Sinonasal Cancer Research Articles

Predictors of distant metastases in sinonasal and skull base cancer patients treated with surgery

ObjectivesSinonasal and skull base tumors comprise a heterogeneous group of malignancies with a significant rate of distant recurrence (DR). The aim of this study was to analyze tumor and host factors, including pretreatment neutrophil-to-lymphocyte ratio (NLR), that predict DR in these patients. Materials and MethodsWe retrospectively reviewed sinonasal tumors and/or tumors involving the skull base treated with surgery between 1973 and 2015 (n = 473). We stratified NLR using the top 5 percentile as cutoff. Factors predictive of outcome were determined by Cox proportional hazards model. ResultsMost tumors were primary (81%) and 67% had skull base resection. The most common site was the nasal cavity (37%) and the most common histology was squamous cell carcinoma (34%). Most patients presented with advanced primary tumor stage (pT3/T4; 80%) and most had no regional neck disease (pNx/N0; 93%). A total of 104 patients developed DR. The 5-year overall and disease-specific survival for patients who developed DR were 36.4% and 35.8%, compared to 69.0% and 74.9% for patients who did not. Patients with DR had a higher percentage of NLR-high patients compared patients without DR (11% vs 3%, p = .006). In a multivariable analysis, melanoma histology (HR = 5.469, 95% CI 3.171–9.433), pT3/T4 (HR = 2.686, 95% CI 1.150–6.275), pN+ (HR = 6.864, 95% CI 3.450–13.653), and NLR-high (HR = 3.489, 95% CI 1.593–7.639) were independent predictors of DR. ConclusionMelanoma histology, pT, pN, and high NLR predict DR, suggesting that both tumor and host factors need to be considered. NLR may act as a surrogate marker of the host́s immune system.

Imaging of Skull Base and Orbital Invasion in Sinonasal Cancer: Correlation with Histopathology.

Simple SummaryPretreatment assessment of local extension in sinonasal cancer is essential for prognostic evaluation and surgical planning. It essentially relies on CT and MRI imaging whose performance is not accurately described in the scientific literature. The aim of this study was to assess the diagnostic performance of CT and MRI for the diagnosis of skull base and orbital invasion in sinonasal cancer by comparing imaging findings to histopathological data. A total of 176 patients were included. Objective data about the diagnostic value of pretreatment imaging in patients with sinonasal cancer were obtained: they suggest that pretreatment assessment of orbital invasion is difficult, even with the combination of CT and MRI.Background: Pretreatment assessment of local extension in sinonasal cancer is essential for prognostic evaluation and surgical planning. The aim of this study was to assess the diagnostic performance of two common imaging techniques (CT and MRI) for the diagnosis of skull base and orbital invasion by comparing imaging findings to histopathological data. Methods: This was a retrospective two-center study including patients with sinonasal cancer involving the skull base and/or the orbit operated on between 2000 and 2019. Patients were included only if pre-operative CT and/or MRI, operative and histopathologic reports were available. A double prospective blinded imaging review was conducted according to predefined radiological parameters. Radiologic tumor extension was compared to histopathological reports, which were considered the gold standard. The predictive positive value (PPV) for the diagnosis of skull base/orbital invasion was calculated for each parameter. Results: A total of 176 patients were included. Ethmoidal intestinal-type adenocarcinoma was the most common type of cancer (41%). The PPV for major modification of the bony skull base was 78% on the CT scan, and 89% on MRI. MRI signs of dural invasion with the highest PPVs were: contact angle over 45° between tumor and dura (86%), irregular deformation of dura adjacent to tumor (87%) and nodular dural enhancement over 2 mm in thickness (87%). Signs of orbital invasion had low PPVs (<50%). Conclusions: This retrospective study provides objective data about the diagnostic value of pretreatment imaging in patients with sinonasal cancer.

Precision Postoperative Radiotherapy in Sinonasal Carcinomas after Endonasal Endoscopic Surgery.

