Nasal vestibule squamous cell carcinoma: a population-based cohort study from DAHANCA.

BACKGROUND: Cancer of the nasal vestibule is a rare type of malignancy dominated by squamous cell carcinoma (SCC), and with poor survival. The treatment is either radiotherapy, surgery or a combination of both. Previous studies have shown a 5-year disease-specific survival of 74% and overall survival (OS) of 50%.Our objective was to describe the consecutive cohort of patients diagnosed with SCC of the nasal vestibule in Denmark from 2008 until 2018 and evaluate prognostic factors and treatment outcome using locoregional failure (LRF), disease-specific mortality (DSM), and OS as endpoints. METHODS: All patients diagnosed with SCC of the nasal vestibule from 2008 until 2018 were identified in the nationwide clinical database, DAHANCA and were followed for LRF and death (DSM and OS) until March 2021. OS was analysed using Kaplan-Meier estimator, and cumulative incidence of LRF and DSM were analysed using the Aalen-Johansen estimator. Analysis of prognostic factors was performed using Cox proportional hazard models. RESULTS: A total of 162 patients were identified. The median age was 71 years and 54% were male. Disease stage at the time of diagnosis were stage I (70%), II (17%), III (2%) and IV (11%). Curatively intended treatment was performed in 146 patients (90%), of which treatment failure occurred in 42 patients (29%). Most failures occurred at the primary tumour site (64%). Cancer Patient Pathways recommended time to treatment was fulfilled in 71% of patients. The 5-year OS and DSM in patients treated with curative intent were 65% and 11%, respectively. Stage was a significant independent prognostic factor. No difference in LRF, DSM or OS were shown between the applied treatments. CONCLUSIONS: Stage is the main independent prognostic factor, and failure most commonly appear at the primary tumour site.

FDG-PET/CT identified distant metastases and synchronous cancer in squamous cell carcinoma of the head and neck: the impact of smoking and P16-s.

PURPOSE: Whole-body FDG-PET-CT is widely used at diagnosis of squamous cell carcinoma of the head and neck (SCCHN) but may identify suspicious lesions outside the neck that require investigation. This study evaluated the impact of smoking and P16-status on the incidence of malignant disease outside the head and neck region in newly diagnosed patients with SCCHN. METHODS: All PET-positive foci outside the head-neck area were registered in 1069 patients planned for postoperative or curative intent radiotherapy with whole-body FDG-PET/CT from 2006 to 2012. All patient files were retrospectively investigated and clinical parameters, tobacco use, HPV (P16)-status and subsequent malignant disease registered. RESULTS: Malignancy outside the neck was diagnosed in 9% of smokers, 2% of never-smokers, and 5% of patients with P16-positive oropharyngeal squamous cell carcinoma (OPSCC). Clinically suspicious PET-positive foci outside the head-neck were malignant in 55% of smokers, 34% of never-smokers, and in 38% of P16-pos OPSCC. All but two patients with cancer occurring outside the head and neck region were smokers. CONCLUSION: Malignancy outside the neck at diagnosis was more frequent in smokers compared to non-smokers or P16-pos OPSCC. A high proportion of clinically suspicious PET-positive foci were non-malignant.

Distant metastases in squamous cell carcinoma of the pharynx and larynx: a population-based DAHANCA study.

BACKGROUND: In head and neck cancer, distant metastases may be present at diagnosis (M1) or occur after treatment (DM). It is unknown whether M1 and DM follow the same clinical development and share prognosis, as population-based studies regarding outcomes are scarce. Therefore, we investigated the incidence, location of metastases and overall survival of patients with M1 and DM. MATERIALS AND METHODS: Patients diagnosed with squamous cell carcinoma of the pharynx and larynx in Denmark 2008-2017 were identified in the Danish Head and Neck Cancer Group (DAHANCA) database. We identified 7300 patients, of whom 197 (3%) had M1 and 498 (8%) developed DM during follow-up. RESULTS: The 5-year cumulative incidence of DM was 8%. 1- and 2-year overall survival for DM (27% and 13%) vs. M1 (28% and 9%) were equally poor. There was no significant difference in location of metastases for M1 and DM and the most frequently involved organs were lungs, bone, lymph nodes and liver, in descending order. In oropharyngeal squamous cell carcinomas, the location of metastases did not differ by p16-status. For p16-positive patients, 21% of DM occurred later than three years of follow-up compared to 7% of p16-negative patients. CONCLUSION: Incidence, location of metastases and prognosis of primary metastatic (M1) or post-treatment metastatic (DM) disease in pharyngeal and laryngeal squamous cell carcinoma are similar in this register-based study.

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.

Separating distant recurrences from second primaries in head and neck squamous cell carcinomas - A DAHANCA group analysis on paired tumor samples.

