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Radiotherapy (RT) plus the anti-EGFR monoclonal antibody Cetuximab (CTX) is an effective combination therapy for a subset of head and neck squamous cell carcinoma (HNSCC) patients. However, predictive markers of efficacy are missing, resulting in many patients treated with disappointing results and unnecessary toxicities. Here, we report that activation of EGFR upregulates miR-9 expression, which sustains the aggressiveness of HNSCC cells and protects from RT-induced cell death. Mechanistically, by targeting KLF5, miR-9 regulates the expression of the transcription factor Sp1 that, in turn, stimulates tumor growth and confers resistance to RT+CTX in vitro and in vivo. Intriguingly, high miR-9 levels have no effect on the sensitivity of HNSCC cells to cisplatin. In primary HNSCC, miR-9 expression correlated with Sp1 mRNA levels and high miR-9 expression predicted poor prognosis in patients treated with RT+CTX. Overall, we have discovered a new signaling axis linking EGFR activation to Sp1 expression that dictates the response to combination treatments in HNSCC. We propose that miR-9 may represent a valuable biomarker to select which HNSCC patients might benefit from RT+CTX therapy., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Low-dose radiotherapy (LDRT) given in 2 × 2 Gy is a highly effective and safe treatment for palliation of indolent lymphomas. Otherwise, very little regarding the use of LDRT for diffuse large B-cell lymphoma (DLBCL) has been investigated. We designed a phase 2 trial of LDRT in patients with DLBCL with indication for palliative radiation. Low-dose radiotherapy was administered on symptomatic areas only. Clinical response was assessed 21 days after LDRT and defined as reduction >50% of maximum diameter of the radiated lesions. Quality of life was scored by the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Tumor subtype (germinal center B-cell type versus activated B-cell type) and the presence of TP53 mutations in pathologic specimens of the target lesion were also evaluated. Twenty-three of twenty-five radiated patients were evaluable for response, and 2 died of disease before the visit at 21 days. The overall response rate was 70% (16 of 23 patients), with 7 complete responses and 9 partial responses (mean duration of response, 6 months; range, 1-39 months). Fifteen patients answered to the QLQ-C30 questionnaires, and an improved quality of life was documented in 9 cases. TP53 mutations were detected in 2 of 6 (33%) nonresponders and in none of the responders (P = .12). Germinal center B-cell type responded better than activated B-cell type (response rate was 83% and 29%, respectively, P = .01). These findings indicate that LDRT is effective for palliation in patients with DLBCL., (Copyright © 2016 John Wiley & Sons, Ltd.)

Objective: The aim of this study was to evaluate the oncologic outcomes after a selective neck dissection (SND), both in elective and therapeutic settings, with particular regard to regional recurrence rate., Methods: Retrospective analysis of 827 patients with head and neck primary tumors submitted to SND from 1999 to 2011 in two large hospital centers of northern Italy., Results: A total of 40 neck recurrences were found in the whole series, with the same incidence after primary or salvage surgery (4.4% and 5.2%, respectively), but only 22 neck recurrences occurred in the same side of the dissected neck (3.0%). Factors predicting an increase of ipsilateral neck relapse were pathologically positive nodes, number of positive nodes, and nodal ratio (ratio between positive nodes and total nodal removed), but the risk of regional relapse did not exceed 5.0% in any subgroups. A total of 320 patients (39%) had postoperative radiotherapy (52.0% and 22.0% after primary and salvage surgery, respectively). Considering the primary surgery group alone, postoperative radiotherapy produced only a light reduction of homolateral neck recurrence rate in patients with pathological positive nodes (2.4% vs. 5.0%), but it impacted significantly disease-specific survival, both in pathological classification of nodes (pN)1 and pN2-3 patients., Conclusion: The SND can be considered a safe and sound procedure both in primary surgery and in salvage setting. Postoperative radiotherapy adds minor advantage to regional control only in node-positive patients but may impact survival., Level of Evidence: 4., (© 2015 The American Laryngological, Rhinological and Otological Society, Inc.)

One hundred fifty-two unselected, consecutive patients with T1-2N0 laryngeal squamous cell carcinoma received radical radiation therapy at the Division of Radiotherapy, Centro di Riferimento Oncologico, Aviano, Italy. Thirty-one (20.4%) of the patients showed disease recurrence or persistence (R/P) after radiotherapy. Flow-cytometric DNA ploidy measurements were performed in 72 cases; 20 had tumor R/P and 52 did not. Tumor R/P occurred more frequently (in 17 [85%] of 20 cases) in patients with diploid tumors. The hazard ratio of recurrence in diploid tumors as compared with aneuploid tumors, after inclusion of all the other significant prognostic factors in a Cox proportional hazards model, was 8.9 (P < .01). Therefore DNA ploidy seems to be an important marker of tumor R/P in patients with T1-2N0 laryngeal carcinoma after radiotherapy.