Magnetic Resonance Imaging after Nasopharyngeal Endoscopic Resection and Skull Base Reconstruction.

Background: Postoperative imaging after nasopharyngeal endoscopic resection (NER) and skull base reconstruction is quite challenging due to the complexity of the post-surgical and regional anatomy. Methods: In this retrospective observational study, we included patients treated with NER from 2009 to 2019 and submitted to Magnetic Resonance Imaging (MRI) 6 and 12 months after surgery. A radiologist with 15 years of experience analyzed all MRI scans. Results: A total of 50 patients were considered in this study, 18 of whom were excluded due to imaging unavailability, and 16 of whom were not considered due to major complications and/or persistent disease. Sixteen patients were evaluated to identify the expected findings. Inflammatory changes were observed in 16/64 subsites, and regression of these changes was observed in 8/64 at 1 year. Fibrosis was observed in 5/64 subsites and was unmodified at 1 year. The nasoseptal flap showed homogeneous enhancement at 6 months (100%) and at 1 year. The temporo-parietal fascia flap (TPFF) showed a decrease in the T2- signal intensity of the mucosal layer in 57% of the patients at 1 year and a decrease in enhancement in 43%. Conclusions: Identifying the expected findings after NER and skull base reconstruction has a pivotal role in the identification of complications and recurrence.

MRI radiomics in head and neck cancer from reproducibility to combined approaches.

The clinical applicability of radiomics in oncology depends on its transferability to real-world settings. However, the absence of standardized radiomics pipelines combined with methodological variability and insufficient reporting may hamper the reproducibility of radiomic analyses, impeding its translation to clinics. This study aimed to identify and replicate published, reproducible radiomic signatures based on magnetic resonance imaging (MRI), for prognosis of overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Seven signatures were identified and reproduced on 58 HNSCC patients from the DB2Decide Project. The analysis focused on: assessing the signatures' reproducibility and replicating them by addressing the insufficient reporting; evaluating their relationship and performances; and proposing a cluster-based approach to combine radiomic signatures, enhancing the prognostic performance. The analysis revealed key insights: (1) despite the signatures were based on different features, high correlations among signatures and features suggested consistency in the description of lesion properties; (2) although the uncertainties in reproducing the signatures, they exhibited a moderate prognostic capability on an external dataset; (3) clustering approaches improved prognostic performance compared to individual signatures. Thus, transparent methodology not only facilitates replication on external datasets but also advances the field, refining prognostic models for potential personalized medicine applications.

Multidisciplinary Decision-Making-ITAlian Consensus After Two Years of Real Practice on the Management of Severe Uncontrolled CRSwNP by Biologics (ITACA Study).

PURPOSE OF REVIEW: We aimed to reach an Italian multidisciplinary consensus on some crucial aspects of treatment decision making in CRSwNP, following 2 years of clinical experience in order to support specialists in the management of CRSwNP in clinical practice. We addressed issues relating to therapeutic decision-making and shared criteria for the treatment choice, as well as appropriate timing and criteria for evaluating treatment response, and highlighted the need for repeated multidisciplinary assessments. RECENT FINDINGS: A national survey has been conducted recently to understand how rhinology practice has changed in Italy with the advent of biologics and how this affects patients with uncontrolled, severe CRSwNP. Despite the many published consensus documents, practical recommendations, and protocols on the use of biologics in CRSwNP, heterogenous behaviors in practice are still observed mainly conditioned by the novelty of the topic. The consensus procedure followed a modified Delphi approach. The scientific board included 18 otorhinolaryngologists and 8 allergists, who selected the 4 main topics to be addressed and developed overall 20 statements. Consensus on these statements was sought by a larger group of 48 additional experts, through two rounds of voting, the first web-based, the second in presence with discussion and possible refinement of the statements. The statements reaching an average score ≥ 7 at the second voting round were approved. Five statements were proposed for each of the following topics: baseline evaluation of patients eligible for biologic therapy; choice between different therapeutic options; assessment of the response to biologic treatment; multidisciplinary management. At the first voting round, 19 out of the 20 statements reached a mean score ≥ 7. Following the discussion and a few consequent amendments, at the second round of voting all the 20 statements were approved.