Simple SummarySinonasal cancers are rare and heterogeneous tumors, mainly carcinomas, with essentially local evolution and a severe vital and functional prognosis. These tumors are more and more being treated in first intent by a mini-morbid endoscopic approach rather than open surgery as the cornerstone of curative treatment. Adjuvant radiotherapy remains necessary owing to non-optimal local control. This article describes the requirements of radiotherapy to ensure adequate delays, the potential of postoperative radiotherapy to increase local and distant disease control and to decrease morbidity further after mini morbid surgery and dose painting techniques, and reviews the criteria that lead to the choice of one technique over another.Radiotherapy plays an important role in the treatment of sinonasal cancer, mainly in the adjuvant setting after surgical resection. Many technological approaches have been described, including intensity-modulated radiotherapy, concomitant chemoradiotherapy, charged particle therapy or combined approaches. The choice is based on general criteria related to the oncological results and morbidity of each technique and their availability, as well as specific criteria related to the tumor (tumor extensions, pathology and quality of margins). The aims of this review are: (i) to provide an overview of the radiotherapy techniques available for the management of sinonasal malignant tumors and (ii) to describe the constraints and opportunities of radiotherapy owing to the recent developments of endonasal endoscopic surgery. The indication and morbidity of the different techniques will be discussed based on a critical literature review.

Surgical Management of Sinonasal Cancers: A Comprehensive Review.

Simple SummarySinonasal cancers are rare. Surgery is often the first step of the therapeutic strategy, possibly complemented by adjuvant therapies. Surgical excision can be performed by an open approach with external incision, by an endoscopic approach using the nasal fossa as a surgical corridor, or by a combination of both. This article describes the main surgical techniques that can be used for the management of sinonasal cancer and reviews the criteria that lead to the choice of one technique over another.Surgery plays an important role in the treatment of sinonasal cancer. Many surgical approaches have been described, including open, endoscopic, or combined approaches. The choice is based on several criteria: general criteria related to the oncological results and morbidity of each technique, specific criteria related to the tumor (tumor extensions, tumor pathology), the patient, or the surgeon himself. The aims of this review are (i) to provide a complete overview of the surgical techniques available for the management of sinonasal malignant tumors, with a special focus on recent developments in the field of transnasal endoscopic surgery; (ii) to summarize the criteria that lead to the choice of one technique over another. In particular, the oncological outcomes, the morbidity of the different techniques, and the specificities of each histologic subtype will be discussed based on a comprehensive literature review.

A quantitative risk assessment of sinonasal cancer as a function of time in workers occupationally exposed to wood dust

The aim of this study is to conduct a quantitative assessment of the risk related to occupational exposure to wood dust and the occurrence of sinonasal epithelial cancer (SNEC) by histotype, depending on the duration of exposure, using mathematical models. The relationship between the occurrence of SNEC by histotype (adenocarcinoma [AR] and tumors of other histotypes) and exposure to wood dust has been studied using the values of the odds ratios for individual periods of employment involving exposure to wood dust, and their 95% confidence intervals. The dose-response curves were constructed (more precisely, the duration of exposure-response curves). The author attempted to match the linear, quadratic or exponential models. In all SNEC cases, there is a relationship between the duration of occupational exposure to wood dust and the relative risk of developing cancer. The estimated relative risk of developing AR after 35 years of exposure to wood dust is about 300, and the estimated risk of developing SNEC is 50, compared to non-exposed people for whom the relative risk is equal to 1. However, the relative risk of developing other types of cancer is <20, also in comparison with non-exposed people. The author has identified a relationship between the duration of occupational exposure to wood dust and the relative risk of developing cancer in all SNEC cases.

OC-0203 Nominal, daily and accumulated target coverage for photon and proton treatment of sinonasal cancer

OC-0203 Nominal, daily and accumulated target coverage for photon and proton treatment of sinonasal cancer

P-70 Recurrence analysis of Danish patients with sinonasal cancer treated with IMRT in 2008–2015. A DAHANCA study

P-70 Recurrence analysis of Danish patients with sinonasal cancer treated with IMRT in 2008–2015. A DAHANCA study

Sinonasal Squamous Cell Carcinoma, a Narrative Reappraisal of the Current Evidence.

