High FLT3 expression increases immune-cell infiltration in the tumor microenvironment and correlates with prolonged disease-free survival in patients with non-small cell lung cancer.

Most of the currently used cancer immunotherapies inhibit the programmed cell death protein 1 (PD1)-programmed cell death 1 ligand 1 (PDL1) axis of T-cells. However, dendritic cells (DCs) controlled by natural killer (NK) cells via the FMS-related tyrosine kinase 3 (FLT3) axis are necessary for activation of T-cells. The aim of the study was to evaluate FLT3 as a prognostic factor and determine its role in immune infiltration (with emphasis on NK cells and DCs). Using The Cancer Genome Atlas (TCGA) database, we performed bioinformatic analysis of the gene expression datasets of 501 lung squamous cell carcinoma (LUSC) and 515 lung adenocarcinoma (LUAD) patient who had corresponding clinical data [analysis was performed in R (version 4.2.0)]. Disease-free survival (DFS) differed between the FLT3-low and FLT3-high expression groups, respectively, in LUSC (61.0 vs 71.3 months P = 0.075) and LUAD (32.7 vs 47.5 months P = 0.045). A tumor microenvironment (TME) with high immune infiltration and rich in T-cell exhaustion markers was observed in the FLT3-high group. We showed overexpression of NK cell and DC gene signatures in the FLT3-high expression group as well as overexpression of key effector genes of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes protein (STING) pathway, which is crucial in response to radiotherapy. High expression of FLT3 in the TME was associated with immune cell infiltration (especially of NK cells and DCs), increased expression of T-cell exhaustion markers and expression of effector genes of the cGAS-STING pathway, which may consequently increase susceptibility to immunotherapy and radiotherapy. High FLT3 expression correlated with prolonged DFS in the LUSC and LUAD cohorts.

Extreme acute radiation-induced toxicity in a patient with polymorphous low-grade adenocarcinoma of the nasopharynx and rare variants in DNA repair genes.

BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) is an extremely rare finding in the nasopharynx. There are no guidelines for the treatment of PLGA in this localization. Radiotherapy may be administered to treat this malignancy; however, in radiosensitive individuals, it is associated with a risk of severe radiotherapy-induced toxicity. METHODS: We present a case of a 73-year-old woman with locally advanced polymorphous low-grade adenocarcinoma of the nasopharynx who developed a severe adverse acute reaction to radiotherapy leading to treatment discontinuation. Despite intensive treatment, the patient died 40 days after RT initiation. Whole genome sequencing was performed using DNA from peripheral blood mononuclear cells in the search for variants that could explain such extreme toxicity. RESULTS: We identified a combination of pathogenic variants that may have contributed to the patient's reaction to radiation therapy, including predisposing variants in XRCC1, XRCC3, and LIG4. We also identified candidate variants, not previously described in this context, which could be associated with radiation toxicity based on plausible mechanisms. We discuss previous reports of this rare tumor from the literature and known contributors to radiation-induced toxicity. CONCLUSIONS: Genetic causes should be considered in cases of extreme radiosensitivity, especially when is not explained by clinical factors.

Algorithms of follow-up in patients with head and neck cancer in relation to primary location and advancement. Consensus of Polish ENT Society Board and Head Neck Experts.

