Waiting times for diagnosis and treatment of head and neck cancer in Denmark in 2010 compared to 1992 and 2002.

BACKGROUND AND AIM: Significant tumour progression was observed during waiting time for treatment of head and neck cancer. To reduce waiting times, a Danish national policy of fast track accelerated clinical pathways was introduced in 2007. This study describes changes in waiting time and the potential influence of fast track by comparing waiting times in 2010 to 2002 and 1992. METHODS: Charts of all new patients diagnosed with squamous cell carcinoma of the oral cavity, pharynx and larynx at the five Danish head and neck oncology centres from January to April 2010 (n=253) were reviewed and compared to similar data from 2002 (n=211) and 1992 (n=168). RESULTS: The median time to diagnosis was 13 days (2010) versus 17 days (2002; p<0.001) and 20 days (1992; p<0.001). Median days from diagnosis to treatment start were 25 (2010) versus 47 (2002; p<0.001) and 31 (1992; p<0.001). Total pre-treatment time was median 41 days in 2010 versus 69 days (2002) (p<0.001) and 50 days (1992; p<0.001). Significantly more diagnostic imaging was done in 2010 compared to 2002 and 1992. When compared to current fast track standards the adherence to diagnosis improved slightly from 47% (1992) to 51% (2002) and 64% (2010); waiting time for radiotherapy was within standards for 7%, 1% and 22% of cases, respectively; waiting time for surgery was within standards for 17%, 22% and 48%, respectively. CONCLUSION: The study showed a significant reduction in delay of diagnosis and treatment of head and neck cancer in 2010, but still less than half of all patients start treatment within the current standards.

Prognostic indicators for malignant tumours of the parotid gland.

The best treatment of malignant parotid tumours still remains to be defined, and a better knowledge about the tumour features that predict the treatment result is needed. The histological classification of parotid tumours may present difficulties on account of their great morphological diversity. In a series of 152 patients with a malignant tumour of the parotid gland, the prognostic factors and treatment results were investigated over a 25-year period. Treatment consisted of surgery, radiation therapy or a combination (49%, 13% and 38% respectively). Crude 5-year survival was 50% with significant differences related to stage (stage I, 65%; stage II, 50%; stage III, 21%; and stage IV, 9%). With respect to histopathology, the adenoid cystic carcinomas and the acinic cell carcinomas had the best prognosis (76% and 67% 5-year crude survival and 53% and 67% 10-year crude survival respectively). There was a significant difference in crude survival between well/intermediate and poorly differentiated tumours (P = 0.007). In a Cox hazard regression analysis including 136 patients and using death from cancer as the end-point, the following parameters were independent prognostic predictors: T-classification (P = 0.002), M-classification (P < 0.0001), N-classification (N+versus N0) (P = 0.005), local invasion (P = 0.003) and histological differentiation of the tumour (P = 0.03). The TNM system is a good predictor of treatment outcome for malignant parotid tumours. The use of a combination of clinical and histological factors will assist the design of treatment strategies for parotid gland tumours.

Comparison of two T-classification systems for sino-nasal carcinoma.

It is often difficult to determine the actual site of origin of tumours originating in the sino-nasal region, and a uniform classification system that covers all tumours in this area is warranted. A retrospective series of 165 consecutive patients with sino-nasal carcinoma, treated and followed at the Aarhus University Hospital between 1963 and 1991, was evaluated and T-staged according to the Lederman classification. The 80 maxillary antrum carcinomas were also staged according to the UICC 1997 system. In univariate analysis, the UICC T-classification was prognostic for locoregional tumour control and disease-specific survival. However, when adjusted for covariates (gender and nodal involvement) in a multivariate analysis, the UICC classification was not a significant independent prognostic parameter. In contrast, the Lederman T-classification was prognostic both in univariate and multivariate analysis. The Lederman T-classification was more prognostic for locoregional control and disease-specific survival than the UICC TNM classification. In addition, the Lederman classification is easy to use and has a broader applicability as it covers all sites in the sino-nasal area.

In vitro radiosensitivity of tumour cells and fibroblasts derived from head and neck carcinomas: mutual relationship and correlation with clinical data.

