Radiotherapy In Cancer Patients Research Articles

The potential characteristics of the sense of coherence in cancer radiotherapy patients and its correlation with coping strategies.

To explore the potential profiles of the sense of coherence (SOC) among cancer radiotherapy patients using latent profile analysis (LPA) and to characterize each category. Additionally, we investigated the correlation between different profiles of the SOC and the coping strategies. Convenience sampling method was used to select 241 cancer radiotherapy patients hospitalized in a specialized hospital in Shanghai from March 2023 to October 2023 as research subjects. The study utilized a general information questionnaire, the Sense of Coherence Scale-13 (SOC-13), and the Medical Coping Modes Questionnaire (MCMQ) for the survey. LPA identified three potential profiles based on varying levels of SOC: "Low level-High meaningfulness" group (n = 38, 15.8%), "Moderate level-High manageability" group (n = 104, 43.2%), and "High level-Balanced" group (n = 99, 41%). Age (OR = 6.544, P = 0.015), residence (OR = 0.217, P = 0.004), initial recurrence (OR = 2.869, P = 0.028), and side effects (OR = 2.862, P = 0.015) were significant predictors. A lower level of the SOC was significantly associated with higher scores in acceptance-resignation (P < 0.001). The SOC among cancer radiotherapy patients can be divided into three potential profiles. Younger patients with side effect have lower levels of the SOC. Adopting a acceptance-resignation coping strategies is related to a lower SOC, suggesting that enhancing the level of the SOC plays a positive role in helping patients cope with stressful events.

Current issues of using metronidazole in clinical practice. Effects and directions of clinical application

Metronidazole is an important drug in clinical and outpatient practice due to its broad antibacterial and antiprotozoal properties. Metronidazole is effective against anaerobic bacteria and some protozoa such as Trichomonas vaginalis and Giardia lamblia. This makes it indispensable in the treatment of infections of various etiologies. The review article contains current information about the clinical pharmacology of metronidazole and its place in the pharmacotherapy of infectious diseases. General and specific issues of the use of metronidazole in the practice of GPs, surgeons, obstetrician-gynecologists, and other specialists are considered. Information is provided on the possibilities and indications for the use of metronidazole in the eradication of Helicobacter pylori, in radiation therapy for cancer patients, dermatovenereology, dentistry, treatment of protozoal infections, as well as in alcoholism. Metronidazole is often used in combination with other antibiotics to enhance the antimicrobial effect, especially in cases of mixed infections or when it is necessary to cover a wider range of pathogens. In surgical practice, metronidazole is used to prevent infectious complications after operations on the abdominal and pelvic organs, where the risk of anaerobic infection is high. In an environment of increasing antibiotic resistance, metronidazole remains an effective treatment against many anaerobic pathogens, highlighting its place in modern practice.

Combining proteomics and Phosphoproteomics to investigate radiation-induced rectal fibrosis in rats and the effects of pSTAT3 inhibitor S3I-201 on human intestinal fibroblasts

