Side Effects Of Radiotherapy Research Articles

Consequences of hyposalivation in relation to cancer treatment and early management of radiation-induced caries: case reports

Given the prevalence of head and neck carcinoma and the salivary changes induced by the oral side effects of radiotherapy, such patients are at higher risk/susceptibility of developing dental caries. Radiation-caries is often under-treated in patients undergoing cervicofacial radiotherapy, yet these lesions can increase the risk of osteoradionecrosis due to necessary subsequent dental extractions. Moreover, xerostomia is accompanied by difficulties with speech, chewing and swallowing. The prevention and/or early management of radiation-induced carious lesions is essential in preventing oral complications and improving patients' quality of life. Based on a French case series, this paper proposes a protocol for the dental management of radiation-induced carious lesions.

Automated acute skin toxicity scoring in a mouse model through deep learning.

This study presents a novel approach to skin toxicity assessment in preclinical radiotherapy trials through an advanced imaging setup and deep learning. Skin reactions, commonly associated with undesirable side effects in radiotherapy, were meticulously evaluated in 160 mice across four studies. A comprehensive dataset containing 7542 images was derived from proton/electron trials with matched manual scoring of the acute toxicity on the right hind leg, which was the target area irradiated in the trials. This dataset was the foundation for the subsequent model training. The two-step deep learning framework incorporated an object detection model for hind leg detection and a classification model for toxicity classification. An observer study involving five experts and the deep learning model, was conducted to analyze the retrospective capabilities and inter-observer variations. The results revealed that the hind leg object detection model exhibited a robust performance, achieving an accuracy of almost 99%. Subsequently, the classification model demonstrated an overall accuracy of about 85%, revealing nuanced challenges in specific toxicity grades. The observer study highlighted high inter-observer agreement and showcased the model's superiority in accuracy and misclassification distance. In conclusion, this study signifies an advancement in objective and reproducible skin toxicity assessment. The imaging and deep learning system not only allows for retrospective toxicity scoring, but also presents a potential for minimizing inter-observer variation and evaluation times, addressing critical gaps in manual scoring methodologies. Future recommendations include refining the system through an expanded training dataset, paving the way for its deployment in preclinical research and radiotherapy trials.

Association of nutritional counselling with the severity of radiation-induced oral mucositis in patients with nasopharyngeal carcinoma: a retrospective study

BackgroundRadiation oral mucositis (RIOM) is one of the most common side effects of radiotherapy (RT) in patients with nasopharyngeal carcinoma (NPC). The nutritional status of the body is an important factor affecting the efficacy of radiotherapy and chemotherapy, as well as the prognosis of patients. The aim of the study was to explore the relationship between nutrition counseling (NC) and radiation-induced oral mucositis (RIOM), and to provide a reference for the prevention and treatment of RIOM in clinical practice. MethodsWe conducted a retrospective cohort study using the data among 147 NPC patients who received radical radiotherapy. Patients were divided into NC group and control group and radiation-induced Oral Mucositis (RIOM) classification i.e. mild RIOM (grade 0–1 group) and severe RIOM (grade≥2 group). Univariate and multivariate analyses were used to analyze the association between baseline data of the patients and severity of RIOM. ResultsOf the 147 patients with NPC, there were 46.9% (69/147) patients who received NC, while control group accounted for 53.1% (78/147). There was no statistically significant difference in age, gender, stage, smoking, drinking, body mass index (BMI) before RT, Patient Generated Subjective Global Assessment (PG-SGA) score and Hospital Anxiety and Depression Scale (HADS) score between NC group and control group. However, there was a significant difference in the incidence of severe RIOM patients between NC group and control group (40.6% vs. 69.2%). Univariate analysis showed that NPC patients had PG-SGA score≥4 (P<0.001; HR : 0.14; 95% CI: 0.04–0.45), the amplitude of weight loss (WL) ≥3% (P<0.001; HR: 0.62; 95% CI: 0.50–0.77), lower hemoglobin (P=0.01; HR: 0.97; 95% CI: 0.95–0.99) and patients with NC (P<0.001; HR: 3.24; 95% CI: 1.64–6.40) were significantly associated with severe RIOM. Multivariate analysis showed that PG-SGA≥4 (P=0.23; HR: 0.23; 95% CI: 0.06–0.86) and WL≥3% (P<0.001; HR: 0.63; 95% CI: 0.50–0.80) were risk factors for severe RIOM, whereas receiving nutrition consultation was a protective factor (P=0.03; HR: 2.49; 95% CI: 1.09–5.66). ConclusionNC was beneficial in reducing severe RIOM and PG-SGA≥4. WL≥3% exacerbate severe RIOM.