The aim was to characterize the variation in the cellular in vitro radiosensitivities in squamous cell carcinomas of the head and neck, and to test for a possible correlation between different measures of radiosensitivity and the clinical and histopathological data. Cellular in vitro radiosensitivities were assessed in tumour biopsies from 71 patients using the modified Courtenay-Mills soft agar clonogenic assay combined with an immunocytochemical analysis. Radiosensitivity was quantified as the surviving fraction after a radiation dose of 2 Gy irrespective of cell type (overall SF2), or based on identification of cell type (tumour cell SF2, fibroblast SF2). Sixty-three biopsies were from primary tumours, and eight were from recurrences. Overall plating efficiency ranged from 0.005 to 1.60% with a median of 0.052%. The majority of the colonies obtained from the biopsies were fibroblast marker-positive; the proportion of tumour marker-positive colonies ranged from 1 to 88% with a median of 15%. The median overall SF2 was 0.47 (range 0.24-0.96), the median tumour cell SF2 was 0.50 (range 0.11-1.0) and the median fibroblast SF2 was 0.49 (range 0.24-1.0). Comparing data from independent experiments, the overall SF2 was significantly correlated with the SF2 of fibroblasts (2P = 0.006) but not with the tumour cell SF2. The tumour cell and fibroblast radiosensitivities measured in the same individuals were not correlated (r= 0.06, 95% CI [-0.19, 0.30]):This finding seems to preclude a strong correlation between the radiosensitivity of tumour cells and fibroblasts. Concerning the clinical characteristics, neither of the measures of tumour radiosensitivity was correlated with T- and N-category, stage, tumour size, sex and age. However, the tumour cell radiosensitivity decreased with increasing grade of histopathological differentiation (2P = 0.012). The same tendency was found in two independent analyses of the same patient material. This correlation was not significant in case of the overall SF2 or the fibroblast SF2.

Lack of predictive value of potential doubling time and iododeoxyuridine labelling index in radiotherapy of squamous cell carcinoma of the head and neck.

PURPOSE: To investigate the prognostic value of T(POT), S-phase time (TS), iododeoxyuridine (IdUrd) labelling index (LI) and DNA index with loco-regional tumour control as the end-point. MATERIALS AND METHODS: Iododeoxyuridine was given to 99 patients with squamous cell carcinomas of the head and neck before the start of radiotherapy. The analysis included FCM parameters (LI, TS, T[POT] and DNA index, n = 87) and LI determined by immunohistology (IHC, n = 45). A hybrid T(POT) was determined by combining the FCM TS and the IHC LI (n = 45). In diploid tumours (n = 39), the FCM LI was underestimated and the FCM T(POT) was overestimated because the flow cytometer was unable to distinguish between tumour and normal cells. The 'tumour LI' was defined as the IHC LI or the FCM LI of aneuploid tumours when a biopsy for IHC evaluation was not available and similarly the 'tumour T(POT)' was determined by the hybrid T(POT) or the FCM T(POT) of aneuploid tumours (n = 63). RESULTS: There was good agreement between the IHC LI and the FCM LI for aneuploid tumours, but there was disagreement for diploid tumours. The median tumour T(POT) was 4.1 days (range 0.6-19.5 days) and the median tumour LI was 12.9% (range 3.1-46.0%). In a univariate analysis there was no prediction of loco-regional tumour control by the LI, the TS or the T(POT) determined by either of the methods. T-classification, N-classification, clinical stage and tumour diameter were related with loco-regional tumour control, whereas clinical stage was the only parameter that yielded independent prognostic significance in a multivariate analysis. CONCLUSIONS: This study does not confirm the significant prognostic value of T(POT) as indicated in some previous reports. Larger clinical studies are needed to draw final conclusions.

Cancer of the nasal cavity and paranasal sinuses. A clinico-pathological study of 277 patients.

