A systematic review on clinical adaptive radiotherapy for head and neck cancer.

INTRODUCTION: Head and neck cancer (HNC) patients' anatomy may undergo significant changes during radiotherapy (RT). This potentially affects dose distribution and compromises conformity between planned and delivered dose. Adaptive radiotherapy (ART) is a promising technique to overcome this problem but requires a significant workload. This systematic review aims to estimate the clinical and dosimetric benefits of ART using prospective data. MATERIAL AND METHODS: A search on PubMed and Web of Science according to the PRISMA guidelines was made on Feb 6, 2023. Search string used was: 'adaptive radiotherapy head neck cancer'. English language filter was applied. All studies were screened for inclusion on title and abstract, and the full text was read and discussed in the research group in case of uncertainty. Inclusion criteria were a prospective ART strategy for HNC investigating clinical or dosimetric outcomes. RESULTS: A total of 1251 articles were identified of which 15 met inclusion criteria. All included studies were published between 2010 and 2023 with a substantial diversity in design, endpoints, and nomenclature. The number of patients treated with ART was small with a median of 20 patients per study (range 4 to 86), undergoing 1-2 replannings. Mean dose to the parotid glands was reduced by 0.4-7.1 Gy. Maximum dose to the spinal cord was reduced by 0.5-4.6 Gy. Only five studies reported clinical outcome and disease control was excellent. Data on toxicity were ambiguous with some studies indicating reduced acute toxicity and xerostomia, while others found reduced quality of life in patients treated with ART. CONCLUSION: The literature on clinical ART in HNC is limited. ART is associated with small reductions in doses to organs at risk, but the influence on toxicity and disease control is uncertain. There is a clear need for larger, prospective trials with a well-defined control group.

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.

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.

Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma.

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

Comparing the patients' subjective experiences of acute side effects during radiotherapy for head and neck cancer with four different patient-reported outcomes questionnaires.

Background: The systematic use of a Patient-Reported Outcome (PRO) as symptom monitoring during cancer treatment and follow-up has the potential to increase symptom awareness, secure timely management of side effects, improve health-related quality of life and improve data quality. This study was conducted to identify the patients' experience during chemoradiotherapy for squamous cell carcinoma of the head and neck (HNSCC) and to investigate how these symptoms correspond with different PRO questionnaires. Material and methods: Semi-structured interviews on acute side effects were performed until saturation with HNSCC patients treated with high-dose radiotherapy (RT) ± concomitant chemotherapy. The symptoms were thematically grouped in organ classes in accordance with Medical Dictionary for Regulatory Activities (MedDRA). PRO questionnaires validated for patients with HNSCC during RT were identified in the literature and were compared to the patients' symptoms. Results: Thirteen patients were interviewed. The most frequently mentioned symptoms were oral pain, decreased appetite, dysphagia, dry mouth, fatigue and hoarseness, in order of frequency. A comparison between the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Head and Neck Cancer (EORTC QLQ-H&N35), the Functional Assessment of Cancer Therapy General and Head and Neck (FACT-H&N), the M.D. Anderson Symptom Inventory Head and Neck questionnaire (MDASI-HN), selected items from the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the symptoms described by the patients showed that the PROs do not cover the same symptoms, and no specific questionnaire covers all patient's experiences. Conclusion: We find, that questionnaires applied in the field of PRO among patients with HNSCC undergoing RT may not fully comprise the experiences of patients and we recommend, that experiences of patients must be included in the design of trials involving PRO, in order to decrease the likelihood of missing out reports of acute side effects.

Swallowing therapy and progressive resistance training in head and neck cancer patients undergoing radiotherapy treatment: randomized control trial protocol and preliminary data.

