Side Effects Of Radiotherapy Research Articles

Connexin 43 Prevents Radiation-Induced Intestinal Damage via the Ca2+-Dependent PI3K/Akt Signaling Pathway.

Radiation-induced intestinal damage (RIID) is a common side effect of radiotherapy in patients with abdominopelvic malignancies. Gap junctions are special structures consisting of connexins (Cxs). This study aimed to investigate the expression and role of connexins in RIID and underlying mechanism. In this study, a calcein-AM fluorescence probe was used to detect changes in gap junctional intercellular communication in intestinal epithelial IEC-6 cells. Our results show that gap junctional intercellular communication of IEC-6 cells was reduced at 6, 12, 24, and 48 h after irradiation, with the most pronounced effect at 24 h. Western blotting and immunofluorescence results showed that the expression of Cx43, but not other connexins, was reduced in irradiated intestinal epithelial cells. Silencing of Cx43 reduced gap junctional intercellular communication between irradiated intestinal epithelial cells with increased ROS and intracellular Ca2+ levels. Furthermore, knockdown of Cx43 reduced the number of clonal clusters, decreased cell proliferation with increased cytotoxicity and apoptosis. Western blotting results showed that silencing of Cx43 resulted in changed γ-H2AX and PI3K/AKT pathway proteins in irradiated intestinal epithelial cells. Administration of the PI3K/AKT pathway inhibitor LY294002 inhibited the radioprotective effects in Cx43-overexpressing intestinal epithelial cells. Our study demonstrated that Cx43 expression is decreased by ionizing radiation, which facilitates the radioprotection of intestinal epithelial cells.

Dosiomics and radiomics-based prediction of pneumonitis after radiotherapy and immune checkpoint inhibition: The relevance of fractionation

ObjectivesPost-therapy pneumonitis (PTP) is a relevant side effect of thoracic radiotherapy and immunotherapy with checkpoint inhibitors (ICI). The influence of the combination of both, including dose fractionation schemes on PTP development is still unclear. This study aims to improve the PTP risk estimation after radio(chemo)therapy (R(C)T) for lung cancer with and without ICI by investigation of the impact of dose fractionation on machine learning (ML)-based prediction. Materials and MethodsData from 100 patients who received fractionated R(C)T were collected. 39 patients received additional ICI therapy. Computed Tomography (CT), RT segmentation and dose data were extracted and physical doses were converted to 2-Gy equivalent doses (EQD2) to account for different fractionation schemes. Features were reduced using Pearson intercorrelation and the Boruta algorithm within 1000-fold bootstrapping. Six single (clinics, Dose Volume Histogram (DVH), ICI, chemotherapy, radiomics, dosiomics) and four combined models (radiomics + dosiomics, radiomics + DVH + Clinics, dosiomics + DVH + Clinics, radiomics + dosiomics + DVH + Clinics) were trained to predict PTP. Dose-based models were tested using physical dose and EQD2. Four ML-algorithms (random forest (rf), logistic elastic net regression, support vector machine, logitBoost) were trained and tested using 5-fold nested cross validation and Synthetic Minority Oversampling Technique (SMOTE) for resampling in R. Prediction was evaluated using the area under the receiver operating characteristic curve (AUC) on the test sets of the outer folds. ResultsThe combined model of all features using EQD2 surpassed all other models (AUC = 0.77, Confidence Interval CI 0.76–0.78). DVH, clinical data and ICI therapy had minor impact on PTP prediction with AUC values between 0.42 and 0.57. All EQD2-based models outperformed models based on physical dose. ConclusionsRadiomics + dosiomics based ML models combined with clinical and dosimetric models were found to be suited best for PTP prediction after R(C)T and could improve pre-treatment decision making. Different RT dose fractionation schemes should be considered for dose-based ML approaches.

