Novel Diagnostic Approaches for Assessment of the Clinically Negative Neck in Head and Neck Cancer Patients.

In head and neck cancer, the presence of nodal disease is a strong determinant of prognosis and treatment. Despite the use of modern multimodality diagnostic imaging, the prevalence of occult nodal metastases is relatively high. This is why in clinically node negative head and neck cancer the lymphatics are treated "electively" to eradicate subclinical tumor deposits. As a consequence, many true node negative patients undergo surgery or irradiation of the neck and suffer from the associated and unnecessary early and long-term morbidity. Safely tailoring head and neck cancer treatment to individual patients requires a more accurate pre-treatment assessment of nodal status. In this review, we discuss the potential of several innovative diagnostic approaches to guide customized management of the clinically negative neck in head and neck cancer patients.

Prophylactic antibiotics reduce hospitalisations and cost in locally advanced head and neck cancer patients treated with chemoradiotherapy: A randomised phase 2 study.

BACKGROUND: Platinum-based chemoradiotherapy for locally advanced head and neck cancer (LAHNC) induces a high rate of acute toxicity, including dysphagia and aspiration pneumonia. We hypothesised that prophylactic antibiotics can prevent pneumonia and hospitalisations and can be cost-effective. PATIENT AND METHODS: In this multicentre randomised trial, patients with LAHNC treated with chemoradiotherapy received prophylactic amoxicillin/clavulanic acid from day 29 after the start of treatment until 14 days after completion of chemoradiotherapy or standard care without prophylaxis. The primary objective was to observe a reduction in pneumonias. Secondary objectives were to evaluate the hospitalisation rate, adverse events, costs and health-related quality of life. RESULTS: One hundred six patients were included; of which, 95 were randomised: 48 patients were allocated to the standard group and 47 patients to the prophylaxis group. A pneumonia during chemoradiotherapy and follow-up until 3.5 months was observed in 22 (45.8%) of 48 patients in the standard group and in 22 (46.8%) of 47 patients in the prophylaxis group (p = 0.54). Hospitalisation rate was significantly higher in the standard group versus the prophylaxis group, 19 of 48 pts (39.6%) versus 9 of 47 pts (19.1%), respectively (p = 0.03). Significantly more episodes with fever of any grade were observed in the standard group (29.2% vs 10.2%, p = 0.028). A significant difference in costs was found, with an average reduction of €1425 per patient in favour of the prophylaxis group. CONCLUSION: Although prophylactic antibiotics during chemoradiotherapy for patients with LAHNC did not reduce the incidence of pneumonias, it did reduce hospitalisation rates and episodes with fever significantly and consequently tended to be cost-effective.

Pathology-based validation of FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer.

PURPOSE: FDG PET is increasingly incorporated into radiation treatment planning of head and neck cancer. However, there are only limited data on the accuracy of radiotherapy target volume delineation by FDG PET. The purpose of this study was to validate FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer against the pathological method as the standard. METHODS: Twelve patients with head and neck cancer and 28 metastatic lymph nodes eligible for therapeutic neck dissection underwent preoperative FDG PET/CT. The metastatic lymph nodes were delineated on CT (NodeCT) and ten PET segmentation tools were used to assess FDG PET-based nodal volumes: interpreting FDG PET visually (PETVIS), applying an isocontour at a standardized uptake value (SUV) of 2.5 (PETSUV), two segmentation tools with a fixed threshold of 40% and 50%, and two adaptive threshold based methods. The latter four tools were applied with the primary tumour as reference and also with the lymph node itself as reference. Nodal volumes were compared with the true volume as determined by pathological examination. RESULTS: Both NodeCT and PETVIS showed good correlations with the pathological volume. PET segmentation tools using the metastatic node as reference all performed well but not better than PETVIS. The tools using the primary tumour as reference correlated poorly with pathology. PETSUV was unsatisfactory in 35% of the patients due to merging of the contours of adjacent nodes. CONCLUSION: FDG PET accurately estimates metastatic lymph node volume, but beyond the detection of lymph node metastases (staging), it has no added value over CT alone for the delineation of routine radiotherapy target volumes. If FDG PET is used in radiotherapy planning, treatment adaptation or response assessment, we recommend an automated segmentation method for purposes of reproducibility and interinstitutional comparison.

Long-term outcome and morbidity after treatment with accelerated radiotherapy and weekly cisplatin for locally advanced head-and-neck cancer: results of a multidisciplinary late morbidity clinic.