BACKGROUND: Head and neck cancer (HNC) patients are often challenged by treatment induced dysphagia and trismus. Traditionally, rehabilitation is initiated when loss of function has already occurred. There is increasing evidence that it is of benefit to patients to initiate an early rehabilitation process before and during treatment. HNC patients have a unique set of functional challenges such as pre- and post-treatment dysphagia, pain and weight loss. The aim of the trial is to investigate the effects of swallowing and mouth-opening exercises combined with progressive resistance training (PRT) during radiotherapy. This report presents the protocol, interim inclusion and feasibility data. MATERIAL AND METHODS: The trial (clinicaltrials.gov NCT02385929) is a multicenter randomized controlled trial (RCT) with a parallel-group randomization (1:1). The planned sample size of 240 HNC patients is randomly assigned to either (1) twice weekly PRT and three times weekly swallowing exercises by physio- and occupational therapists, respectively, as well as daily home exercises throughout radiotherapy or (2) standard care. Inclusion criteria are patients with cancer in the larynx, pharynx, oral cavity, or unknown primary tumor who are referred to radiotherapy with curative intent. Outcomes are measured at end-of-treatment and two, five, and 12 months post-treatment. Interim results: In 16 months, 321 HNC patients were screened for eligibility. Of these, 131 (41%) were eligible according to inclusion criteria. One-hundred-and-fifteen patients were invited to participate of which 69 (60%) were enrolled in the trial and randomized for either intervention or control group with 10 drop-outs (14%). The six pilot patients adhered more than 90% to the program. CONCLUSION: Preliminary results show that exercise according to protocol is tolerable and feasible.

Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study.

BACKGROUND: Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) aimed to develop a TNM classification specific to HPV+ oropharyngeal cancer. METHODS: The ICON-S study included patients with non-metastatic oropharyngeal cancer from seven cancer centres located across Europe and North America; one centre comprised the training cohort and six formed the validation cohorts. We ascertained patients' HPV status with p16 staining or in-situ hybridisation. We compared overall survival at 5 years between training and validation cohorts according to 7th edition TNM classifications and HPV status. We used recursive partitioning analysis (RPA) and adjusted hazard ratio (AHR) modelling methods to derive new staging classifications for HPV+ oropharyngeal cancer. Recent hypotheses concerning the effect of lower neck lymph nodes and number of lymph nodes were also investigated in an exploratory training cohort to assess relevance within the ICON-S classification. FINDINGS: Of 1907 patients with HPV+ oropharyngeal cancer, 661 (35%) were recruited at the training centre and 1246 (65%) were enrolled at the validation centres. 5-year overall survival was similar for 7th edition TNM stage I, II, III, and IVA (respectively; 88% [95% CI 74-100]; 82% [71-95]; 84% [79-89]; and 81% [79-83]; global p=0·25) but was lower for stage IVB (60% [53-68]; p<0·0001). 5-year overall survival did not differ among N0 (80% [95% CI 73-87]), N1-N2a (87% [83-90]), and N2b (83% [80-86]) subsets, but was significantly lower for those with N3 disease (59% [51-69]; p<0·0001). Stage classifications derived by RPA and AHR models were ranked according to survival performance, and AHR-New was ranked first, followed by AHR-Orig, RPA, and 7th edition TNM. AHR-New was selected as the proposed ICON-S stage classification. Because 5-year overall survival was similar for patients classed as T4a and T4b, T4 is no longer subdivided in the re-termed ICON-S T categories. Since 5-year overall survival was similar among N1, N2a, and N2b, we re-termed the 7th edition N categories as follows: ICON-S N0, no lymph nodes; ICON-S N1, ipsilateral lymph nodes; ICON-S N2, bilateral or contralateral lymph nodes; and ICON-S N3, lymph nodes larger than 6 cm. This resembles the N classification of nasopharyngeal carcinoma but without a lower neck lymph node variable. The proposed ICON-S classification is stage I (T1-T2N0-N1), stage II (T1-T2N2 or T3N0-N2), and stage III (T4 or N3). Metastatic disease (M1) is classified as ICON-S stage IV. In an exploratory training cohort (n=702), lower lymph node neck involvement had a significant effect on survival in ICON-S stage III but had no effect in ICON-S stage I and II and was not significant as an independent factor. Overall survival was similar for patients with fewer than five lymph nodes and those with five or more lymph nodes, within all ICON-S stages. INTERPRETATION: Our proposed ICON-S staging system for HPV+ oropharyngeal cancer is suitable for the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer TNM classification. Future work is needed to ascertain whether T and N categories should be further refined and whether non-anatomical factors might augment the full classification. FUNDING: None.

