Acinic cell carcinomas (AciCCs) are malignant tumours of the salivary glands. The aim of this work was to analyse data from the national REFCOR multicenter cohort (i) to investigate the prognostic ...factors influencing survival outcomes in AciCC, (ii) to assess the impact on survival of postoperative radiotherapy (RT) in patients treated for AciCC without high-grade transformation and (iii) to explore the prognostic impact of prophylactic neck dissection (ND) in patients treated for AciCC of the major salivary glands.
Data from all the patients treated for salivary AciCC between 2009 and 2020 were extracted from the REFCOR database. Survival outcomes and prognostic factors influencing Disease-Free Survival (DFS) and Overall Survival (OS) were investigated using univariate and multivariate analyses. Propensity score matching was used to assess the impact of postoperative RT and prophylactic ND on DFS.
A total of 187 patients were included. After a median follow-up of 53 months, their 5-year OS and DFS rates were 92.8% and 76.2%, respectively. In multivariate analysis, male sex, older age, higher T and N status, and high grade were independently associated with a worse DFS. In the subpopulation analysed after propensity score matching, patients with cN0 AciCC without high-grade transformation who were treated by surgery and RT did not have an improved DFS compared to patients who were treated by surgery alone (hazard ratio (HR) = 0.87, p = 0.8). Factors associated with nodal invasion were T3–T4 status and intermediate/high histological grade. After propensity score matching, prophylactic ND was associated with a trend toward a better DFS (HR = 0.46, p = 0.16).
These results suggest that (i) long-term follow-up (>5 years) should be considered in patients with AciCC, (ii) treatment by surgery alone could be an option in selected cN0 patients with AciCC without high-grade transformation and (iii) prophylactic ND may be considered preferentially in patients with T3–T4 status and/or intermediate/high histological grade.
•The 5-year OS and DFS were 92.8% and 76.2%, respectively.•Male sex, higher T/N status, and high grade were independently associated with a worse DFS.•T3–T4 status and intermediate/high histological grade were associated with N+ status.•After PS matching, prophylactic ND was associated with a trend toward a better DFS.
Objective
Osteoradionecrosis (ORN) of the sphenoid is a rare but potentially lethal complication that can occur after irradiation of nasopharyngeal and clival malignancies. The objective of this ...study was to describe a multimodal treatment strategy tailored to the clinical signs and to the radiological extent of the disease, and to report on its preliminary results.
Methods
Retrospective monocentric study at a tertiary skull base center. Patients treated for a sphenoid ORN from January 2014 to August 2018 were identified and charts were retrospectively reviewed for demographics, histologic tumor type, previous treatments of the tumor, clinical signs at presentation, radiological data, treatment, and outcomes. Sphenoid ORN was treated by a combination of medical therapy, endovascular treatment, and/or surgery. The use of each of these therapeutic modalities was based on the extent of ORN and on the presenting signs.
Results
Seven patients were included: four patients underwent endovascular treatment with occlusion of the internal carotid artery, five patients underwent surgical debridement, and covering of the exposed bone by a local flap, seven patients received antibiotics (in combination with pentoxyphilline, tocopherol, and clodronate in one case). Three patients died after progression of the ORN. The global survival rate was 57% (4/7) with a mean follow‐up of 24 months. In one case, ORN was treated successfully by medical treatment only, with a combination of antibiotics, pentoxyphilline, tocopherol, and clodronate.
Conclusion
This retrospective study describes the results of a management strategy adapted to the extent of the disease in sphenoid ORN and based on medical therapy only, or on a combination of medical therapy, interventional radiology, and/or surgery.
Level of evidence
4
This study reports on 7 cases with sphenoid ORN and their management by a combination of medical therapy, endovascular treatment and/or surgery. The global survival rate was 57% (4/7) with a mean follow‐up of 24 months. One patient was successfully treated by medical treatment only, with a combination of antibiotics, pentoxyphilline, tocopherol and clodronate.
Objectives
The purpose of this work was to report outcomes of patients with nonmetastatic sinonasal squamous cell carcinoma (SNSCC) and to discuss the impact of elective neck irradiation (ENI) and ...selective neck dissection (SND) in clinically negative lymph node (N0) patients.
