The Danish Head and Neck Cancer database Overgaard, Jens; Jovanovic, Aleksandar; Godballe, Christian ...
Clinical epidemiology,
01/2016, Volume:
8
Journal Article
Peer reviewed
Open access
The Danish Head and Neck Cancer database is a nationwide clinical quality database that contains prospective data collected since the early 1960s. The overall aim of this study was to describe the ...outcome of the national strategy for multidisciplinary treatment of head and neck cancer in Denmark and to create a basis for clinical trials.
The study population consisted of all Danish patients referred for treatment of squamous cell carcinoma of the larynx, pharynx, oral cavity, or neck nodes from unknown primary or any histopathological type (except lymphoma) of cancer in the nasal sinuses, salivary glands, or thyroid gland (corresponding to the International Classification of Diseases, tenth revision, classifications C.01-C.11, C.30-C.32, C.73, and C.80).
The main variables used in the study were symptoms and the duration of the symptoms; etiological factors; pretreatment and diagnostic evaluation, including tumor-node-metastasis classification, imaging, histopathology, and laboratory tests; primary treatment with semidetailed information of radiotherapy, surgery, and medical treatment; follow-up registration of tumor status and side effects; registration of relapse and treatment thereof; and registration of death and cause of death.
Data from >33,000 patients have been recorded during a period of >45 years. In this period, the outcome of treatment improved substantially, partly due to better treatment as a result of a series of continuous clinical trials and subsequent implementation in national guidelines. The database has furthermore been used to describe the effect of reduced waiting time, changed epidemiology, and influence of comorbidity and socioeconomic parameters.
Half a century of registration of head and neck cancer treatment and outcome has created the basis for understanding and has substantially contributed to improve the treatment of head and neck cancer at both national and international levels.
Abstract Aim EGFR and HPV-associated p16 are among the most investigated biomarkers in head and neck cancer. The aim was to investigate the correlation and interaction between these two markers and ...to evaluate their potential prognostic significance when combined. Materials and methods 336 Oropharyngeal carcinomas treated with primary radiotherapy (66–68 Gy, 2 fx/day, 10–12 Gy/week) and with known EGFR/p16-status estimated semiquantitatively by immunohistochemistry were included in the study. Data were evaluated by EGFR-expression (high/low) and p16-status (positive/negative) consequently dividing tumours into four groups by combination of the biomarkers. Patient/tumour characteristics and complete 5-year follow-up were available. Results Low EGFR-expression was significantly more common in p16-positive tumours compared to p16-negative, p < 0.0001. p16 positivity showed a strong prognostic impact ( p < 0.0001, HR = 0.22 0.13–0.38), whereas EGFR was a weak prognostic marker when local control was used as endpoint ( p = 0.03, HR = 0.53 0.29–0.94). Combination of EGFR/p16 did not add significant information to p16 alone and by multivariable analysis only p16 showed significant prognostic information for all evaluated endpoints. Conclusions Both EGFR and p16 bear prognostic information in oropharyngeal cancer, although p16 is, by far, the strongest prognostic factor. The markers seem to be correlated and this might have influence when evaluating the effect of EGFR inhibition in oropharyngeal tumours.
Abstract Background HPV/p16-positive head and neck cancers (HNSCC) show superior response to radiotherapy, compared with virus-negative tumours. Tumour hypoxia induces radioresistance and the ...randomised DAHANCA 5 trial found that the hypoxic cell radiosensitiser nimorazole significantly improved the outcome in HNSCC. Using p16-status as a retrospective stratification parameter, we aimed to assess the influence of p16-expression on the response to nimorazole in HNSCC. Materials and methods Pre-treatment tumour blocks were available from 331 of the 414 patients in the DAHANCA 5 trial and evaluated by immunohistochemistry for p16-expression. The influence of p16-expression on outcome was analysed as a function of treatment group (nimorazole/placebo) 5 years after radiotherapy. Results Overall, patients treated with nimorazole had significantly better loco-regional control than did those given placebo: hazard ratio (HR) 0.70 95% CI 0.52–0.93. Positive expression of p16 also significantly improved outcome after radiotherapy (0.41 0.28–0.61). In the subgroup of patients with p16-negative tumours, loco-regional failure was more frequent in the placebo group than in the nimorazole group (0.69 0.50–0.95). However, in the p16-positive group, patients treated with nimorazole had a loco-regional control rate similar to patients given placebo (0.93 0.45–1.91). Conclusions HPV/p16-expression significantly improved outcome after radiotherapy in HNSCC. Hypoxic modification improved outcome in HPV/p16-negative tumours but was of no significant benefit in HPV/p16-positive tumours, suggesting that hypoxic radioresistance may not be clinically relevant in these tumours.
