Cancer radiotherapy (RT) may induce what is referred to as the “abscopal effect,” a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute “Fondazione G.Pascale” through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1–4). Median overall survival (OS) for all 21 patients was 13 months (range 6–26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5–50.3) vs. 8.3 months (range 7.6–9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.

Prostate cancer is a main urological disease associated with significant morbidity and mortality. Radical prostatectomy and radiotherapy are potentially curative for localized prostate cancer, while androgen deprivation therapy is the initial systemic therapy for metastatic prostate disease. However, despite temporary response, most patients relapse and evolve into castration resistant cancer.Epithelial-mesenchymal transition (EMT) is a complex gradual process that occurs during embryonic development and/or tumor progression. During this process, cells lose their epithelial characteristics and acquire mesenchymal features. Increasing evidences indicate that EMT promotes prostate cancer metastatic progression and it is closely correlated with increased stemness and drug resistance.In this review, we discuss the main molecular events that directly or indirectly govern the EMT program in prostate cancer, in order to better define the role and the mechanisms underlying this process in prostate cancer progression and therapeutic resistance.

Prostate cancer is the second highest cause of cancer mortality after lung tumours. In USA it affects about 2.8 million men and the incidence increases with age in many countries. Therefore, early diagnosis is a very important step for patient clinical evaluation and for a selective and efficient therapy. The study of miRNAs' functions and molecular mechanisms has brought new knowledge in biological processes of cancer. In prostate cancer there is a deregulation of several miRNAs that may function as tumour suppressors or oncogenes. The aim of this review is to analyze the progress made to our understanding of the role of miRNA dysregulation in prostate cancer tumourigenesis.

Nasopharyngeal carcinoma is a rare disease in Western countries. Nevertheless, its incidence in China, Singapore, and other Eastern countries reaches 20 cases per 100,000 people. Being an extremely chemo- and radiosensitive disease, upfront treatment often consists in the association of intensity-modulated radiation therapy and concurrent cisplatin. Unfortunately, about 20% of the patients suffer from a radioresistant disease which recurs after upfront therapy. For these patients, mainly available therapeutic options consist in systemic therapy, in particular poly-chemotherapy. In those showing a single locoregional recurrence, chemotherapy is not considered to be the preferred approach and other different strategies may be employed. Re-irradiation and surgery are strategies that are always used more often, albeit related to high risk of morbidity. Immunotherapy and targeted therapy, such as heavy ions-based re-irradiations, are experimental but very intriguing options.

Background: Oropharyngeal mucositis occurs in virtually all patients with head and neck cancer receiving radiochemotherapy. The manipulation of the oral cavity microbiota represents an intriguing and challenging target. Patients and Methods: A total of 75 patients were enrolled to receive Lactobacillus brevis CD2 lozenges or oral care regimen with sodium bicarbonate mouthwashes. The primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment. Results: There was no statistical difference in the incidence of grade 3-4 oropharyngeal mucositis between the intervention and control groups (40.6% vs. 41.6% respectively, p=0.974). The incidence of pain, dysphagia, body weight loss and quality of life were not different between the experimental and standard arm. Conclusion: Our study was not able to demonstrate the efficacy of L. brevis CD2 lozenges in preventing radiation-induced mucositis in patients with head and neck cancer. Although modulating homeostasis of the salivary microbiota in the oral cavity seems attractive, it clearly needs further study.Acute radiation-related toxicities represent a clinicallyrelevant problem during curative radiotherapy (RT) for patients with head and neck cancer (HNC). Among different side-effects, oropharyngeal mucositis (OM) remains one of the most important issues for patients with HNC, with a negative impact on their quality of life (QoL), and also on locoregional control due to the need for treatment breaks that extend the planned treatment time (1-6).The development of OM is complex and begins from clonogenic death of basal stem cells due to DNA strand breaks caused by reactive oxygen species (7). Through the complex activation of several transcription factors, it seems to end with the production of pro-inflammatory cytokines that promote and amplify cellular damage to the oral mucosa (8). Despite recent improvements in our understanding of these processes, preventive and therapeutic management of OM is still a debated and open question. A large number of 1935 This article is freely accessible online.Correspondence to:

Background and purposeThe purpose of this study was to add, to the objective evaluation, an instrumental assessment of the skin damage induced by radiation therapy.Materials and methodsA group of 100 patients affected by breast cancer was recruited in the study over one year. Patients were divided into five groups of 20 patients. For each group it was prescribed a different topical treatment. The following products were used: Betaglucan, sodium hyaluronate (Neoviderm®), Vitis vinifera A. s-I-M.t-O.dij (Ixoderm®), Alga Atlantica plus Ethylbisiminomethylguaicolo and Manganese Cloruro (Radioskin1®) and Metal Esculetina plus Ginko Biloba and Aloe vera (Radioskin 2®); Natural triglycerides-fitosterols (Xderit®); Selectiose plus thermal water of Avene (Trixera+®). All hydrating creams were applied twice a day starting 15 days before and one month after treatment with radiations. Before and during treatment patients underwent weekly skin assessments and corneometry to evaluate the symptoms related to skin toxicity and state of hydration. Evaluation of acute cutaneous toxicity was defined according to the RTOG scale.ResultsAll patients completed radiotherapy; 72% of patients presented a G1 cutaneous toxicity, 18% developed a G2 cutaneous toxicity, 10% developed a G3 toxicity, no one presented G4 toxicity. The corneometry study confirmed the protective role of effective creams used in radiation therapy of breast cancer and showed its usefulness to identify radiation-induced dermatitis in a very early stage.ConclusionsThe preventive use of topic products reduces the incidence of skin side effects in patients treated with radiotherapy for breast cancer. An instrumental evaluation of skin hydration can help the radiation oncologist to use strategies that prevent the onset of toxicity of high degree. All moisturizing creams used in this study were equally valid in the treatment of skin damage induced by radiotherapy.

OBJECTIVE:To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years. METHODS: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed. RESULTS: Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two-and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001). CONCLUSION: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

Small-cell lung cancer (SCLC) is an aggressive tumor type with limited therapeutic options and poor prognosis. Chemotherapy regimens containing platinum represent the cornerstone of treatment for patients with extensive disease, but there has been no real progress for 30 years. The evidence that SCLC is characterized by a high mutational burden led to the development of immune-checkpoint inhibitors as single agents or in combination with chemotherapy. Randomized phase III trials demonstrated that the combination of atezolizumab (IMpower-133) or durvalumab (CASPIAN) with platinum-etoposide chemotherapy improved overall survival of patients with extensive disease. Instead, the KEYNOTE-604 study demonstrated that the addition of pembrolizumab to chemotherapy failed to significantly improve overall survival, but it prolonged progression-free survival. The safety profile of these combinations was similar with the known safety profiles of all single agents and no new adverse events were observed. Nivolumab and pembrolizumab single agents showed anti-tumor activity and acceptable safety profile in Checkmate 032 and KEYNOTE 028/158 trials, respectively, in patients with SCLC after platinum-based therapy and at least one prior line of therapy. Future challenges are the identification predictive biomarkers of response to immunotherapy in SCLC and the definition of the role of immunotherapy in patients with limited stage SCLC, in combination with radiotherapy or with other biological agents.