Does age affect prognosis in salivary gland carcinoma patients? A national Danish study.

AIM: To compare incidence, histology, treatment modalities, disease stages, and outcome in elderly patients (≥70 years) compared to younger (<70 years). METHODS: From the national Danish salivary gland carcinoma database, 871 patients diagnosed with a primary salivary gland carcinoma from January 1990 to December 2005 were identified. Variables necessary for statistical analyses were extracted from the database. RESULTS: The younger patients have a significantly better crude, disease-specific and recurrence-free survival than the elderly ones. In univariate analysis, significantly more patients in the young group were WHO performance status 0 and in disease stage I + II, and they presented with significantly more histological low grade tumors. In multivariate analysis, chronological age seemed to be of no prognostic significance to salivary gland carcinoma patients as opposed to performance status, disease stage and histological grade. CONCLUSIONS: Salivary gland carcinoma patients over the age of 70 years have a poor prognosis compared to younger patients, which can be explained by higher disease stages, more histological high grade subtypes and a poorer performance status at the time of diagnosis.

Salivary duct carcinoma: a Danish national study.

BACKGROUND: To present the first national series of salivary duct carcinoma patients, including survival rates and an analysis of prognostic factors. METHODS: By merging three Danish nationwide registries that encompass an entire population, 34 patients diagnosed with salivary duct carcinoma from 1990 to 2005 were identified. Histological slides were reviewed, and data concerning demographics, tumour site, clinical stage, treatment profiles and follow-up were retrieved. Survival estimates and prognostic factors were evaluated by comparing Kaplan-Meier plots using the Mantel-Haenszel log-rank test. RESULTS: Salivary duct carcinoma showed an incidence of 0.04/100.000 inhabitants/year. Distant recurrence was seen in 52% of patients. Five-year overall survival, disease-specific survival and recurrence-free survival were 32%, 42% and 35%, respectively. Univariate analyses suggested that overall stage (III/IV) and vascular invasion have a negative impact on all survival measures. Involved resection margins correlated with a poorer overall survival and disease-specific survival, whereas adjuvant radiotherapy improved overall survival and recurrence-free survival. CONCLUSIONS: Salivary duct carcinoma incidence averages to two episodes per year in the entire Kingdom of Denmark. With half of patients in this study experiencing distant recurrences and only a third surviving at 5 years, prognosis is dismal. Advanced overall stage, vascular invasion and involved resection margins all seem to correlate with a poorer survival, while adjuvant radiotherapy significantly improved outcome. Extensive T-site surgery, neck dissection and adjuvant radiotherapy are therefore recommended.

Spatio-temporal stability of pre-treatment 18F-Fludeoxyglucose uptake in head and neck squamous cell carcinomas sufficient for dose painting.