ObjectiveTo investigate the regulatory mechanisms of radiation-induced rectal fibrosis (RIRF) and assess the therapeutic potential of S3I-201. MethodsSprague-Dawley rats were divided into control and radiation groups, with the latter exposed to 20 Gray pelvic X-rays. After 10 weeks, rectal tissues were analyzed using tandem mass tag (TMT) proteomics and phosphoproteomics. Pathway enrichment was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, with secondary annotation using Cluego. Representative proteins and their phosphorylated counterparts were validated through immunoblotting in another cohort. STAT3 levels in rectal tissues from irradiated and non-irradiated colorectal cancer patients were examined, and the effects of S3I-201 on human rectal fibroblasts were evaluated. ResultsThe radiation group showed significant inflammatory responses and collagen deposition in the rat rectal walls. Enrichment analysis revealed that radiation-induced proteins and phosphoproteins were primarily involved in extracellular matrix-receptor interaction and the MAPK signaling pathway. Immunoblotting indicated increased expression of p-CAMKII, p-MRACKS, p-Cfl1, p-Myl9, and p-STAT3 in the radiation group compared to the control, while p-AKT1 expression decreased. Elevated phosphorylation of STAT3 was observed in submucosal fibroblasts of the post-radiation human rectum. S3I-201 specifically inhibited STAT3 phosphorylation and suppressed activation of human rectal fibroblasts, also inhibiting the pro-fibrotic effects of the classical TGF-β/Smad/CTGF pathway. ConclusionBy integrating phosphoproteomics and proteomics, this study elucidated the protein regulatory network of RIRF and identified the potential therapeutic targets, including phosphoproteins such as STAT3 in managing RIRF. SignificanceIn our research, we employed TMT labeling alongside LC-MS/MS techniques to comprehensively explore the proteomic and phosphoproteomic landscapes in rat models of radiation-induced intestinal fibrosis (RIRF). Our analysis revealed the function and pathways of proteins and phosphorylated proteins triggered by radiation, as well as those with protective roles. We mapped a network of interactions among these proteins and validated key protein expression levels using quantitative methods. Furthermore, we investigated STAT3 as a potential therapeutic target, assessing the efficacy of the inhibitor S3I-201 in laboratory settings, and highlighting its potential for RIRF treatment. Overall, our findings provide groundbreaking insights into the mechanisms underlying RIRF, paving the way for the development of future antifibrotic therapies.

Management of laryngeal chondroradionecrosis: A single-center experience.

Laryngeal chondroradionecrosis (LCRN) is a rare but severe complication of radiation therapy. The study aimed to review the management of LCRN and evaluate the clinical benefit of hyperbaric oxygen therapy (HBOT). We retrospectively analyzed all radiation-induced LCRN patients between 2006 and 2019 at a tertiary medical center. Diagnosis was based on signs and symptoms of Chandler's classification, imaging, and/or histopathology report. The primary outcome was improvement in Chandler's grade after HBOT. Of 678 irradiated laryngeal cancer patients, 29 (4.3%) were diagnosed with LCRN. The most common primary management was tracheostomy with intravenous steroids and antibiotics (59%). Ten patients received HBOT (34.5%), and six underwent total laryngectomy (21%). In HBOT-treated patients, Chandler's grade significantly improved from a median of 4 (range 2-4) to 2.5 (range 1-4; p = 0.005). HBOT may benefit in the management of patients with persistence and unresponsive symptoms of LCRN following radiation therapy for laryngeal SCC.

Increased dicentric chromosome in peripheral lymphocytes is related to acute skin toxicity induced by radiotherapy in cancer patients

ObjectiveTo investigate the impacts of radiotherapy (RT) on dicentric chromosomes in peripheral blood lymphocytes of cancer patients, in order to explore the relationship between dicentric chromosomes and RT-induced adverse reactions. MethodsA total of 33 cancer patients after postoperative RT in a tertiary hospital from October 2021 to May 2022 were enrolled in this study. These patients were grouped according to the grade of acute skin and marrow toxicities determined based on the scoring criteria for acute morbidity developed by the Radiation Therapy Oncology Group (RTOG). Peripheral blood samples were collected from each patient before and after RT, followed by whole-blood lymphocyte culture and chromosome analysis. Dicentric chromosomes were searched automatically using a high-throughput chromosome analysis system and were then confirmed manually. Finally, the relationships of the frequency of dicentric chromosomes (also referred to as the dic frequency) with acute skin and marrow toxicities were assessed. ResultsAfter RT, the mean counts of white blood cells (WBCs), lymphocytes, and platelets significantly decreased, while the red blood cells (RBCs) and hemoglobin notably increased (P ​< ​0.001), while the dic frequency was elevated remarkably, significantly higher in patients with higher-grade (>1) acute skin toxicities compared to those with lower-grade (=1) acute skin toxicities (Z ​= ​−1.985, P ​= ​0.047). However, no significant relationship was observed between the dic frequency and acute marrow toxicity after RT (P ​> ​0.05). Logistic regression showed that radiosensitivity denoted by the post-RT dic frequency in peripheral blood lymphocytes produced insignificant impacts on the severity of RT-induced acute skin toxicities (P ​= ​0.060). ConclusionThe elevated dic frequency in peripheral blood lymphocytes of cancer patients with higher-grade acute skin toxicities suggests enhanced radiosensitivity of peripheral blood lymphocytes, which is associated with the occurrence of RT-induced adverse reactions.

