Does variation in the in vitro cellular radiosensitivity explain the shallow clinical dose-control curve for malignant melanoma?

In radiotherapy, clinical dose-control curves are generally more shallow than what should be expected from in vitro dose-survival curves for human cells of the same histology. One possible explanation is that a considerable inter-tumor heterogeneity in radiosensitivity flattens out the presumably steep individual dose-control curves. This paper compares dose-control curves for malignant melanomas derived from clinical data with curves derived from in vitro cell-survival experiments. Although inter-tumour variability in the in vitro dose and fractionation sensitivity may explain parts of the discrepancy between the steepness of clinical and in vitro dose-control curves, the present calculation indicates that a considerable additional variability, undetected by current in vitro assays, must be assumed to exist in order to resolve the discrepancy.

[1]  L. Milas,et al.  The proportion of stem cells in murine tumors. , 1989, International journal of radiation oncology, biology, physics.

[2]  E. Rofstad,et al.  Differential responses to radiation and hyperthermia of cloned cell lines derived from a single human melanoma xenograft. , 1984, International journal of radiation oncology, biology, physics.

[3]  G. Steel,et al.  The radioresponsiveness of human tumours and the initial slope of the cell survival curve. , 1984, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[4]  T. R. Munro,et al.  The relation between tumour lethal doses and the radiosensitivity of tumour cells. , 1961, The British journal of radiology.

[5]  H. Thames,et al.  The effect of patient-to-patient variability on the accuracy of predictive assays of tumor response to radiotherapy: a theoretical evaluation. , 1989, International journal of radiation oncology, biology, physics.

[6]  Carl de Boor,et al.  A Practical Guide to Splines , 1978, Applied Mathematical Sciences.

[7]  B. Fertil,et al.  Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves. , 1985, International journal of radiation oncology, biology, physics.

[8]  H. Thames,et al.  Clinical radiobiology of malignant melanoma. , 1989, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  W A Brock,et al.  Predictive Assays of Tumor Radiocurability , 1988, American journal of clinical oncology.

[10]  Predictors of tumor response to radiotherapy. , 1985, Radiation research. Supplement.

[11]  R. Durand Repair and proliferation: major determinants of the multifraction radiation response. , 1988, International journal of radiation oncology, biology, physics.

[12]  J. Overgaard The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study. , 1986, International journal of radiation oncology, biology, physics.

[13]  B. Fertil,et al.  Inherent cellular radiosensitivity as a basic concept for human tumor radiotherapy. , 1981, International journal of radiation oncology, biology, physics.

[14]  G. Stoyan de Boor, C., A Practical Guide to Splines. Applied Mathematical Sciences 27. Berlin‐Heidelberg‐New York, Springer‐Verlag 1978. XXIV, 392 S., DM 32,50. US $ 17.90 , 1980 .

[15]  J. Moore,et al.  Is the steepness of dose-incidence curves for tumour control or complications due to variation before, or as a result of, irradiation? , 1984, The British journal of radiology.

[16]  E. Rofstad,et al.  Radioresponsiveness of human melanoma xenografts given fractionated irradiation in vivo--relationship to the initial slope of the cell survival curves in vitro. , 1987, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[17]  M Tubiana,et al.  Klaas Breur Medal lecture 1985. The growth and progression of human tumors: implications for management strategy. , 1986, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[18]  E. Rofstad Radiation biology of malignant melanoma. , 1986, Acta radiologica. Oncology.

[19]  B. Efron Bootstrap Methods: Another Look at the Jackknife , 1979 .

[20]  Durand Re Repair during multifraction exposures: spheroids versus monolayers. , 1984 .

[21]  S. Rockwell Effects of clumps and clusters on survival measurements with clonogenic assays. , 1985, Cancer research.

[22]  T E Schultheiss,et al.  Inter-tumor heterogeneity and radiation dose-control curves. , 1987, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[23]  G H Fletcher,et al.  Changes in early and late radiation responses with altered dose fractionation: implications for dose-survival relationships. , 1982, International journal of radiation oncology, biology, physics.

[24]  P. Diaconis,et al.  Computer-Intensive Methods in Statistics , 1983 .

[25]  A Brahme,et al.  Dosimetric precision requirements in radiation therapy. , 1984, Acta radiologica. Oncology.