Peter Wahlberg

Carcinoma of the parotid and submandibular glands-a study of survival in 2465 patients.

Salivary gland carcinomas demonstrate a wide diversity of histopathological types and biological behavior. The aim of this study was to analyze relative survival of patients with major salivary gland carcinomas with special reference to histopathology, gender and age. All new carcinomas of the major salivary glands reported to the National Swedish Cancer Registry 1960-1995 were searched for and the vital status of the cases was updated by record linkage to the Swedish Population Registry through December 31 1996. The study comprised 2465 patients with carcinoma of the parotid or submandibular glands. Relative survival differed markedly according to histopathological typing (P<0.001). For parotid tumors, acinic cell carcinomas had the best prognosis with a 10-year relative survival of 88%. The corresponding figures for mucoepidermoid carcinomas, adenoidcystic carcinomas and carcinoma ex pleomorphic adenoma were 80, 74 and 73%. Adenocarcinoma NOS and undifferentiated carcinoma had worse prognosis, with 10-year relative survival of 55 and 44%. Patients with submandibular gland cancer had similar relative survival to those with parotid cancers, besides those with mucoepidermoid cancer and adenocarcinoma NOS, who carried worse prognosis. Age and gender had an impact on relative survival for patients with mucoepidermoid carcinoma, adenocarcinoma and undifferentiated cancer of the parotid.

Anaplastic thyroid carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery

Patients with anaplastic thyroid carcinoma can rarely be cured, but every effort should be made to prevent death due to suffocation. Between 1984 and 1999, 55 consecutive patients with anaplastic thyroid carcinoma were prospectively treated according to a combined regimen consisting of hyperfractionated radiotherapy, doxorubicin, and when feasible surgery. Radiotherapy was carried out for 5 days a week. The daily fraction until 1988 was 1.0 Gy × 2 (A) and 1989–92 1.3 Gy × 2 (B) . Thereafter 1.6 Gy × 2 (C) was administered. Radiotherapy was administered to a total target dose of 46 Gy; of which 30 Gy was administered preoperatively in the first two protocols (A and B), while the whole dose was given preoperatively in the third protocol (C). The therapy was otherwise identical. Twenty mg doxorubicin was administered intravenously weekly. Surgery was possible in 40 patients. No patient failed to complete the protocol due to toxicity. In only 13 cases (24%) was death attributed to local failure. Five patients (9%) ‘had a survival’ exceeding 2 years. No signs of local recurrence were seen in 33 patients (60%); 5 out of 16 patients in Protocol A, 11 out of 17 patients in Protocol B, 17 out of 22 patients in Protocol C (P=0.017). In the 40 patients undergoing additional surgery, no signs of local recurrence were seen in 5 out of 9 patients, 11 out of 14 patients and 17 out of 17 patients, respectively (P=0.005).

p53 mutation, but not p53 overexpression, correlates with survival in head and neck squamous cell carcinoma

Survival in squamous cell carcinoma of the head and neck (HNSCC) was compared with overexpression and mutation of the p53 gene. Archival tissue from 77 tumours was analysed for protein expression using immunohistochemistry (IHC) with the monoclonal antibody Do-7, and for the presence of mutation in exons 5-8 using single-stranded conformation polymorphism (SSCP), followed by DNA sequencing in SSCP-positive cases. p53 expression was scored as high (>70% nuclei stained) in 25 (32%) tumours, as intermediate (10-70% nuclei stained) in 19 (25%) tumours and as low (<10% nuclei stained) in 33 (43%) tumours. Twelve (18%) tumours exhibited gene mutation (ten missense and two nonsense mutations) and an additional five tumours contained changes that could not result in amino acid substitution or protein truncation. There was no correlation between gene expression and mutation, mutations being equally frequent in tumours with either high (4/25), intermediate (4/19) or low protein expression (4/33). Fifty-eight patients were eligible for survival analysis. There was a strong correlation between p53 mutation and cause-specific survival; median survival among mutated cases was 12.5 months compared with >160 months among non-mutated patients (P < 0.005). There was no correlation between p53 overexpression and survival. The results suggest that p53 mutation status is an important prognostic factor in HNSCC, and that IHC analysis of protein overexpression is an inadequate measure of gene mutation in these tumours.

Carcinoma of the hypopharynx: Analysis of incidence and survival in Sweden over a 30‐year period

The aim of the study was to analyze whether there were any changes in incidence and prognosis of hypopharyngeal carcinomas diagnosed between 1960 and 1989 in Sweden.

p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in xenografted human squamous cell carcinomas from head and neck

To investigate the response of tumour growth to cisplatin treatment, in relation to p53 mutation and cyclin D1 dysregulation on DNA and protein level, biopsies from seven xenografted human squamous cell carcinomas from the head and neck were analysed with immunohistochemistry for p53 expression and cyclin D1 expression. Polymerase chain reaction -singlestranded conformation polymorphism was used to determine p53 mutations. Fluorescence in situ hybridization was performed to analyse cyclin D1 amplification. The mice were injected i.p. with NaCl (controls) or cisplatin. After injection the tumour volume were measured. The inhibition of tumour growth by cisplatin was defined as the area under the growth curves, and compared with the growth curves of the tumours in the control group. Xenografts with p53 mutation showed significantly higher resistance to cisplatin (p < 0.001) and also tumours with cyclin D1 amplification showed significantly higher resistance (p < 0.001).