Evaluation of cardiac implantable electronic device lead parameters before and after radiotherapy.

Radiotherapy in cancer patients with a pacemaker or an implantable cardioverter defibrillator might damage the device and possibly result in malfunction of the device. We aimed to examine device malfunction and change in lead parameters in this group. The medical records of pacemaker/implantable cardioverter defibrillator patients who underwent radiotherapy at Aalborg University Hospital between July 1, 2016, and June 30, 2021, were reviewed. Treatment was planned according to risk of device malfunction, assessed using local guidelines. Bootstrap linear regression was used to identify possible differences in lead parameters depending on beam energy and anatomical location. One hundred nine patients with a pacemaker/implantable cardioverter defibrillator who received a total of 122 radiotherapy courses in the study period were identified. No device malfunctions or significant changes in lead parameters during radiotherapy were observed. Only the left ventricle lead threshold and impedance were found to be significantly different when compared by beam energy; however, these changes were relatively small and unlikely to be of clinical relevance. No device malfunction or clinically relevant changes in lead parameters were identified in this study, suggesting that radiotherapy of pacemaker/implantable cardioverter defibrillator patients can be regarded as safe when following relevant safety precautions.

Psychological Intervention During Radiotherapy for Cancer Patients

Psychological Intervention During Radiotherapy for Cancer Patients

Analysis of Treatment Response With Proteins Related to Tumor Immunity in Postoperative Irradiated Cervical Cancer Patients.

This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.

Preventing skeletal related events with radiation therapy in cancer patients with bone metastases

Preventing skeletal related events with radiation therapy in cancer patients with bone metastases

Translation and Validation of the Greek Version of the Questionnaire for Assessing Fear of Radiotherapy in Oncology Patients.

This study aims to validate the Greek translation of the Questionnaire for Assessing Fear of Radiotherapy in Oncology Patients (QAFRT). Conducted as a cross-sectional pilot study, it involved 149 cancer patients from two radiotherapy departments in Thessaloniki, Greece. The sample included patients with various cancer types and stages, all of whom were undergoing radiation treatment. The QAFRT, originally containing 15 items measured on a Likert scale, was translated into Greek using the back-translation method. Exploratory factor analysis was performed on the translated version, resulting in a refined 13-item questionnaire encompassing four factors: fear of radiotherapy effectiveness, fear of illness during radiotherapy, fear of radiotherapy's impact on daily life, and fear of side effects and relationships. The reliability of the QAFRT was confirmed with Cronbach's α of 0.82 and intraclass correlation coefficient coefficients ranging from 0.92 to 0.98. The study concludes that the Greek version of the QAFRT is a reliable and valid tool for assessing the fear of radiotherapy in cancer patients, highlighting the need for adequate psychological support for those with high levels of fear.

Acute skin toxicity and self-management ability among Chinese breast cancer radiotherapy patients: a qualitative study

ObjectivesRadiation dermatitis is the most common reaction to radiotherapy, almost all breast cancer patients receive radiotherapy on an outpatient basis. Currently, there are no studies on the experience of radiation dermatitis and the ability to self-manage it. Therefore, we aimed to use qualitative approaches to gain a deeper understanding of the actual experiences and self-management ability in order to provide a reference for further improving the effectiveness of self-management and to optimize symptom management strategies.MethodsA descriptive qualitative study was conducted using purposive sampling to select 17 breast cancer patients undergoing radiotherapy. Semi-structured interviews were conducted from September to November 2023. The Colaizzi seven-step analysis method was used to classify the data into summarized themes.ResultsFour themes were identified from the interview responses: (1) multiple self-reported skin symptoms in breast cancer patients with radiation dermatitis; (2) the multidimensional impact on patient’s quality of life, especially pruritus, ulceration; (3) the ability to self-manage radiation dermatitis: strong mental toughness, positive response, and self-doubt; (4) challenges faced: concerns about radiotherapy side effects and recurrence, targeted symptom management and continuity of care after the radiotherapy.ConclusionsHealthcare professionals should consider patients’ self-reported symptoms when assessing radiation dermatitis. For pruritus and pain, we can enhance precision symptom management to improve patients’ quality of life. By utilizing information technology tools, we can increase breast cancer patients’ ability and confidence in managing radiation dermatitis effectively while enhancing accurate symptom management during radiotherapy.