BACKGROUND: The pre-treatment 18F-Fludeoxyglucose (FDG) avid subvolume of the tumor has shown promise as a potential target for dose painting in patients with in head and neck squamous cell carcinomas (HNSCC). PURPOSE: The purposes of this study are: 1) to assess the pre-treatment spatio-temporal variability of FDG PET/CT target volumes and 2) to assess the impact of this variability on dose distribution in dose painting plans in patients with HNSCC. MATERIAL AND METHODS: Thirty patients were enrolled and scanned twice, three days apart, days prior to treatment. Delineation of the FDG avid subvolume of the tumor and lymph nodes on both scans was performed by a specialist in nuclear medicine yielding GTVPET1 and GTVPET2 and segmentation based on SUV iso-contours were constructed yielding two metabolic target volumes, MTV1 and MTV2. Images were co-registered rigidly and dose painting plans with dose escalation up to 82 Gy to GTVPET1 were planned and GTVPET2 was copied from the co-registered images to the dose planning scan. Variation in dose to the target and modeled tumor control probability were assessed as measures of the impact of imaging variations in a dose painting scenario. RESULTS: Twenty-four patients were available for full analysis. The median mismatch between GTVPET1 and GTVPET2 was 14.2% (1.7 cm(3)). The median difference in dose to the FDG planning target volume was 0.3 Gy (PTVPET) and 0.4 Gy (PTVMTV). Median difference in the modeled tumor control probability (TCP) was < 0.2% and 23 of 24 patients had a difference in expected TCP < 1%. CONCLUSIONS: Pre-treatment FDG PET/CT target volumes were stable and day-to-day variability had no relevant impact on dose distribution and expected tumor control in dose painting plans.

The impact of comorbidity on outcome in 12 623 Danish head and neck cancer patients: a population based study from the DAHANCA database.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is primarily caused by smoking and alcohol. Besides having a carcinogenic effect, smoking also leads to other diseases and thus contributes to a high prevalence of comorbidities among HNSCC patients. Furthermore, the world population is becoming older resulting in more elderly patients with HNSCC. The aim of this study was to investigate the prevalence and impact of comorbidity in a retrospective nationwide population-based study of all Danish HNSCC patients diagnosed from 1992 to 2008. MATERIAL AND METHODS: A total of 12 623 patients diagnosed with HNSCC in the period from 1992 to 2008 were identified through the Danish Head and Neck Cancer group (DAHANCA) database. By linking to the Danish registers, information on somatic comorbidity present prior to the HNSCC diagnosis was obtained and adapted to the Charlson Comorbidity Index (CCI). The influence of comorbidity on overall survival and cancer specific death was evaluated and the type and prevalence of comorbidity described. RESULTS: In total, 36% of patients had comorbidity according to CCI. Increasing age was significantly associated with increasing CCI. In multivariate analyses, the CCI score remained a strong independent prognostic factor for overall survival, the HR being 1.16 (95% CI 1.08; 1.25), 1.34 (1.22; 1.46), 1.63 (1.51; 1.80) for patients with CCI score 1, 2, and 3+, respectively. The CCI score did not influence cancer specific death. CONCLUSION: Comorbidity is common among HNSCC patients and has a negative prognostic impact on overall survival. Cancer specific death was not affected by comorbidity suggesting that patients die from their comorbidities rather than their cancer. In the future, more elderly patients with comorbidity will require treatment which will demand a change in the healthcare system with a multidisciplinary approach required in order to take care of both their cancer and their comorbidities.

Using Biometric Sensor Data to Monitor Cancer Patients During Radiotherapy: Protocol for the OncoWatch Feasibility Study.

BACKGROUND: Patients with head and neck cancer (HNC) experience severe side effects during radiotherapy (RT). Ongoing technological advances in wearable biometric sensors allow for the collection of objective data (eg, physical activity and heart rate), which might, in the future, help detect and counter side effects before they become severe. A smartwatch such as the Apple Watch allows for objective data monitoring outside the hospital with minimal effort from the patient. To determine whether such tools can be implemented in the oncological setting, feasibility studies are needed. OBJECTIVE: This protocol describes the design of the OncoWatch 1.0 feasibility study that assesses the adherence of patients with HNC to an Apple Watch during RT. METHODS: A prospective, single-cohort trial will be conducted at the Department of Oncology, Rigshospitalet (Copenhagen, Denmark). Patients aged ≥18 years intended for primary or postoperative curatively intended RT for HNC will be recruited. Consenting patients will be asked to wear an Apple Watch on the wrist during and until 2 weeks after RT. The study will include 10 patients. Data on adherence, data acquisition, and biometric data will be collected. Demographic data, objective toxicity scores, and hospitalizations will be documented. RESULTS: The primary outcome is to determine if it is feasible for the patients to wear a smartwatch continuously (minimum 12 hours/day) during RT. Furthermore, we will explore how the heart rate and physical activity change over the treatment course. CONCLUSIONS: The study will assess the feasibility of using the Apple Watch for home monitoring of patients with HNC. Our findings may provide novel insights into the patient's activity levels and variations in heart rate during the treatment course. The knowledge obtained from this study will be essential for further investigating how biometric data can be used as part of symptom monitoring for patients with HNC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04613232; https://clinicaltrials.gov/ct2/show/NCT04613232. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26096.