Measuring financial toxicity in head and neck cancer: a systematic review.

Objective: The current study systematically reviews the literature about financial toxicity (FT) in head and neck cancer patients. Three databases were reviewed: PubMed, Scopus and Web of Science. Methods: Full text English papers published from 2000 to 2022 reporting on quantitative results about FT in head and neck cancer survivors collected through structured questionnaires or interviews were included. Results: Twenty-seven articles were included. Most of the articles were published after 2015 and from United States. There was a slight prevalence of papers dealing with oropharyngeal cancer, squamous-cell carcinoma and locally advanced head and neck cancer. Measures of FT were obtained through validated questionnaires like COST, FIT and FDQ. Collected data were mostly referrable to financial spending, financial resources, psychosocial aspect, support seeking, coping care and coping lifestyle subdomain. FT scores by COST were found to be worse in the COVID era. Financial counseling and adequate information about the costs of treatment were two effective strategies to mitigate FT. Conclusions: FT is a relatively new challenge in head and neck cancer treatment, whose expenses are higher than therapies for other cancers. A universal method to assess FT and a unified guideline for the administration of questionnaires are needed to mitigate FT and to improve patient outcomes.

Evaluation of DNA methylation levels of SEPT9 and SHOX2 in plasma of patients with head and neck squamous cell carcinoma using droplet digital PCR.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most commonly diagnosed cancer globally. HNSCC develops from the mucosa of the oral cavity, pharynx and larynx. Methylation levels of septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in circulating cell­free DNA (ccfDNA) are considered epigenetic biomarkers and have shown predictive value in preliminary reports in HNSCC. Liquid biopsy is a non­invasive procedure that collects tumor­derived molecules, including ccfDNA. In the present study, a droplet digital PCR (ddPCR)­based assay was developed to detect DNA methylation levels of circulating SEPT9 and SHOX2 in the plasma of patients with HNSCC. The assay was first set up using commercial methylated and unmethylated DNA. The dynamic changes in the methylation levels of SEPT9 and SHOX2 were then quantified in 20 patients with HNSCC during follow­up. The results highlighted: i) The ability of the ddPCR­based assay to detect very low copies of methylated molecules; ii) the significant decrease in SEPT9 and SHOX2 methylation levels in the plasma of patients with HNSCC at the first time points of follow­up with respect to T0; iii) a different trend of longitudinally DNA methylation variations in small groups of stratified patients. The absolute and precise quantification of SEPT9 and SHOX2 methylation levels in HNSCC may be useful for studies with translational potential.

Compartmental surgery for T4b oral squamous cell carcinoma involving the masticatory space.

PURPOSE OF REVIEW: This review aims to describe the oncological outcomes of T4b oral squamous cell carcinomas (OSCC) with masticatory space involvement as well as the surgical approaches that are able to achieve compartmental 'en bloc' resection of these lesions. RECENT FINDINGS: The masticatory space is subdivided into infra-notch and supra-notch spaces according to the axial plane passing through the mandibular notch between the coronoid process and the condyle neck. Compartmental resection for T4b OSCC with masticatory space invasion can be successfully achieved via purely external approaches or combining external and transnasal endoscopic routes. Infra-notch T4b OSCC showed survival outcomes comparable to T4a OSCC, thus prompting treatment with curative intent. SUMMARY: Compartmental resection of the masticatory space is technically feasible with comprehensive control of tumour margins. Use of a transnasal endoscopic anterior route within a multiportal approach may provide better control of margins at the level of the pterygo-maxillary fissure. Equivalent survival outcomes between T4a and infra-notch T4b OSCC are reported. Thus, a downstaging of the latter to T4a is advisable and compartmental surgery of such advanced lesions could be considered as a first-line treatment option in selected patients.

Nasoseptal flap with extended pedicle dissection based on the maxillary artery: Clinical series of 55 cases.

KEY POINTS: Nasoseptal flap with extended pedicle dissection is a low morbidity and high success rate flap. It is a flap that can be applied to reconstruct a wide range of ipsilateral skull base defects.