The Trajectory of Oral Mucositis in Head and Neck Cancer Patients Undergoing Radiotherapy and its Influencing Factors

Background: Oral mucositis (OM) is a common and severe side effect of radiotherapy in head and neck cancer (HNC). The study aimed to investigate the longitudinal changes in OM and its influencing factors in patients with HNC during radiotherapy. Methods: This was a retrospective longitudinal observational study. From July 2022 to March 2023, patients with HNC undergoing radiation therapy were enrolled. OM, oral hygiene, oral infections, oral pain, feeding route, and laboratory indicators were measured at 7 times. The influencing factors of OM were analyzed using generalized estimation equations (GEEs). Results: A total of 160 patients were included in this study. The prevalence of severe OM at T0, T1, T2, T3, T4, T5, and T6 was 0, 0, 2.5%, 9.4%, 26.9%, 24.4%, and 26.9%, respectively. The prevalence of grade 1-2 OM at T0, T1, T2, T3, T4, T5, and T6 was 0, 16.3%, 53.1%, 65.1%, 61.9%, 70.7%, and 71.3%, respectively. Duration of diagnosis, clinical stage, N stage, M stage, surgery, diabetes, radiotherapy dose, oral hygiene, oral infection, oral pain, feeding route, and lymphocyte impacted OM significantly in the GEEs multivariate model. Conclusions: OM occurs in almost all patients with HNC who undergo radiotherapy. Changes in the severity of OM are a dynamic process, with the severity increasing with the cumulative radiotherapy dose. Specialist oral evaluation and oral care are needed to alleviate the severity of OM in HNC patients.

Meta analysis of the second course of radiotherapy for recurrent esophageal cancer1.

How to improve efficacy and reduce side effects in treating recurrent esophageal cancer by applying the second course of radiotherapy alone and its combination with chemotherapy has been attracting broad research interest. This review paper aims to systematically evaluate efficacy and side effects of applying the second course of anterograde radiotherapy alone and its combination with chemotherapy in treating recurrent esophageal cancer. First, the relevant research papers are retrieved from PubMed, CNKI and Wanfang databases. Next, Redman 5.3 software is used to calculate the relative risk and 95% confidence interval to evaluate the efficacy and adverse reactions of applying the single-stage radiotherapy with and without combining single/multi dose chemotherapy to treat recurrent esophageal cancer. Then, a meta data analysis is applied to examine the effectiveness and side effects of radiation alone and re-course radiotherapy plus chemotherapy in treating esophageal cancer recurrence after the first radiotherapy. Fifteen papers are retrieved, which included 956 patients. Among them, 476 patients received radiotherapy combined with single drug/multi drug chemotherapy (observation) and others received only radiotherapy (control). Data analysis results show that the incidence of radiation induced lung injury and bone marrow suppression is high in the observation group. Subgroup analysis also shows the higher effective rate or one-year overall survival rate of patients treated with the second course radiotherapy combined with single drug chemotherapy. The meta-analysis result demonstrates that combining the second course of radiotherapy with single-drug chemotherapy has advantages in treating recurrent esophageal cancer with the manageable side effects. However, due to insufficient data, it is not possible to conduct the further subgroup analysis comparing the side effects of restorative radiation with the combined chemotherapy using between a single drug and multiple drugs.

Abstract A082: Stretching towards relief: The Kent-Collins protocol for radiation-induced eustachian tube dysfunction

Abstract Background: Eustachian tube dysfunction is a common side effect of radiotherapy for head and neck cancers or brain tumors, although few effective treatments exist. The Kent-Collins Protocol represents a novel therapeutic option for post-radiotherapy Eustachian tube dysfunction. Case Presentation: The Kent-Collins Protocol was employed in one patient with Eustachian tube dysfunction following fractionated stereotactic radiotherapy for HER-2 positive breast cancer with cerebral metastases. The Kent-Collins Protocol provided relief of symptoms (conductive hearing loss, aural fullness, and otalgia) for a range of 5 to 45 minutes. The protocol could be repeated when symptoms returned to provide additional relief. The patient also reported psychological benefit from this protocol, knowing the hearing loss was reversible and not likely to be permanent. Conclusions: This case demonstrates the potential of The Kent-Collins Protocol for the treatment of post-radiotherapy Eustachian tube dysfunction. The protocol is effective, inexpensive, easy to teach, and safe, offering an alternative to invasive therapies currently in existence. Citation Format: Matthew E Kent, Patrick J Colllins, Ayal A Aizer. Stretching towards relief: The Kent-Collins protocol for radiation-induced eustachian tube dysfunction [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A082.