Methods
Data from 104 nonmetastatic SNSCC patients treated with curative intent were retrospectively analysed. Uni- and multivariate analyses were used to assess prognostic factors of overall survival (OS) and locoregional control (LRC).
Results
Median follow-up was 4.5 years. Eighty-five percent of tumours were stage III–IV. Treatments included induction chemotherapy (52.9 %), surgery (72 %) and radiotherapy (RT; 87 %). The 5‑year OS, progression-free survival, and LRC rates were 48, 44 and 57 %, respectively. Absence of surgery predicted a decrease of OS (hazard ratio HR 2.6; 95 % confidence interval CI 1.4–4.7), and LRC (HR 3.5; 95 % CI 1.8–6.8). Regional relapse was observed in 13/104 (13 %) patients and most common sites were level II (
n
= 12; 70.6 %), level III (
n
= 5; 29.4 %) and level Ib (
n
= 4; 23.5 %). Management of the neck in N0 patients (
n
= 87) included 11 % SND alone, 32 % ENI alone, 20 % SND + ENI and 37 % no neck treatment. In this population, a better LRC was found according to the management of the neck in favour of SND (94 % vs. 47 %;
p
= 0.002) but not ENI.
Conclusion
SND may detect occult cervical positive nodes, allowing selective postoperative RT. ENI (ipsilateral level II, ±Ib and III or bilateral) needs to be proposed in selected patients, especially when SND has not been performed.
: Nasopharyngeal carcinoma (NPC) is a major public health problem in several countries, especially those in Southeast Asia and North Africa. In its typical poorly differentiated form, the ...Epstein-Barr virus (EBV) genome is present in the nuclei of all malignant cells with restricted expression of a few viral genes. The malignant phenotype of NPC cells results from the influence of these viral products in combination with cellular genetic, epigenetic and functional alterations. With regard to host/tumor interactions, NPC is a remarkable example of immune escape in the context of a hot tumor.
: This article has an emphasis on emerging therapeutic targets that are considered upstream or at an early stage of clinical application. It examines targets related to cellular oncogenic alterations, latent EBV infection and tumor interactions with the immune system.
: There is a remarkable emergence of new agents that target EBV products. The clinical application of these agents would benefit from a systematic and comprehensive molecular classification of NPCs and from easy access to pre-clinical models in public repositories. There is a strong rationale for more investigations on the potential of immune modulators, especially those related to NK cells.
Patients with synchronous metastatic head and neck squamous cell carcinomas (mHNSCC) are at risk of locoregional progression associated with significant morbidity and mortality. The aim of this study ...is to assess whether the addition of aggressive locoregional treatment to systemic therapy could be associated with an improved overall survival (OS) compared to systemic therapy alone in upfront mHNSCC patients.
This retrospective study included patients presenting with previously untreated mHNSCC who underwent first-line systemic therapy at a single institution between 1998 and 2018. Locoregional treatment was defined as either exclusive locoregional radiotherapy (RT) or surgery with or without adjuvant RT.
One hundred forty-eight patients were included. Eighty patients were treated with systemic therapy alone and 68 patients were treated with a combination of locoregional treatment and systemic therapy. Median overall survival (OS) was 13 months 10.7-15 and median progression free survival (PFS) was 7.7 month 6.5-8.9. The addition of a locoregional treatment to systemic therapy compared to systemic therapy alone was associated with improved survival (1-year OS, 65.8% vs. 41.1%, p < .001, and 1-year PFS, 42.5% vs. 18.5%, p < .001). Moreover, RT dose equal to 70 Gy was associated with even longer OS compared to a RT dose below 70 Gy and to no locoregional treatment (23.4 vs. 12.7 vs 7.5 months respectively). In a subgroup analysis on 75 patients presenting with a responding or stable metastatic disease after first-line systemic therapy, oropharyngeal primary tumor site and the addition of a locoregional treatment, especially a high radiation dose of 70 Gy, were evidenced as independent prognostic factors for improved OS.
The addition of a high-dose RT locoregional treatment to systemic therapy is associated with prolonged OS in patients with synchronous mHNSCC and should be discussed for patients who respond to or have a stable disease after first-line systemic therapy.