Computer-aided designed 3D-printed polymeric scaffolds for personalized reconstruction of maxillary and mandibular defects: a proof-of-concept study.

PURPOSE: To investigate the potential reconstruction of complex maxillofacial defects using computer-aided design 3D-printed polymeric scaffolds by defining the production process, simulating the surgical procedure, and explore the feasibility and reproducibility of the whole algorithm. METHODS: This a preclinical study to investigate feasibility, reproducibility and efficacy of the reconstruction algorithm proposed. It encompassed 3 phases: (1) scaffold production (CAD and 3D-printing in polylactic acid); (2) surgical simulation on cadaver heads (navigation-guided osteotomies and scaffold fixation); (3) assessment of reconstruction (bone and occlusal morphological conformance, symmetry, and mechanical stress tests). RESULTS: Six cadaver heads were dissected. Six types of defects (3 mandibular and 3 maxillary) with different degree of complexity were tested. In all case the reconstruction algorithm could be successfully completed. Bone morphological conformance was optimal while the occlusal one was slightly higher. Mechanical stress tests were good (mean value, 318.6 and 286.4 N for maxillary and mandibular defects, respectively). CONCLUSIONS: Our reconstructive algorithm was feasible and reproducible in a preclinical setting. Functional and aesthetic outcomes were satisfactory independently of the complexity of the defect.

Prognostic Value of Anteroposterior Extension in Oral Tongue and Floor Squamous Cell Carcinoma.

Importance: The tongue and oral floor represent the most involved subsite by oral cancer, and there are no reported systems to classify anteroposterior tumor extension with prognostic effect. In other cancers, the anterior vs posterior tumor extension is a relevant prognostic factor. Objective: To establish whether anterior vs posterior tumor extension may represent a prognostic factor in oral tongue and floor squamous cell carcinoma (OTFSCC). Design, Setting, and Participants: This was a retrospective cohort study of patients who underwent surgery for OTFSCC from January 1, 2010, to December 31, 2021, at 2 tertiary-level academic institutions in Italy (University of Padua and University of Brescia). Patients eligible for the study had histologically proven primary OTFSCC; underwent surgery-based, curative treatment; and had available preoperative contrast-enhanced imaging. Exposures: Four anatomical lines were designed to assess tumor extension: (1) chin-palate line (CPL), (2) chin-basion line, (3) Stensen duct line, and (4) lingual septum line. Preoperative imaging was re-evaluated, and tumor extension was classified as either anterior or posterior according to the lines. Main Outcomes and Measures: Overall survival and time to recurrence (TTR) were evaluated according to tumor extension. These outcomes were reported as 5-year survival rates with 95% CIs. Results: Of the 133 patients included, 79 (59.4%) were male, and the mean (SD) age was 62.7 (15.4) years. The 5-year TTR difference was higher for posterior vs anterior OTFSCC classified according to CPL (21.0%; 95% CI, 8.3%-33.7%), Stensen duct line (15.5%; 95% CI, 1.0%-30.0%), and lingual septum line (17.2%; 95% CI, 2.2%-32.3%). Overall survival analysis showed similar results. At the multivariable analysis on TTR, N status (adjusted hazard ratio [HR], 3.0; 95% CI, 1.2-7.1) and anteroposterior classification according to CPL (adjusted HR, 7.1; 95% CI, 0.9-54.6) were the variables associated with the highest adjusted HRs. Conclusions and Relevance: In this cohort study, OTFSCC with a posterior extension to the CPL was associated with a higher risk of recurrence and death. This analysis suggests that the poor prognosis conveyed by the posterior tumor extension is independent of other relevant prognosticators except for the burden of nodal disease. This estimate is not precise and does not allow for definitive clinically important conclusions; therefore, further prospective studies are necessary to confirm these data.

Stability of circulating miRNA in saliva: The influence of sample associated pre-analytical variables.