Background
Patients with pre‐existing severe mental disorders are significantly less likely to receive guideline‐recommended cancer treatment and seems to have a significantly lower rate of cancer ...survival compared to patients with cancer without mental disorders.
Aim
To perform a systematic review on barriers at patient‐, provider‐ and system‐levels in cancer trajectories of patients with pre‐existing severe mental disorders.
Method
A systematic review was performed following the PRISMA guidelines (PROSPERO ID: CRD42022316020).
Results
Nine eligible studies were identified. Barriers at patient‐level included lack of self‐care and ability to recognize physical symptoms and signs. Provider‐level barriers included stigma from health care professionals on mental disorders, whereas system‐level barriers included fragmented health care and consequences of this.
Conclusion
This systematic review found that barriers at patient‐, provider‐ and system‐levels exist in cancer trajectories for patients with severe mental disorders, causing disparities in cancer care. Further research is needed to improve cancer trajectories for patients with severe mental disorder.
Although radiotherapy continues to evolve as a mainstay of the oncological armamentarium, research and innovation in radiotherapy in low-income and middle-income countries (LMICs) faces challenges. ...This third Series paper examines the current state of LMIC radiotherapy research and provides new data from a 2022 survey undertaken by the International Atomic Energy Agency and new data on funding. In the context of LMIC-related challenges and impediments, we explore several developments and advances—such as deep phenotyping, real-time targeting, and artificial intelligence—to flag specific opportunities with applicability and relevance for resource-constrained settings. Given the pressing nature of cancer in LMICs, we also highlight some best practices and address the broader need to develop the research workforce of the future. This Series paper thereby serves as a resource for radiation professionals.
We compare outcomes in two large‐scale contemporaneously treated HPV‐positive (HPV+) oropharynx cancer (OPC) cohorts treated with definitive radiotherapy/chemoradiotherapy (RT/CRT). p16‐confirmed ...HPV+ OPC treated between 2007 and 2015 at PMH and DAHANCA were identified. Locoregional failure (LRF), distant metastasis (DM), and overall survival (OS) were compared. Multivariable analysis (MVA) calculated adjusted‐hazard‐ratio (aHR) with 95% confidence interval (95% CI), adjusting for cohort, age, gender, performance status, smoking pack‐years, T‐category and N‐category and chemotherapy. Compared to PMH (n = 701), DAHANCA (n = 1174) contained lower TNM‐8T‐categories (T1‐T2: 77% vs 56%), N‐categories (N0‐N1: 77% vs 67%) and stages (stage I: 63% vs 44% (all P < .001). PMH used standard‐fractionation CRT in 69% (481) while 31% (220) received hypofractionated or moderately accelerated RT‐alone. All DAHANCA patients were treated with moderately accelerated RT; 96% (1129) received nimorazole (NIM) and 73% (856) concurrent weekly cisplatin. DAHANCA had shorter overall‐treatment‐time (P < .001), lower gross tumor (66‐68 vs 70 Gy) and elective neck (50 vs 56 Gy) doses. Median follow‐up was 4.8 years. DAHANCA had higher 5‐year LRF (13% vs 7%, aHR = 0.47 0.34‐0.67), comparable DM (7% vs 12%, aHR = 1.32 0.95‐1.82), but better OS (85% vs 80%, aHR = 1.30 1.01‐1.68). CRT patients had a lower risk of LRF (aHR 0.56 0.39‐0.82), DM (aHR 0.70 0.50‐1.00) and death (aHR 0.39 0.29‐0.52) vs RT‐alone. We observed exemplary outcomes for two large‐scale trans‐Atlantic HPV+ OPC cohorts treated in a similar manner. Concurrent chemotherapy was a strong, independent prognostic factor for all endpoints. Our findings underscore the need for a very careful approach to de‐intensification of treatment for this disease.