Ultrasound Findings After Breast Cancer Radiation Therapy: Cutaneous, Pleural, Pulmonary, and Cardiac Changes.

External beam radiation therapy (RT) can induce toxicity in patients surgically treated for breast cancer. Modern irradiation techniques have lowered the incidence and severity of radiation-induced injuries; however, their side effects on normal tissues remain challenging. This review illustrates early and late changes observed using ultrasound (US) imaging, including echocardiography, at the skin, muscle, pleura, lungs, and heart levels. The US findings and the potential role of this technique in detecting and grading early and late complications of RT are highlighted in this article. US has proven useful in the differential diagnosis of post-RT complications, including but not limited to cancer recurrence and toxicity from other sources, such as anticancer drugs. Additionally, considering the progressive nature of RT-induced injury, early detection of toxicity may be helpful in the individual stratification of damage risk and serve as a tool for patient screening and management. In these cases, US can be used as a radiation-free biomarker of RT side effects at the subclinical stage.

Heart is a heavy burden: cardiac toxicity in radiation oncology.

Over the years, radiotherapy has seen continual improvements and has become a standard treatment for most malignant tumors. Cardiotoxicity is a well-known radiotherapy side effect, leading to the risk of long-term morbidity and mortality in cancer survivors. Therefore, minimizing radiotherapy-related cardiotoxicity remains an important challenge in cancer care management. Indeed, multiple dose constraints were proposed for the heart and its substructures. In addition, sparing techniques were developed to reduce the exposure of the heart to ionizing radiation and are currently used in daily clinical routine. The purpose of this review is to summarize the current knowledge about radiation-induced cardiotoxicity, to discuss the previously cardiac dose constraints, and to evaluate the various management strategies.

Immunomodulatory hydrogel patches loaded with curcumin and tannic acid assembled nanoparticles for radiation dermatitis repair and radioprotection

Radiation dermatitis, as a major side effect of radiotherapy, is a form of skin injury linked to the production of reactive oxygen species (ROS). Development of functional patches with excellent ROS scavenging ability and biosafety is crucial for radioactive dermatitis repair. Herein, we present a nanohybrid hydrogel patch composed with natural-derived substances. The patch possesses dual functionalities of chemically scavenging ROS and physically absorbing radiation, thereby alleviating radiation damage. Curcumin@tannic acid (Cur@TA) nanoparticles are synthesized through spontaneous coordination of TA and iron ions (Fe3+), enabling the encapsulation of Cur. The nanoparticles are then loaded into gelatin methacryloyl (GelMA) hydrogel patches, which endow the hydrogel with tissue adhesion as well as photothermal properties. Simultaneously, the patch exhibits powerful ROS scavenging capability and promotes M2 polarization of macrophages. Additionally, the high-water content of the GelMA hydrogel enables physical absorption of low-energy X-rays, providing radiation shielding. Based on these characteristics, we have demonstrated the augmented therapeutic efficacy of the hydrogel patch loaded with Cur@TA nanoparticles in the mouse model of radiation dermatitis. Our findings introduce a novel therapeutic approach for radiation protection and treatment, with potential clinical applications.

Radiotherapy plus lenvatinib versus radiotherapy plus sorafenib for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study.