Simple SummarySinonasal squamous cell carcinomas are a group of diverse tumors affecting the nasal cavity and paranasal sinuses. As a direct consequence of their rarity and heterogeneity, diagnosis is challenging, and treatment does not follow universally accepted protocols. Though surgery represents the mainstay of treatment, neoadjuvant and adjuvant therapies have pivotal roles in improving outcomes of patients treated with curative intent. Indications to endoscopic surgery have been expanding over the last three decades, but a considerable number of patients affected by sinonasal squamous cell carcinoma still need open surgical procedures. Management of the neck in patients affected by sinonasal squamous cell carcinoma is controversial. Curative-intended treatment of recurrent and/or metastatic tumors, alongside palliation of uncurable cases, represent poorly explored aspects of this disease.Sinonasal squamous cell carcinoma is a rare tumor affecting the nasal cavity and paranasal sinuses. Several aspects of this disease, ranging from epidemiology to biology, pathology, diagnosis, staging, treatment, and post-treatment surveillance are controversial, and consensus on how to manage this sinonasal cancer is lacking. A narrative literature review was performed to summarize the current evidence and provide the reader with available data supporting the decision-making process in patients affected by sinonasal squamous cell carcinoma, alongside the authors’ personal opinion on the unsolved issues of this tumor. The review has highlighted several advances in molecular definition of epithelial cancers of the sinonasal tract. Surgery represents the pivot of treatment and is performed through an endoscopic transnasal approach whenever feasible. Open surgery is required for a large proportion of cases. Reconstruction of the defect follows principles of skull base and cranio-maxillo-facial reconstruction. Chemotherapy is given as neoadjuvant treatment or concomitantly to radiotherapy. Photon-based radiation therapy has a crucial role in the adjuvant setting. Particle therapy is providing promising results. Management of the neck should be planned based on the presence of clinically appreciable metastases, primary tumor extension, and need for recipient vessels. Biotherapy and immunotherapy are still underexplored therapeutical modalities.

Long-term Outcomes from Proton Therapy for Sinonasal Cancers.

PurposeTo report long-term disease control, survival, and toxicity after proton therapy for sinonasal cancer.Patients and MethodsWe reviewed 143 cases of adults with nonmetastatic sinonasal cancers treated with primary (18%; n = 26) or adjuvant (82%; n = 117) proton therapy. The most common histologies were squamous cell carcinoma (29%; n = 42), olfactory neuroblastoma (23%; n = 33), and adenoid cystic carcinoma (16%; n = 23). Patients had predominantly advanced-stage disease (T3, 24%, n = 35; T4, 66%, n = 94) and high-grade histology (52%; n = 74). Surgery included endoscopic resection alone (50%) with craniotomy (10%) or open resection (40%), and 31% had gross disease present at radiotherapy. Most (91%) received high-dose (median, 73.6 Gy radiobiological equivalent [GyRBE]; 84% >70 GyRBE) passive-scatter proton therapy using accelerated hyperfractionation (1.2 GyRBE twice daily) and concurrent chemotherapy (70%). Univariate and multivariate models assessed prognostic factors. Grade 3+ toxicities were recorded per Common Terminology Criteria, version 4. Median follow-up was 3.4 years (range, 0.1–12.5 years) overall and 4.9 years (range, 0.9–12.5 years) for living patients.ResultsThe 5-year outcomes were as follows: local control (LC), 80%; neck control, 96%; local-regional control, 78%; freedom from distant metastases, 71%; and disease-free survival, 62%; cause-specific survival, 64%; and overall survival, 59%. Surgery improved LC, but only with gross total resection (5-year LC 87% versus subtotal resection 62.9%, and biopsy alone 55% (P < 0.001). Gross residual disease was the only significant prognostic factor for local-regional control on multivariate analysis. High-grade, T4, and local recurrence were associated with decreased overall survival. Late (G3+) toxicity occurred in 22% (32 of 143), including central nervous system necrosis and vision loss in 6% (9 of 143) and 3.5% (5 of 143), respectively.ConclusionProton therapy after gross-total resection provides excellent long-term LC in patients with locally advanced, high-grade sinonasal cancer. Moreover, LC remains strongly associated with long-term survival. With gross disease, about 60% of patients had long-term LC with proton therapy and induction or concurrent chemotherapy.

