DNA measurement – An objective predictor of response to irradiation? A review of 24 squamous cell carcinomas of the oral cavity

Franzen, G; Klintenberg, Claes; Olofsson, Jan; Risberg, Bjørn

doi:10.1038/bjc.1986.108

Cited by 42 publications

(11 citation statements)

References 12 publications

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“…Twenty-five of these tumours were aneuploid, three were diploid. The potential doubling time of aneuploid tumours was significantly less than that of diploid tumours which may explain the observation that aneuploid tumours are often more responsive to therapy (Franzen et al, 1986;Barlogie et al, 1987;Guo et al, 1989). We have previously reported that in advanced unresectable squamous carcinoma of the head and neck there was a significant prolongation of survival in patients with aneuploid tumours compared with patients with diploid tumours when treated with cisplatin (Cooke et al, 1990).…”

Section: Discussionmentioning

confidence: 83%

“…The method developed by Begg et al (1985) (Friedlander et al, 1984;Volm et al, 1985) including some head and neck tumours (Holm, 1982;Franzen et al, 1986) 11.5 7.9 14.8 P<0.01 (2.6-30.0) (2.6-14.7) (7.6-30.0) in breast cancer where high TLI correlates with reduced survival (Meyer & Hixon, 1979;Gentili et al, 1981) and may also predict tumour radio and chemosensitivity (Silvestrini et al, 1984). The relationship between TLI and prognosis is not so well established in head and neck cancer where unlike in breast cancer the median TLI fails to divide patients into two groups with significantly different outlook (Courdi et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

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Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry

Forster

Cooke²,

Cooke³

et al. 1992

Br J Cancer

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Summary The cell kinetics of 82 squamous cell carcinomas of the head and neck were studied by in vivo administration of the thymidine analogue, bromodeoxyuridine (BrdUrd). Ploidy, BrdUrd labelling index (LI), duration of S-phase (Ts), potential doubling time (Tpot) and S-phase (Steel, 1977;Meyer, 1982). Cell kinetic studies in man, until recently, have been limited to in vitro investigations because of the ethical constraints of administering radioactive DNA precursors to patients. Tritiated thymidine labelling of freshly excised tissue followed by autoradiography has been widely used (Gentili et al., 1981;Brandt & Olsson, 1987;Courdi et al., 1989;Meyer & Bauer, 1975). The development of flow cytometric methods for measuring DNA content, particularly in paraffin embedded archival material, has resulted in DNA ploidy and S-phase fraction analysis being performed for many tumour types (Cornelisse et al., 1987;Armitage, 1985;Feichter et al., 1987

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry

Forster

Cooke²,

Cooke³

et al. 1992

Br J Cancer

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“…They concluded that Sphase fraction was of high prognostic significance, particularly in breast cancers, non-Hodgkin's lymphomas, ovarian cancers, neuroblastoma, bladder and lung cancers. It is not clear whether they attempted a comprehensive review of all publications up to 1988 when the manuscript was submitted, but within the head and neck region they omitted the paper by Franzen et al (1986). Despite Tubiana and Courdi's strong conclusion on the prognostic usefulness of SPF there have been subsequent large series in both breast and ovarian cancer which found no correlation between SPF and prognosis (Conte et al, 1989;Cooke et al, 1992).…”

Section: Statisticsmentioning

confidence: 99%

“…Ensley et al (1989) reported that three-quarters of 165 patients with squamous carcinomas of the head and neck had an S-phase fraction (SPF) above 15% and that there was a strong direct correlation between DNA index and SPF. Franzen et al (1986) found a mean SPF of 6.4% in diploid tumours, 10% in polyploid tumours and 19% in aneuploid tumours, with a range of 1-30% amongst 24 oral cavity carcinomas. Johnson et al (1985) reported a mean SPF of 19% with a range of 4-45% in 45 patients with tumours at various sites within the head and neck.…”

Section: Statisticsmentioning

confidence: 99%

“…There have been very few publications examining tumour growth rates and prognosis in tumours of the head and neck region. Franzen et al (1986) reported that the mean SPF was higher (16.1%) in a small group of eight oral cavity tumours eradicated by preoperative radiotherapy than for 13 that did not respond (8.1%). In contrast, pretreatment thymidine labelling index was not related to short-or longterm response to radiotherapy in another series of 52 oral cavity carcinomas, but a reduction of more than 70% in the thymidine labelling index after the first 10 Gy was associated with a good prognosis (Silvestrini et al, 1984).…”