Summary: The algorithm of follow-up in patients with head and neck cancer (HNC) has been prepared by a board of Polish Head Neck and Oncology Experts. The aim of this research is to focus on the specificity of HNC monitoring, to review the current trends in follow-up, and to adapt the evidence-based medicine international standards to the capabilities of the local healthcare service. Materials and methods: The first methodological step was to categorize HNCs according to the estimated risk of failure after the adequate first-line treatment and according to the possibility of effective salvage treatment, resulting in improved overall survival. The final method used in this work was to prepare an authors' original monitoring algorithm for HNC groups with a high, moderate, and low risk of recurrence in combination with a high or low probability of using an effective salvage. Results: Four categories were established: Ia. low risk of recurrence + effective organ preservation feasible; Ib. low risk of recurrence + effective salvage feasible; II. moderate risk of recurrence + effective salvage feasible; III. high risk of recurrence + effective salvage feasible; and IV. high risk of recurrence + no effective salvage feasible. Follow-up visit consisting of 1. ENT examination + neck ultrasound, 2. imaging HN tests, 3. chest imaging, 4. blood tests, and 5. rehabilitation (speech and swallowing) was scheduled with a very different frequency, at the proposed monthly intervals, tailored to the needs of the group. The number of visits for individual groups varies from 1 to 8 in the first 2 years and from 1 to 17 in the entire 5-year monitoring period. Group IV has not been included in regular follow-up, visits on own initiative of the patient if symptomatic, or supportive care needs, having in mind that third-line therapy and immune checkpoint inhibitors are available. Conclusion: Universal monitoring algorithm for HNC four groups with a high, moderate, and low risk of recurrence after the adequate treatment in combination with a high or low probability of using an effective salvage is an innovative approach to redeploying system resources and ensuring maximum benefit for patients with HNC.

QUAD SHOT - an effective hypofractionated palliative radiotherapy in patients with non-melanoma skin cancer. A single-institution experience.

Introduction: The primary approach for managing skin cancer involves surgery, although radical radiotherapy (RT) may be considered as an alternative option in cases where patients decline the treatment themselves or are not eligible for surgical intervention. Herein we assess single-institution material in terms of the use of hypofractionated QUAD SHOT RT in patients disqualified from surgery. Material and methods: Between December 2019 and December 2022, nine patients with locally advanced non-melanoma skin cancer were disqualified from surgery and as a result were treated at the Radom Oncology Centre, Poland. Patients were treated with the Radiation Therapy Oncology Group 8502 QUAD SHOT regimen (14.8 Gy/4 fractions, twice-daily treatment with a 6 h interval, on 2 consecutive days). Courses were repeated every 4 weeks 3 times using volumetric modulated arc therapy (VMAT). Results: Grade 2 toxicities were observed in 4 of 9 (44.4%) patients, no grade ≥ 3 acute toxicity was observed. The median age was 79.1 (60-98) years. Irradiated areas were as follows: nose skin (2), cheek (2), eyebrow with eyelid (1), forehead (1), temple (1), sternum (1), and scapula (1). Performance status was as follows: WHO II - 5 patients (55.6%), WHO I - 3 patients, WHO III - one patient. One patient underwent 3 RT courses in 2 areas for a total of 6 treatment courses, 6 patients received 3 courses of treatment, and 2 patients received 2 courses. Additionally, as of 14 March 2023, four patients died of non-malignant causes. Conclusions: QUAD SHOT schedule with VMAT RT may be an effective palliative treatment method with a good response rate, which positively affects patients' quality of life in locally advanced non-melanoma skin cancer patients disqualified from surgery.

The role of PET/CT with fluorine-18-deoxyglucose in the detection of relapsed serous ovarian cancer in patients with normal serum CA125 levels.

OBJECTIVES: To assess the role of the positron emission tomography with fluorine-18-deoxyglucose (PET/CT) in the detection of recurrent serous ovarian cancer in patients with normal serum CA125 level. MATERIAL AND METHODS: Thirty-one patients with suspected recurrent serous ovarian cancer with normal (< 35 IU/mL) serum CA125 level and no prior recurrence underwent PET/CT imaging. The results of the PET/CT were analyzed considering clinical data of the patients, histological diagnosis and 6 months follow-up. RESULTS: The patients were referred to the PET/CT due to suspected relapse in imaging tests (CT - 11 cases, US - 3 cases, MRI - 2 cases; n = 16; 51.6%), clinical examination (n = 4; 12.9%) and clinical symptoms (n = 11; 35.5%). The recurrent serous ovarian cancer was present in 16 patients (51.6%). In 9 these cases (56.3%) the recurrences were diagnosed in patients aged 51-70 years. In 15 cases (93.8%) the recurrences were diagnosed within 24 months after treatment. There were 15 true positive (48.4%), 12 true negative (38.7%), 3 false positive (9.7%) and 1 false negative (3.2%) PET/CT results. Sensitivity, specificity, positive and negative predictive value of the PET/CT were calculated as 93.8% (95% CI, 86.1-97.4%), 80.0% (95% CI, 69.7-88.9%), 83.3% (95% CI, 74.3-90.4%) and 92.3% (95% CI, 84.2-98.3%), respectively. CONCLUSIONS: In patients with a diagnosis of complete remission after treatment for serous ovarian cancer, even a multifocal recurrence may occur during follow up despite normal serum CA125 levels. Our results showed a usefulness of the PET/CT in detecting and differentiating malignant from benign lesions in patients with normal serum CA125 levels but inconclusive results in other imaging tests. We observed false results of the PET/CT for lesions in parotid gland, mesorectal adipose tissue and mediastinal lymph nodes.