Oral glutamine: Is there a role in the amelioration of radiation-induced mucositis? A prospective case-control study at a tertiary care centre in North India.

The most frequently occurring painful and dose-limiting side effect of radiation therapy (RT) to the head and neck region is oral mucositis (OM). Several studies demonstrated that glutamine may reduce the severity and the duration of OM significantly during RT and chemo-radiotherapy in patients with head and neck cancer (HNC). Between January 2021 and August 2022, a prospective single institutional case-control study compared the efficacy and safety of oral glutamine on radiation-induced mucositis in patients with HNC. Of 60 biopsy-proven patients with HNC, 30 patients in the study arm received oral glutamine suspension (10 g in 500 mL of water) orally once daily, 2 hours before RT, receiving definitive or adjuvant RT and chemo-radiotherapy, while as 30 patients in the control arm received placebo with the same dose and schedule (n = 30 in the study arm and n = 30 in the control arm). A total of 27 (90%) in the glutamine arm and 28 (93.33%) patients in the control arm developed mucositis. Grade 3 mucositis (13.33%) and Grade 4 mucositis (6.66%), respectively, were significantly less ( P = .040 and P = .004) in the glutamine arm. The mean duration of grade 3 and grade 4 mucositis was significantly less in the glutamine arm (8.94 days in the study arm vs. 14.54 in the control arm; P = .0001). The mean time of onset of OM was significantly delayed in the glutamine arm in comparison to the control arm with P < .001. Glutamine delays the onset of OM and decreases the severity of OM in patients of HNC receiving RT with or without chemotherapy.

Comparative Characterisation of Proliferation and Apoptosis of Colonic Epithelium after Electron Irradiation with 2 GY and 25 GY.

Development of new techniques for multimodal treatment and diagnostics of various neoplasms and the improvement of current techniques can significantly increase the life expectancy of patients with carcinomas of the colon and abdominal-cavity organs, since prevention of various side effects of radiation therapy is one of the main problems of oncological care. Electron irradiation is one of the most promising types of radiation therapy. There are no data on proliferation and apoptosis of the colon epithelium after irradiation with electrons, especially in different modes (single and summary). Morphological evaluation of apoptosis and proliferation of colonic epithelium after local irradiation with electrons were conducted at doses of 2 Gy (Gray) and 25 Gy. Colon fragments from sexually mature Wistar rats (n = 50, body weight 200 ± 10 g) were divided into three groups: I-control (n = 10); II-experimental group (n = 20; local single electron irradiation at a dose of 2 Gy); III-experimental group (n = 30) with local fractional irradiation with electrons at a total dose of 25 Gy. They were studied using light microscopy using hematoxylin and eosin staining and immunohistochemical reactions with antibodies to Ki-67 and caspase-3 (Cas3). Morphological disorders were accompanied by increased expression of pro-apoptotic molecules (caspase-3), and the period of regeneration by proliferative marker (Ki-67). Colon electron irradiation led to disturbances in the histoarchitecture of varying severity, and an increase in cell apoptosis was observed (increased expression of caspase-3 and decrease in Ki-67). In addition, modulation of the PI3K/AKT and MAPK/ERK signalling pathways was detected. The most pronounced destructive changes were observed in the group of 25 Gy fractionated electron irradiation.

