RANK expression in EBV positive nasopharyngeal carcinoma metastasis: A ready-to-treat target?

Epstein Barr Virus (EBV) related Nasopharyngeal Carcinoma (NPC), is an highly chemo- and radiosensitive endemic malignancy in southeast Asia. More than one third of locally advanced cases relapse after curative treatment, especially because of bone, liver and lung metastases. Lymphocyte sub-populations favour EBV-associated carcinogenesis and tumour progression and several strategies aim to reverse this phenomenon. Receptor activator of NF-kB (RANK) and its Ligand (RANKL), key regulator of bone metabolisms, are expressed in several malignancies and tumorinfiltrating Tregs. We collected 17 paired FFPE specimen of primary and metachronous metastatic or regionally relapsed EBV related NPC and evaluated RANK expression by immunohistochemistry. All primary tumour specimens resulted not evaluable whereas all metastatic specimens, regardless of sites, showed high RANK IHC expression in the tumor with no staining in normal surrounding tissues. This observation deserves further clarifications and could open the way to trials testing the hypotesis that targeting the RANK/RANKL pathway with denosumab, an already available, clinically approved monoclonal antibody for metastatic bone lesions, might restore proper antitumor immune response in NPC metastatic patients

Failure of Further Validation for Survival Nomograms in Oropharyngeal Cancer: Issues and Challenges

Purpose: To retrospectively test 2 nomograms recently validated as prognostic tools for patients with oropharyngeal cancer treated with curative radiation-based therapy, in 184 consecutive subjects treated from April 2004 to January 2016. Patient and Methods: Complete information regarding disease, survival status, and nomogram covariates was retrieved for 174 patients, with a median follow-up of 51 months. Calibration of the nomograms was obtained by evaluating the ability to accurately predict the absolute risk level; discriminative ability estimated by the Harrell C statistic was tested by assessing the ability of the nomograms to rank the patients from low risk to high risk. Results: The outcome predicted by the nomograms was worse than observed, especially for progression-free survival. This may be due to several factors: geographic and genetic background, smoking, alcohol use, the different national health system organization, which provides universal and free-of-charge coverage to all individuals, and the setting of treatment in clinical practice, outside of clinical trials. Conclusions: Our results show that the usefulness of nomograms to predict outcome of oropharyngeal cancer may not be generalizable to patients of different countries. Further studies are needed to clarify whether sociodemographic, epidemiologic, and cultural scenarios may seriously affect the prognostic ability of newly developed predictive tools

Postoperative radiotherapy (PORT) for early oral cavity cancer (pT1-2,N0-1): A review

Early stage (T1-2, N0-1) oral squamous cell carcinoma (OSCC) has a generally favorable prognostic outcome. However, locoregional recurrences can occur in up to 30\u201335% of patients, and 20% will eventually die of disease. National and international treatment guidelines do not recommend the use of postoperative radiotherapy (PORT) in a setting of early OSCC, and highlight surgery alone as the standard single modality treatment. Notwithstanding, the negative prognostic impact of some adverse pathological features, such as perineural and lymphovascular invasion, poor differentiation, depth of invasion >4\u2009mm, and presence of nodal metastasis, is well known. The advantages of PORT in such scenarios are still debated. The aim of this study was to review the more recent literature to provide evidence on the benefits of PORT in the context of early stage OSCC

Multivariable model for predicting acute oral mucositis during combined IMRT and chemotherapy for locally advanced nasopharyngeal cancer patients

Introduction/objective: Oral and oropharyngeal mucositis (OM) represents a multifactorial and complex interplay of patient-, tumor-, and treatment-related factors. We aimed to build a predictive model for acute OM for locally advanced nasopharyngeal carcinoma (NPC) patients by combining clinical and dosimetric factors. Materials/methods: A series of consecutive NPC patients treated curatively with IMRT/VMAT + chemotherapy at 70 Gy (2–2.12 Gy/fr) was considered. For each patient, clinical- tumor- and treatment-related data were retrospectively collected. oral cavity (OC) and parotid glands (PG, considered as a single organ) were selected as organs-at-risk (OARs). Acute OM was assessed according to CTCAE v4.0 at baseline and weekly during RT. Two endpoints were considered: grade ≥3 and mean grade ≥1.5. DVHs were reduced to Equivalent Uniform Dose (EUD). Dosimetric and clinical/treatment features selected via LASSO were inserted into a multivariable logistic model. Goodness of fit was evaluated through Hosmer-Lemeshow test and calibration plot. Results: Data were collected for 132 patients. G ≥ 3 and mean G ≥ 1.5 OM were reported in 40 patients (30%). Analyses resulted in a 3-variables model for G ≥ 3 OM, including OC EUD with n = 0.05 (OR = 1.02), PG EUD with n = 1 (OR = 1.06), BMI ≥ 30 (OR = 3.8, for obese patients), and a single variable model for mean G ≥ 1.5 OM, i.e. OC EUD with n = 1 (mean dose) (OR = 1.07). Calibration was good in both cases. Conclusion: OC mean dose was found to impact most on OM duration (mean G ≥ 1.5), while G ≥ 3 OM was associated to a synergic effect between PG mean dose and high dose received by small OC volumes, with BMI acting as a dose-modifying factor

Multivariable model for predicting acute oral mucositis during combined IMRT and chemotherapy for locally advanced nasopharyngeal cancer patients

Introduction/objective: Oral and oropharyngeal mucositis (OM) represents a multifactorial and complex interplay of patient-, tumor-, and treatment-related factors. We aimed to build a predictive model for acute OM for locally advanced nasopharyngeal carcinoma (NPC) patients by combining clinical and dosimetric factors. Materials/methods: A series of consecutive NPC patients treated curatively with IMRT/VMAT + chemotherapy at 70 Gy (2\u20132.12 Gy/fr) was considered. For each patient, clinical- tumor- and treatment-related data were retrospectively collected. oral cavity (OC) and parotid glands (PG, considered as a single organ) were selected as organs-at-risk (OARs). Acute OM was assessed according to CTCAE v4.0 at baseline and weekly during RT. Two endpoints were considered: grade 653 and mean grade 651.5. DVHs were reduced to Equivalent Uniform Dose (EUD). Dosimetric and clinical/treatment features selected via LASSO were inserted into a multivariable logistic model. Goodness of fit was evaluated through Hosmer-Lemeshow test and calibration plot. Results: Data were collected for 132 patients. G 65 3 and mean G 65 1.5 OM were reported in 40 patients (30%). Analyses resulted in a 3-variables model for G 65 3 OM, including OC EUD with n = 0.05 (OR = 1.02), PG EUD with n = 1 (OR = 1.06), BMI 65 30 (OR = 3.8, for obese patients), and a single variable model for mean G 65 1.5 OM, i.e. OC EUD with n = 1 (mean dose) (OR = 1.07). Calibration was good in both cases. Conclusion: OC mean dose was found to impact most on OM duration (mean G 65 1.5), while G 65 3 OM was associated to a synergic effect between PG mean dose and high dose received by small OC volumes, with BMI acting as a dose-modifying factor