•In a database comprising 8,134 patients, the 5-year overall survival rate for rare head and neck cancers was 71% (95% CI: 0.69–0.73), while the 5-year event-free survival rate was comparatively ...lower at 46% (95% CI: 0.44–0.48).•Among the ten most common histologies, acinar cell carcinoma demonstrated a more favourable prognosis. Conversely, mucous melanoma exhibited the poorest prognosis, with a median survival of 43 months.•Furthermore, patients diagnosed with salivary gland cancers exhibited superior 5-year overall survival rates and a lower incidence of recurrences compared to those with rare cancers in the nasal fossae/sinus or laryngeal/hypopharyngeal regions.
Rare cancers constitute less than 10% of head and neck cancers and lack sufficient evidence for standardized care. The French Rare Head and Neck Cancer Expert Network (REFCOR) as established a national database to collect data on these rare cancers. This study aims to describe patient and tumour characteristics in this database.
Prospective data collection was conducted across multiple centers. Survival analyses were performed using Kaplan Meier method and Log Rank test. Odds ratios were used for comparing proportions.
A total of 7208 patients were included over a period of 10 years. The most frequent histologies were: Not Otherwise Specified (NOS) adenocarcinoma 13 %, adenoid cystic carcinoma 12 %, squamous cell carcinoma of rare locations 10 %, mucoepidermoid carcinoma 9 %, intestinal-type adenocarcinoma (8 %). Tumours were located in sinonasal area (38 %); salivary glands (32 %); oral cavity / oropharynx / nasopharynx (16 %); larynx / hypopharynx (3 %); ears (1 %); others (3 %). Tumours were predominantly classified as T4 (23 %), N0 (54 %), and M0 (62 %). Primary treatment approach involved tumour resection (78 %) and / or radiotherapy (63 %). Patients with salivary gland cancers exhibited better 5-year overall survival (OS) rates (p < 0.05), and lower recurrence rates compared to patients with sinonasal, laryngeal/ hypopharyngeal cancers. No significant differences were observed in the other comparisons. Acinar cell carcinoma demonstrated the best OS while mucous melanoma had the poorest prognosis.
Melanoma, carcinoma NOS, and sinonasal undifferenciated carcinoma still have poor prognoses. Efforts are being made, including training and guidelines, to expand network coverage (REFCOR, EURACAN), improve data collection and contribute to personalized therapies.
EBV-related nasopharyngeal carcinomas (NPCs) still raise serious therapeutic problems. The therapeutic potential of the histone-deacetylase (HDAC) inhibitor Abexinostat was investigated using 5 ...preclinical NPC models including 2 patient-derived xenografts (C15 and C17). The cytotoxicity of Abexinostat used either alone or in combination with cis-platin or irradiation was assessed in vitro by MTT and clonogenic assays using 2 EBV-negative (CNE1 and HONE1) and 3 EBV-positive NPC models (C15, C17 and C666-1). Subsequently, the 3 EBV-positive models were used under the form of xenografts to assess the impact of systemic treatments by Abexinostat or combinations of Abexinostat with cis-platin or irradiation. Several cell proteins known to be affected by HDAC inhibitors and the small viral non-coding RNA EBER1 were investigated in the treated tumors. Synergistic cytotoxic effects of Abexinostat combined with cis-platin or irradiation were demonstrated in vitro for each NPC model. When using xenografts, Abexinostat by itself (12.5 mg/kg, BID, 4 days a week for 3 weeks) had significant anti-tumor effects against C17. Cooperative effects with cis-platin (2 mg/kg, IP, at days 3, 10 and 17) and irradiation (1 Gy) were observed for the C15 and C17 xenografts. Simultaneously two types of biological alterations were induced in the tumor tissue, especially in the C17 model: a depletion of the DNA-repair protein RAD51 and a stronger in situ detection of the small viral RNA EBER1. Overall, these results support implementation of phase I/II clinical trials of Abexinostat for the treatment of NPC. A depletion of RAD51 is likely to contribute to the cooperation of Abexinostat with DNA damaging agents. Reduction of RAD51 combined to enhanced detection of EBER 1 might be helpful for early assessment of tumor response.