What's new?
HPV‐positive oropharyngeal cancer (OPC) represents a unique subgroup which has very different epidemiology, molecular biology, and response to radiotherapy/chemo‐radiotherapy (RT/CRT) than HPV‐negative squamous cell carcinoma of the head and neck (HNSCC). In this study, the authors compared two large cohorts of HPV‐positive OPC, and found significantly better outcomes in patients that routinely received concurrent chemoradiotherapy with cisplatin compared with radiotherapy alone. The authors conclude that these findings underscore the need for a cautious approach to efforts aimed at de‐intensifying treatment for this disease.
Patients with head and neck squamous cell carcinoma (HNSCC) undergoing radiotherapy (RT) or chemoradiation (CRT) may become immunocompromised. In this population-based study, we aimed to investigate ...the risk factors, microbiological aetiologies, prognosis and impact on early non-cancer mortality of bloodstream infections (BSIs) after RT/CRT.
Patients with HNSCC of the pharynx, larynx and oral cavity treated with curative-intent RT/CRT in Denmark between 2010 and 2017 and subsequent BSI episodes occurring within 18 months of RT/CRT initiation were identified in national registries.
We included 5674 patients and observed 238 BSIs. Increasing age, stage and performance status were significantly associated with an elevated BSI risk, while sex, smoking and high-grade mucositis were not. Human papillomavirus-positive oropharyngeal cancer patients had a decreased risk. Staphylococcus aureus accounted for 34% of episodes occurring during the first 3 months. The 30-day post-BSI mortality rate was 26% (95% confidence interval: 19-32) and BSIs were involved in 10% of early non-cancer deaths.
The risk of BSI development is associated with several patient- and disease-related factors and BSIs contribute considerably to early non-cancer mortality. Empiric antibiotic treatment regimens should prioritise coverage for S. aureus when treating suspected systemic infection in this population.
•Application of consensus guidelines results in increased consistency in high-dose CTV1.•A 3-year local control is not influenced by GTV-CTV1 margin.•Half of analysable radiology-verified local ...recurrences are in primary GTV.•76 % of radiology-verified local recurrences are inside CTV1 using 5 mm margin consensus.
Treatment planning using a five-millimetre geometrical margin from GTV to high-dose CTV (CTV1) has been used in DAHANCA treatment centres since 2013. We aimed to evaluate changes in CTV1 volumes, local control (LC), and recurrence pattern after the implementation of five-millimetre geometrical margins nationally.
1,948 patients with pharyngeal, and laryngeal squamous cell carcinomas completed definitive IMRT-based treatment in 2010–2012 and 2013–2015 in three centres. The patient-specific margin was calculated as median surface distance from primary tumour GTV (GTV-T) to CTV1. Radiologically verified local recurrences were analysed using a centre of mass (COM) of the delineated recurrence volume, measuring the shortest distance between COM to GTV-T and CTV1 boundaries.
Median GTV-CTV1 was 0.9 (0.0–0.97) and 0.47 cm (0.4–0.5) for 2010–2012 and 2013–2015, respectively. Median CTV1 changed in three centres from 76, 28, 42 cm3 to 61, 53, 62 cm3 for 2010–2012 and 2013–2015, respectively. Local failures occurred at 247 patients during first three years after radiotherapy. The 3-year LC rate for 2010–2012 and 2013–2015 was 0.84 and 0.87 (p = 0.06).
Out of 146 radiology-verified analysable local recurrences, 102 (69.9%) were inside the CTV1. In 74.6% and 91% of cases, the LRs were covered by 95% isodose in 2010–2012 and 2013–2015, respectively.
DAHANCA radiotherapy guidelines based on a geometrically generated isotropic CTV1 margin led to less variation in treatment volumes and between centres than previous guidelines. The transition towards consensus GTV-CTV1 margins did not influence local tumour control. The majority of local recurrences were inside CTV1 and covered by the prescription dose.
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