The increasing complexity of management strategies for patients with head and neck squamous cell carcinoma (HN-SCC) calls for the investigation of new objective prognostic parameters to subdivide patients according to the tumor's biological aggressiveness.
Methods
We evaluated in 35 HN-SCC patients the pretreatment cell kinetics parameters and DNA ploidy after in vivo infusion of bromodeoxyuridine and flow cytometric analysis. Patients were treated with radical surgery followed by conventional radiation therapy. Locoregional control data are available for follow-up times above five years.
Results
We found that the likelihood of locoregional control for patients with rapidly proliferating HN-SCC characterized by a short potential doubling time (Tpot <5 days) was significantly smaller than for HN-SCC patients with slow tumor proliferation (Tpot >5 days). Moreover, when patients were stratified according to DNA ploidy and Tpot value, we found that the locoregional failure rate for rapidly proliferating tumors was significantly higher for diploid HN-SCCs than for aneuploid HN-SCCs.
Conclusion
The present data suggest that patients with resectable HN-SCC characterized by fast growth might have a worse prognosis after surgery and adjuvant conventional radiotherapy and might benefit from more aggressive radiother-apeutic modalities.
AmdurR.J.ParsonJ.T.MendenhallW.H.MillionR.StringerS.P.CassisiN.J.: Postoperative irradiation for squamous cell carcinoma of the head and neck. An analysis of treatment: results and complications.Int. J. Radiat. Oncol. Biol. Phys., 16: 25–36, 1989.
2.
AntognoniP.TerryN.H.RichettiA.LuraghiR.TordiglioneM.DanovaM.: The predictive role of flow cytometry-derived tumor potential doubling time (Tpot) in radiotherapy: open questions and future perspectives.Int. J. Oncol., 12: 245–256, 1998.
3.
AwwadH.K.KhafagyY.BarsoumM.EzzarS.El-AttarI.FaragH.AkoushH.MeabidH.RaghloulM.L.: Accelerated versus conventional fractionation in the postoperative irradiation of locally advanced head and neck cancer: influence of tumor proliferation.Radiother. Oncol., 25: 261–266, 1992.
4.
BeggA.C.McNallyN.J.ShrieveD.C.HarcherH.: A method to measure the duration of the DNA synthesis and the potential doubling time from a single sample.Cytometry, 6: 620–626, 1985.
5.
BeggA.C.HaustermansK.HartA.A.M.DischeS.SaundersM.ZackrissonB.GustaffsonH.CouckeP.PaschoudN.HoyerM.OvergaardJ.AntognoniP.RichettiA.BourhisJ.BartelinkH.HoriotJ.C.CorvòR.GiarettiW.AwwadH.ShoumanT.JouffroyT.MaciorowskiZ.DobrowskiW.StruikmansH.RutgersD.WilsonG.D.: The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis.Radiother. Oncol.50: 13–24, 1999.
6.
ChachinY.EschwedgeF.: Combination of radiotherapy and surgery in the treatment of head and neck cancer.Cancer Treat. Rep., 2: 177–191, 1975.
7.
ChauvelP.CourdiA.GiovanniJ.VallicioniJ.SantiniJ.DemardF.: The labelling index: a prognostic factor in head and neck carcinoma.Radiother. Oncol., 14: 231–237, 1989.
8.
CooperJ.S.: Postoperative irradiation in head and neck cancer.Int J. Radiat. Oncol. Biol. Phys., 26: 181–182, 1993.
9.
CorvòR.GiarettiW.SanguinetiG.GeidoE.OrecchiaR.GuenziM.MargarinoG.BacigalupoA.GaraventaG.BarbieriM.VitaleV.: In vivo cell kinetics in head and neck squamous cell carcinomas predicts local control and helps guide radiotherapy regimen.J. Clin. Oncol., 13: 1843–1850, 1995.
10.
CorvòR.GiarettiW.GeidoE.SanguinetiG.OrecchiaR.ScalaM.GaraventaG.MoraE.VitaleV.: Cell kinetics and tumor regression during radiotherapy in head and neck squamous cell carcinoma.Int. J. Cancer, 68: 151–155, 1996.
11.
CorvòR.GiarettiW.SanguinetiG.GeidoE.BacigalupoA.OrecchiaR.BenassoM.NumicoG.M.MerlanoM.MargarinoG.VitaleV.: Chemo-radiotherapy as an alternative to radiotherapy alone in fast proliferative head and neck squamous cell carcinomas.Clin. Cancer Res., 3: 1191–1196, 1997.
12.