The value of [18F]FDG PET/CT examination in the detection and differentiation of recurrent ovarian cancer.

BACKGROUND: The exact role of positron emission tomography with fluorine-18-deoxyglucose ([18F]FDG PET/CT) in an early diagnosis of relapsed ovarian cancer is not clearly defined. The aim of the study was to assess the value of [18F]FDG PET/CT in the detection and differentiation of recurrent ovarian cancer. MATERIAL AND METHODS: Eighty-four patients with suspected recurrent ovarian cancer underwent [18F]FDG PET/CT examination. Results of PET/CT were analyzed taking into account clinical data of the patients, histological diagnosis, and 6-month follow-up. RESULTS: The [18F]FDG PET/CT examinations showed abnormal findings in 67 patients (79.76%). There were 63 true positive results (75.00%), 14 true negative (16.67%), 4 false positive (4.76%), and 3 false negative (3.57%) results. Sensitivity, specificity, positive and negative predictive values of [18F]FDG PET/CT were 95%, 78%, 94%, and 82%, respectively. In patients with elevated serum Ca 125 concentration (n = 43), sensitivity and specificity of [18F]FDG PET/CT was 95.00% and 66.67%, respectively. Recurrence was confirmed in 22 (88.00%) of 25 patients referred for [18F]FDG PET/CT due to suspected relapse in imaging tests. CONCLUSIONS: A high frequency of recurrent ovarian cancer detected in the [18F]FDG PET/CT examinations due to increased Ca 125 concentration in patients without clinical symptoms and without changes in other imaging tests confirmed the usefulness of [18F]FDG PET/CT in such cases. In patients with suspected recurrent ovarian cancer implied in radiological findings, [18F]FDG PET/CT results in most cases differed from the original results of imaging examination. Our results showed high accuracy of [18F]FDG PET/CT in the evaluation of recurrent ovarian cancer and presented this diagnostic method as a useful tool in detecting and differentiating suspected lesions in this group of patients.

Radiation-induced circulating microRNAs linked to echocardiography parameters after radiotherapy.

Introduction: Patients treated with radiotherapy to the chest region are at risk of cardiac sequelae, however, identification of those with greatest risk of complications remains difficult. Here, we sought to determine whether short-term changes in circulating miRNA expression are related to measures of cardiac dysfunction in follow-up. Materials and methods: Two parallel patient cohorts were enrolled and followed up for 3 years after completion of RT to treat left-sided breast cancer. In the primary group (N=28) we used a a panel of 752 miRNAs to identify miRNAs associated with radiation and cardiac indices at follow up. In the second, independent cohort (N=56) we validated those candidate miRNAs with a targeted qPCR panel. In both cohorts. serum samples were collected before RT, 24h after the last dose and 1 month after RT; cardiac echocardiography was performed 2.5-3 year after RT. Results: Seven miRNAs in the primary group showed marked changes in serum miRNAs immediately after RT compared to baseline and associations with cardiopulmonary dose-volume histogram metrics. Among those miRNAs: miR-15b-5p, miR-22-3p, miR-424-5p and miR-451a were confirmed to show significant decrease of expression 24 hours post-RT in the validation cohort. Moreover, miR-29c, miR-451 and miR-424 were correlated with the end-diastolic diameter of the left ventricle, which was also confirmed in multivariable analysis adjusting for RT-associated factors. Conclusion: We identified a subset of circulating miRNAs predictive for cardiac function impairment in patients treated for left-sided breast cancer, although longer clinical observation could determine if these can be used to predict major clinical endpoints.

Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients.

BACKGROUND: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival. MATERIALS AND METHODS: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing. RESULTS: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression. CONCLUSIONS: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.

Prospective analysis of the impact of adjuvant treatment with external beam radiation therapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma.

OBJECTIVES: Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high dose rate brachytherapy (HDR BT) on health related quality of life (HRQL) in patients with early stage endometrioid endometrial carcinoma. MATERIAL AND METHODS: From March 2019 to February 2021, 60 patients were enrolled with early stage endometrioid endometrial carcinoma, and qualified to adjuvant treatment after hysterectomy. HRQL was assessed using the EORTC QLQ-C30 questionnaire, with the endometrial cancer-specific HRQL module EORTC QLQ-EN24. Questionnaires were completed in four timepoints during adjuvant radiotherapy. RESULTS: A significant decrease in mean global health status / quality of life (p < 0.001) and role functioning (p = 0.028) was noted, as assessed in EORTC QLQ-C30 scale. Among the EORTC QLQ-C30 symptoms scales, significant differences were noted in the fatigue scale (p = 0.003), pain scale (p = 0.001), constipation scale (p < 0.001) and diarrhea scale (p < 0.001) over time. The EORTC QRQ-EN24 analysis showed significant deterioration in the urological symptoms scale (p < 0.001), gastrointestinal symptoms scale (p < 0.001) and in the mean pain in back and pelvis scale (p = 0.003). CONCLUSIONS: Adjuvant radiotherapy in patients with early-stage endometrioid endometrial cancer after hysterectomy is associated with worse quality of life, especially due to the toxicity of the treatment in relation to the gastrointestinal tract and urinary system.

Retrospective analysis of the effectiveness of volumetric modulated arc therapy half­body irradiation in palliation of pain in patients with multiple bone metastases.

Bone metastases are the most common cause of cancer-related pain. It has been reported that radiotherapy is efficient in the palliation of pain caused by bone metastases. Half-body irradiation (HBI) is a method of palliative treatment in patients with multiple metastases to bones. The present study aimed to evaluate the efficiency of upper and lower HBI in reducing pain in patients with multiple bone metastases treated with volumetric modulated arc therapy (VMAT) HBI. A total of 22 patients received HBI based on the VMAT technique between July 2018 and July 2020. Treatment plans were subject to a dosimetric analysis. The absorbed doses ranged from 6 to 8 Gy in a single fraction. The patients rated pain on the 11-point (0-10) verbal numeric pain score (VNPS) before irradiation and after 1 month of follow-up. To assess the analgesic effect of HBI radiotherapy, data from 19 patients who attended the follow-up visit were analyzed. Before the treatment, the median VNPS of pain was 5 (IQR, 3-8); after the follow-up period, it was 3 (IQR, 1-4) (P=0.003). The median VNPS of the maximum pain within the last month before treatment was 8 (IQR, 7-10) and after irradiation it was 5 (IQR, 4-7) (P<0.001). The median VNPS of the average pain within the last month before the treatment was 5 (IQR, 4-7); after the treatment, it was 3 (IQR, 2-5) (P=0.003). In conclusion, conformal VMAT-intensity-modulated radiation therapy HBI is an effective method for reducing pain in patients with painful multiple bone metastases. Conformal techniques of radiation allow for the reduction of doses to organs at risk thus potentially reducing the toxicity of treatment.

The Kinetics of FMS-Related Tyrosine Kinase 3 Ligand (Flt-3L) during Chemoradiotherapy Suggests a Potential Gain from the Earlier Initiation of Immunotherapy.