Targeting CD38/ ADP-ribosyl cyclase as a novel therapeutic strategy for identification of three potent agonists for leukopenia treatment

Leukopenia is the most common side effect of chemotherapy and radiotherapy. It potentially deteriorates into a life-threatening complication in cancer patients. Despite several agents being approved for clinical administration, there are still high incidences of pathogen-related disease due to a lack of functional immune cells. ADP-ribosyl cyclase of CD38 displays a regulatory effect on leukopoiesis and the immune system. To explore whether the ADP-ribosyl cyclase was a potential therapeutic target of leukopenia. We established a drug screening model based on an ADP-ribosyl cyclase-based pharmacophore generation algorithm and discovered three novel ADP-ribosyl cyclase agonists: ziyuglycoside II (ZGSII), brevifolincarboxylic acid (BA), and 3,4-dihydroxy-5-methoxybenzoic acid (DMA). Then, in vitro experiments demonstrated that these three natural compounds significantly promoted myeloid differentiation and antibacterial activity in NB4 cells. In vivo, experiments confirmed that the compounds also stimulated the recovery of leukocytes in irradiation-induced mice and zebrafish. The mechanism was investigated by network pharmacology, and the top 12 biological processes and the top 20 signaling pathways were obtained by intersecting target genes among ZGSII, BA, DMA, and leukopenia. The potential signaling molecules involved were further explored through experiments. Finally, the ADP-ribosyl cyclase agonists (ZGSII, BA, and DMA) has been found to regenerate microbicidal myeloid cells to effectively ameliorate leukopenia-associated infection by activating CD38/ADP-ribosyl cyclase-Ca2+-NFAT. In summary, this study constructs a drug screening model to discover active compounds against leukopenia, reveals the critical roles of ADP-ribosyl cyclase in promoting myeloid differentiation and the immune response, and provides a promising strategy for the treatment of radiation-induced leukopenia.

Functionality of bone marrow mesenchymal stromal cells derived from head and neck cancer patients – A FDA-IND enabling study regarding MSC-based treatments for radiation-induced xerostomia

PurposeSalivary dysfunction is a significant side effect of radiation therapy for head and neck cancer (HNC). Preliminary data suggests that mesenchymal stromal cells (MSCs) can improve salivary function. Whether MSCs from HNC patients who have completed chemoradiation are functionally similar to those from healthy patients is unknown. We performed a pilot clinical study to determine whether bone marrow-derived MSCs [MSC(M)] from HNC patients could be used for the treatment of RT-induced salivary dysfunction. MethodsAn IRB-approved pilot clinical study was undertaken on HNC patients with xerostomia who had completed treatment two or more years prior. Patients underwent iliac crest bone marrow aspirate and MSC(M) were isolated and cultured. Culture-expanded MSC(M) were stimulated with IFNγ and cryopreserved prior to reanimation and profiling for functional markers by flow cytometry and ELISA. MSC(M) were additionally injected into mice with radiation-induced xerostomia and the changes in salivary gland histology and salivary production were examined. ResultsA total of six subjects were enrolled. MSC(M) from all subjects were culture expanded to > 20 million cells in a median of 15.5 days (range 8–20 days). Flow cytometry confirmed that cultured cells from HNC patients were MSC(M). Functional flow cytometry demonstrated that these IFNγ-stimulated MSC(M) acquired an immunosuppressive phenotype. IFNγ-stimulated MSC(M) from HNC patients were found to express GDNF, WNT1, and R-spondin 1 as well as pro-angiogenesis and immunomodulatory cytokines. In mice, IFNγ-stimulated MSC(M) injection after radiation decreased the loss of acinar cells, decreased the formation of fibrosis, and increased salivary production. ConclusionsMSC (M) from previously treated HNC patients can be expanded for auto-transplantation and are functionally active. Furthermore IFNγ-stimulated MSC(M) express proteins implicated in salivary gland regeneration. This study provides preliminary data supporting the feasibility of using autologous MSC(M) from HNC patients to treat RT-induced salivary dysfunction

Developing symptom-specific dietary leaflets to address radiotherapy side effects using an eDelphi method