Bevacizumab is associated with a higher gastrointestinal/genitourinary fistula or perforation risk in cervical cancer patients undergoing pelvic radiotherapy.

Bevacizumab serves as an effective treatment in cervical cancer patients with metastatic, recurrent, or advanced disease. However, gastrointestinal (GI)/genitourinary (GU) toxicities have been observed after bevacizumab treatment. Radiotherapy (RT) is the mainstay of treatment of cervical cancer. To investigate the risk of GI/GU toxicities with bevacizumab plus RT compared with RT alone in cervical cancer patients. In this meta-analysis, PubMed, Embase, Web of Science, and Cochrane databases were searched from inception to September 25, 2022. Cohort studies evaluating the association between bevacizumab and GI/GU fistula or perforation in irradiated metastatic, recurrent, or advanced cervical cancer patients. Results are expressed as odds ratios (OR) with 95% confidence intervals (CI). The inconsistency test (I2) was used to assess heterogeneity. Egger's regression test with a two-tailed P value was used to evaluate publication bias. Four cohort studies met the inclusion criteria with a total of 597 women included. There was a significant association between GI fistula/perforation and GU fistula/perforation in irradiated cervical cancer patients receiving bevacizumab (OR 4.03 [95% CI: 1.76-9.20] and OR 4.71 [95% CI: 1.51-14.70], respectively). The bevacizumab-containing regimen was associated with an increased risk of GI or GU toxicities in cervical cancer individuals undergoing pelvic RT. These results suggest the bevacizumab-associated benefits and risk should be better weighted to reach an optimal treatment strategy. Further investigation on optimal dosage and timing of bevacizumab and RT is vital to minimize the adverse events and maximize the benefits.

813: The treatment quality of SG-DIBH on postmastectomy left breast cancer radiotherapy patients

813: The treatment quality of SG-DIBH on postmastectomy left breast cancer radiotherapy patients

Perceived control, self-management efficacy, and quality of life in patients treated with radiation therapy for breast cancer: a longitudinal study.

This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (β = 0.30, P < 0.001), presence of chemotherapy (β = 18.33, P = 0.024), and duration of illness (β = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (β = - 2.95, P < 0.001), cancer experience (β = - 0.46, P < 0.001), and type of medical insurance (β = - 2.77, P = 0.021) had the negative effect on the change in QoL. The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.

Immunogenicity Parameters of Cancer Patients Receiving the mRNA Vaccine BNT162b2 While Obtaining Radiotherapy: A Longitudinal Cohort Evaluation.

Cancer patients are highly prone to infectious diseases. While undergoing antineoplastic treatment, the risk of severe symptoms upon infection increases, necessitating efficient protective measures, such as vaccination. For patients receiving radiotherapy, there is no specific information about humoral immunity. During the COVID-19 pandemic, serial antibody measurements were therefore offered to cancer patients, following SARS-CoV-2 vaccination while obtaining radiotherapy. Out of 74 enrolled patients, 46 met the inclusion criteria. Two cohorts were allocated, depending on an association with chemotherapy or pure radiotherapy. An additional healthy control cohort of 16 healthcare workers was enrolled. All participants followed a two-fold BNT162b2 vaccine schedule. SARS-CoV-2 binding antibodies were measured serially in a 7-day cycle for 35 days and over the long-term, using the Elecsys® Anti-SARS-CoV-2 immunoassay. Cancer patients under pure radiotherapy have a comparable humoral vaccination response and long-term persistency of antibodies to healthy controls. Patients receiving additional chemotherapy show a significantly delayed immune response and decreased antibody titers. The vaccine was well tolerated in all cohorts. Pure radiotherapy in cancer patients does not interfere with the vaccine-induced humoral immune response or other immunogenetic aspects, whereas previous or simultaneous chemotherapy does. Findings are of particular relevance for future epidemic or pandemic scenarios.