PURPOSE: To evaluate the long-term outcome and morbidity after intensified treatment for locally advanced head-and-neck cancer. METHODS AND MATERIALS: Between May 2003 and December 2007, 77 patients with Stage III to IV head-and-neck cancer were treated with curative intent. Treatment consisted of accelerated radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors were invited to a multidisciplinary outpatient clinic for a comprehensive assessment of late morbidity with special emphasis on dysphagia, including radiological evaluation of swallowing function in all patients. RESULTS: Compliance with the treatment protocol was high, with 87% of the patients receiving at least five cycles of cisplatin and all but 1 patient completing the radiotherapy as planned. The 5-year actuarial disease-free survival and overall survival rates were 40% and 47%, respectively. Locoregional recurrence-free survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively. Radiologic evaluation after a median follow-up of 44 months demonstrated impaired swallowing in 57% of the patients, including 23% with silent aspiration. Subjective assessment using a systematic scoring system indicated normalcy of diet in only 15.6% of the patients. CONCLUSION: This regimen of accelerated radiotherapy with weekly cisplatin produced favorable tumor control rates and survival rates while compliance was high. However, comprehensive assessment by a multidisciplinary team of medical and paramedical specialists revealed significant long-term morbidity in the majority of the patients, with dysphagia being a major concern.

PET-CT for response assessment and treatment adaptation in head and neck cancer.

Preferred treatment strategies for advanced-stage squamous cell carcinoma of the head and neck have shifted from surgery to organ-preservation approaches such as radiotherapy, which can be combined with chemotherapy or giving of biologically modifying molecules. Preclinical and clinical researchers aim to customise these treatments on the basis of biological tumour characteristics, including tumour cell proliferation, hypoxia, and apoptosis--important resistance mechanisms for cytotoxic antitumour therapy. Monitoring of these biologically relevant variables before and early during treatment could improve patient selection for specific treatment strategies and guide adaptation of treatment at an early stage. PET provides a non-invasive molecular imaging method with the potential ability to undertake repetitive non-invasive quantification of relevant tumour characteristics. We discuss the role of PET scanning and available radiopharmaceutical tracers for treatment selection, early response monitoring, and treatment adaptation in head and neck cancer.

Effect of routine follow-up after treatment for laryngeal cancer on life expectancy and mortality: results of a Markov model analysis.

BACKGROUND: Routine follow-up is offered to all patients with laryngeal cancer who are treated with curative intent. Although time and resources are devoted to surveillance, the effect of asymptomatic recurrence detection is not well understood. For this study, the authors evaluated the effect that routine follow-up may have on life expectancy and disease-specific mortality rate for patients with laryngeal cancer. METHODS: Using a Markov model, a cohort simulation was performed on 4 hypothetical age groups of patients with laryngeal cancer. Three different follow-up strategies were compared-the current schedule, no follow-up, and the perfect follow-up-in which all recurrences were detected asymptomatically. Sensitivity analyses were performed to study the impact of variations in the transition rates on life expectancy. RESULTS: Compared with no follow-up, the current schedule showed a gain in life expectancy with a range from 0.3 years to 1.5 years that decreased with advancing age. Abolishing the current follow-up schedule raised the disease-specific mortality rate; the increase ranged from 2.8% to 5.9%. Variations of +/-25% in the transition rates produced only a modest effect on life expectancy. CONCLUSIONS: A small reduction in life expectancy was observed when follow-up was withheld from the majority of patients. Disease-specific mortality rates rose when no follow-up was provided. These rates probably were overestimated. A simplified version of the current follow-up protocol may be implemented.

Compliance and efficiency before and after implementation of a clinical practice guideline for laryngeal carcinomas.

We evaluated whether the implementation of a nationwide clinical practice guideline for diagnosis, treatment and follow-up of laryngeal carcinomas led to changes in hospital costs, balanced against clinical changes observed following the guideline's implementation. Charts of 822 patients with larynx carcinoma (459 treated before the introduction of the guideline and 363 thereafter) in five hospitals were retrospectively investigated. In all phases, no differences in total hospital costs were observed after the guideline's implementation. Total mean costs were Euro 3,207 (95%CI 3,091-3,395) for diagnosis, Euro 3,169 (2,153-4,182), Euro 5,026 (3,996-6,057), Euro 6,458 (5,579-7,337), Euro 8,037 (7,469-8,606), Euro 12,765 (10,763-14,769), Euro 19,227 (16,848-21,605) for treatment of dysplasia, carcinoma in situ, T1, T2, T3 and T4 carcinoma, respectively, and Euro 1,856 (1,491-2,220) for 1 year disease-free follow-up. In an earlier study, we observed several positive changes after the guideline's implementation. Balanced against the equal costs before and after the guideline's implementation, we conclude that the efficiency of the care process improved.