1.
Engellau, Jacob, et al.
(author)
Time dependence of prognostic factors for patients with soft tissue sarcoma : a Scandinavian Sarcoma Group Study of 338 malignant fibrous histiocytomas
2004
In: Cancer. - : Wiley. - 1097-0142 .- 0008-543X. ; 100:10, s. 2233-2239
Journal article (peer-reviewed) abstract
BACKGROUND: Prognostic factors for metastasis in soft tissue sarcoma govern decisions regarding adjuvant treatment. However, the significance of initial tumor-related prognostic factors over time is largely unknown.METHODS: The current study included 338 patients with malignant fibrous histiocytoma (MFH) of the extremities or the trunk wall whose tumors were reviewed by the Scandinavian Sarcoma Pathology Review Group. Of these 338 patients, 329 (97%) had high-grade tumors. The median follow-up period was 7 years. Metastases occurred in 110 of 338 of patients after a median follow-up period of 14 months, with roughly one-third (32 of 110) occurring after 2 years. The authors investigated the prognostic significance of tumor size, tumor depth, histologic grade, microscopic tumor necrosis, vascular invasion, mitotic rate, and local tumor recurrence at various time intervals using metastases as an endpoint.RESULTS: On univariate analysis, all investigated factors were found to be correlated with metastases for the entire follow-up period and also for the first 2 years of follow-up; beyond this time point, only size, tumor depth, and local recurrence were significant. On multivariate analysis, necrosis and local tumor recurrence were significant for the entire follow-up duration and also for the first 2 years of follow-up, whereas only tumor depth and local recurrence were significant beyond 2 years of follow-up. For all initial factors, the annual metastasis risks in the high-risk and low-risk groups converged to < 0.1 after 2 years and to near 0 after 5 years.CONCLUSIONS: Prognostic factors for metastasis in MFH were time dependent. The predictive value of the initial prognostic factors was limited to the first 2 years of follow-up. The lack of observed prognostic value beyond 2 years of follow-up probably was attributable to heterogeneity within risk categories as a result of measurement errors and unknown biologic variations.
2.
Holmberg, L, et al.
(author)
HABITS (hormonal replacement therapy after breast cancer - is it safe?), a randomised comparison: trial stopped
2004
In: The Lancet. - 1474-547X. ; 363:9407, s. 453-455
Journal article (peer-reviewed) abstract
In the 1990s, two randomised clinical trials started in Scandinavia addressing whether hormone replacement therapy (HRT) is safe for women with previous breast cancer. We report the findings of the safety analysis in HABITS (hormonal replacement therapy after breast cancer-is it safe?), an open randomised clinical trial with allocation to either HRT or best treatment without hormones. The main endpoint was any new breast cancer event. All analyses were done according to intention-to-treat. Until September, 2003, 434 women were randomised; 345 had at least one follow-up report. After a median follow-up of 2.1 years, 26 women in the HRT group and seven in the non-HRT group had a new breast-cancer event. All women with an event in the HRT group and two of those in the non-HRT group were exposed to HRT and most women had their event when on treatment. We decided that these findings indicated an unacceptable risk for women exposed to HRT in the HABITS trial, and the trial was terminated on Dec 17, 2003.
3.
Holmberg, L, et al.
(author)
Stopping HABITS - Reply
2004
In: The Lancet. - 1474-547X. ; 363:9419, s. 1477-1477
Journal article (other academic/artistic)
4.
Åkervall, Jan, et al.
(author)
Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients
2004
In: Clinical Cancer Research. - 1078-0432. ; 10:24, s. 8204-8213
Journal article (peer-reviewed) abstract
Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines. Experimental Design: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy. Results: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified similar to60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026). Conclusions: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.