Portal vein tumor thrombus (PVTT) occurs frequently in hepatocellular carcinoma (HCC) patients. However, there is currently no satisfactory treatment. Radiotherapy (RT) and tyrosine kinase inhibitors (TKI) are currently commonly used. However, whether their combined use provides a survival benefit is debatable. This retrospective study compared the efficacy and safety between radiotherapy plus lenvatinib (RT + L) and radiotherapy plus sorafenib (RT + S) in the treatment of hepatocellular carcinoma with portal vein tumor thrombus (PVTT). Among patients with PVTT who received RT + L or RT + S between March 2017 and September 2022, the primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse effects. The prognostic factors were also assessed. The analysis included 152 patients (RT + L: 48; RL: 25; RT + S: 55; S: 24). Compared with the RT + S group, the RT + L group had a longer OS and PFS. Among patients with type I/II PVTT, the median OS times were 19.8 months and 13.5 months (p = 0.047) and the median PFS was 12.3 months and 7.3 months (p = 0.042), respectively. And the median OS of the patients with type I/II PVTT were 14.4 months and 8.3 months (p = 0.030) and the median PFS was 8.3 months and 6.2 months (p = 0.026). ORR and DCR in RT + L group (25.0% and 75.0%) were also little higher than those in RT + S group (20.0% and 70.9%), but not statistically significant. In univariate analysis, etiology, Type of PVTT, alpha-fetoprotein (AFP) level, Child-Pugh score, and treatment method influenced OS. Multivariate analysis confirmed that treatment method, etiology, alpha-fetoprotein (AFP) level, and Child-Pugh score were independent prognostic factors for OS. Similar safety profiles were observed in the RT + L and RT + S groups. The most common adverse events were myelosuppression, decreased liver function, fatigue, diarrhea, nausea, and vomiting. Most adverse reactions were grade 1-2. The side effects of radiotherapy plus lenvatinib were acceptable. Compared to RT + S, RT + L had good efficacy in the treatment of hepatocellular carcinoma with PVTT. Validation is needed in prospective studies with larger sample sizes.

Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade

The efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5–2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8+ T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations.

Radiation-Induced Intraosseous Malignant Peripheral Nerve Sheath Tumor: A Case Report.

The significance of radiation therapy in cancer treatment comes with associated complications, including fibrosis, osteonecrosis, and the development of secondary malignancies, such as malignant peripheral nerve sheath tumors (MPNSTs). We emphasize the importance of understanding these complications for an effective patient management. We report a 47-year-old man with a history of squamous cell carcinoma of the tongue, treated with surgery, chemotherapy, and radiation therapy. The patient later presented with symptoms that led to the discovery of an intraosseous MPNST. Histopathological examination revealed characteristic features of MPNST, including spindle cells arranged is sweeping fascicles with contrasting hypercellular and hypocellular areas, producing a marble-like pattern, with atypical wavy, buckled, hyperchromatic nuclei, and brisk mitotic activity. Immunohistochemical analysis showed patchy positive staining for S100 and SOX10, and a complete loss of H3K27me3 expression. This report underscores the challenge of diagnosing secondary malignancies post-radiation therapy and the importance of careful histological examination to differentiate them from other conditions. In conclusion, radiation-induced secondary malignancies are a significant late side effect of radiation therapy that can profoundly impact treatment decision-making and requires a high index of suspicion during post radiation surveillance. Malignant peripheral nerve sheath tumor serves as a pertinent example, highlighting the importance of considering long-term risks when developing optimal management plans for cancer patients.

Barriers to the Completion of Radiation Therapy in Cervical Cancer Treatment in Nigeria: A Review of Socioeconomic, Geographical, and Psychosocial Factors.

Cervical cancer is a major health concern in Nigeria, where it is one of the primary causes of cancer-related deaths among women. Despite the crucial role of radiation therapy in treating cervical cancer, many patients in Nigeria do not complete their prescribed treatment courses. This review examines the barriers contributing to this issue. Factors such as low awareness and utilization of Pap smears, inadequate HPV vaccination, financial constraints, insufficient radiotherapy infrastructure, and the psychological burden of cancer treatment are explored. Limited screening and vaccination efforts exacerbate the high incidence of cervical cancer in Nigeria. Financial barriers are a primary obstacle, with many patients unable to afford the high cost of radiotherapy. Nigeria's radiotherapy infrastructure is severely lacking leading to significant treatment delays and cancellations. Geographical barriers further complicate access, as many patients must travel long distances to reach treatment centers. Psychosocial issues, including anxiety and depression, significantly impact treatment adherence and completion. These psychological factors, coupled with the physical side effects of radiotherapy, contribute to high rates of treatment interruption. To address these challenges, the review suggests enhancing cervical cancer prevention through increased human papillomavirus (HPV) vaccination and screening, expanding radiotherapy capacity by increasing the number of treatment centers, and providing comprehensive support systems to address financial and psychosocial barriers. By implementing these strategies, it is possible to improve treatment adherence and outcomes for cervical cancer patients in Nigeria.