BACKGROUND AND AIMS: Increasing evidence supports the practicability of salivary cell-free (cf) miRNA as liquid biopsy markers in cancers. Its successful translation in the clinical setting requires reproducible approaches for saliva manipulation, in order to control for pre-analytical variables influencing miRNA stability. This study aims to define the optimal conditions to maintain the integrity of saliva during collection, transport and processing with respect to cf-miRNA quantification. MATERIALS AND METHODS: Saliva was collected from 20 healthy subjects and 8 oral cancer patients. Two sampling methods were tested and different storage temperatures and times were evaluated. Salivary expression level of target miRNAs was quantified by qPCR. Comparison between group mean values at specific conditions were performed using paired t-tests. Agreement between measurements was evaluated using a Bland-Altman plot. RESULTS: Different collection methods revealed comparable levels of salivary miR-484 and miR-106b-5p in both subject cohorts. MiRNAs were stable for up to 48 h at 4 °C in saliva supernatant, showing significant alteration after 96 h. Mid-term storage of supernatant at -20 °C decreased miRNA stability significantly compared to standard -80 °C. CONCLUSIONS: Cf-miRNA in saliva were slightly altered by collection methods and storage conditions, both in healthy and in pathological contexts, and remained stable for a period of time compatible with main clinical routine needs.

Chronic Rhinosinusitis with Nasal Polyps: A Survey on Routine Management and Evaluation of Disease Control in Practice.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease with a significant impact on quality of life. The overall goal of CRSwNP management, as with other chronic conditions, is to achieve "disease control", and for that reason, a definition of control of disease is pivotal in deciding the best treatment strategy. Although many staging systems have already been developed to evaluate the disease, disease control is not yet to be standardized, and a specific tool that is consistently applied and accepted by all practitioners is still missing in daily clinical practice. To gain an overview of the implementation and limitations of existing guidelines and to shed light on real-life definitions of control and disease severity, we conducted a nationwide survey of otorhinolaryngologists routinely treating CRSwNP to identify unmet clinical needs in Italy. The results showed homogeneous responses regarding the knowledge contained in international guidelines while highlighting the difficulty of their implementation in day-to-day practice. Respondents called attention to the importance of clinical symptoms, giving more weight to the patient's perspective. Among the symptoms to be considered, respondents emphasized nasal obstruction, followed by loss of sense of smell and rhinorrhea. Others also believe that the physician's perspective should be considered, and the inclusion of endoscopy as a measure of control was warranted by many. The need for a specific tool that is able to unequivocally ascertain disease control is increasingly pivotal in this new era of biologics for treating CRSwNP.

Hemicricoidectomy with modified rotational thyro-crico-tracheal anastomosis: a newborn in the family of crico-tracheal resection and anastomosis techniques.

Objective: The aim of the present study is to describe our novel surgical technique of hemicricoidectomy and reconstruction with modified rotational thyro-crico-tracheal anastomosis for the treatment of non-squamous cell subglottic tumours. The procedure has been defined as Type E crico-tracheal resection and anastomosis (CTRA) following the University of Brescia (C)TRA classification introduced elsewhere. Methods: A detailed anatomical step-by-step dissection was reproduced and illustrated on a cadaveric laryngo-tracheal specimen. Moreover, oncological and functional outcomes of the first 5 patients who underwent Type E CTRA at our Institution between October 2016 and September 2022 are described. Results: Three patients underwent Type E CTRA for cricoid chondrosarcoma (CS) and 2 patients for subglottic adenoid cystic carcinoma (ACC). No post-operative complication was reported. All patients maintained intact oral intake and an intelligible voice at discharge. All but one patient with obstructive sleep apnoea hypopnea syndrome and lung comorbidity were successfully decannulated before discharge. At the last follow-up (April 2023), one patient experienced local recurrence of CS that was still amenable to conservative treatment by transoral debulking, while the remaining patients were free of disease. Conclusions: With the proper indications, Type E CTRA is a feasible and effective conservative surgical technique for selected non-squamous cell subglottic tumours.

Treatment and outcomes of minor salivary gland cancers of the larynx and trachea: a systematic review.