In the period 1963-1991, a total of 277 consecutive patients with malignant tumours of the nasal cavity and paranasal sinuses were treated at Aarhus University Hospital. The major histological types included squamous cell carcinoma (46%), lymphoma (14%), adenocarcinoma (13%), and malignant melanoma (9%). Kaplan-Meier estimates of 5-year corrected survival (death from cancer) showed the best prognosis for adenoid cystic carcinoma (87%), adenocarcinoma (65%) and lymphoma (56%), and the poorest prognosis for undifferentiated carcinoma (17%) and malignant melanoma (24%). The 5-year corrected survival for squamous cell carcinoma was 35%. Of the 180 patients with treatment failure, the vast majority occurred locally (n = 166); a minor proportion was regional (n = 23) or distant (n = 30). For the 195 patients with carcinoma, the following parameters were of statistical prognostic significance (5-year corrected survival): histological differentiation (moderate-well 65% vs. poor 22%), primary T-site (nasal cavity 56% vs. maxillary antrum 39% vs. other sinuses 24%), tumour stage (T2 68% vs. T3 37% vs. T4 29%), nodal stage (N0 48% vs. N1-3 21%), treatment (radiotherapy + surgery 56% vs. radiation alone 35%).

Histopathologic, stereologic, epidemiologic, and clinical parameters in the prognostic evaluation of squamous cell carcinoma of the oral cavity.

BACKGROUND: Prognostic indicators that could assist in a more precise selection of patients with oral cancer for differentiated therapy would be clinically valuable. METHODS: A consecutive series of 161 cases of intraoral squamous cell carcinoma (SCC) occurring during a 5-year period in a population of 1.4 million inhabitants, was evaluated by histopathologic (the modified classification of Jakobsson et al.), stereologic, clinical, and epidemiologic parameters and the serum markers hemoglobin and rhesus blood group. RESULTS: Univariate analysis established a significant prognostic value in terms of cause-specific survival for T stage (P < .0001), stage (P < .0001), maximum tumor diameter (P < .0001), N stage (N+/NO) (P < .0001), alcohol consumption (P = .03), stereologic estimates of nuclear volume (P = .04), and the histomorphologic parameters mode of invasion (P = .001), pattern (P = .01), vascular invasion (P = .02), depth (P = .006), and mean histologic score. Tobacco consumption was borderline significant (P = .055). A multivariate analysis using the Cox proportional hazard analysis showed that both clinical (stage, P < .0001; size, P = .0027), epidemiologic (tobacco consumption, P = .0054), morphohistopathologic (mode of invasion P < .0001), and stereologic (nuclear volume, P = .0010) parameters had an independent significant effect on survival. Inversely, the mean histologic score had no prognostic value. From the final regression model prognostic forecasts were calculated. Twelve patients (25%) with stage I disease had unfavorable histologic and stereologic parameters. The observed survival (+/- 1 standard error of the estimate) for these patients was 33% +/- 18%. The observed survival for stage I patients with more favorable histologic and stereologic characteristics (n = 36) was 76% +/- 8%. CONCLUSION: The use of a combination of clinical, histologic, epidemiologic, and stereologic parameters will assist the design of treatment strategies for intraoral SCC.

[Consumption of tobacco and alcohol as prognostic factors in oral cancer]. / Tobaks- og alkoholforbrug som prognostiske faktorer ved oral cancer.

The aim of the study was to assess the potential prognostic value of tobacco and alcohol consumption. 161 consecutive patients with intra-oral squamous cell carcinoma were included in a prospective follow-up study and valid data on tobacco and alcohol consumption were obtained. Univariate analysis showed that alcohol consumption had a significant influence and tobacco consumption had a borderline significant influence on the prognosis. Tobacco and alcohol consumption were strong correlated and each of these correlated to sex. Clinical staging (TNM), tumor size and sex all had a significant prognostic impact. A multivariate analysis showed that clinical stage, tumor size and tobacco consumption, but not alcohol consumption had significant influence on the prognosis. Thus tobacco smoking is an important clinical parameter both from a prophylactic and a therapeutic point of view.

Histological differentiation of oral squamous cell cancer in relation to tobacco smoking.

The aim of this study was to assess the potential effect of tobacco and alcohol consumption on the histological differentiation of oral squamous cell carcinomas in 161 consecutive patients. The patients were included in a prospective study to secure valid data on tobacco and alcohol consumption. The histopathological grading system included eight morphological qualities describing both the tumour cell population and the interaction between tumour and host. A mean histological score was calculated as the arithmetic mean of the scored individual morphological parameters. Tobacco consumption, as opposed to alcohol consumption, was shown to be significantly correlated with the mean histological score (P = 0.0009), and with the four morphological qualities describing the tumour cell population: pattern (P = 0.0044), cytoplasmic differentiation (P = 0.0008), nuclear differentiation (P = 0.0054) and mitosis (P = 0.0001). Thus, tobacco consumption seems to cause the tumour cells of oral squamous cell carcinomas to undergo a more pronounced dedifferentiation which makes them more aggressive. This effect is enhanced with increasing exposure to tobacco smoke.