The optimal sequence of chemoradiotherapy with immunotherapy is still not established. The patient's immune status may play a role in determining this order. We aim to determine the kinetics of a multi-potential haemopoietic factor FMS-related tyrosine kinase 3 ligand (Flt-3L) during chemoradiotherapy. Our pilot, a single arm prospective study, enrolled patients with rectal cancer who qualified for neoadjuvant chemoradiotherapy. Blood samples for Flt-3L were collected before and every second week of chemoradiotherapy for a complete blood count every week. The kinetics of Flt-3L were assessed using Friedman's ANOVA. A multiple factor analysis (MFA) was performed to find relevant factors affecting levels of serum Flt-3L during chemoradiotherapy. FactoMineR and factoextra R packages were used for analysis. In the 33 patients enrolled, the level of Flt-3L increased from the second week and remained elevated until the end of treatment (p < 0.01). All patients experienced Grade ≥2 lymphopenia with a nadir detected mostly in the 5/6th week. MFA revealed the spatial partitioning of patients among the first and second dimensions (explained by 38.49% and 23.14% variance). The distribution along these dimensions represents the magnitude of early changes of Flt-3L. Patients with the lowest values of Flt-3L change showed the highest lymphocyte nadirs and lowest dose/volume parameters of active bone marrow. Our hypothesis-generating study supports the concept of early initiation of immuno-therapy when the concentration of Flt-3L is high and no lymphopenia has yet occurred.

Clinical significance of CD34, podoplanin and Ki-67 expression in patients with locally advanced squamous cell cervical carcinoma.

The aim of the study was to assess immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB, a relationship with selected clinical and histological parameters and its prognostic significance. This prospective study included 52 patients. Microvessel density (MVD) by CD34, lymphatic vessel density (LVD) by podoplanin and the Ki-67 index in specimens from paraffin blocks with cervical SCC tissues were examined. The relationship between these data and selected clinical and histological parameters was analysed. Positive correlation of MVD and the Ki-67 index was observed. No correlation was observed for MVD, LVD and the Ki-67 index in the tumour with staging, grading, length of treatment and squamous cell carcinoma antigen (SCC-Ag) concentration before and after treatment. The expression of MVD, LVD and the Ki-67 index in cervical SCC did not contribute to the risk of relapse and cancer-related death. No relationship was found for MVD, LVD and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum SCC-Ag level. MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death.Impact StatementWhat is already known on this subject? In many patients, invasive cervical squamous cell carcinoma (SCC) is diagnosed in a locally advanced stage, when the prognosis depends on many well-known factors connected with tumour biology, staging and general condition of the patient. Despite numerous studies, the value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of these patients is still not well defined.What do the results of this study add? In our prospective study, no relationship for microvessel density (MVD), lymphatic vessel density (LVD) and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum squamous cell carcinoma antigen (SCC-Ag) level was found. Additionally, MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death.What are the implications of these findings for clinical practice and/or further research? Our study underlines the limited value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with locally advanced cervical SCC. Further research should be focussed on identifying and validating novel prognostic and predictive factors.

Adjuvant radiotherapy in parotid gland pleomorphic adenoma - recommendations.

<b>Introduction:</b> Standard treatment for pleomorhic adenoma (PA) of the parotid gland is complete surgical excision. Radiotherapy (RT) as a primary treatment method is controversial and generally is not applied. However, RT might be considered as an adjuvant therapy in some selected cases. </br></br> <b>Aim:</b> The aim of this work was to define recommendations for RT in patients with parotid gland PA after primary surgical treatment.</br></br> <b>Material and methods:</b> Based on the results currently published in the literature and the authors' own experiences from leading Polish laryngological and oncological clinical centers dealing with the treatment of salivary gland tumors, the indications for irradia- tion and its methods in patients with PA of the salivary glands were discussed. </br></br> <b>Results and discussion:</b> Authors recommend personalized treatment based on multidisciplinary panel decisions in each patient. Adjuvant RT should be considered in cases of suboptimal resection of primary PA (close margin, intraoperative tumor spillage, risk of recurrence based on clinical factors and histological features), and in cases of PA recurrence. Doses/ fractions and techniques of irradiation are recommended depending on the clinical extension of the primary or recurrent tumor. </br></br> <b> Conclusions:</b> Adjuvant RT in PA treatment should be a result of a personalized multidisciplinary decision after considering all possible risks of irradiation consequences. Recommendations for this treatment should be taken into consideration.

Assessment of cervical vascularization density in patients with locally advanced squamous cell cervical carcinoma evaluated in colour Doppler and power Doppler functions.