Patients-Reported Outcomes of Acute Side Effects During Head and Neck Cancer Radiotherapy: A Cross-Sectional Study at Andalas University Hospital Padang

Background: Head and neck cancer is a malignancy originating from the upper aerodigestive tract. Head and neck cancer patients undergoing radiotherapy using brachytherapy, 2DRT, 3CDRT, and IMRT techniques. Patients undergoing radiotherapy will experience several acute side effects consisting of mucositis, dysphagia, xerostomia, and dermatitis. This is influenced by the technique and dose given. This study aims to grade and time the acute side effects of radiotherapy for head and neck cancer at the Andalas University Hospital Padang. Methods: A quantitative descriptive method with a cross-sectional approach is used. Secondary data with a total sample of 88 patients. This research uses medical record data and is analyzed using statistical analysis methods. Results: This study found that the most head and neck cancer patients who underwent radiotherapy were male 57 (64.8%) patients, nasopharyngeal subsite 41 (46.6%) patients with non-keratinizing nasopharyngeal carcinoma 32 (36.4%) patients. The most common radiotherapy technique for head and neck cancer was IMRT in 58 (65.9%) patients with a dose of 61-70 Gy in 78 (88.6%) patients and the most common stage was IV A in 51 (58%) patients. Patients did not undergo chemotherapy treatment in 51 (58%) and surgery in 69 (78.4%). Body mass index (BMI) before radiotherapy was normal in 74 (84.1%) patients and after radiotherapy became underweight in 57 (64.8%) patients resulting in weight loss 1 kg in 83 (94.3%) patients. The highest grade of radiotherapy side effects was grade 1 which consisted of mucositis 84 (95.5%), dysphagia 83 (94.3%), xerostomia 78 (88.6%), and dermatitis 78 (88.6%) patients. The most frequent timing of mucositis side effects occurred in the 3rd week in 40 (45%) patients, dysphagia in the 3rd week in 41 (47%) patients, xerostomia in the 3rd week in 33 (38%) patients, and dermatitis at week 6 in 24 (27%) patients. Conclusions: Patients with head and neck cancer who undergo radiotherapy from week 1 to week 7 will experience side effects, including mucositis, dysphagia, xerostomia, and dermatitis. The average side effect appears in the 3rd week with grade 1.

Prediction of new-onset atrial fibrillation in patients with non-small cell lung cancer treated with curative-intent conventional radiotherapy

BackgroundAtrial fibrillation (AF) is an important side effect of thoracic Radiotherapy (RT), which may impair quality of life and survival. This study aimed to develop a prediction model for new-onset AF in patients with Non-Small Cell Lung Cancer (NSCLC) receiving RT alone or as a part of their multi-modal treatment. Patients and MethodsPatients with stage I-IV NSCLC treated with curative-intent conventional photon RT were included. The baseline electrocardiogram (ECG) was compared with follow-up ECGs to identify the occurrence of new-onset AF. A wide range of potential clinical predictors and dose-volume measures on the whole heart and six automatically contoured cardiac substructures, including chambers and conduction nodes, were considered for statistical modeling. Internal validation with optimism-correction was performed. A nomogram was made. Results374 patients (mean age 69 ± 10 years, 57 % male) were included. At baseline, 9.1 % of patients had AF, and 42 (11.2 %) patients developed new-onset AF. The following parameters were predictive: older age (OR=1.04, 95 % CI: 1.013–1.068), being overweight or obese (OR=1.791, 95 % CI: 1.139–2.816), alcohol use (OR=4.052, 95 % CI: 2.445–6.715), history of cardiac procedures (OR=2.329, 95 % CI: 1.287–4.215), tumor located in the upper lobe (OR=2.571, 95 % CI: 1.518–4.355), higher forced expiratory volume in 1 s (OR=0.989, 95 % CI: 0.979–0.999), higher creatinine (OR=1.008, 95 % CI: 1.002–1.014), concurrent chemotherapy (OR=3.266, 95 % CI: 1.757 to 6.07) and left atrium Dmax (OR=1.022, 95 % CI: 1.012–1.032). The model showed good discrimination (area under the curve = 0.80, 95 % CI: 0.76–0.84), calibration and positive net benefits. ConclusionThis prediction model employs readily available predictors to identify patients at high risk of new-onset AF who could potentially benefit from active screening and timely management of post-RT AF.

