Cancer treatment-induced oral mucositis

Oral mucositis is one of the main complications in non-surgical cancer treatments. It represents the major dose-limiting toxicity for some chemotherapeutic agents, for radiotherapy of the head and neck region and for some radiochemotherapy combined treatments. Many reviews and clinical studies have been published in order to define the best clinical protocol for prophylaxis or treatment of mucositis, but a consensus has not yet been obtained. This paper represents an updated review of prophylaxis and treatment of antineoplastic-therapy-related mucositis using a MEDLINE search up to May 2006, in which more than 260 clinical studies have been found. They have been divided according to antineoplastic therapy (chemotherapy, radiotherapy, chemo-radiotherapy, high-dose chemotherapy). The prophylactic or therapeutic use of the analysed agents, the number of enrolled patients and the study design (randomized or not) were also specified for most studies. Accurate pre-treatment assessment of oral cavity hygiene, frequent review of symptoms during treatment, use of traditional mouthwashes to obtain mechanical cleaning of the oral cavity and administration of some agents like benzydamine, imidazole antibiotics, tryazolic antimycotics, povidone iodine, keratinocyte growth factor and vitamin E seem to reduce the intensity of mucositis. Physical approaches like cryotherapy, low energy Helium-Neon laser or the use of modern radiotherapy techniques with the exclusion of the oral cavity from radiation fields have been shown to be efficacious in preventing mucositis onset. Nevertheless a consensus protocol of prophylaxis and treatment of oral mucositis has not yet been obtained

L19-IL2 immunocytokine in combination with the anti-syndecan-1 46F2SIP antibody format: A new targeted treatment approach in an ovarian carcinoma model

Epithelial ovarian cancer (EOC) is the fifth most common cancer affecting the female population. At present, different targeted treatment approaches may improve currently employed therapies leading either to the delay of tumor recurrence or to disease stabilization. In this study we show that syndecan-1 (SDC1) and tumor angiogenic-associated B-fibronectin isoform (B-FN) are involved in EOC progression and we describe the prominent role of SDC1 in the vasculogenic mimicry (VM) process. We also investigate a possible employment of L19-IL2, an immunocytokine specific for B-FN, and anti-SDC1 46F2SIP (small immuno protein) antibody in combination therapy in a human ovarian carcinoma model. A tumor growth reduction of 78% was obtained in the 46F2SIP/L19-IL2-treated group compared to the control group. We observed that combined treatment was effective in modulation of epithelial-mesenchymal transition (EMT) markers, loss of stemness properties of tumor cells, and in alleviating hypoxia. These effects correlated with reduction of VM structures in tumors from treated mice. Interestingly, the improved pericyte coverage in vascular structures suggested that combined therapy could be efficacious in induction of vessel normalization. These data could pave the way for a possible use of L19-IL2 combined with 46F2SIP antibody as a novel therapeutic strategy in EOC

Three-times daily radiotherapy after chemotherapy in stage III non-small cell lung cancer. Single-institution prospective study

Aim: A prospective study for stage IIIA-B non-small cell lung cancer (NSCLC), with three-times daily (3td) radiotherapy (RT), after induction chemotherapy (iCT), with or without surgery. Patients and Methods: Induction cisplatin and gemcitabine chemotherapy was delivered. Surgery and postoperative (post-op) radiotherapy were planned for responsive stage IIIA patients; definitive irradiation was performed in unresectable III A and IIIB patients. Doses of 54.4 and 64.6 Gy were delivered for the post-op and definitive treatments, respectively. Results: Out of 52 patients (pts), 37 received 3tdRT as definitive (18 pts) or post-op treatment (19 pts). Overall, the failures were similar between post-op and definitive 3tdRT (78.9% vs. 77.8%). In the post-op treatment, metastases and local failures were 52.6% and 10.5%, respectively and in the definitive radiotherapy, the incidence was similar (local 33.3% vs. systemic 44.4%). The five-year overall survival (OS) was 25% for the post-op and 21% for the definitive patients (p=0.87). Conclusion: Three-times daily postoperative radiotherapy did not improve the outcome in NSCLC, but for unresectable patients, this approach may have a role in selected cases

Machine Learning-Based Models for Prediction of Toxicity Outcomes in Radiotherapy

In order to limit radiotherapy (RT)-related side effects, effective toxicity prediction and assessment schemes are essential. In recent years, the growing interest toward artificial intelligence and machine learning (ML) within the science community has led to the implementation of innovative tools in RT. Several researchers have demonstrated the high performance of ML-based models in predicting toxicity, but the application of these approaches in clinics is still lagging, partly due to their low interpretability. Therefore, an overview of contemporary research is needed in order to familiarize practitioners with common methods and strategies. Here, we present a review of ML-based models for predicting and classifying RT-induced complications from both a methodological and a clinical standpoint, focusing on the type of features considered, the ML methods used, and the main results achieved. Our work overviews published research in multiple cancer sites, including brain, breast, esophagus, gynecological, head and neck, liver, lung, and prostate cancers. The aim is to define the current state of the art and main achievements within the field for both researchers and clinicians

Radioablation +/- hormonotherapy for prostate cancer oligorecurrences (Radiosa trial): Potential of imaging and biology (AIRC IG-22159)

Background: Prostate cancer (PCa) is the second most common cancer among men. New imaging-modalities have increased the diagnosed patients with limited number of metastasis after primary curative therapy, introducing so-called oligometastatic state. Stereotactic body radiotherapy (SBRT) is emerging as a low-toxicity treatment to erase PCa localizations and postpone androgen deprivation therapy (ADT). A deeper understanding of the predictive role of biomarkers is desirable for a targeted treatment selection and surveillance programs. The aims of the RADIOSA trial are: Compare SBRT +/- ADT for oligorecurrent-castration-sensitive PCa (OCS-PCa) in terms of efficacy, toxicity and Quality of Life (QoL).Develop biology/imaging based prognostic tool that allows identifying OCS-PCa subclasses. Methods This is a randomized phase II clinical trial, recruiting 160 OCS-PCa in 3years, with progression-free survival (PFS) as primary endpoint. Three tasks will be developed: Randomized clinical study (3years for accrual and 2years for follow-up and data analysis);Imaging study, including imaging registration and METastasis Reporting and Data System (MET-RADS) criteria;Pre-clinical study, development of a biobank of blood samples for the analysis of neutrophil-to-lymphocyte ratio and preparatory for a subsequent miRNA profiling.We aim to determine which arm is justified for testing in a subsequent Phase III trial. A decision-tree algorithm, based on prognosis, biological phenotype and imaging profile, will be developed. Discussion Recruiting will start in July 2019. SBRT will allow obtaining excellent PFS, local control, QoL and low toxicity. In SBRT arm, ADT deferral will allow for a drug-holiday, delaying the detrimental impact on QoL. A sufficient number of blood samples will be collected to perform biological patient profiling. A stratification tool will be established with an analysis of morphological and functional imaging, based on the use of MET-RADS criteria.So, in conclusion, RADIOSA aims to define the optimal management of bone/nodal PCa relapses in a SBRT regimen. This study will increase our knowledge on low-burden metastatic PCa in the era of high precision and high technology personalized medicine, offering highly effective therapy in terms of clinical outcome and cost-effectiveness. Trial registration The RADIOSA study was prospectively registered at clinicaltrials.gov (NCT03940235, May 2019)