PURPOSE: The aim of the prospective study was to assess changes during treatment and prognostic significance of cervical vascularization density in patients with cervical squamous cell carcinoma (SCC) staged II B and III B and to find relationship of cervical vascularization density with tumour diameter, grading, staging and age of patients. METHODS: The study group included 50 patients who underwent transvaginal Doppler ultrasonography prior to chemoradiotherapy, after external beam radiation therapy (EBRT) and 6 weeks after HDR brachytherapy. The colour Doppler (CD) vascularity index (CDVI) and the power Doppler (PD) vascularity index (PDVI) in cervical tumour were examined. RESULTS: CDVI and PDVI values decreased significantly during radiotherapy (0.13 (95% CI 0.09-0.16); 0.09 (95% CI 0.07-0.11) and 0.05 (95% CI 0.03-0.06) for CDVI (p < 0.001) and 0.26 (95% CI 0.22-0.31); 0.18 (95% CI 0.14-0.22) and 0.08 (95% CI 0.06-0.11) for PDVI (p < 0.001)). No statistically significant associations of CDVI and PDVI with tumour diameter, grading, staging and age of patients were found. The higher (above median) CDVI values before EBRT were associated with better OS (p = 0.041). The higher (above median) PDVI values before EBRT were associated with superior DFS (p = 0.011) and OS (p < 0.001). DFS and OS did not differ significantly regarding CDVI and PDVI values after EBRT and after the treatment. CONCLUSIONS: In the study group, cervical vascularization density evaluated in CD and PD functions did not depend on tumour diameter, grading, staging and age of patients and decreased during radiotherapy. The prognosis for our patients with CDVI and PDVI before the treatment above the median value was better than compared to patients with these parameters below the median value.

Prediction of Radiation-Induced Hypothyroidism Using Radiomic Data Analysis Does Not Show Superiority over Standard Normal Tissue Complication Models.

State-of-art normal tissue complication probability (NTCP) models do not take into account more complex individual anatomical variations, which can be objectively quantitated and compared in radiomic analysis. The goal of this project was development of radiomic NTCP model for radiation-induced hypothyroidism (RIHT) using imaging biomarkers (radiomics). We gathered CT images and clinical data from 98 patients, who underwent intensity-modulated radiation therapy (IMRT) for head and neck cancers with a planned total dose of 70.0 Gy (33-35 fractions). During the 28-month (median) follow-up 27 patients (28%) developed RIHT. For each patient, we extracted 1316 radiomic features from original and transformed images using manually contoured thyroid masks. Creating models based on clinical, radiomic features or a combination thereof, we considered 3 variants of data preprocessing. Based on their performance metrics (sensitivity, specificity), we picked best models for each variant ((0.8, 0.96), (0.9, 0.93), (0.9, 0.89) variant-wise) and compared them with external NTCP models ((0.82, 0.88), (0.82, 0.88), (0.76, 0.91)). We showed that radiomic-based models did not outperform state-of-art NTCP models (p > 0.05). The potential benefit of radiomic-based approach is that it is dose-independent, and models can be used prior to treatment planning allowing faster selection of susceptible population.

Serum MicroRNAs as Xerostomia Biomarkers in Patients With Oropharyngeal Cancer Undergoing Radiation Therapy.