Karnofsky Performance Score - An Independent Prognostic Factor of Survival After Palliative Irradiation for Sino-nasal Cancer.

Sino-nasal cancer is rare and often diagnosed at advanced stages. Some patients cannot receive curative treatment and are treated with palliative irradiation. We aimed to identify prognostic factors for survival to facilitate treatment personalization for this group. Twelve patients treated with palliative radiotherapy for locally advanced sino-nasal cancer were retrospectively analyzed for survival. Ten characteristics were evaluated including age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin, tumor site, lymph node involvement, histology, equivalent dose in 2 Gy-fractions, completion of radiotherapy and concurrent chemotherapy. On univariate analysis, KPS ≥70 (p<0.001) and completion of radiotherapy (p<0.001) were significantly associated with better survival. Chemotherapy showed a trend (p=0.097). In the multivariate analysis, KPS ≥70 was significant (p=0.025), and completion of radiotherapy showed a trend (p=0.080). KPS is an independent predictor of survival for palliative irradiation of sino-nasal cancer. Patients require close monitoring and care for side effects, since completion of radiotherapy is important for survival.

Critical review of multidisciplinary approaches for managing sinonasal tumors with orbital involvement.

SUMMARYOrbital invasion is frequently observed in tumors involving the maxillary, ethmoid and frontal sinuses given the proximity of the orbit to the sinonasal tract and ventral skull base. The main objective of the present review is to determine the existing evidences on the frequency, treatment, and outcomes of orbital invasion in benign and malignant sinonasal tumors. A systematic review of the literature published from 1995 to 2020 was performed and data sources included PubMed, Cochrane library, NCBI Bookshelf, National Guideline Clearinghouse. Orbital invasion was reported in 2-4% of inverted papillomas, 12-15% of fibro-osseous lesions, 27-32% of juvenile angiofibromas, 35-45% of low-grade malignancies, and 50-80% of high-grade cancers. Surgical resection with negative margins represents the cornerstone of management for benign and low-grade malignant tumors. Histology-specific induction chemotherapy can be used for high-grade sinonasal cancers in order to downstage the tumor and increase the possibility of orbital preservation. When a significant response to induction chemotherapy is observed, exclusive chemoradiation should be offered to improve overall survival rates. Appropriate reconstruction of any surgical defects is essential in order to minimize complications and optimize functional and aesthetic outcomes. Orbital apex invasion represents a negative prognostic factor. In conclusion, a multidisciplinary teamwork is mandatory to maximize local control, minimize morbidity and improve orbital preservation rates.

Ophthalmic Presentation and Outcomes for Malignant Sinonasal Tumors.