DolbeareF.GratznerH.G.PallaviciniM.C.GrayJ.: Flow cytometry measurement of total DNA content and incorporated bromodeoxyuridine.Proc. Natl. Acad. Sci. (Washington), 80: 5573–5570, 1983.
13.
EnsleyJ.F.MaciorowskiZ.: Clinical applications of DNA content parameters in patients with squamous cell carcinoma of the head and neck.Sem. Oncol., 21: 330–339, 1994.
14.
FietkauR.IroH.Altendorf-HofmannA.SauerR.: Prognostic value of cellular DNA content and S-phase fraction in head and neck squamous cell carcinoma in relation to different treatment modalities.Radiat. Oncol. Invest., 1: 50–62, 1993.
15.
FleissJ.L.: The design and analysis of clinical experiments.John Wiley and Sons, New York, 1986.
16.
FowlerJ.F.LindstromM.J.: Loss of control with prolungation in radiotherapy.Int. J. Radiat. Oncol. Biol. Phys., 23: 457–467, 1992.
17.
HiddemanW.SchumannJ.AndreffM.BarlogieB.HermanC.J.LeifR.C.MayallB.H.MurphyR.F.SandbergA.A.: Convention on nomenclature for DNA cytometry.Cancer Genet. Cytogenet., 134: 181–183, 1984.
18.
KaplanE.L.MeierP.: Non parametric estimation from incomplete observations.J. Am. Stat. Assoc, 53: 457–481, 1958.
19.
MarcusR.B.MillionR.R.CassisiN.J.: Postoperative irradiation for squamous cell carcinoma of the head and neck: analysis of time-dose factors related to control above the clavicles.Int. J. Radiat. Oncol. Biol. Phys., 5: 1943–1949, 1979.
20.
MatturriL.BiondoB.TamplenizzaP.OttavianiA.LavezziA.M.: DNA content and thymidine labeling index correlated with prognosis in squamous cell carcinoma of the larynx.Cancer Det. Prev., 21: 319–325, 1997.
21.
MillerA.B.HoostatenB.StauetM.WinklerA.: Reporting results of cancer treatment.Cancer, 47: 207–214, 1981.
22.
MillionR.R.CassisiN.J.: Management of head and neck cancer: a multidisciplinary approach, second edition, pp. 61–73, Lippincott Company, Philadelphia, 1994.
23.
PetersL.J.WithersR.: Applying radiobiological principles to combined modality treatment of head and neck cancer.The time factors. Int. J. Radiat. Oncol. Biol. Phys., 39: 831–836, 1997.
24.
RutgersD.H.Van der LindenP.M.PerpzeelH.: DNA flow-cytometry of squamous carcinoma from the human uterine cervix: the identification of prognostically different subgroups.Radiother. Oncol., 7: 249–258, 1986.
25.
SanguinetiG.CorvòR.VitaleV.LionettoR.FoppianoF.: Postoperative radiotherapy for head and neck squamous cell carcinomas: feasibility of a biphasic accelerated treatment schedule.Int. J. Radiat. Oncol. Biol. Phys., 36: 1143–1147, 1996.
26.
StellG.G.: Basic clinical radiobiology, pp. 14–24, Oxford University Press, 1997.
27.
TannockI.F.: Combined modality treatment with radiotherapy and chemotherapy.Radiother. Oncol., 16: 83–101, 1989.
28.
TrottiA.KlotchD.EndicottJ.RidleyM.GreenbergH.: A prospective trial of accelerated radiation therapy in the postoperative treatment of high risk squamous cell carcinoma of the head and neck.Int. J. Radiat. Oncol. Biol. Phys., 26: 13–21, 1993.
29.
UICC:TNM classification of malignant tumors.Springer Verlag, New York, 1997.
30.
VokesE.E.WeichselbaumR.R.LippmanS.M.HongW.K.: Head and neck cancer.NEJM, 328: 184–191, 1993.
31.
WilsonG.D.DischeS.SaundersM.I.: Studies with bromodeoxyuridine in head and neck and accelerated radiotherapy.Radiother. Oncol., 36: 189–197, 1995.
32.
WilsonG.D.PashoudN.PavyJ.J.WeberK.WeberP.DubrayB.CouckeP.A.: Reproducibility of measurements of potential doubling time of tumor cells in the multicentre National Cancer Institute Protocol T92-0045.Br. J. Cancer, 78: 323–332, 1999.
33.
ZackrissonB.GustafssonH.StenlingR.FlygareP.WilsonG.D.: Predictive value of potential doubling time in head and neck cancer patients treated by conventional radiotherapy.Int. J. Radiat. Oncol. Biol. Phys., 38: 677–683, 1997.
