBRT was perceived, and a significant degree of heterogeneity concerning clinical protocols for their combination. Moreover, it emphasizes the low number of patients who have received this treatment approach nationwide.

Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in Apc1638N/+ mice.

Exposure to ionizing radiation (IR), both low-LET (e.g., X-rays, γ rays) and high-LET (e.g., heavy ions), increases the risk of gastrointestinal (GI) cancer. Previous studies have linked IR-induced GI cancer to cellular senescence associated secretory phenotype (SASP) signaling. This study explores the potential of senolytic therapy to mitigate IR-induced GI carcinogenesis. Male Apc1638N/+ mice were exposed to γ and 28Si-ions (69 keV/μm) IR. Two months later, they were treated with the senolytic agent ABT-263 orally for 5 days/week until euthanasia, followed by tumor counting and biospecimen collection at five months post-exposure. Tumors were classified as adenoma or carcinoma by a pathologist. Serum cytokine levels were measured, and the markers of senescence (p16), SASP (IL6), and oncogenic β-catenin signaling were assessed using in-situ immunostaining of intestinal tissue. Both low- and high-LET radiation exposure led to an increased frequency of adenoma and carcinoma in Apc1638N/+ mice, accompanied by increased cellular senescence, acquisition of SASP, and overexpression of BCL-XL protein in a subset of these cells. Furthermore, administration of ABT-263 resulted in the elimination of senescent/SASP cells, a decrease in pro-inflammatory cytokines (TNFRSF1B, CCL20, CXCL4, P-selectin, CCL27, and CXCL16) at the systemic level, and downregulation of β-catenin signaling that coincided with decreased GI cancer development. This study suggests a link between IR-induced senescent/SASP cell accumulation and GI cancer development. It also shows that the senolytic agent ABT-263 can regulate IR-induced inflammatory cytokines and carcinogenic mediators both systemically and in intestinal tissue. These findings support the potential of senolytic intervention to reduce IR-induced GI cancer risk.

Multimodal data deep learning method for predicting symptomatic pneumonitis caused by lung cancer radiotherapy combined with immunotherapy

Multimodal data deep learning method for predicting symptomatic pneumonitis caused by lung cancer radiotherapy combined with immunotherapy

Into the light: A story about breast cancer radiation treatment.

Into the light: A story about breast cancer radiation treatment.

Lifetime Attributable Risk in Mammography Screenings in Dubai: The Influence of Breast Thickness and Age on Radiation Exposure.

Background/Objectives: This study investigated the lifetime attributable risk (LAR) of radiation-induced breast cancer from mammography screening in Dubai. It aimed to explore the relationship between breast thickness, patient age, and the associated radiation dose during mammographic examinations. Methods: A retrospective analysis was conducted on 2601 patients aged 40 to 69 across five screening facilities in Dubai's healthcare system. Due to a low correlation between the mean glandular dose (MGD) and breast thickness, both glandular and non-glandular doses were included in calculations as the organ dose (OD). This comprehensive approach examined the impact of whole breast tissue on risk assessments. Key exposure parameters such as the kilovoltage peak (kVp), milliampere-seconds (mAs), and source-to-skin distance were extracted from the dose survey. Results: Our findings reveal that the organ dose increases with breast thickness, emphasizing the need for dose optimization in denser tissues. The LAR decreases with age across all thickness categories, but higher initial LAR values were seen in younger patients with thicker tissue. This study emphasizes the increased sensitivity of younger women, who usually have denser breast tissue, to radiation-induced cancer risks. Conclusions: Personalized screening protocols considering age and breast thickness are crucial for balancing early cancer detection benefits with radiation risks. Future research should improve mammography protocols, explore alternative methods, and consider generic testing for young high-risk patients to mitigate risks while maintaining diagnostic efficacy.

Phenotypic plasticity and increased infiltration of peripheral blood-derived TREM1+ mono-macrophages following radiotherapy in rectal cancer.

In our previously reported phase 2 and phase 3 studies, the combination of short-course radiotherapy and neoadjuvant immunochemotherapy (SIC) is established as effective cancer therapies for locally advanced rectal cancer (LARC). Here, we apply multi-omic analyses to paired pre- and post-treatment LARC specimens undergoing SIC. The peripheral blood-derived TREM1+ mono-macrophage subsets that display a pro-inflammatory phenotype are identified and correlate with complete response to SIC. Mechanically, ionizing radiation (IR) induces peripheral TREM1+ mono-macrophage expansion in tumors. Following IR, the loss of TREM1 in mono-macrophages undermines antitumor immunity by altering mono-macrophage differentiation and inhibiting CD8+ Tcell infiltration and activation. The TREM1+ mono-macrophage response may rely on activation of key inflammatory pathways, including nuclear factor κB (NF-κB) signaling and Toll-like receptor pathway. Pharmacological inhibition of TREM1 signaling abolishes IR-induced immunoactivation and reduces combined IR and/or anti-PD-1 treatment. Thus, we establish a crucial role of a mono-macrophage state in mediating effective cancer therapy.