Johannes A. Langendijk

Peripheral blood IFN-γ-secreting Vα24+Vβ11+ NKT cell numbers are decreased in cancer patients independent of tumor type or tumor load

Natural killer T (NKT) cells are CD1d‐restricted lymphoid cells and are characterized by an invariant T‐cell receptor, which in humans consists of a Vα24 chain paired with a Vβ11 chain. These cells are known for their rapid production of large amounts of cytokines (e.g., IFN‐γ and IL‐4), thereby modulating other cells of the immune system such as T cells, NK cells and dendritic cells. NKT cells have been reported to play important regulatory roles in many immune responses, including antitumor immune responses. Here, we demonstrate an age‐dependent decrease in circulating Vα24+Vβ11+ NKT cell numbers in both healthy controls and cancer patients and demonstrate that in both groups females have higher NKT cell levels compared to males. In a large group of 120 cancer patients, we show that circulating Vα24+Vβ11+ NKT cell numbers are about 50% lower than in age‐ and gender‐matched healthy controls and that this decrease is independent of tumor type or tumor load. This decrease was not restored upon tumor removal by means of surgery or radiotherapy. Even though the percentage of NKT cells that secrete IFN‐γ, as detected by ELISPOT, is normal in cancer patients, the absolute number of circulating IFN‐γ‐secreting NKT cells is reduced. Together, our results suggest that the reduced circulating Vα24+Vβ11+ NKT cell numbers in cancer patients are not affected by tumor load, but might actually reflect a risk factor for tumor development, e.g., by hampering efficient tumor immunosurveillance.

Health status and voice outcome after treatment for T1a glottic carcinoma

Radiotherapy as well as endoscopic laser surgery as the most widely used treatment modalities for T1a glottic carcinoma cause minor morbidity and negligible mortality and result in more or less comparable, excellent cure and larynx preservation rates. Therefore, other outcome measures such as voice-related problems and health status are important factors in the choice of treatment for T1a glottic cancer. The present study focuses on voice-related problems in the daily life of patients treated by radiotherapy or endoscopic laser surgery for T1a glottic cancer. Self ratings on health status assessed by means of COOP/WONCA health status charts and voice problems evaluated with a validated voice-specific questionnaire (the Voice Handicap Index) and overall judgment on voice quality were obtained. A total of 102 patients (56 treated by endoscopic laser surgery and 46 treated by radiotherapy) with at least 1-year follow-up were included. Response scores were high: 52 (93%) patients after endoscopic laser surgery versus 40 (87%) patients after radiation therapy completed and returned the questionnaires. A high percentage of patients reported voice problems in daily life: 58% of the patients following radiotherapy and 40% of the patients following endoscopic treatment had abnormal VHI scores. The difference between both treatment modalities proved to be significant. No significant differences were found concerning health status or overall judgment of voice quality. Moderate correlations were found between total VHI score and voice quality judgment and the COOP/WONCA social activities chart. This study reveals that treatment for T1a glottic cancer often does result in voice problems in daily life, negatively influencing patients social activities. Patients selected for endoscopic laser surgery on average report fewer voice-related problems than those who underwent radiotherapy.

Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy

The objective of this study was to define different prognostic groups with regard to locoregional control (LRC) derived from recursive partitioning analysis (RPA).

Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer

A feasibility study was performed to assess the toxicity and efficacy of a combination of gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable LAPC were included; the median age of the patients was 63 years (range 39-74 years). The performance status ranged from 0 to 2. Gemcitabine was administered at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy, on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the response and toxicity. All patients were evaluable for toxicity and response. The objective response rate was 29.2% (1 complete remission+6 partial remissions); 12 patients had stable disease. However, 2 of the radiological partial remissions were shown to be complete remissions by pathology assessment. Median duration of response was 3 months (range 1-35+months). Median time to progression was 7 months (range 2-37+months). Median survival was 10 months (range 3-37+months). Dose reduction or omission of gemcitabine was necessary in 10 patients. Non-haematological toxicity consisted of 87.5% nausea and vomiting grade I-II, diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months after treatment. Anaemia grade III-IV was observed in 8.3% of the patients. Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in 16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour cells were found. In addition, in the patient who suddenly died of a fistula between the duodenum and aorta, no viable tumour cells were detectable at autopsy. Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination.