To evaluate the ophthalmic clinical features and functional outcomes for patients with malignant sinonasal tumors who initially presented with orbital symptoms. Retrospective chart review for patients seen at Moorfields Eye Hospital between 1997 and 2020. Patient demographics and clinical features, radiology, histology, and treatment outcomes were reviewed. Forty patients (22 females; 55%) with sinonasal cancers first presented to an ophthalmologist at an average age of 53.9 years (median 56; range 8-92 years), with their having had first symptoms at 53.6 years (median 55.8; range 7.8-91.9 years). The commonest symptoms were persistent periorbital ache (19/40; 48%), periocular swelling (18; 45%), proptosis (16; 40%), and diplopia (15; 38%). All midface tumors affected only 1 orbit, and 13 of 40 (33%) eyes presented with an acuity of 20/60 or worse-5 having no perception of light-and 10 eyes (25%) had a relative afferent pupillary defect. An average of 4.5 mm relative exophthalmos was present (median 4 mm; range 0-9 mm), and a palpable mass in 19 of 40 (48%) orbits. Reduced eye movements and nonaxial displacement were recorded in 29 (73%) and 34 (85%) patients, respectively, and 9 (23%) had an abnormal optic disc or fundus. Bone erosion affected 95% of orbits, and almost a half had involvement of the neighboring extraocular muscles, orbital apex, or intracranially. The commonest tumor groups were sinonasal carcinomas (45%), sarcomas (28%), or lymphomas (11%). Of 37 globe-sparing treatments, 25 (68%) had persistence of previously impaired ophthalmic functions and 6 of 37 (16%) developed new impairment; only 6 of 37 (16%) of affected orbits retained normal function, and 6 patients lost all vision on the affected side. Sinonasal malignancies that present with orbital invasion are probably at the more aggressive end of the cancer spectrum, might be expected to carry a worse prognosis, and usually arise from the ethmoid or maxillary sinuses. In our series, carcinomas and sarcomas were the commonest malignancies, with similar 5-year overall survivals (of just over 50%), and over three-quarters of patients developed permanent impairment of orbital function and/or visual loss.

Sinonasal cancers treatments: state of the art.

The present review provides the reader with the state-of-the-art concepts of sinonasal oncology in view of the latest literature data. Most recent publications in sinonasal oncology assessed treatment timing, centralization, surgical approach, margin status, orbit/neck management, salvage strategies, emerging surgical technologies, intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), particle radiotherapy, and neoadjuvant chemotherapy. Indications to endoscopic surgery for sinonasal cancer have plateaued and are unlikely to further expand. Endoscopic surgery provides noninferior results compared to open surgery and best suits timing constraints imposed by multimodal treatment. Management of orbit-encroaching sinonasal cancer is remarkably improving mostly owing to optimal use of nonsurgical strategies. Prognostic value of the margin status and management of the nodal basin and recurrent sinonasal tumors are far from being fully elucidated. Most promising surgical technologies are surgical navigation, optical imaging, and radiofrequency-aided ablation. IMRT and VMAT have theoretical technical advantages that are in the process of being clinically demonstrated. Pieces of evidence are progressively confirming the physical and radiobiological advantages offered by particle radiotherapy. Systemic therapy is being tested mostly in the neoadjuvant setting with the aim of improving outcomes in locally advanced sinonasal cancers; response to induction chemotherapy could better select a further locoregional approach.

Radical Exenteration of the Skull Base for End-Stage, Locally Advanced Sinonasal Malignancies: Challenging the Dictum of Unresectability

The role of surgery is not well defined in locally advanced sinonasal cancers with intracranial involvement after all medical options have been exhausted. We hypothesize that patients whose tumors are deemed unresectable and referred to palliative care may benefit from radical salvage surgery. We performed a single-center retrospective review of patients with malignant, locally advanced (stage T4b) sinonasal cancers with intracranial involvement from 2000 to 2020, inclusive. Data were collected on the patient demographics, details of chemotherapy, radiation, histology, perioperative complications, surgical approaches, and survival. We compared the survival outcomes of patients with different duration of disease before presentation. We identified 17 patients who had undergone salvage surgical resection of treatment-recalcitrant, locally advanced sinonasal tumors. Almost all patients had undergone prior surgery, radiotherapy, and chemotherapy. Perioperative complications occurred in 6 of 17 patients with 1 death. Patients with clinically less aggressive disease had significantly longer progression-free and overall survival compared with the more aggressive group. Salvage surgery for locally advanced sinonasal cancers with intracranial invasion that is recalcitrant to all other therapies should be considered for patients who otherwise have no other treatment options.