BACKGROUND: Because latent Epstein Barr (EBV)-infection is a specific characteristic of malignant nasopharyngeal carcinoma (NPC), various molecules of viral origin are obvious candidate biomarkers in ...this disease. In a previous study, we could show in a few clinical samples that it was possible to detect a category of EBV microRNAs called miR-BARTs in the plasma of at least a fraction of NPC patients. The first aim of the present study was to investigate the status of circulating miR-BART17-5p (one of the miR-BARTs hereafter called miR-BART17) and EBV DNA in a larger series of NPC plasma samples. The second aim was to determine whether or not circulating miR-BART17 was carried by plasma exosomes. PATIENTS AND METHODS: Plasma samples were collected from 26 NPC patients and 10 control donors, including 9 patients with non-NPC Head and Neck squamous cell carcinoma and one healthy EBV carrier. Concentrations of miR-BART17 and two cellular microRNAs (hsa-miR-16 and -146a) were assessed by real-time quantitative PCR with spike-in normalization and absolute quantification. In addition, for 2 patients, exosome distributions of miR-BART17 and miR-16 were investigated following plasma lipoprotein fractionation by isopycnic density gradient ultrcentrifugation. RESULTS: The miR-BART17 was significantly more abundant in plasma samples from NPC patients compared to non-NPC donors. Above a threshold of 506 copies/mL, detection of miR-BART17 was highly specific for NPC patients (ROC curve analysis: AUC=0.87 with true positive rate = 0.77, false positive rate = 0.10). In this relatively small series, the concentration of plasma miR-BART17 and the plasma EBV DNA load were not correlated. When plasma samples were fractionated, miR-BART17 co-purified with a protein-rich fraction but not with exosomes. CONCLUSIONS: Detection of high concentrations of plasma miR-BART17 is consistent in NPC patients. This parameter is, at least in part, independent of the viral DNA load. Circulating miR-BART17 does not co-purify with exosomes.
Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common, potentially severe and dose-limiting adverse effect; however, it is poorly investigated at an early stage due to the lack of a simple ...assessment tool. As sweat glands are innervated by small autonomic C-fibers, sudomotor function testing has been suggested for early screening of peripheral neuropathy. This study aimed to evaluate Sudoscan, a non-invasive and quantitative method to assess sudomotor function, in the detection and follow-up of CIPN. Eighty-eight patients receiving at least two infusions of Oxaliplatin only (45.4 %), Paclitaxel only (14.8 %), another drug only (28.4 %) or two drugs (11.4 %) were enrolled in the study. At each chemotherapy infusion the accumulated dose of chemotherapy was calculated and the Total Neuropathy Score clinical version (TNSc) was carried out. Small fiber neuropathy was assessed using Sudoscan (a 3-min test). The device measures the Electrochemical Skin Conductance (ESC) of the hands and feet expressed in microSiemens (µS). For patients receiving Oxaliplatin mean hands ESC changed from 73 ± 2 to 63 ± 2 and feet ESC from 77 ± 2 to 66 ± 3 µS (p < 0.001) while TNSc changed from 2.9 ± 0.5 to 4.3 ± 0.4. Similar results were observed in patients receiving Paclitaxel or another neurotoxic chemotherapy. During the follow-up, ESC values of both hands and feet with a corresponding TNSc < 2 were 70 ± 2 and 73 ± 2 µS respectively while they were 59 ± 1.4 and 64 ± 1.5 µS with a corresponding TNSc ≥ 6 (p < 0.0001 and p = 0.0003 respectively). This preliminary study suggests that small fiber neuropathy could be screened and followed using Sudoscan in patients receiving chemotherapy.
Abstract Circulating (CTCs) and disseminated tumor cells (DTCs) are two different steps in the metastatic process. Several recent techniques have allowed detection of these cells in patients, and ...have generated many results using different isolation techniques in small cohorts. Herein, we review the detection results and their clinical consequence in esophageal, gastric, pancreatic, colorectal, and liver carcinomas, and discuss their possible applications as new biomarkers.
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