Caloric Restriction Diet Attenuates Systemic Bone Fragility after Radiotherapy.

Bone fragility is a well-documented long-term side effect of radiotherapy, which currently has no preventative treatments. In this study, we applied a caloric restriction (CR) diet to attenuate both local and systemic bone loss after irradiation (RTx) in an established female Balb/c mouse model (4 consecutive daily doses of 5 Gy to the right hindlimb only). CR mice were tapered down to a 30% reduced calorie diet (RTx/CR) one week before irradiation, while regular diet (RD) mice received food ad libitum (RTx/RD). Unirradiated (sham) mice received either a 30% CR diet (SH/CR) or received food ad libitum (SH/RD). Irradiated, contralateral, and unirradiated hindlimbs were evaluated at 2, 4, and 8 weeks postirradiation using micro-computed tomography (μCT) to assess bone morphology and 3-point bending to quantify femur strength. Histological analysis of irradiated and unirradiated tibiae was performed to examine general bone tissue cytology and serum biomarker analysis was performed using terminal blood draw samples. After treatment, femur strength and metaphyseal bone quantity was decreased in irradiated and contralateral femora of RTx/RD mice compared to SH/RD femurs; this finding is consistent with previous studies. RTx/CR mice had positive effects when compared to RTx/RD mice, including increased strength relative to body mass in both the irradiated and contralateral limb, increased trabecular bone mass, and decreased marrow adiposity. However, a number of adverse effects were also observed, including a significant decrease in body mass and decreased cortical bone. Overall, CR shows promise as a preventative treatment for postirradiated bone fragility, yet questions remain to be addressed in future studies. Ideal diet duration, impact to normal tissue, and mechanism of action must be explored to better understand the clinical implication of a CR diet.

Utilizing CT imaging for evaluating late gastrointestinal tract side effects of radiotherapy in uterine cervical cancer: a risk regression analysis

BackgroundRadiotherapy (RT) is effective for cervical cancer but causes late side effects (SE) to nearby organs. These late SE occur more than 3 months after RT and are rated by clinical findings to determine their severity. While imaging studies describe late gastrointestinal (GI) SE, none demonstrate the correlation between the findings and the toxicity grading. In this study, we demonstrated the late GI toxicity prevalence, CT findings, and their correlation.MethodsWe retrospectively studied uterine cervical cancer patients treated with RT between 2015 and 2018. Patient characteristics and treatment(s) were obtained from the hospital’s databases. Late RTOG/EORTC GI SE and CT images were obtained during the follow-up. Post-RT GI changes were reviewed from CT images using pre-defined criteria. Risk ratios (RR) were calculated for CT findings, and multivariable log binomial regression determined adjusted RRs.ResultsThis study included 153 patients, with a median age of 57 years (IQR 49–65). The prevalence of ≥ grade 2 RTOG/EORTC late GI SE was 33 (27.5%). CT findings showed 91 patients (59.48%) with enhanced bowel wall (BW) thickening, 3 (1.96%) with bowel obstruction, 7 (4.58%) with bowel perforation, 6 (3.92%) with fistula, 0 (0%) with bowel ischemia, and 0 (0%) with GI bleeding. Adjusted RRs showed that enhanced BW thickening (RR 9.77, 95% CI 2.64–36.07, p = 0.001), bowel obstruction (RR 5.05, 95% CI 2.30–11.09, p < 0.001), and bowel perforation (RR 3.82, 95% CI 1.96–7.44, p < 0.001) associated with higher late GI toxicity grades.ConclusionsOur study shows CT findings correlate with grade 2–4 late GI toxicity. Future research should validate and refine these findings with different imaging and toxicity grading systems to assess their potential predictive value.

83 Prospective Evaluation of Gastrointestinal and Genitourinary Side Effects of Pelvic Radiotherapy: Association Between Patient-Reported Outcomes and Clinician-Reported Outcomes with a View to Improving Quality of Care

83 Prospective Evaluation of Gastrointestinal and Genitourinary Side Effects of Pelvic Radiotherapy: Association Between Patient-Reported Outcomes and Clinician-Reported Outcomes with a View to Improving Quality of Care

Oxytocin: A Shield against Radiation-Induced Lung Injury in Rats.