Methodologies for localizing loco-regional hypopharyngeal carcinoma recurrences in relation to FDG-PET positive and clinical radiation therapy target volumes.

BACKGROUND: Focal methods to determine the source of recurrence are presented, tested for reproducibility and compared to volumetric approaches with respect to the number of recurrences ascribed to the FDG-PET positive and high dose volumes. MATERIAL AND METHODS: Six patients treated for hypopharyngeal squamous cell carcinoma were extracted from archives. Inclusion criteria were: FDG-PET/CT for primary radiotherapy planning and clinical complete remission followed by loco-regional relapse. CT scan at the time of recurrence was also required. The recurrence volume was delineated in the follow-up scans by a radiologist. Putative points of origin (PO) of the recurrence were determined by two strategies 1) defined by an oncologist or 2) as the center-of-volume (COV) of the recurrence. The most likely recurrence point of origin on the treatment planning scan was also determined. All expert based points of origin were repeated to estimate reproducibility. The recurrence volume and PO were propagated to the treatment planning scan using a rigid transformation. Relations of the PO to target volumes, radiation doses and therapy-points-of-origin were quantified. For the volumetric methods, the overlap of the recurrence volume and target volumes was used to determine the source of the recurrence. RESULTS: All recurrences were located in-field, but the volumetric approaches tended to designate fewer recurrences in the PET positive volume (25% for the 95% threshold, 95% confidence interval (CI):3-65%) than the observer-based methods (50% for the COV and both expert evaluations on the recurrence scan, 95% CI: 16-84%). The reproducibility of the expert POs is better on the recurrence scan than on the therapy scan. CONCLUSION: Volumetric approaches favor large target volumes as the source of the recurrence, thus underestimating the number of recurrences originating in the PET positive volume. Expert based and COV approaches on the recurrence scan are the most reproducible methods to determine the PO.

Carcinoma of the nasal cavity and paranasal sinuses in Denmark 1995-2004.

OBJECTIVE: To evaluate the treatment outcome for sino-nasal carcinomas in Denmark from 1995-2004 and compare the results to the previous Danish survey covering 1982-1991. DESIGN: Retrospective follow-up. MATERIALS AND METHODS: In the five Danish head and neck oncology centres, charts of all consecutive patients with sino-nasal carcinomas were reviewed and data extracted to a common database. Altogether 242 patients from the period 1995-2004 were identified. Of these 162 (67%) were male and 80 (33%) female. Histologies included squamous cell carcinoma (55%), adenocarcinoma (28.5%), adenoid-cystic carcinoma (5.0%), undifferentiated carcinoma (4.5%), transitiocellular carcinoma (1.7%), mucoepidermoid carcinoma (0.8%), neuroendocrine carcinoma (2.5%), small cell carcinomas (1.2%) and carcinomas not otherwise specified (0.8%). Treatments included radiotherapy alone 79 (33%), surgery alone 29 (12%), combined surgery and radiotherapy 96 (40%), palliative/no treatment 38 (16%). A total of 204 (86%) patients were treated with curative intent. RESULTS: Of the 204 patients treated with curative intent, 94 (46%) relapsed. Most failures were in T-site (63, 30%). N-site failures were 10 (5%) and M-site failures six (3%). Failure occurring in T+N-site, T+M-site, N+M-site and T+N+M-site were seven (3%), two (1%), one (0.5%) and five (3%) respectively. The 5-year actuarial local, nodal and loco-regional control rates were 55 + or - 4%, 86 + or - 3%, 49 + or - 4%, respectively. The overall 5-year actuarial survival rate for the entire cohort was 47 + or - 3%, and the corresponding cancer-specific 5-year actuarial survival rate was 57 + or - 3%. Female gender, nasal cavity tumour, adenocarcinoma and low clinical stage were significant positive prognostic factors in univariate analysis. A Cox multivariate analysis showed that only tumour site and clinical stage were independent significant prognostic factors. CONCLUSION: The current series has confirmed stage and tumour site as independent prognostic factors. Compared to the previous Danish survey covering the period 1982-1991, the overall survival and cancer-specific survival rates have improved significantly.