Objectives: Malignant minor salivary glands carcinomas (MiSGC) of the larynx and trachea are rare tumours and published evidence is sparse. We conducted a systematic review to describe shareable treatment strategies and oncological outcomes of these neoplastic entities. Methods: Full text English manuscripts published from January 1st 2000 to December 14th 2022 were included. Data on demographics, treatments and outcomes were collected. A pooled analysis of 5-year overall survival (OS) was performed. Results: Seventeen articles and 365 patients met the inclusion criteria. The most common subsites involved were subglottic and distal trachea. Adenoid cystic carcinoma was, by far, the most frequent histotype. The first-choice treatment strategy was surgery (86.8%), while adjuvant treatments were delivered in 57.4% of patients. Only 12.9% were treated with definitive radiotherapy with/without chemotherapy. The mean follow-up was 68.3 months. One hundred nine (34.9%) deaths were recorded and 62.4% were cancer-related. Five-year OS ranged from 20% to 100% and, at pooled analysis, it was 83% (range, 78-87%). Conclusions: In case of MiSGC of the larynx and trachea, surgery remains the mainstay of treatment. Adjuvant treatments are frequently delivered. Survival estimates are good overall, but highly heterogeneous.

Revisiting the concept of neoadjuvant and induction therapy in head and neck cancer with the advent of immunotherapy.

The treatment of locally advanced (LA) Head and Neck Squamous Cell Carcinoma (HNSCC) is based on surgery followed by (chemo)radiation or on curative (chemo)radiation, depending on site and stage. Despite optimal locoregional treatment, about 50% of patients recur, with a huge impact on prognosis and substantial morbidity. The advent of immunotherapy (IT) with immune checkpoint inhibitors (ICIs) changed the paradigm of systemic treatment for recurrent/metastatic (RM) disease, showing activity, efficacy, and safety in both platinum-resistant and platinum-naïve patients. Such data led clinicians to design clinical trials to investigate early administration of IT even in the neoadjuvant or window of opportunity setting. In this review, we examine the published and ongoing trials investigating IT in the neoadjuvant setting for LA HNSCC. We address the current challenges of this treatment modality: optimal patient selection for neoadjuvant IT; choosing the appropriate systemic approach to enhance response without compromising tolerability; determining the ideal study endpoint, with a focus on major pathological response as a potential surrogate for overall survival; evaluating treatment response through imaging, considering the discordance between radiological and pathological assessments; and the influence of neoadjuvant IT response on locoregional treatment de-escalation strategies.

Compartmental tongue surgery for intermediate-advanced squamous cell carcinoma: A multicentric study.

BACKGROUND: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). METHODS: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. RESULTS: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). CONCLUSION: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC.

Training models and simulators for endoscopic transsphenoidal surgery: a systematic review.

Endoscopic transsphenoidal surgery is a novel surgical technique requiring specific training. Different models and simulators have been recently suggested for it, but no systematic review is available. To provide a systematic and critical literature review and up-to-date description of the training models or simulators dedicated to endoscopic transsphenoidal surgery. A search was performed on PubMed and Scopus databases for articles published until February 2023; Google was also searched to document commercially available. For each model, the following features were recorded: training performed, tumor/arachnoid reproduction, assessment and validation, and cost. Of the 1199 retrieved articles, 101 were included in the final analysis. The described models can be subdivided into 5 major categories: (1) enhanced cadaveric heads; (2) animal models; (3) training artificial solutions, with increasing complexity (from "box-trainers" to multi-material, ct-based models); (4) training simulators, based on virtual or augmented reality; (5) Pre-operative planning models and simulators. Each available training model has specific advantages and limitations. Costs are high for cadaver-based solutions and vary significantly for the other solutions. Cheaper solutions seem useful only for the first stages of training. Most models do not provide a simulation of the sellar tumor, and a realistic simulation of the suprasellar arachnoid. Most artificial models do not provide a realistic and cost-efficient simulation of the most delicate and relatively common phase of surgery, i.e., tumor removal with arachnoid preservation; current research should optimize this to train future neurosurgical generations efficiently and safely.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Perineural Invasion: An International Multicenter Study.