Radiation-induced lung injury (RILI), a serious side effect of thoracic radiotherapy, can lead to acute radiation pneumonitis (RP) and chronic pulmonary fibrosis (PF). Despite various interventions, no effective protocol exists to prevent pneumonitis. Oxytocin (OT), known for its anti-inflammatory, antiapoptotic, and antioxidant properties, has not been explored for its potential in mitigating RILI. This study involved 24 female Wistar albino rats, divided into three groups: control group, radiation (RAD) + saline, and RAD + OT. The RAD groups received 18 Gy of whole-thorax irradiation. The RAD + OT group was treated with OT (0.1 mg/kg/day) intraperitoneally for 16 weeks. Computerizing tomography (CT) imaging and histopathological, biochemical, and blood gas analyses were performed to assess lung tissue damage and inflammation. Histopathological examination showed significant reduction in alveolar wall thickening, inflammation, and vascular changes in the RAD + OT group compared to the RAD + saline group. Biochemical analysis revealed decreased levels of TGF-beta, VEGF, and PDGF, and increased BMP-7 and prostacyclin in the RAD + oxytocin group (p < 0.05). Morphometric analysis indicated significant reductions in fibrosis, edema, and immune cell infiltration. CT imaging demonstrated near-normal lung parenchyma density in the RAD + oxytocin group (p < 0.001). Oxytocin administration significantly mitigates radiation-induced pneumonitis in rats, implying that is has potential as a therapeutic agent for preventing and treating RILI.

CT-based radiomics for predicting breast cancer radiotherapy side effects

Skin inflammation with the potential sequel of moist epitheliolysis and edema constitute the most frequent breast radiotherapy (RT) acute side effects. The aim of this study was to compare the predictive value of tissue-derived radiomics features to the total breast volume (TBV) for the moist cells epitheliolysis as a surrogate for skin inflammation, and edema. Radiomics features were extracted from computed tomography (CT) scans of 252 breast cancer patients from two volumes of interest: TBV and glandular tissue (GT). Machine learning classifiers were trained on radiomics and clinical features, which were evaluated for both side effects. The best radiomics model was a least absolute shrinkage and selection operator (LASSO) classifier, using TBV features, predicting moist cells epitheliolysis, achieving an area under the receiver operating characteristic (AUROC) of 0.74. This was comparable to TBV breast volume (AUROC of 0.75). Combined models of radiomics and clinical features did not improve performance. Exclusion of volume-correlated features slightly reduced the predictive performance (AUROC 0.71). We could demonstrate the general propensity of planning CT-based radiomics models to predict breast RT-dependent side effects. Mammary tissue was more predictive than glandular tissue. The radiomics features performance was influenced by their high correlation to TBV volume.

Salivary gland organoid transplantation as a therapeutic option for radiation-induced xerostomia

BackgroundXerostomia is a pathological condition characterized by decreased salivation due to salivary gland dysfunction and is frequently attributed to irreversible damage as a side effect of radiation therapy. Stem cell–derived organoid therapy has garnered attention as a promising avenue for resolving this issue. However, Matrigel, a hydrogel commonly used in organoid culture, is considered inappropriate for clinical use due to its undefined composition and immunogenicity. In this study, we aimed to develop a method for culturing collagen-based human salivary gland organoids (hSGOs) suitable for clinical applications and evaluated their therapeutic effectiveness.MethodsHuman salivary gland stem cells were isolated from the salivary gland tissues and cultured in both Matrigel and collagen. We compared the gene and protein expression patterns of salivary gland–specific markers and measured amylase activity in the two types of hSGOs. To evaluate the therapeutic effects, we performed xenogeneic and allogeneic transplantation using human and mouse salivary gland organoids (hSGOs and mSGOs), respectively, in a mouse model of radiation-induced xerostomia.ResultshSGOs cultured in Matrigel exhibited self-renewal capacity and differentiated into acinar and ductal cell lineages. In collagen, they maintained a comparable self-renewal ability and more closely replicated the characteristics of salivary gland tissue following differentiation. Upon xenotransplantation of collagen-based hSGOs, we observed engraftment, which was verified by detecting human-specific nucleoli and E-cadherin expression. The expression of mucins, especially MUC5B, within the transplanted hSGOs suggested a potential improvement in the salivary composition. Moreover, the allograft procedure using mSGOs led to increased salivation, validating the efficacy of our approach.ConclusionsThis study showed that collagen-based hSGOs can be used appropriately in clinical settings and demonstrated the effectiveness of an allograft procedure. Our research has laid the groundwork for the future application of collagen-based hSGOs in allogeneic clinical trials.