BACKGROUND: In head and neck squamous cell carcinomas (HNSCC), there is no clinically available method to separate distant metastases (DMs) from SCC secondary primary tumors. The study aimed to assess the genetic relationship in paired tumor samples. METHODS: Patients with pairs of solid biopsies from the primary HNSCC and suspected DMs were identified (2007-2017). Targeted next-generation sequencing of 22 genes was applied, including TP53, supplemented with human papillomavirus (HPV) genotyping. RESULTS: Of 55 pairs obtained, 33 were successfully analyzed. Distant biopsies included lung, liver, and bone. A genetic match was found in 23/33 (70%) patients, primarily with identical TP53 mutations or HPV genotypes. In 10/33 patients (30%), the genetic relationship was absent, all with lung involvement. In patients with no lung involvement, 8/8 had a match. CONCLUSIONS: One-third of patients with DMs in HNSCC lack a genetic relationship with the primary tumors. The risk of misclassification is most prominent for patients with lung involvement.

The influence of tumor volume on the risk of distant metastases in head and neck squamous cell carcinomas.

BACKGROUND AND PURPOSE: Distant metastases (DM) in head and neck squamous cell carcinomas (HNSCC) are in most circumstances non-curable. The TNM staging system is insufficient to predict the risk of DM. This study investigates if the DM risk can be predicted using a multivariate model including pre-treatment total tumor volume for both p16-positive oropharyngeal squamous cell carcinoma (OPSCC) and all other sites (other HNSCC). MATERIALS AND METHODS: The study includes patients with localized pharyngeal and laryngeal squamous cell carcinomas treated with primary radiotherapy from 2008-2017 from three head and neck cancer centers. Patients were identified in the Danish Head and Neck Cancer (DAHANCA) database. Total (nodal and primary) tumor volume (Gross Tumor Volume, GTV) was extracted from local treatment planning systems. The GTV was grouped by volume (cm3) in four intervals and included in a multivariate Cox proportional hazard regression controlled for pre-selected clinical values incl. stage. RESULTS: The study includes 2,865 patients, of which 321 (11 %) had DM post-treatment. The risk of DM was assessed in a multivariate model based on 2,751 patients (p16-positive OPSCC: 1,032; and other HNSCC: 1,719). There was a significant association between GTV and the risk of DM, and in tumor volumes ≥ 50 cm3 hazard ratios of 7.6 (2.5-23.4) for p16-positive OPSCC and 4.1 (2.3-7.2) in other HNSCC were observed. CONCLUSION: Tumor volume is an independent risk factor for DM. The addition of total tumor volume to a predictive model is important to identify subgroups of HNSCC patients at high risk of DM.

Elective Nodal Irradiation and Patterns of Failure in Head and Neck Cancer After Primary Radiation Therapy.

PURPOSE: The delineation of elective clinical target volumes in head and neck cancer (HNC) is important; however, the extent of lymph node levels necessary to include is debated. A comprehensive analysis of recurrence patterns in a large cohort of patients with HNC was performed, with an emphasis on recurrence in the retropharyngeal region and level IB. METHODS AND MATERIALS: From 2005 to 2012, 942 patients with oropharyngeal, hypopharyngeal, laryngeal or oral cavity carcinomas were curatively treated with primary radiation therapy. The median follow-up period was 34 months, and 77% of the patients underwent intensity modulated radiation therapy. The retropharyngeal region was only routinely included in cases of involvement of the posterior pharynx wall and level IB only in cases of involvement of the oral cavity. In patients with regional recurrence, the anatomic site of the recurrence was assessed from the surgical descriptions or computed tomography scans and compared with the original radiation treatment plan (available from 2007 onward). The p16 status was available for 282 oropharynx carcinoma cases, with 65% p16-positive. RESULTS: Of the 942 patients, 376 (40%) developed recurrences: 228 (24.2%) local, 123 (13.1%) regional, and 109 (11.6%) distant. In 700 patients with available treatment plans, retropharyngeal and level IB recurrence was observed in 2 and 7 patients, respectively. Eight patients (1.1%) had recurrence in a lymph node level not included in their primary treatment plan. For oropharynx carcinoma, the locoregional control rate (90% vs 70%) but not distant control rate (92% vs 87%), was significantly better in the p16-positive than in the p16-negative patients. Although fewer recurrences developed in the p16-positive group, patients with recurrence of p16-positive tumors were more likely to develop recurrence in distant sites. CONCLUSIONS: Retropharyngeal or level IB recurrence after primary HNC radiation therapy is rare. Thus, inclusion of these regions in the elective treatment volumes should be limited to patients with involvement of the posterior pharyngeal wall or oral cavity.