Section: Statisticsmentioning

confidence: 99%

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Prospective evaluation of cell kinetics in head and neck squamous carcinoma: the relationship to tumour factors and survival

Cooke

Cooke²,

Forster³

et al. 1994

Br J Cancer

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Summary Tumour growth rates were measured in 105 patients using in vivo incorporation of bromodeoxyuridine (BrdU) and investigated for any relationship to tumour factors or survival. The median labelling index (LI) was 8.7%, the duration of S-phase (Ts) was 14 h and the potential doubling time (Tpo) was 5.9 days. The labelling index in aneuploid tumours was significantly higher than that in diploid tumours. However the total labelling index (TLI) did not differ significantly between aneuploid and diploid tumours, and so it would seem likely that the difference in LI is due to the dilutional effect of benign tissue upon the calculation of LI in diploid tumours. The total labelling index, duration of S-phase and potential doubling time were not related to the tumour factors examined (site, T The general approach to measuring cell kinetics is to identify a 'window' in the cell cycle and measure the movement of a particular cohort of cells through this window. BrdU, an analogue of thymidine, is incorporated into cells during the S-phase of the cell cycle. BrdU is non-toxic and non-radioactive and can be given intravenously to human patients. Infusions of BrdU at higher dosage can be tolerated for several weeks without severe myelosuppression (Mitchell et al., 1983;Kinsella et al., 1984) and there have been no reports of toxic reactions in any patients receiving BrdU at 200 mg m2. It is taken up by the tumour, and the proportion of cells that have taken up BrdU can be detected using monoclonal antibodies. Furthermore, a pulse label of BrdU can be given approximately 6 h before biopsy or excision of the tumour, allowing the length of S-phase to be calculated (Begg et al., 1985). The simultaneous measurement of BrdU and DNA content using flow cytometry enables several cell kinetic parameters to be quantified. We have previously reported upon the cell kinetic results in 82 tumours and demonstrated their reproducibility (Forster et al., 1992).In this study we present further cell kinetic data on 105 patients with squamous cell tumours of the head and neck and investigate the relationship to tumour stage, site and prognosis.

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Results of radiation therapy in carcinoma of the base of the tongue. The curie institute experience with about 166 cases

Jaulerry

Rodriguez

Brunin

et al. 1991

Cancer

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Between 1960 and 1980, 166 patients with squamous cell carcinoma of the base of the tongue were treated with primary irradiation at the Curie Institute (Paris, France). Distribution according to the TNM system 1978 International Union Against Cancer (UICC) was the following: 22 T1 lesions, 47 T2 lesions, 64 T3 lesions, and 33 T4 lesions. Regional nodes were not palpable in 50 cases, 35 had N1 nodes, 12 had N2 nodes, and 69 had N3 nodes. All patients received external beam radiation. The 2-year, 3-year, and 5-year overall survival rates for all patients were, respectively, 45%, 37%, and 27%. Local control was significantly related to the initial status of the primary, to the tumor regression at the end of the radiation therapy, and to the histologic differentiation. The 2-year local control was 96% for T1 lesions, 57% for T2 lesions, 45% for T3 lesions, and 23% for T4 lesions. Local control was 70% if the tumor regression was complete at the end of the treatment and 27% if the tumor regression was partial. No significant differences were found in primary local control with respect to degree of infiltration, age, and dose of radiation therapy over a dose of 60 Gy in 6 weeks. The 3-year regional control was 86% for N0, 78% for N1, and 60% for N2 and N3. Among the tumor characteristics analyzed, the most useful ones for predicting local control and survival were clinical tumor staging parameters and tumor radiation-induced regression. A new therapeutic approach based on the evaluation of the tumor regression at 50/55 Gy is under discussion.

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DNA measurement – An objective predictor of response to irradiation? A review of 24 squamous cell carcinomas of the oral cavity

Cited by 42 publications

References 12 publications

Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry

Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry

Prospective evaluation of cell kinetics in head and neck squamous carcinoma: the relationship to tumour factors and survival

Results of radiation therapy in carcinoma of the base of the tongue. The curie institute experience with about 166 cases

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