Explainable prediction model for the human papillomavirus status in patients with oropharyngeal squamous cell carcinoma using CNN on CT images.

Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV-) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV-), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.

Corrigendum: Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer.

[This corrects the article DOI: 10.3389/fmed.2022.993395.].

Transfer learning approach based on computed tomography images for predicting late xerostomia after radiotherapy in patients with oropharyngeal cancer.

Background and purpose: Although the latest breakthroughs in radiotherapy (RT) techniques have led to a decrease in adverse event rates, these techniques are still associated with substantial toxicity, including xerostomia. Imaging biomarkers could be useful to predict the toxicity risk related to each individual patient. Our preliminary work aims to develop a radiomic-based support tool exploiting pre-treatment CT images to predict late xerostomia risk in 3 months after RT in patients with oropharyngeal cancer (OPC). Materials and methods: We performed a multicenter data collection. We enrolled 61 patients referred to three care centers in Apulia, Italy, out of which 22 patients experienced at least mild xerostomia 3 months after the end of the RT cycle. Pre-treatment CT images, clinical and dose features, and alcohol-smoking habits were collected. We proposed a transfer learning approach to extract quantitative imaging features from CT images by means of a pre-trained convolutional neural network (CNN) architecture. An optimal feature subset was then identified to train an SVM classifier. To evaluate the robustness of the proposed model with respect to different manual contouring practices on CTs, we repeated the same image analysis pipeline on "fake" parotid contours. Results: The best performances were achieved by the model exploiting the radiomic features alone. On the independent test, the model reached median AUC, accuracy, sensitivity, and specificity values of 81.17, 83.33, 71.43, and 90.91%, respectively. The model was robust with respect to diverse manual parotid contouring procedures. Conclusion: Radiomic analysis could help to develop a valid support tool for clinicians in planning radiotherapy treatment, by providing a risk score of the toxicity development for each individual patient, thus improving the quality of life of the same patient, without compromising patient care.

[Integrated management method in the prevention department of a COVID-19 epidemic outbreak in a large meat processing plant in Bari province]. / Modalità di gestione integrata nel dipartimento di prevenzione di un focolaio epidemico di COVID-19 in un grande stabilimento di lavorazione di carni della provincia di Bari.

Aim of this paper is to describe the management of an outbreak of COVID-19 in a slaughtering and meat processing plant in Bari Province (Southern Italy). At the end of the outbreak investigation, 18.4% of the employees were positive to the molecular test for SARS-CoV-2. Higher prevalence has been reported in the bovine slaughtering house and swine meat processing plant.In addition to lack of physical distancing and correct use of personal protective equipment, the spread of the virus has been eased by low level of literacy, indoor microclimate, intensive working time, and aerosol-generating procedures in specific areas of the processing plant where more positive cases have been detected. The analysis of this cluster may suggest specific actions to prevent similar outbreaks in the future.

Role of radiotherapy in the treatment of renal cell cancer: updated and critical review.

PURPOSE: The growing incidence of renal cell carcinoma (RCC) raises many questions about the management of these patients. The late clinical presentation, the presence of locally advanced or metastatic disease at diagnosis, the difficulty of radical surgical excision, and radioresistance make it one of the more challenging tumors to treat. The primary objective of this article is to propose an updated and critical review of the role of radiotherapy (RT) in the treatment of RCC. METHODS: This literature review is based on data from meta-analyses and randomized, prospective, and retrospective studies. We collected reports from 1970 to the present about preoperative RT, postoperative RT, stereotactic body RT, radiosurgery, and intraoperative RT in locally advanced renal cancer and in metastatic diseases. RESULTS: We emphasize the progress made in RT technology that allowed the creation of a more personalized and focused treatment with a minimum rate of complications. CONCLUSIONS: In the coming years, new studies will be published to confirm and increase the indications for use of RT.

Persistent Haglund's disease after conventional treatments: the innovative role of radiotherapy.

Haglund's disease, an inflammation of the retrocalcaneal bursa and a bone enlargement on the back of the heel, is a painful syndrome mainly caused by the exostotic prominence of the posterior calcaneus. Conventional treatment consists of rest, shoewear modification, medical therapy and, in selected cases, surgery. We report the case of a 59-year-old male with a history of severe atraumatic monolateral heel pain treated with foot orthotics, rest and surgery with partial regression of symptoms. Owing to the persistent heel pain and physical impairment after surgery, the patient underwent radiotherapy, which was successful in relieving his symptoms.

Intermediate neoadjuvant radiotherapy for T3 low/middle rectal cancer: postoperative outcomes of a non-controlled clinical trial.

BACKGROUND: The benefits of adjuvant radiotherapy in rectal carcinoma are well known. However, there is still considerable uncertainty about the optimal radiation treatment. There is an ongoing debate about the choice between very short treatments immediately followed by surgical resection and prolonged treatments with delayed surgery. In this paper, we describe an interim analysis of a non-controlled clinical trial in which radiotherapy delivered with intermediate dose/duration was followed by surgery after about 2 weeks to improve local control and survival after curative radiosurgery for cT3 low/middle rectal cancer. METHODS: Preoperative radiotherapy (36 Gy in 3 weeks) was delivered in 248 consecutive patients with cT3NxM0 rectal adenocarcinoma within 10 cm from the anal verge, followed by surgery within the third week after treatment completion. RESULTS: 166 patients (66.94%) underwent anterior resection, 80 patients (32.26%) the Miles' procedure and 2 patients (0.8%) the Hartmann's procedure. Local resectability rate was 99.6%, with 226 curative-intent resections. The overall rate of complications was 27.4%. 5-year oncologic outcomes were evaluated on 223 patients. The median follow-up time was 8.9 years (range 5-17.4 years); local recurrence (LR) rate and distal recurrence (DR) rate after 5 years were 6.28% and 21.97%, respectively. Overall survival was 74.2%; disease free survival was 73.5%; local control was 93.4 % and metastasis-free survival was 82.1%. CONCLUSIONS: preoperative radiotherapy with intermediate dose/duration and interval between radiotherapy and surgery achieves high local control in patients with cT3NxM0 rectal cancer, and high DR rate seems to be the major limitation to improved survival.