PURPOSE: Severe xerostomia is noted in the majority of patients irradiated for oropharyngeal cancer. Extracellular microRNAs (miRNAs) may serve as effective tools allowing prediction of radiation-related toxicity. The aim of this study was to create an efficient prognostic miRNA-based test for severe, patient-rated xerostomia 3 months after primary treatment. METHODS AND MATERIALS: This prospective study enrolled patients with oropharyngeal cancer treated between 2016 and 2018 in 3 centers in Poland. The primary endpoint was severe (grade ≥3) xerostomia as assessed by the European Organisation for Research and Treatment of Cancer H&N-35 questionnaires. Initially, a group of 10 patients with severe xerostomia was randomly selected and matched with a comparative group of 10 patients without severe xerostomia. Samples were collected before radiation therapy, after receiving 20 Gy, and within 24 hours after treatment completion. Quantitative real-time polymerase chain reaction arrays (QIAGEN, Hilden, Germany) were used to quantify expression levels of 752 miRNAs in the serum at all timepoints. The resulting logistic-regression based model was validated in additional 60 patients: 30 with grade >3 xerostomia and 30 without. RESULTS: Of 152 eligible patients, we successfully recruited 111 patients. Severe xerostomia 3 months after treatment was reported by 63 patients (56.8%). Mean dose delivered to parotid glands was higher in both the exploratory and validation cohort. The model based on miR-185-5p and miR-425-5p expression levels measured before the start of radiation therapy had an area under the curve of 0.96 (95% confidence interval, 0.88-1.00). The model based on the same miRNAs remained robust when parameters were measured after 20 Gy (area under the curve 0.90; 95% confidence interval, 0.75-1.00). These results were confirmed in the validation group. In the validation group, preradiation therapy model application yielded 73.3% sensitivity and 80.0% specificity. In the samples taken after 20 Gy, the same 2 miRNAs yielded 67.7% sensitivity and 72.4% specificity. The model including pretreatment miR-185-5p and miR-425-5p levels together with mean parotid dose yielded 90.0% sensitivity and 80.0% specificity. In the validation cohort, this model yielded 80.6% sensitivity and 55.2% specificity. The model based on miRNA levels measured after 20 Gy and mean parotid dose had 80.0% sensitivity and 100% specificity in the exploratory group. In the validation cohort its performance fell to 71.0% sensitivity and 58.6% specificity. CONCLUSIONS: Serum expression levels of miR-425-5p and miR-185-5p measured before the start of radiation therapy or during therapy (after 20 Gy) had significant prognostic value for the occurrence of severe xerostomia 3 months after treatment completion. The variability explained by miRNAs appears to be, at least partially, independent from that related to the dosimetric data.

The impact of adjuvant treatment with external beam radiotherapy and vaginal brachytherapy on health-related quality of life in patients with early-stage endometrioid endometrial carcinoma - initial results of a prospective study.

OBJECTIVES: Our study evaluates the impact of adjuvant treatment with external beam radiotherapy (EBRT) combined with vaginal high-dose-rate brachytherapy (HDR BT) on health-related quality of life (HRQL) in patients with early-stage endometrioid endometrial carcinoma. MATERIAL AND METHODS: We assessed HRQL of patients based on the EORTC QLQ-C30 questionnaire, with endometrial cancer specific HRQL module - EORTC QLQ-EN24. From March 2019 to April 2020 we enrolled 20 patients with early-stage endometrioid endometrial carcinoma, qualified for adjuvant treatment after hysterectomy. We compared the scores measured with the questionnaires at the beginning and at the end of the treatment. RESULTS: There was a statistically significant decrease in the mean of global health status/quality of life assessed according to the EORTC QLQ-C30 scale, from 62.25 ± 13.12 at the beginning of the adjuvant radiotherapy to 55.85 ± 14.68 at the end of the treatment (p = 0.047). The mean appetite loss score was higher at the onset of the treatment as compared to its value after EBRT, 19.9 ± 27.33 vs 11.6 ± 19.52 (p = 0.043). Similarly to the mean constipation score, which was 29.85 ± 30.40 vs 11.6 ± 19.52 (p = 0.013). The mean diarrhoea symptom scale increased from 16.55 ± 20.16 to 56.75 ± 36.10 (p = 0.001). In the EORTC QLQ-EN24 scales, gastrointestinal symptoms scores were higher at the end of the treatment, (with the mean of 26.45 ± 22.76) as compared to 14.30 ± 16.52 at the beginning of EBRT (p = 0.003). CONCLUSIONS: Patients who receive adjuvant radiotherapy have decreased quality of life during the treatment reporting more serious gastrointestinal symptoms. The potential risk of treatment-related toxicity should be taken into account during the treatment planning process in order to minimize the deterioration of HRQL.

Radiotherapy in the Management of Pediatric and Adult Osteosarcomas: A Multi-Institutional Cohort Analysis.