Radiation-induced trismus in the ARTSCAN head and neck trial

Abstract Trismus, a well-known sequelae after treatment of head and neck cancer, decreases a patients oral function and quality of life. The main objectives of this study were to: 1) investigate the long-term prevalence of radiation-induced trismus in patients treated for head and neck cancer according to two different fractionation schedules; and 2) model a dose–response relationship for trismus. Material and methods. Patients were recruited from the Swedish ARTSCAN trial, a prospective randomised multicentre study comparing conventional and accelerated fractionation. A total of 124 patients agreed to a clinical ENT examination 21–127 months (median 66 months) after beginning radiation therapy. Trismus-related scores were assessed using the EORTC H&N35 Quality of Life questionnaire. The TheraBite® range of motion scale was used to measure maximal interincisal distance. The dose–response relationship for structures important for mastication and the temporomandibular joints was investigated by normal tissue complication probability modelling. Results. No significant differences in patient-reported trismus or maximal interincisal distance were found between the two trial arms. Patient-reported moderate to high scores regarding trismus increased from 3% at the start of radiation therapy to 25% at the long-term follow-up. Maximal interincisal distance correlated significantly with patient-reported scores of trismus. The best dose–response fit to the endpoint data was found for the dose to the ipsilateral masseter. Conclusions. Trismus is a persistent complication after radiotherapy with 3D-conformal radiation therapy. We found no difference between the severity and prevalence of trismus between conventional and accelerated fractionation, but a significant correlation between the absorbed dose to the mastication structures and opening of the mouth. Further prospective studies may determine whether a reduced dose to structures important for mastication using intensity-modulated radiation therapy will reduce problems with trismus.

Differences in estimates of cisplatin-induced cell kill in vitro between colorimetric and cell count/colony assays

SummaryThe aim of this study was to evaluate some bioassays that are different in principle: cell counting, colony forming assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), sulforhodamine B (SRB), crystal violet, and alamarBlue, with respect to their ability to measure cisplatin-induced cell death of in vitro-cultivated squamous cell carcinoma of the head and neck (SCCHN). Cisplatin was applied in concentrations of 1.0, 5.0, 10.0, 50.0, and 100 μM. The cells were incubated for 1 h, and the cell survival was measured 5 d after treatment. We found the colorimetric assays and cell counting to be comparable. The colony forming assay indicated a higher degree of cell kill compared with the other techniques. Measurement of cell survival after treatment with cisplatin can be done by use of any of the above tested assays. However, the majority of SCCHN cell lines available do not form colonies easily, or at all. Therefore, comparing the chemosensitivity between such cell lines is limited to alternative assays. In this respect, any of the tested colorimetric assays can be used. However, they seem to underestimate cell kill. Cell counting is also an alternative. This technique, however, is time consuming and operator dependent, as in the case of manual counting, or relatively expensive when counting is performed electronically, compared with the colorimetric assays.

Fluorescence investigations to classify malignant laryngeal lesions in vivo.

The extent of surgical resection for malignant laryngeal lesions influences voice quality. An instrument to estimate histopathologic grading of dysplasia in vivo may spare normal tissue without increasing the risk of local failure.

Prognostic value of histopathological response to radiotherapy and microvessel density in oral squamous cell carcinomas

The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.The prognostic value of histopathological response to preoperative radiotherapy (50 Gy) in radically resected oral carcinomas was studied in 39 consecutive patients. Microvessel density (MVD) was evaluated for relation to radioresponse and outcome. Resected tumour tissue was examined histopathologically and response to radiotherapy was scored according to induced morphological changes. Pretreatment biopsies were stained with antibodies to von Willebrand factor to evaluate MVD in hot-spot regions, in stromal tissue and in tumour epithelial tissue. Histopathological response to radiotherapy was highly prognostic of local failures and survival (p = 0.002), though microscopic surgical radicality was obtained. In good responders to preoperative radiotherapy, the 5-year survival rate was 68% compared with 24% in poor responders. In 12 patients with local recurrence after radical surgery, 11 had poor histopathological radiotherapy responses. In univariate analysis, a high MVD score in tumour epithelium was associated with poor clinical outcome but MVD did not correlate with histopathological radiotherapy response.

Distribution of non-diploid flow-cytometric DNA indices and their relation to the nodal metastasis in squamous cell carcinomas of the head and neck

Squamous cell carcinomas of the head and neck (HNSCC) evolve from diploid epithelial cells of the mucosa. At the time of diagnosis about two thirds of clinically diagnosed HNSCC are non-diploid according to flow-cytometric (FCM) analysis, indicating that during tumour progression there must be an acquisition and accumulation of chromosomal aberrations. At diagnosis one third to one half of HNSCC have clinically positive neck nodes. The objective of the present study was to see whether the progression to a metastatic phenotype is reflected in the distribution of FCM DNA ploidy in node-negative and node-positive HNSCC. The series comprised 200 patients with HNSCC. Tumour samples were obtained from diagnostic biopsies or primary surgery. A multistep preparation method and propidium iodide staining of nuclear DNA content was used for FCM. One hundred and forty one (71%) of the tumours were non-diploid. Only two tumours were hypodiploid (DNA index 0.73 and 0.93, respectively). Ten of the tumours exhibited two non-diploid stem cell lines. The frequency of non-diploidy in node-negative tumours was 65% and in node-positive ones about 80%. The frequency distribution of non-diploid DNA indices clustered in the hypotetraploid region (with a modal value of 1.71–1.74) and did not differ between node-negative and node-positive tumours. The hypothesis that the disposition to metastasis is reflected in the frequency distribution of non-diploid DNA indices could thus not be verified.