IntroductionPatients suffering from head and neck (HN) cancer undergoing Radiotherapy (RT) suffer from various debilitating side effects that greatly hinder their eating ability. This leads to patients having a poor nutritional status causing weight loss. This study aimed to assess if an e-Delphi method variation allowed efficiently developing dietary advice leaflets addressing these side effects and achieving a consensus among healthcare professionals. MethodsAn e-Delphi style approach was used. Six participants representing the professions working with HN patients were asked to give feedback on four symptom-specific dietary leaflets. These leaflets were designed based on a previous extensive literature review. After each round, the participants’ suggested changes were applied. Before applying major changes to the leaflet, the participants were asked to vote if they agreed with each major change. ResultsOverall consensus was reached after three rounds since all participants voted “highly likely” to use it in their clinical practice. Most suggestions by the participants agreed with the existing literature. The only change (accepted as a result of voting) that contradicted the literature was concerning sugar intake. ConclusionThe participants reached consensus and developed leaflets that were based on literature recommendations for use for patients that, in their opinion, were acceptable for clinical use. This e-Delphi variation proved to be efficient to achieve consensus among healthcare professionals regarding patient information tools. Implications for practiceThis eDelphi method is an efficient and effective way to revise and achieve consensus regarding the development of patient information material.

A QUASI-EXPERIMENTAL STUDY TO ASSESS THE EFFECTIVENESS OF TOPICAL APPLICATION OF HONEY ON ORAL MUCOSITIS AMONG HEAD AND NECK CANCER PATIENTS UNDERGOING RADIATION THERAPY IN TERTIARY CARE HOSPITAL OF AMRITSAR, PUNJAB.

Cancer is the leading cause of death around the world. Radiation therapy is made to kill growing cancer cells but certain normal cells get effected too, this damage to normal cell cause side effects of radiation therapy. The most debilitating side effect is radiation induced Oral Mucositis. This is major concern for attention, so there is need to provide conventional therapies to head and neck cancer patients to reduce the severity of oral mucositis. A Quasi-experimental study was conducted to assess the effectiveness of topical application of honey among 60 head and neck cancer patients undergoing radiation therapy at Sri Guru Ram Dass Institute of Medical Science and Research, Vallah, Amritsar, Punjab. Purposive sampling technique was used to collect data. The data wa

Implementation Readiness and Initial Effects of a Brief Mindfulness Audio Intervention Compared With a Brief Music Control During Daily Radiation Therapy for Prostate Cancer: A Randomized Pilot Study.

The most common and debilitating side effects of radiation therapy (RT) for prostate cancer (PC) are fatigue, sleep disturbance, anxiety, and depression. Previous research has reported palliative benefits from certain self-management approaches, such as mindfulness meditation. To develop, pre-test, and evaluate the feasibility, acceptability and initial benefit of brief, audio-based mindfulness delivered during daily RT for PC compared to a relaxing music control. Following intervention development, participants were randomized to either brief guided mindfulness audio recordings or a relaxing music control during daily RT. A pre-testing phase was first conducted to determine optimal program start time, length, and content most associated with retention. A final program (n = 26) was delivered daily, starting on day one of week 2 of RT and lasting 4 consecutive weeks. Feasibility was defined as ≥70% on enrollment rate, retention, and audio program adherence. Acceptability was measured with a 12-item post-study survey. A secondary focus compared between group changes on patient reported outcomes of fatigue, anxiety, depression, sleep disturbance, and related outcomes at baseline and follow up assessments. Descriptive statistics and general linear models were used. Overall, 76% (n = 38) of approached men enrolled. Pre-testing retention rates were <70% while the final program's retention rate was 89%. The majority of acceptability criteria were met in both conditions, with relatively higher ratings in the mindfulness arm. Compared to music controls, mindfulness participants demonstrated significantly less uncertainty intolerance at 4-weeks (P = .046, d = .95); and significantly lower fatigue scores (P = .049, d = 1.3) and lower sleep disturbance scores (P = .035, d = 1.1) at the 3months follow up. The final intervention met feasibility and acceptability criteria. Pre-testing refinements played a key role for optimal program delivery and retention. Audio-based mindfulness delivered during RT for PC hold potential to help decrease RT-related physical and emotional side effects.