BACKGROUND: Due to the rarity of osteosarcoma and limited indications for radiotherapy (RT), data on RT for this tumor are scarce. This study aimed to investigate the utilization of RT for osteosarcomas in the recent 20 years and to identify factors related to patients' response to radiation. METHODS: We performed a retrospective analysis of patients irradiated for osteosarcoma treatment. We planned to assess differences in the utilization of RT between the periods of 2000-2010 and 2011-2020, identify the risk factors associated with local progression (LP), determine whether RT-related parameters are associated with LP, and calculate patients' survival. RESULTS: A total of 126 patients with osteosarcoma who received 181 RT treatments were identified. We found a difference in RT techniques between RT performed in the years 2000-2010 and that performed in the years 2011-2020. LP was observed after 37 (20.4%) RT treatments. Intent of RT, distant metastases, and concomitant systemic treatment affected the risk of LP. Five-year overall survival was 33% (95% confidence interval (26%-43%)). CONCLUSIONS: RT for osteosarcoma treatment has evolved from simple two-dimensional palliative irradiation into more conformal RT applied for new indications including oligometastatic and oligoprogressive disease. RT may be a valuable treatment modality for selected patients with osteosarcoma.

Assessment of cervical volume and spectral Doppler parameters in tumour dominant vessel of patients with locally advanced squamous cell cervical carcinoma.

We evaluated cervical volume and spectral Doppler parameters: peak systolic velocity (PSV), resistance index (RI) and pulsatility index (PI) in the tumour dominant vessel of 50 patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB and their changes during treatment. The patients underwent transvaginal Doppler ultrasonography prior to treatment, after external beam radiation therapy (EBRT) and 6 weeks after brachytherapy. Radiotherapy decreased cervical volume and PSV values of the tumour dominant vessel. The PSV values before EBRT in G1 + G2 tumours were higher than in G3 tumours. No correlations between cervical volume, PSV, RI and PI values with disease-free survival (DFS) and overall survival (OS) were found. We concluded, that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results. Spectral Doppler parameters PSV, RI and PI of tumour dominant vessel did not predict prognosis for these patients.Impact StatementWhat is already known on this subject? Transvaginal Doppler sonography is considered as a useful diagnostic method in patients with cervical carcinoma. However, despite numerous studies, the value of spectral Doppler parameters in tumour dominant vessel and cervical volume of patients with locally advanced cervical SCC is still not well defined.What the results of this study add? In our prospective study, we found that sonographic assessment of changes in cervical volume of patients with locally advanced cervical SCC during treatment did not allow to predict treatment results and spectral Doppler parameters of tumour dominant vessel did not predict prognosis for these patients.What the implications are of these findings for clinical practice and/or further research? Our study underlines the limited value of spectral Doppler technique in patients with cervical carcinoma. Further research should be focussed on identifying and validating novel prognostic and predictive factors.

Radiation Oncology Training in Poland: Multi-institutional Survey.

To evaluate the quality of radiation oncology training in Poland and to identify difficulties and needs of radiation oncology trainees (ROTs), an anonymous online survey using Google Forms was conducted in November 2018. All ROTs from Poland (n = 154) were invited to complete the survey. The survey consisted of 30 questions and regarded aspects such as satisfaction from training, cooperation with the supervisor, and education. During the study period, 105 ROTs from 22 Polish cities responded (the response rate was 68%). Almost 85% were satisfied with the choice of specialty, 43% with training and 81% with the teaching place. Clinical cooperation with the supervisor was described as difficult by 25%. With education, 38% of responders experienced obstacles and another 25% stated that educational cooperation with their supervisor was none. "Good practice" understood as treatment according to the latest guidelines or internal protocols were reported by 71%. Obligatory traineeships were shorter than recommended according to 67% of the responders, usually due to shortage of medical staff. Almost two-thirds of ROTs work only in clinics, while 34% perform both clinical and scientific work. The responders suggested that the introduction of organ-specified courses is an appropriate modification of the current program. Noteworthy, current diagnostic imaging and physics courses are not sufficient for the majority of participants (81% and 80%, respectively). Radiation oncology training is conducted relatively well in Poland. Some hospitals need to improve clinical and educational cooperation between trainees and their supervisors.