Delay in the diagnosis of oral squamous cell carcinoma.

Delay in diagnosis was recorded prospectively in 167 patients with an oral squamous cell carcinoma. The median total delay was 4 months of which two-thirds was patient delay. The corrected survival did not correlate with the total delay. The patient delay was not significantly correlated with tumour or patient factors and the unreliable nature of patient delay information makes such data clinically unusable. In contrast, the professional delay correlated significantly with some of these factors. The delay was longer for women than for men and the older the patient, the longer the delay. The professional delay was longest in patients with small tumours. Thus, registration of the professional delay provides information to be used to improve the diagnostic efficiency of the health care system.

Case-control study of squamous cell cancer of the oral cavity in Denmark.

A population-based case-control study was designed to examine if the risk of developing intra-oral squamous-cell carcinoma in Denmark was associated with occupation, marital status, residence, dental status, and exposure to coffee, tea, tobacco, and alcohol. Cases consisted of 161 consecutively-admitted incident patients with histologically verified, primary, intra-oral squamous-cell carcinoma treated at the Aarhus University Hospital from January 1986 to November 1990. For each case, three controls of the same gender and age were selected randomly from among nonhospitalized residents in the hospital's catchment area (some 1.4 m inhabitants). Four hundred of the selected 483 controls participated in the study. Risk was associated significantly with marital status, residence, dental status, alcohol consumption, and exposure to tobacco. When correcting for tobacco and alcohol consumption, only marital status and dental status remained significant. The association between risk and marital status was particularly prominent among divorced compared with married persons (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.1-4.6). Persons with less than five teeth had an OR of 2.4 (CI 1.3-4.1) compared with persons with 15 or more teeth. Tobacco and alcohol exposure were the strongest individual risk-indicators in both lifetime and current consumption estimates, and their composite effect was particularly strong. Compared with nonusers, OR for tobacco (> 20 g/d) adjusted for alcohol = 5.8 (CI = 3.1-10.9); OR for alcohol (> 5 drinks/d) adjusted for tobacco = 8.4 (CI = 4.0-17.6). The OR for heavy users of tobacco and alcohol (> 20 g tobacco/d and > 5 drinks/d) was 80.7 (CI = 21.8-298.8). These results confirm that tobacco and alcohol contribute significantly to the risk of developing oral cancer. There were no significant differences between the risk estimates for the two genders or young and old persons. Two simulation studies indicate that the observed risk associated with tobacco and alcohol consumption cannot be explained reasonably by a high consumption among the 83 nonrespondents.

The prognostic effect of tobacco and alcohol consumption in intra-oral squamous cell carcinoma.

The aim of this study was to assess the potential prognostic value of tobacco and alcohol consumption in 161 consecutive patients with intra-oral squamous cell carcinoma. The patients were included in a prospective clinico-experimental and epidemiological study to secure valid data on tobacco and alcohol consumption. Univariate analysis showed that patients with an alcohol consumption above the median had a significantly (P = 0.03) poorer prognosis than other patients, with 5-year cause-specific survivals of 54 +/- 6 and 33 +/- 6%, respectively. Similarly, patients with a tobacco consumption above the median had a worse prognosis than other patients, with 5-year cause-specific survivals of 55 +/- 6 and 39 +/- 6%, respectively. This difference was on the borderline of significance, P = 0.056. Tobacco and alcohol consumption were correlated and each of them correlated with sex, males having a higher consumption than females. T-stage, N-stage, clinical stage, tumour size and sex all had a significant prognostic impact. To elucidate whether tobacco and alcohol consumption had an independent prognostic value, a multivariate analysis by means of the Cox proportional hazards regression analysis was performed. This analysis showed that clinical stage (P = 2 x 10(-5)), tumour size (P = 0.007) and tobacco consumption (P = 0.046), but not alcohol consumption, had significant influences on prognosis. Thus, smoking cessation programmes seem warranted both from a prophylactic and a therapeutic point of view.

Oral squamous cell cancer in non-users of tobacco and alcohol.