Oncocytic carcinoma of the salivary glands: A Danish national study.

OBJECTIVES: To present a Danish national series of oncocytic carcinoma (OC) patients, including data on treatment, recurrence and survival. METHODS: From the national Danish database of salivary gland carcinomas, all patients diagnosed with OC from 1990 to 2005 were identified and data concerning demographics, tumor site, clinical stage and treatment profiles were extracted. A follow-up was carried out. RESULTS: Of the 15 cases of salivary gland OC, eight were female. The incidence was 0.02/100.000 inhabitants per year in Denmark, 13 patients presented with OC in the parotid gland and two patients with OC in the submandibular gland. Eight patients had nodal involvement at the time of diagnosis. None of the patients had distant metastases at the time of diagnosis. All patients were treated with primary surgery and seven patients received adjuvant radiotherapy. Half of the patients had recurrence. Six patients were alive at 5 years follow up and one patient was alive without recurrence at 10 years follow up. CONCLUSIONS: This study is the first to report a national incidence of oncocytic carcinoma in the salivary glands. The results confirm oncocytic carcinoma to be a salivary gland carcinoma with a poor prognosis. All patients experiencing recurrence died of the disease. Treatment must be aggressive. National registries are necessary to achieve further knowledge for future treatment recommendations.

Effect of bupivacaine lozenges on oral mucositis pain: a randomized controlled multicenter phase II study.

INTRODUCTION: A nonblinded parallel-group randomized controlled study investigated the efficacy and tolerability of repeated administration of a bupivacaine lozenge (25 mg) as pain management for oral mucositis pain in head and neck cancer patients as add-on to standard systemic pain management. OBJECTIVE: The primary end point was the difference between the intervention group (Lozenge group) and the Control group in daily mean pain scores in the oral cavity or pharynx (whichever was higher). METHOD: Fifty patients from 2 hospitals in Denmark were randomized 1:1 to 7 days of treatment with bupivacaine lozenges (taken up to every 2 hours) plus standard pain treatment minus topical lidocaine (Lozenge group) or standard pain treatment including topical lidocaine (Control group). The efficacy analysis included 38 patients, as 12 patients were excluded because of changes in study design and missing data. RESULTS: Mean pain in the oral cavity or pharynx (whichever was higher) was significantly lower 60 minutes after taking lozenges (35 mm [n = 22]) than for the Control group (51 mm [n = 16]) (difference between groups -16 mm, 95% confidence interval: -26 to -6, P = 0.0032). Pain in the oral cavity was also significantly lower in the Lozenge group (18 mm) vs the Control group (36 mm, P = 0.0002). Pharyngeal mucositis pain did not differ significantly (37 mm [Lozenge group] vs 48 mm [Control group], P = 0.0630). No serious adverse events were reported. CONCLUSION: These results show that the bupivacaine lozenge as an add-on to standard pain treatment had a clinically significant pain-relieving effect in patients with oral mucositis. CLINICALTRIALSGOV: NCT02252926.