Research Progress on Improving the Toxic Side Effects of Tumor Radiotherapy with Traditional Chinese Medicine

Research Progress on Improving the Toxic Side Effects of Tumor Radiotherapy with Traditional Chinese Medicine

Effect of propolis on oral mucositis in patients treated with radiotherapy: a literature review

Cancer is a major global public health problem, with increasing incidence. When detected early, life-saving treatments can be applied. Radiotherapy eliminates malignant cells but damages healthy tissues. A common oral side effect is oral mucositis: inflammation, ulcers, pain, difficulty ingesting nutrients, treatment interruption. Propolis, a natural product from bees, has wound healing, anti-inflammatory, antibiotic, and antioxidant properties. Studies indicate its effectiveness against radiation-induced oral mucositis. The objective of the present work was to analyze the effect of propolis in the treatment of oral mucositis in patients undergoing radiotherapy, based on the critical review of clinical and review studies. A literature review study was conducted on scientific articles found in databases such as PubMed, Web of Science, and Scopus, in order to obtain information to support the use of propolis as a complement to conventional treatment of oral mucositis in patients undergoing radiotherapy. Numerous studies have demonstrated the effectiveness of propolis in treating oral mucositis, especially when applied directly to the mucosa. Additionally, its use has been proven safe and does not cause adverse effects in patients. It is evident that oral mucositis is a common side effect of radiotherapy, which can occur from the first week of treatment, causing pain, difficulty swallowing, and even interruption of cancer treatment. Propolis represents a promising therapeutic option to improve and delay the onset of this condition, enhancing the quality of life of patients

Radiation-induced skin injury in the head and neck region: pathogenesis, clinics, prevention, treatment considerations and proposal for management algorithm.

Worldwide increase of head and neck cancers ranks these malignancies among top causes of cancer in human population. Radiation induced skin injury (RISI) is one of the major side effects of radiotherapy (RT). Skin of the neck is exposed to radiation due to necessity of therapeutic or prophylactic (elective) irradiation of neck lymph nodes and target organs, including the larynx and hypopharynx. The location of the neck exposes these regions of the skin to various additional exposomes such as ultraviolet radiation (UVR), pollution and cigarette smoke. There are many controversies or inconsistencies regarding RISI, from molecular aspects and therapy to terminology. There is lack of high-quality and large-sample studies in both forms of RISI: acute (aRISI) and chronic (cRISI). Finally, no gold standards in the management of aRISI and cRISI have been established yet. In this article, the authors discuss the pathogenesis, clinical picture, prevention and clinical interventions and present a proposed treatment algorithm.

Implications of oral dysbiosis and HPV infection in head and neck cancer: from molecular and cellular mechanisms to early diagnosis and therapy.

Head and neck cancer (HNC) is the sixth most common type of cancer, with more than half a million new cases annually. This review focuses on the role of oral dysbiosis and HPV infection in HNCs, presenting the involved taxons, molecular effectors and pathways, as well as the HPV-associated particularities of genetic and epigenetic changes and of the tumor microenvironment occurred in different stages of tumor development. Oral dysbiosis is associated with the evolution of HNCs, through multiple mechanisms such as inflammation, genotoxins release, modulation of the innate and acquired immune response, carcinogens and anticarcinogens production, generation of oxidative stress, induction of mutations. Thus, novel microbiome-derived biomarkers and interventions could significantly contribute to achieving the desideratum of personalized management of oncologic patients, regarding both early diagnosis and treatment. The results reported by different studies are not always congruent regarding the variations in the abundance of different taxons in HNCs. However, there is a consistent reporting of a higher abundance of Gram-negative species such as Fusobacterium, Leptotrichia, Treponema, Porphyromonas gingivalis, Prevotella, Bacteroidetes, Haemophilus, Veillonella, Pseudomonas, Enterobacterales, which are probably responsible of chronic inflammation and modulation of tumor microenvironment. Candida albicans is the dominant fungi found in oral carcinoma being also associated with shorter survival rate. Specific microbial signatures (e.g., F. nucleatum, Bacteroidetes and Peptostreptococcus) have been associated with later stages and larger tumor, suggesting their potential to be used as biomarkers for tumor stratification and prognosis. On the other hand, increased abundance of Corynebacterium, Kingella, Abiotrophia is associated with a reduced risk of HNC. Microbiome could also provide biomarkers for differentiating between oropharyngeal and hypopharyngeal cancers as well as between HPV-positive and HPV-negative tumors. Ongoing clinical trials aim to validate non-invasive tests for microbiome-derived biomarkers detection in oral and throat cancers, especially within high-risk populations. Oro-pharyngeal dysbiosis could also impact the HNCs therapy and associated side-effects of radiotherapy, chemotherapy, and immunotherapy. HPV-positive tumors harbor fewer mutations, as well as different DNA methylation pattern and tumor microenvironment. Therefore, elucidation of the molecular mechanisms by which oral microbiota and HPV infection influence the HNC initiation and progression, screening for HPV infection and vaccination against HPV, adopting a good oral hygiene, and preventing oral dysbiosis are important tools for advancing in the battle with this public health global challenge.