Sinonasal cancer in Denmark 2008–2015: a population-based phase-4 cohort study from DAHANCA

Background Sinonasal cancer is considered a rare disease with poor survival. Its treatment has changed profoundly in recent years, primarily following the introduction of intensity-modulated radiation therapy (IMRT) and minimally invasive endoscopic surgery. Danish national guidelines on treatment of patients diagnosed with sinonasal carcinoma were introduced in 2007. The aim of this phase-4 study was to assess the effect of the implementation of guidelines by describing treatment outcomes in a consecutive nationwide cohort. Methods All patients diagnosed with sinonasal carcinoma in Denmark from 2008 to 2015 were identified in the nationwide clinical database, DAHANCA, and were followed until May 2020. Overall survival (OS) was analysed using Kaplan–Meier estimator. Cumulative incidence of locoregional failure (LRF) and disease-specific mortality (DSM) were analysed using the Aalen–Johansen estimator. Competing risks were death from other causes (DSM) and distant failure and death (LRF). Analysis of prognostic factors was performed using Cox proportional hazard analysis. Start of follow-up was time of diagnosis. The results are presented as estimates with 95% confidence intervals (95% CIs). Results A total of 331 patients were identified. Curatively intended treatment was performed in 264 patients (80%). Non-compliance with treatment guidelines was registered in 24 patients (9%). Non-compliance was associated with LRF (hazard ratio [HR], 2.0 [95% CI: 1.1–3.5]). Among patients qualified for curative treatment, failure occurred in 109 patients (41%), primarily at the primary tumour site (81%). Anatomical tumour site and disease stage were independent prognostic factors. The 5-year OS was 56% in patients treated with curative intent, and a combined treatment strategy showed reduced LRF (HR, 0.53 [95% CI: 0.30–0.92]) in a multivariate analysis. Conclusions Guideline compliance and a combined treatment approach reduced the incidence of LRF and thereby increased OS. Our results confirm those of international studies. Treatment of sinonasal carcinoma remains a challenge that requires multidisciplinary team coordination.

The new national guidelines for the keeping of the Italian Sinonasal Cancer Registry (ReNaTuNS)

Sinonasal cancers (SNC) are rare tumours with predominant occupational aetiology associated with exposures to specific carcinogens. In Italy, SNC incidence has been under compulsory surveillance since 2008, through the National Sinonasal Cancer Registry (ReNaTuNS), a nationwide cancer registry coordinated by the National Institute for Insurance Against Accidents at Work (Inail). The ReNaTuNS has a regional structure with local registries, established at Regional Operating Centres (CORs). Currently, seven Italian Regions are active in SNC search and, together with Inail, have recently released a new version of the national guidelines for keeping the Registry (available on the Inail website). The aim of this text is to present the new guidelines, an updating version, and to underline the relevance of this tool in enforcing the role of the ReNaTuNS, considering the high occupational fraction of SNC and the unicity of the Italian Registry, which collects all the information available on occupational exposures of each SNC case registered. It is recommended that the active search for SNC cases and the analysis of exposure become a systematic and well-organized activity to prevent or reduce risks of exposure and to support and improve the efficiency of the compensation and welfare system.

Sinonasal cancer encroaching the orbit: Ablation or preservation?

Encroachment on the orbital cavity represents a challenge in the management of sinonasal cancer. Criteria guiding orbital preservation lack univocal consensus. Stage of orbital involvement is best assessed through magnetic resonance imaging (MRI). Patients affected by orbit-encroaching sinonasal cancer with available preoperative MRI, receiving surgery-based treatment at the University of Brescia between May 2005 and October 2018 were included. All cases were reviewed by expert radiologists and pathologists. Diagnostic performance of MRI was calculated using pathological information as reference. Survival analysis was performed. The study included 123 patients. The orbit was abutted in 53 (43.1%) patients, whereas orbital invasion reached the periorbit in 18 (14.6%), extraconal fat and/or medial lacrimal sac in 29 (23.6%), extrinsic ocular muscles in 7 (5.7%), intraconal compartment in 4 (3.3%), and orbital apex in 12 (9.8%). Seventy-six (61.8%) patients received orbit-sparing surgery, 47 (38.2%) underwent orbital ablation (OA). Accuracy of MRI in detecting involvement by cancer was ≥80.0% for the orbital wall, extraconal fat, and muscles, and <80.0% for the periorbit and intraconal compartment. Previous surgery, neoadjuvant chemotherapy, and perineural invasion decreased MRI accuracy. Age, histology, tumor grade, pT category, N status, perineural invasion, orbital invasion stage, and need for OA were found to affect prognosis. Five-year orbital dysfunction-free survival was 92.8%. Conservative management of sinonasal cancers encroaching the orbit is feasible. MRI is essential to preoperatively stage orbital invasion, yet with some limitation. Given the dismal prognosis despite aggressive surgery, neoadjuvant non-surgical therapies should be considered in patients requiring OA.