The objective of this study is to determine if the incorporation of perineural invasion (PNI) into the T-classification would improve the prognostic performance of TNM-8. An international, multicenter study of 1049 patients with oral cavity squamous cell carcinoma that were treated from 1994 to 2018 is performed. Various classification models are developed within each T-category and evaluated using the Harrel-concordance index (C-index), Akaike-information criterion (AIC), and visual inspection. Stratification into distinct prognostic categories, with internal validation, is performed using bootstrapping analysis (SPSS and R-software). Through multivariate analysis, PNI is significantly associated with disease-specific survival (p < 0.001). PNI integration into the staging system results in a significantly improved model compared with the current T category alone (lower AIC, p < 0.001). The PNI-integrated model is superior in predicting differential outcomes between T3 and T4 patients. A new model for T-classification of oral cavity squamous cell carcinoma is proposed, which is based on incorporating PNI into the staging system. These data can be used for future evaluations of the TNM staging system.

MRI-based radiomic prognostic signature for locally advanced oral cavity squamous cell carcinoma: development, testing and comparison with genomic prognostic signatures.

BACKGROUND: . At present, the prognostic prediction in advanced oral cavity squamous cell carcinoma (OCSCC) is based on the tumor-node-metastasis (TNM) staging system, and the most used imaging modality in these patients is magnetic resonance image (MRI). With the aim to improve the prediction, we developed an MRI-based radiomic signature as a prognostic marker for overall survival (OS) in OCSCC patients and compared it with published gene expression signatures for prognosis of OS in head and neck cancer patients, replicated herein on our OCSCC dataset. METHODS: For each patient, 1072 radiomic features were extracted from T1 and T2-weighted MRI (T1w and T2w). Features selection was performed, and an optimal set of five of them was used to fit a Cox proportional hazard regression model for OS. The radiomic signature was developed on a multi-centric locally advanced OCSCC retrospective dataset (n = 123) and validated on a prospective cohort (n = 108). RESULTS: The performance of the signature was evaluated in terms of C-index (0.68 (IQR 0.66-0.70)), hazard ratio (HR 2.64 (95% CI 1.62-4.31)), and high/low risk group stratification (log-rank p < 0.001, Kaplan-Meier curves). When tested on a multi-centric prospective cohort (n = 108), the signature had a C-index of 0.62 (IQR 0.58-0.64) and outperformed the clinical and pathologic TNM stage and six out of seven gene expression prognostic signatures. In addition, the significant difference of the radiomic signature between stages III and IVa/b in patients receiving surgery suggests a potential association of MRI features with the pathologic stage. CONCLUSIONS: Overall, the present study suggests that MRI signatures, containing non-invasive and cost-effective remarkable information, could be exploited as prognostic tools.

Treatment of loco-regional recurrence of nasopharyngeal carcinoma in a non-endemic area: oncologic outcomes, morbidity, and proposal of a prognostic nomogram.

Introduction: The study assessed outcomes and toxicities of different treatment modalities for local and/or regional recurrent nasopharyngeal carcinoma (NPC) in a non-endemic area. Methods: Patients treated with curative intent for recurrent NPC with salvage surgery, photon-based radiotherapy, proton therapy (PT), with or without chemotherapy, at different Italian referral centers between 1998 and 2020 were included. Adverse events and complications were classified according to the Common Terminology Criteria for Adverse Events. Characteristics of the patients, tumors, treatments, and complications are presented along with uni- and multivariate analysis of prognostic factors. A survival predictive nomogram is also provided. Results: A total of 140 patients treated from 1998 to 2020 were retrospectively assessed. Cases with lower age, comorbidity rate, stage, and shorter disease-free interval (DFI) preferentially underwent endoscopic surgery. More advanced cases underwent re-irradiation, fairly distributed between photon-based radiotherapy and PT. Age and DFI were independent factors influencing overall survival. No independent prognostic effect of treatment modality was observed. No significant difference in the morbidity profile of treatments was observed, with 40% of patients experiencing at least one adverse event classified as G3 or higher. Conclusion: Recurrent NPC in a non-endemic area has dissimilar aspects compared to its endemic counterpart, suggesting the need for further studies that can guide the choice of the best treatment modality.