Interobserver delineation variability of computed tomography-based radiomic features of the parotid gland.

To assess the interobserver delineation variability of radiomic features of the parotid gland from computed tomography (CT) images and evaluate the correlation of these features for head and neck cancer (HNC) radiotherapy patients. Contrast-enhanced CT images of 20 HNC patients were utilized. The parotid glands were delineated by treating radiation oncologists (ROs), a selected RO and AccuContour auto-segmentation software. Dice similarity coefficients (DSCs) between each pair of observers were calculated. A total of 107 radiomic features were extracted, whose robustness to interobserver delineation was assessed using the intraclass correlation coefficient (ICC). Pearson correlation coefficients (r) were calculated to determine the relationship between the features. The influence of excluding unrobust features from normal tissue complication probability (NTCP) modeling was investigated for severe oral mucositis (grade ≥3). The average DSC was 0.84 (95% confidence interval, 0.83-0.86). Most of the shape features demonstrated robustness (ICC ≥0.75), while the first-order and texture features were influenced by delineation variability. Among the three observers investigated, 42 features were sufficiently robust, out of which 36 features exhibited weak correlation (|r|<0.8). No significant difference in the robustness level was found when comparing manual segmentation by a single RO or automated segmentation with the actual clinical contour data made by treating ROs. Excluding unrobust features from the NTCP model for severe oral mucositis did not deteriorate the model performance. Interobserver delineation variability had substantial impact on radiomic features of the parotid gland. Both manual and automated segmentation methods contributed similarly to this variation.

Transcriptional Inflammatory Signature in Healthy Donors and Different Radiotherapy Cancer Patients.

Cancer and ionizing radiation exposure are associated with inflammation. To identify a set of radiation-specific signatures of inflammation-associated genes in the blood of partially exposed radiotherapy patients, differential expression of 249 inflammatory genes was analyzed in blood samples from cancer patients and healthy individuals. The gene expression analysis on a cohort of 63 cancer patients (endometrial, head and neck, and prostate cancer) before and during radiotherapy (24 h, 48 h, ~1 week, ~4-8 weeks, and 1 month after the last fraction) identified 31 genes and 15 up- and 16 down-regulated genes. Transcription variability under normal conditions was determined using blood drawn on three separate occasions from four healthy donors. No difference in inflammatory expression between healthy donors and cancer patients could be detected prior to radiotherapy. Remarkably, repeated sampling of healthy donors revealed an individual endogenous inflammatory signature. Next, the potential confounding effect of concomitant inflammation was studied in the blood of seven healthy donors taken before and 24 h after a flu vaccine or ex vivo LPS (lipopolysaccharide) treatment; flu vaccination was not detected at the transcriptional level and LPS did not have any effect on the radiation-induced signature identified. Finally, we identified a radiation-specific signature of 31 genes in the blood of radiotherapy patients that were common for all cancers, regardless of the immune status of patients. Confirmation via MQRT-PCR was obtained for BCL6, MYD88, MYC, IL7, CCR4 and CCR7. This study offers the foundation for future research on biomarkers of radiation exposure, radiation sensitivity, and radiation toxicity for personalized radiotherapy treatment.

Analysis of nutritional risk, skeletal muscle depletion, and lipid metabolism phenotype in acute radiation enteritis.