Outcomes of the Endoscopic Endonasal Approach for the Treatment of Clival Chordomas: A Single-Center Experience.

Objective Chordoma is a low-grade malignant tumor that originates from the remnant tissue of the embryonic notochord. Postoperative or definitive radiotherapy (RT) has been used to enhance local control. This study aims to assess the outcomes of the expanded endoscopic endonasal approach (EEA) for maximal removal of clival chordomas followed by RT for visualized residual or tumor recurrence. Materials and Methods A retrospective review was performed on consecutive patients with clival chordoma who underwent endoscopic endonasal resection in the otorhinolaryngology and neurosurgery departments, between 2016 and 2021. We included all patients with pathologically confirmed clival chordoma who were treated using the EEA. Patients who underwent combined external and endoscopic approaches or transcranial surgery were excluded. Results Seventeen patients were included in this study. Most of them had tumors located in the middle clivus. Regarding RT, the majority of patients underwent postoperative RT. Almost half of them underwent CyberKnife (CK) RT. None of them had severe toxicities (grade 3 or higher). Three patients died, resulting in a mortality rate of 17.6% none of them related to radiation side effect. The 2-year overall survival was 82.4% (mean standard error [SE] = 1.765, 95% confidence interval [CI] = 1.505-2.024), and the progression-free survival (PFS) was 76.5% (mean SE = 3.403, 95% CI = 2.791-4.016). No distal metastasis was reported in our series. Conclusion This series demonstrates that expanded endoscopic endonasal approach (EEA) for the resection of skull base chordomas, followed by CyberKnife radiosurgery, presents a viable alternative to proton beam therapy; however, further research is necessary to directly compare these modalities.

Early, non-invasive detection of radiation-induced lung injury using PET/CT by targeting CXCR4.

Radiation-induced lung injury (RILI) is a severe side effect of radiotherapy (RT) for thoracic malignancies and we currently lack established methods for the early detection of RILI. In this study, we synthesized a new tracer, [18F]AlF-NOTA-QHY-04, targeting C-X-C-chemokine-receptor-type-4 (CXCR4) and investigated its feasibility to detect RILI. An RILI rat model was constructed and scanned with [18F]AlF-NOTA-QHY-04 PET/CT and [18F]FDG PET/CT periodically after RT. Dynamic, blocking, autoradiography, and histopathological studies were performed on the day of peak uptake. Fourteen patients with radiation pneumonia, developed during or after thoracic RT, were subjected to PET scan using [18F]AlF-NOTA-QHY-04. The yield of [18F]AlF-NOTA-QHY-04 was 28.5-43.2%, and the specific activity was 27-33GBq/μmol. [18F]AlF-NOTA-QHY-04 was mainly excreted through the kidney. Significant increased [18F]AlF-NOTA-QHY-04 uptake in the irradiated lung compared with that in the normal lung in the RILI model was observed on day 6 post-RT and peaked on day 14 post-RT, whereas no apparent uptake of [18F]FDG was shown on days 7 and 15 post-RT. MicroCT imaging did not show pneumonia until 42days post-RT. Significant intense [18F]AlF-NOTA-QHY-04 uptake was confirmed by autoradiography. Immunofluorescence staining demonstrated expression of CXCR4 was significantly increased in the irradiated lung tissue, which correlated with results obtained from hematoxylin-eosin and Masson's trichrome staining. In 14 patients with radiation pneumonia, maximum standardized uptake values (SUVmax) were significantly higher in the irradiated lung compared with those in the normal lung. SUVmax of patients with grade 2 RILI was significantly higher than that of patients with grade 1 RILI. This study indicated that [18F]AlF-NOTA-QHY-04 PET/CT imaging can detect RILI non-invasively and earlier than [18F]FDG PET/CT in a rat model. Clinical studies verified its feasibility, suggesting the clinical potential of [18F]AlF-NOTA-QHY-04 as a PET/CT tracer for early monitoring of RILI.