Combined modality treatments in pancreatic cancer.

INTRODUCTION: Of all the carcinomas, pancreatic carcinoma (PC) has the highest mortality rate, with a 1- and 5-year survival rate of 25% and less than 5% respectively. This is regardless of the stage at diagnosis. AREAS COVERED: In this review relevant literature assessing the evidence regarding preoperative and adjuvant chemoradiotherapy (CRT) is discussed. Furthermore, new therapeutic approaches are summarized, while the future direction regarding the multimodality approach to PC is also discussed. EXPERT OPINION: The role of combined-modality therapy for PC is continuously evolving. There have been several recent developments, as well as the completion of major, multi-institutional clinical trials. One of the challenges for the busy clinician is to appreciate the variation in staging, surgical expertise, and application of either definitive CRT or neo-adjuvant CRT for local and/or borderline disease.

Regulation of KEAP1 expression by promoter methylation in malignant gliomas and association with patient's outcome.

In light with the view that KEAP1 loss of function may impact tumour behavior and modify response to chemotherapeutical agents, we sought to determine whether KEAP1 gene is epigenetically regulated in malignant gliomas. We developed a Quantitative Methylation Specific PCR (QMSP) assay to analyze 86 malignant gliomas and 20 normal brain tissues. The discriminatory power of the assay was assessed by Receiving Operating Characteristics (ROC) curve analysis. The AUC value of the curve was 0.823 (95%CI: 0.764-0.883) with an optimal cut off value of 0.133 yielding a 74% sensitivity (95%CI: 63%-82%) and an 85% specificity (95%CI: 64%-95%). Bisulfite sequencing analysis confirmed QMSP results and demonstrated a direct correlation between percentage of methylated CpGs and methylation levels (Spearman's Rho 0.929, P=0.003). Remarkably, a strong inverse correlation was observed between methylation levels and KEAP1 mRNA transcript in tumour tissue (Spearman's Rho -0.656 P=0.0001) and in a cell line before and after treatment with 5-azacytidine (P=0.003). RECPAM multivariate statistical analysis studying the interaction between MGMT and KEAP1 methylation in subjects treated with radiotherapy and temozolomide (n=70), identified three prognostic classes of glioma patients at different risk to progress. While simultaneous methylation of MGMT and KEAP1 promoters was associated with the lowest risk to progress, patients showing only MGMT methylation were the subgroup at the higher risk (HR 5.54, 95% CI 1.35-22.74). Our results further suggest that KEAP1 expression is epigenetically regulated. In addition we demonstrated that KEAP1 is frequently methylated in malignant gliomas and a predictor of patient's outcome.

Giant keloid of left buttock treated with post-excisional radiotherapy.

Keloids are defined as excessive scar tissue formation extending beyond the area of the original skin injury and occurring in predisposed individuals. While no single treatment has proven widely effective, several series report excellent outcomes for keloids with post-surgery radiation therapy as described in the literature. We present a patient with recurrent giant keloid of left buttock after several surgical removals, that at physical examination shows the size of 40×22×10 cm in the largest dimension. Patient underwent a surgical excision of gluteal lesion and postoperative radiotherapy using photons at 8 MV of linear accelerator: the total dose delivered was 22 Gy in 11 days, with a daily fraction of 2 Gy. No relapse was showed at 36 months post-therapy. Several methods seem unsatisfactory for preventing keloid recurrence. The combination of surgery and adjuvant radiotherapy seems an excellent strategy to prevent recurrent disease.

Temozolomide and radiotherapy as first-line treatment of high-grade gliomas.

AIMS AND BACKGROUND: Temozolomide, a novel alkylating agent, has shown promising results in the treatment of patients with high-grade gliomas, when used as single agent as well as in combination with radiation therapy. MATERIALS AND METHODS: In this report we retrospectively reviewed the clinical outcome of 128 consecutive patients with a diagnosis of high-grade gliomas referred to our Institutions from April 1994 to November 2001. The first 64 patients were treated with radiotherapy alone and the other 64 with a combination of radiotherapy and temozolomide (31 with radiotherapy and adjuvant temozolomide and 33 with radiotherapy and concomitant temozolomide followed by adjuvant temozolomide). RESULTS: Grade 3 hematological toxicity was scored in 9% of 64 patients treated with radiotherapy and temozolomide. No grade 4 hematological toxicity was reported, and the other acute side effects observed were mild or easily controlled with medications. Age, histology and administration of temozolomide were statistically significant prognostic factors associated with better 2-year overall survival. In contrast, we did not observe a significant difference in overall survival between adjuvant and concomitant/adjuvant temozolomide administration. CONCLUSIONS: We report the favorable results of a schedule combining radiotherapy and temozolomide in the treatment of patients with high-grade gliomas. The literature data and above all the findings of the phase III EORTC-NCIC 26981 trial suggest that actually the schedule can be used routinely in clinical practice. Further clinical studies, using temozolomide in combination with other agents, are required.