Evaluation of ocular and systemic endpoints after radiation of posterior uveal melanoma – A systematic review and meta-analysis

BackgroundDue to the large number of radiotherapeutic options for treatment of posterior uveal melanoma (UM), advantages of each option regarding important clinical endpoints have yet to be determined. Therefore, objective of this systematic review was to analyze the numerous pro- and retrospective cohort studies focusing on the efficacy of different radiotherapeutic options for UM in adults, considering local tumor control, overall survival, visual acuity, eye preservation, metastasis, radiation side effects and dose rates. MethodsThe Review was performed based on the Cochrane Handbook of Systematic Reviews. The PubMed database was searched for studies published from January 1st, 2000, up to December 31st, 2021. Research, study selection and critical appraisal was performed by two reviewers. The risk of bias assessment was performed through the revised Cochrane risk of bias tools RoB 2 and ROBINS-I. A meta-analysis of proportions was performed using R (R version 4.1.3, library: meta, procedure: metaprop). This systematic review was registered with Prospero (ID CRD42022311758). ResultsOf 4886 studies identified in the database, a total of 20 studies with 4979 participants were included in the qualitative synthesis. Through critical appraisal with ROBINS-I and RoB 2, studies received a ‘moderate’, ‘serious’ or ‘some concerns’ overall risk of bias. Heterogeneity analysis allowed for meta-analysis of proportion of 3 outcome-therapy combinations: local tumor control with I-125 Brachytherapy (proportion: 0.94, CI 95 %: 0.91–0.98), local tumor control with proton therapy (proportion: 0.96, CI 95 %: 0.92–1.00) and eye preservation with I-125 brachytherapy (proportion: 0.91, CI 95 %: 0.88–0.93). This shows local tumor control to be at 94 % with I-125 brachytherapy and at 96 % with proton therapy, as well as an eye preservation rate of 91 % with I-125 brachytherapy. DiscussionThe evaluation of outcomes of radiotherapy in UM is limited because of missing data on radiation doses as well as great heterogeneity of study protocols. Radiation therapy outcomes are so far not comparable. Therefore, we recommend for upcoming studies on this topic to provide the biological effective dose (BED) or the equivalent dose in 2 Gy fractions (EQD2) per eye structure, thereby enabling a comparison of outcomes of different forms of radiation therapy.

Tongue squamous cell carcinoma treated by 5-aminolevulinic acid administrated through Microdrop method

BackgroundPostoperative recurrence of tongue squamous cell carcinoma (TSCC) has always been a clinical problem for patients and doctors. Surgery and radiotherapy are the main treatment methods for TSCC, but reoperation often leads to functional impairment. Side effects of radiotherapy include mucosal gland damage, dry mouth, weakened or lost taste. Improved treatment is needed. ObjectiveTo evaluate the clinical outcome of a patient with TSCC treated with Microdrop aminolevulinic acid (ALA) photodynamic treatment (PDT) twice. MethodsALA was dissolved in 5 % lidocaine and the concentration of ALA was 20 % by Microdrop method. Then, the tumor tissue was expanded 1 cm outward, and the injection points were evenly distributed with an upper and lower left and right interval of 2–3 mm. The 1 ml syringe was used to perform the injection in the skin of the tumor area, and there was a small cuticle at each injection point. A pathologically confirmed patient with TSCC received twice Microdrop ALA-PDT treatments, which were evaluated at 1 month and 4 months later. ResultsAfter 3 h of Microdrop ALA injection, the wavelength of semiconductor laser was set to 630 nm, and the energy of 300 mW /cm2 was irradiated for 30 min. After two treatments, the lesions were not visible, and no recurrence occurred after 4 months of follow-up. The patient's tongue function was well preserved and the cosmetic effect was good. ConclusionMicrodrop ALA-PDT may be effective in the salvage treatment of select tongue squamous cell carcinoma.