Reduced mouth opening in patients with head and neck cancer treated with radiation therapy: an analysis of the Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad)

ObjectivesTrismus/reduced mouth opening (RMO) is a common side effect of radiotherapy (RT) for head and neck cancer (HNC). The objective was to measure RMO, identify risk factors for RMO, and determine its impact on quality of life (QOL). Patients and MethodsOraRad is an observational, prospective multicenter cohort study of patients receiving curative intent RT for HNC. Interincisal mouth opening measurements (n = 565) and patient reported outcomes were recorded before RT and every 6 months for 2 years. Linear mixed-effects models were used to evaluate change in mouth opening and assess the relationship between trismus history and change in QOL measures. ResultsInter-incisal distance decreased from a mean (SE) of 45.1 (0.42) mm at baseline to 42.2 (0.44) at 6-months with slight recovery at 18-months (43.3, 0.46 mm), but no additional improvement by 24-months. The odds of trismus (opening <35mm) were significantly higher at 6 months (OR=2.21, 95% CI: 1.30 to 3.76) and 12 months (OR=1.87, 95% CI: 1.08 to 3.25) compared to baseline. Females were more likely to experience trismus at baseline and during follow up (p<0.01). Patients with oral cavity cancer had highest risk for trismus at baseline and post-RT (p<0.01). RMO was associated with higher RT dose to primary site and receiving concomitant chemotherapy (p<0.01). Trismus was associated with self-reported difficulty opening the mouth and dry mouth (p<0.01). ConclusionsDecrease in mouth opening is a common treatment-related toxicity after RT with some recovery by 18-months. Trismus has a significant impact on survivor QOL. Statement of Clinical RelevanceDecrease in mouth opening is a common treatment related toxicity after RT, which has a significant impact on survivor QOL. Variability in restricted mouth opening after RT is related to specific patient, cancer, or treatment characteristics.

Role of microbiota in radiation-induced small-bowel damage.

Radiation-induced gastrointestinal damage is a common acute radiation syndrome. Previous studies have highlighted that Galectin-1 and Interleukin-6 (IL-6) are associated with flaking of small intestinal villi and intestinal radioresistance. Therefore, our goal is to study whether gut bacteria regulated by galectin-1 or IL-6 can mitigate radiation-induced small intestine damage. In this study, differences between galectin-1, sgp130-regulated and wild-type (WT) mice were analyzed by microbiome array. The effects of the Firmicutes/Bacteroidetes (F/B) ratio and the proportion of bacterial distribution at the phylum level were observed after 18 Gy whole abdomen radiation. Fecal microbiota transplantation was used to implant radioresistant gut flora into WT mice, and the number of viable small intestinal crypt foci was observed by immunohistochemistry. Fecal transplantation from galectin-1 knockout and sgp130 transgenic mice, with higher radiation resistance, into WT mice significantly increased the number of surviving small intestinal crypts. This radiation resistance, generated through gene regulation, was not affected by the F/B ratio. We initially found that the small intestinal villi of WT mice receiving radioresistant mouse fecal bacteria demonstrated better repair outcomes after radiation exposure. These results indicate the need for a focus on the identification and application of superior radioresistant bacterial strains. In our laboratory, we will further investigate specific radioresistant bacterial strains to alleviate acute side effects of radiation therapy to improve the patients' immune ability and postoperative quality of life.