In a well-defined group of 161 consecutive patients with intra-oral squamous cell carcinoma we found 23 non-users of tobacco and alcohol. The non-users in this prospective study were compared with users of tobacco and alcohol in the study, and to a sex- and age-matched control group drawn at random from the Danish Central Citizenry Registration. The users in the patient group represented a significantly higher number than in the control group. As to non-users, women represented a higher number in the patient group compared with the control group. Among users and non-users differences were found in the location of the primary tumour and in the degree of differentiation of the tumour. Haematological status and liver function parameters were different in the two groups. There was no difference in dental or oral hygiene status or risk occupation among the groups. The stage and the course of the disease (corrected survival) showed only insignificant differences. The non-user group contained especially older women, and only one of them had anaemia.

A functional evaluation of patients treated for oral cancer. A prospective study.

The oral function of 81 consecutive patients with intraoral squamous cell carcinoma was assessed at diagnosis and during the follow-up 1-2 years after diagnosis. Patients received either radiotherapy, surgery, or radiotherapy and surgery. Speech function and tongue mobility were better among patients who received radiotherapy alone than among patients treated with surgery or combined therapy. Subjective complaints about mucositis, poor dental status, and loss of teeth were most pronounced among patients who received radiotherapy. Patients with tumor recurrence reported a poorer quality of life and found it more difficult to accept their treatment than patients with successful primary therapy. Patients with stage I tumors, notably patients treated with surgery, felt that their quality of life was good after treatment.

Stereologic, histopathologic, flow cytometric, and clinical parameters in the prognostic evaluation of 74 patients with intraoral squamous cell carcinomas.

BACKGROUND AND METHODS: A consecutive series of all 78 incident cases of intraoral squamous cell carcinoma occurring during a 2-year period in a population of 1.4 million inhabitants were evaluated by histologic score (the modified classification of Jacobsson et al.), flow cytometry, stereology, tumor size, and the TNM classification. RESULTS: The investigation showed a significant difference between the volume-weighted mean nuclear volume (nuclear vv) of oral leukoplakia (n = 29) and oral squamous cell carcinomas (P = 0.001). The value of the parameters as prognostic indicators of survival and recurrence was tested with Kaplan-Meier plots and Cox multiple hazard regression analysis. Tumor size, T-stage, stereologically estimated nuclear vv, and mean nuclear profile area were all of significant prognostic value in single factor analysis with reference to both survival and recurrence. The histologic parameters of mitotic activity, morphologic nuclear dedifferentiation, and histologic mean malignancy score and the DNA ploidy level had no prognostic value. A prognostic index based on the results of the Cox analysis that included T-stage and nuclear vv was correlated highly with survival (P = 0.00001) and recurrence (P = 0.002). CONCLUSION: These findings may contribute to optimal and individualized therapy.

Treatment of glomus tumours. A retrospective survey.

A retrospective survey of symptomatology, treatment and course of disease in 45 patients with glomus tumours treated between 1959 and 1986 at the Radium Centre and ENT Department of the Aarhus University Hospital is presented. Nine patients were treated surgically, 7 had surgery and irradiation combined, and 25 patients were treated solely with radiation therapy. Six patients developed recurrence of tumours. Two patients died of tumour, one of them with pulmonary metastases.

Catheter perforation of distal oesophagus with duodenal re-entry of catheter. Report of a case.

An unusual case of perforation of the oesophagus is presented. A nasogastric tube had perforated the oesophagus and re-penetrated into the duodenum, and thereby re-entered the gastrointestinal tract without perforating the peritoneum and without causing the classical clinical signs of oesophageal perforation. Treatment was started 31 days after the perforation.

Sarcomatous change in a previously benign osteofibroma in the maxillary sinus.

Ossifying fibromas of the jaws are generally well-defined benign tumors, so that adequate surgical treatment is usually associated with good therapeutic results. However, there are cases--especially in younger individuals with maxillary tumors--in which recurrences are seen, often with aggressive growth and subsequent local destruction. There is no characteristic histological appearance that identifies these "recurring types." A case is presented in which a benign ossifying fibroma was extirpated from a 17-year-old man. Twenty years later a recurrent tumor was found, in which histological examination showed development of a osteosarcoma. The clinical implications of this case are discussed.