Radiation enteritis, which often occurs during radiation-induced acute intestinal symptoms (RIAIS), is the most common and important complication during radiotherapy for cervical cancer. RIAIS caused by abdominal and pelvic radiotherapy will affect nutrient intake, digestion, absorption, and metabolism, leading to malnutrition or poorer nutritional status. In patients with malignant tumors, malnutrition can adversely affect the curative effect and response of radiotherapy by reducing radiosensitivity, affecting the precision of radiotherapy placement and increasing the incidence of radiotherapy-related adverse reactions. To analyze nutritional risk, skeletal muscle depletion, and lipid metabolism phenotype in acute radiation enteritis. Fifty patients with cervical cancer received external beam radiotherapy, and 15 patients received brachytherapy after external beam radiotherapy. Body weight, body composition parameters, nutritional risk screening (NRS) 2002 score, and blood biochemical indices of patients with cervical cancer during periradiation were tested by a one-way repeated measures analysis of variance. Metabolomics analysis was used to identify characteristic lipid metabolism pathways. Clinical factors that affect linoleic acid changes were screened using the generalized evaluation equation. Among the 50 patients, 37 had RIAIS, including 34 patients with grade 1-2 RIAIS and 3 patients with grade 3 RIAIS. The NRS 2002 score of patients who underwent cervical cancer radiotherapy continued to increase during the periradiation period, and 42 patients who underwent cancer radiotherapy had nutritional deficits (NRS 2002 score ≥ 3 points) at the end of radiotherapy. Correlation analyses revealed that body weight and body mass index changes were closely associated with body fat content (R2 = 0.64/0.51). The results of the univariate analysis showed that radiotherapy time, percentage reduction of serum albumin, and percentage reduction of serum prealbumin were the key factors affecting skeletal muscle exhaustion (P < 0.05). Metabolomic analysis of fecal supernatants of cervical cancer patients during the periradiation period revealed the involvement of linoleic acid, cholic acid, arachidonic acid, and N-acetyl-L-benzene alanine in the metabolic pathway of linoleic acid. Cervical cancer radiotherapy patients faced nutritional risks, decreased serum albumin synthesis, and increased risk of skeletal muscle exhaustion. Linoleic acid was a biomarker of high nutritional risk.

Clinical and Molecular Characterization of Patients with Therapy Related Myeloid Neoplasms (TRMN)

Acknowledgements Chemotherapy and/or radiotherapy in cancer patients compose a future risk of developing a therapy related myeloid neoplasm (TRMN). However, the presence of a germline landscape might contribute and modify the overall risk. It has been suggested that around 18.5% of TRMN patients have a germline cancer mutation. In particular, cancer predisposing genes or syndromes involving alterations in the DNA repair mechanism such as CHEK2, BRCA1, BRCA2, MLH1, MSH2, MSH6 or PMS2 might be enriched in patients who develop a primary tumor (PT) and a subsequent secondary myeloid neoplasm. The role of the alterations in cancer susceptibility genes in association with the treatment for the PT in the development of TRMN is still unclear. To evaluate the clinical and genetic landscape of TRMN patients to understand the role of different risk factors and provide tools for differential diagnosis and clinical management. Clinical evaluation of 96 patients with TRMN and 12 patients with a secondary myeloid neoplasm after a non-treated with chemotherapy primary tumor (nTMN) was performed. In addition, germline landscape and somatic alterations were studied in the TRMN series by tNGS (N=49) and WES (N=47). Tumoral sample was obtained from bone marrow. CD3+ T lymphocytes from peripheral blood (PB) were enriched by immunomagnetic selection and used as germline/control sample. A minimum of 98% purity in CD3+ was selected to prevent myeloid contamination. Variant frequency (VAF) &amp;lt;30% found in tumor but not in CD3+ sample was annotated as somatic alteration. Only pathogenic/likely pathogenic variants were considered. The median age of onset was 62.3 and 71.1 years for the PT and the TRMN, respectively. 32.5% had complex karyotype. Similar positive correlation was found between the age of onset of the PT and the age of onset of the TRMN and nTNM. A negative correlation was found between the age of onset of the PT and the latency until the TRMN and nTMN diagnosis, which suggests that elderly age condition is more relevant than the cytotoxic treatment (Fig.1). No differences in latencies were found between MN subtypes, despite ring sideroblasts and del(5q) myeloid subtypes correlated with shorter and higher latencies, respectively. Different latencies were neither found when the PT was solid or hematologic, but interestingly, TRMN patients with previous colorectal cancer had shorter latencies. On the other hand, 91.3% of the TRMN patients presented a molecular alteration (considering both genetic or cytogenetic alterations), including 60.9% and 75% of patients with germline and acquired alterations, respectively. Germline mutations included 52.2% and 47.8% annotated in cancer predisposition genes of the DNA repair mechanisms and myeloid genes, respectively. Only 39.1% of TRMN patients were found with pathogenic somatic variants in myeloid genes while 68.75% were found with an abnormal karyotype. Finally, higher number of germline and somatic mutations was found in TRMN patients with an abnormal karyotype. However, a higher percentage of germline mutations in myeloid genes was found in TRMN with a normal karyotype (Fig.2). Higher percentage of molecular alterations (both germline and somatic) in myeloid genes was found in TRMN patients with a previous solid PT. However, higher percentage of mutations in cancer predisposition genes was found when the PT was hematologic. Our results highlight the role of mutations in cancer predisposition genes in the development of TRMN. Similar latency associations were found for TRMN and nTMN patients, which suggest that other risk factors different than treatment might contribute to the TRMN development. Altered karyotypes in TRMN patients are associated with acquired mutations in myeloid genes but not with germline mutations, which suggests two different entities with different prognosis. Molecular alterations in myeloid genes are more relevant in TRMN patients with solid PT, while molecular alterations in cancer predisposition genes are associated with TRMN patients with hematologic PT. This work was supported in part by a grant from the Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Spain (PI 20/00531)(Co-funded by European Regional Development Fund. ERDF, a way to build Europe). 2021 SGR 00560 (GRC) Generalitat de Catalunya; economical support from CERCA Programme and Fundació Adey.

