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.

Serum and Saliva Level of miR-31-5p and miR-let 7a in EBV Associated Oropharyngeal Cancer.

Epstein-Barr virus (EBV) has a well-documented association with head and neck neoplasms, including nasopharyngeal carcinoma (NPC). In the last few years, research aimed at elucidating the role of the miRs in the pathogenesis of head and neck cancer (HNC) has gained importance. The study of miRs expression has set new directions in the search for biomarkers with diagnostic and prognostic value, and even in the search for new therapeutic targets for various tumors, including HNC. The aim of current study was to approximate the importance of miR-31-5p and miR-let 7a in the pathogenesis of EBV associated oropharyngeal cancer. For this purpose, experiments were carried out to determine the level of mentioned miRs in serum among patients diagnosed with oropharyngeal cancer linked to EBV infection, depending on histological differentiation-grading (G1-G3) and TNM classification. All clinical specimens stratified by HPV status were HPV negative. The level of antibodies EBNA and EBVCA was also assessed. The obtained results showed a significantly increased serum level of miR-31-5p but decreased level of miR-let 7a in EBV positive oropharyngeal cancer patients. We demonstrated association between the level of tested miRs and clinical stage. Our findings showed that miR-31-5p and miR-let-7a may be involved in development and progression of EBV associated oropharyngeal cancer. Therefore, it seems important to further study these molecules, as well as to determine whether they could be important biomarkers in the diagnosis of oropharyngeal cancer associated with EBV infection.

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.

Radiation-Induced Hypothyroidism in Patients with Oropharyngeal Cancer Treated with IMRT: Independent and External Validation of Five Normal Tissue Complication Probability Models.

We aimed to externally validate five normal tissue complication probability (NTCP) models for radiation-induced hypothyroidism (RIHT) in a prospectively recruited cohort of 108 patients with oropharyngeal cancer (OPC). NTCP scores were calculated using original published formulas. Plasma thyrotropin (TSH) level was additionally assessed in the short-term after RT. After a median of 28 months of follow-up, thirty one (28.7%) patients developed RIHT. Thyroid mean dose and thyroid volume were significant predictors of RIHT: odds ratio equal to 1.11 (95% CI 1.03-1.19) for mean thyroid dose and 0.87 (95%CI 0.81-0.93) for thyroid volume in univariate analyses. Two of the evaluated NTCP models, published by Rønjom et al. and by Boomsma et al., had satisfactory performance with accuracies of 0.87 (95%CI 0.79-0.93) and 0.84 (95%CI: 0.76-0.91), respectively. Three remaining models, by Cella et al., Bakhshandeh et al. and Vogelius et al., performed significantly worse, overestimating the risk of RIHT in this patient cohort. A short-term TSH level change relative to baseline was not indicative of RIHT development in the follow-up (OR 0.96, 95%CI: 0.65-1.42, p = 0.825). In conclusion, the models by Rønjom et al. and by Boomsma et al. demonstrated external validity and feasibility for long-term prediction of RIHT in survivors of OPC treated with Intensity-Modulated Radiation Therapy (IMRT).

The analysis of prognostic factors affecting post-radiation acute reaction after conformal radiotherapy for non-small cell lung cancer.

INTRODUCTION: The aim was to evaluate the risk of acute side effects in the lung after 3-dimensional conformal radiotherapy (3D-CRT) in patients treated for non-small cell lung cancer (NSCLC). An attempt was made to single out clinical factors and factors related to treatment technique which may induce acute post-radiation pneumonitis. MATERIAL AND METHODS: The analysis concerned 34 consecutive patients who underwent radical radiation therapy for NSCLC. Intensity of early toxicity was evaluated using modified RTOG/EORTC toxicity score. The endpoint for this analysis was the occurrence of radiation pneumonitis of grade 2 or higher. Factors related to treatment techniques were included in the statistical analysis. RESULTS: Fifty-three percent of patients included in the study suffered from acute post-radiation pneumonitis. The results of the study revealed the existence of lung tissue sensitivity to low doses of ionizing radiation. The multivariate analysis showed that total lung volume receiving a low dose of 10 Gy increased the risk of post-radiation pneumonitis (p = 0.01). CONCLUSIONS: Acute post-radiation pneumonitis was a relevant clinical problem in patients who underwent radical radiotherapy for non-small cell lung cancer. The lung volume receiving a dose of 10 Gy was the most important dosimetric factor which influenced the post-radiation acute pneumonitis.

Long-term survival of endometrioid endometrial cancer patients.

INTRODUCTION: To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer. MATERIAL AND METHODS: A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival. RESULTS: In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS. CONCLUSIONS: The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.