title: A challenge to traditional radiation oncology.
abstract: OBJECTIVE
  To investigate and compare the biologically effective doses, equivalent doses in 2-Gy fractions, log tumor cells killed, and late effects that can be estimated for the large fractions in short overall times that are now being delivered in various clinically used schedules in several countries for the treatment of cancer in human lungs, liver, and kidney.
  
  
  METHODS
  Linear quadratic (LQ) modeling is employed with only the standard assumptions that tumor alpha/beta ratio is 10 Gy, pneumonitis and late complication alpha/beta ratios are 3 Gy, that intrinsic radiosensitivity of tumor cells is 0.35 ln/Gy, that no tumor repopulation occurs within 2 weeks, and that LQ modeling is valid up to 23 Gy per fraction. As well as the planning target volume (PTV), we propose a practical term called the prescription isodose volume (PIV) to be used in this discussion. In the ideal case of 100% conformity, PIV equals PTV, but usually PIV is larger than the PTV. Biologically effective doses (BED) in Gy(10) for tumors or Gy(3) for normal lung are calculated and converted to equivalent doses in 2 Gy fractions (= normalized total doses [NTD]), and to estimated log cell kill. How such large biologic doses might be delivered to tissues is discussed.
  
  
  RESULTS
  Tumor cell kill varies between 16 and 27 logs to base 10 for schedules from 4F x 12 Gy to 3F x 23 Gy. The rationale for the high end of this scale is the possible presence of hypoxic or otherwise extraordinarily resistant cells, but how many tumors and which ones require such doses is not known. How can such large doses be tolerated? In "parallel type organs," it is shown to be theoretically possible, provided that suitably small volumes are irradiated, with rapid fall-off of dose outside the PTV, and a mean dose (excluding PTV and allowing for local fraction size) to both lungs of less than 19 Gy NTD. If suitably small PTVs were used, local late BEDs have been given which were as large as 600 Gy(3), equivalent to 2 Gy x 180F = 360 Gy in 2-Gy fractions, with remarkably few complications reported clinically. Questions of concurrent chemotherapy and microscopic extension of lung tumor cells are discussed briefly.
  
  
  CONCLUSIONS
  Such large doses can apparently be given, with suitable precautions and experience. Ongoing clinical trials from an increasing number of centers will be reporting the results of tumor control and complications from this new modality of biologically higher doses.
authors.affiliation: Department of Human Oncology, Medical School of the University of Wisconsin, Madison, WI, USA. jackfowler@btinternet.com
authors.forename: Jack F
authors.initials: JF
authors.lastname: Fowler
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Tomé
authors.forename: John D
authors.initials: JD
authors.lastname: Fenwick
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
mesh_terms: D000465:Algorithms; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D006801:Humans; D016014:Linear Models; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008954:Models, Biological; D018787:Radiation Oncology / Q000379:methods; D017564:Radiation Pneumonitis / Q000209:etiology; D011836:Radiation Tolerance; D012062:Relative Biological Effectiveness; D013238:Stereotaxic Techniques