Development of Organoid-Based Cytotherapeutics for Taste Loss Induced By Anti-Cancer Chemotherapy and Radiotherapy

Introduction Ulcerative mucositis and taste loss are common side effects induced by cancer therapy, including chemotherapy and radiation therapy. These conditions cause significant oral pain and loss of taste, impacting food intake and physical health abnormalities such as malnutrition, as well as depression and mental health deterioration, which can affect prognosis. To address these challenges, an appropriate treatment for oral mucositis is required. While various types of oral mucositis treatments have been developed (e.g., patch, spray, ointment), most show indirect healing effects such as pain control and inflammation relief. Thus, a direct method for treating oral lesions should be developed. This research was supported by the Korean Fund for Regenerative Medi- cine (KFRM) grant funded by the Korea Government (the Ministry of Science and ICT, the Ministry of Health &amp; Welfare) (21C0712L1-11). Methods To compensate for the difficulty in supplying human tissue, we conducted preliminary experiments using mice to establish protocols for manufacturing human oral tissue-derived cell therapeutics. we devised an organoid-derived cell sheet transplantation. First, we generated organoids derived from oral mucosa and prepared a cell sheet using a temperature-responsive cell culture dish. The harvested cell sheet was transplanted to the lesion site to enable structural and functional recovery of the oral mucosa and gustatory organs. Results We have developed a cell-therapeutic platform based on regenerative medicine technology to recover oral lesions in cancer chemotherapy and radiotherapy patients. Specifically, we developed a method for producing autologous cell therapeutics. The oral mucosa tissue of a patient scheduled for anticancer treatment was collected, and epithelial cells were obtained from the tissue. Using these cells, we generated organoids with differentiated taste bud cells, and isolated cells from the organoids were seeded onto temperature-responsive cell culture dishes and cultured beyond confluence for the formation of a sheet. We performed immunostaining to detect various types of taste cells in the cell sheet. We also confirmed the success of cell sheet transplantation and the subsequent healing effect. Conclusion Improving the prognosis and acquiring the will to recover of cancer chemotherapy and radiotherapy patients through repairing taste function and rapid healing of lesions are crucial. We have developed a cell therapy technology that enables the structural and functional recovery of the oral mucosa and gustatory organs, providing a promising solution to treat the side effects of anti-cancer treatment. Our research provides an R&amp;D initiative for the treatment and prevention of intractable diseases by culturing, manufacturing, and transplanting living autologous cells.