Paranasal Carcinoma: A Case Series

Objective: To emphasize the importance of early diagnosis of cancer of paranasal sinus. Method: This is retrospective case series done in Liaquat National Hospital. Data were retrieved from August to October 2020. Results: Data of a total of 5 patients with sinonasal cancer was reviewed. Four patients presented with extensive disease. Three patients were male and two were female. The age of patients was between 40 and 70 years. All these five patients underwent surgery. Four patients were referred for concurrent chemoradiotherapy (CCRT) and one patient expired after surgery. Conclusion: Malignant tumors of the nose and sinuses are rare constituting 3% of head and neck malignancies. The early symptoms are relatively innocuous and are often ignored by the patient, their general practitioners and even ENT surgeons leading to a delayed diagnosis and treatment. Although paranasal tumors are rare they should be in our differential.

Immunotherapy in head and neck squamous cell carcinoma and rare head and neck malignancies.

The dismal prognosis of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) prompted recent advances in the field of therapeutic approaches beyond cytotoxic cancer therapy. In recent years, the deeper and increasing knowledge on the genomic landscape and the upcoming new data on immunotherapy enacted by HNSCCs have led to successful therapeutic targeting of the immune system. Immune checkpoint inhibitors (ICIs) have changed state of the art in R/M patients and could have a potential role even in early disease. The purpose of this work is to summarize the role of immunotherapy for R/M HNSCC in clinical practice, with insights about future perspectives. Updated immunotherapy results in other R/M head and neck cancers such as thyroid, salivary glands, nasopharynx, sinonasal cancers, and nuclear protein in testis (NUT) are presented.

Air variability in maxillary sinus during radiotherapy for sinonasal carcinoma

IntroductionThe aim was to characterise patterns and predictability of aeration changes in the ipsilateral maxillary sinus during intensity-modulated radiotherapy (IMRT) for sinonasal cancer (SNC), and in a sample evaluate the dosimetric effects of aeration changes for both photon and proton therapy. Materials and methodsThe study included patients treated withIMRT for SNC in a single institution in 2009–2017. The volume of air in the ipsilateral maxillary sinus was recorded in1578 daily cone beam computer tomography (CBCT) from 53 patients.Patterns of changing air volumes were categorised as ‘stable’,increasing’, ‘decreasing’, or ‘erratic’. For the prediction analysis, categorisation was performed based both on the entire treatment course and the first five fractions (F1–5).Photon and proton therapy plans were generated for four patients, the one from each category with the largest aeration variation. Synthetic CT images were generated for each CBCT and all plans were recalculated on the daily synthetic CTs. ResultsThe absolute volume of air varied considerably during the treatment course, ranging from 0 to 25.9 cm3. Changes within a single participant varied in the range of 0–18.7 cm3. In the categorisation of patterns, most patients hadincreasingaeration of the sinus. Generally, patterns of aeration could not be predicted from F1–5. Patients categorised asincreasingin F1–5 had the best prediction, with 78% predicted correctly as increasing for the entire treatment course. The numeric correlation coefficients for target coverage and air volumewere low for 3/4scenarios(photons 0.03–0.23, protons 0.26–0.48). No straightforward correlation between the dosimetric effect and the volume changes could be detected in the sample test of four patients for neither photon nor proton therapy. ConclusionThe variation of aeration was large and unpredictable. No clear dosimetric consequences of the aerationvariation were evident for neither IMRT nor proton therapyfor the patients investigated.