Positive surgical margins in neck dissection specimens in patients with head and neck squamous cell carcinoma and the effect of radiotherapy

To evaluate the outcome after surgery and radiotherapy for extensive nodal disease in patients with primary head and neck cancer.

Radiotherapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly : A prospective randomized study in squamous cell head and neck cancer

The main objective of this study was to investigate whether nondaily intravenous administration of amifostine was as effective as daily intravenous administration with regard to the reduction of the incidence of Grade 2 or greater xerostomia in patients with head and neck cancer.

The prevalence of hypothyroidism after treatment for laryngeal and hypopharyngeal carcinomas: are autoantibodies of influence?

Conclusions. The incidence rate of hypothyroidism after treatment for laryngeal and hypopharyngeal cancer is high, especially after combination treatment. An association between hypothyroidism and autoantibodies was found. Objectives. The incidences of hypothyroidism and autoantibodies were assessed retrospectively in 156 patients with laryngeal and hypopharyngeal carcinoma who were treated with surgery and/or radiotherapy between 1977 and 2002. Patients and methods. Patients treated for T2–T4 carcinoma or a recurrence after T1 who visited the outpatient clinic for their regular follow-up visit were included. All patients were evaluated for the development of hypothyroidism, defined as increased thyroid-stimulating hormone level (>4.5 mU/L) and the presence of autoantibodies. A questionnaire regarding symptoms was administered. Results. The prevalence of undiagnosed hypothyroidism following treatment of laryngeal carcinoma was 28.2%: 18.6% subclinical hypothyroidism and 9.6% clinical hypothyroidism. The prevalence of circulating antithyroid antibodies (anti-thyreoperoxidase and/or anti-thyreoglobulin) was 10.5%. Univariate analysis showed that patients with laryngectomy, hemithyroidectomy, ipsilateral neck dissection and autoantibodies had a higher risk of hypothyroidism. The combination of surgery and radiotherapy increased the risk. Symptoms such as weight gain and cold intolerance were significantly associated with hypothyroidism. Multivariate analysis showed hemithyroidectomy, autoantibodies, weight gain and cold intolerance to be prognostic factors for the development of hypothyroidism.

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 € 3,207 (95%CI 3,091–3,395) for diagnosis, € 3,169 (2,153–4,182), € 5,026 (3,996–6,057), € 6,458 (5,579–7,337), € 8,037 (7,469–8,606), € 12,765 (10,763–14,769), € 19,227 (16,848–21,605) for treatment of dysplasia, carcinoma in situ, T1, T2, T3 and T4 carcinoma, respectively, and € 1,856 (1,491–2,220) for 1xa0year 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.

OC-0534: An RCT on the value of postoperative accelerated radiotherapy in squamous cell head and neck cancer: final results

All measured values were evaluated using the gamma index with dose difference/distance-to-agreement criteria of 3%/2 mm (γ3%/2 mm) for the area receiving more than 10% isodose as compared with a static pattern. A γ passing rate > 90% was considered acceptable in this study. Results: For Group A, γ3%/2 mm was less than 90% for translational errors ≥ 3 mm in the LAT and VRT directions and ≥ 2 mm in the LNG direction. For Group B, γ3%/2 mm was less than 90% for rotational errors ≥ 3° (Table 1). Table 2 summarizes γ3%/2 mm for Group C. Translational errors of 2 mm and rotational errors of 2° always gave a γ3%/2 mm of less than 90%. γ3%/2 mm was less than 90% for tilt and roll angles of 2°, even without translational errors. Even when translational errors were 1 mm, γ3%/2 mm was less than 90% for two patterns with rotational errors of 1°. By correcting the translational errors, γ3%/2 mm was more than 90% for tilt and roll angles of 1°. Note that correction of the translational errors degraded γ3%/2 mm for the pattern with a tilt angle of 1° and roll angle of -1° and with a tile angle of 2° and roll angle of -2°.