### Abstract

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. Linear quadratic (LQ) modeling is employed with only the standard assumptions that tumor α/β ratio is 10 Gy, pneumonitis and late complication α/β 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 LQmodeling 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. Tumor cell kill varies between 16 and 27 logs to base 10 for schedules from 4F × 12 Gy to 3F × 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 × 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. 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.

Original language | English (US) |
---|---|

Pages (from-to) | 1241-1256 |

Number of pages | 16 |

Journal | International Journal of Radiation Oncology Biology Physics |

Volume | 60 |

Issue number | 4 |

DOIs | |

State | Published - Nov 15 2004 |

Externally published | Yes |

### Fingerprint

### Keywords

- Ablation
- Biologically effective dose
- Lung cancer
- Parallel tissues
- Pneumonitis
- Stereotactic extracranial
- Tumor control
- Volume

### ASJC Scopus subject areas

- Oncology
- Radiology Nuclear Medicine and imaging
- Radiation

### Cite this

*International Journal of Radiation Oncology Biology Physics*,

*60*(4), 1241-1256. https://doi.org/10.1016/j.ijrobp.2004.07.691

**A challenge to traditional radiation oncology.** / Fowler, Jack F.; Tome, Wolfgang A.; Fenwick, John D.; Mehta, Minesh P.

Research output: Contribution to journal › Article

*International Journal of Radiation Oncology Biology Physics*, vol. 60, no. 4, pp. 1241-1256. https://doi.org/10.1016/j.ijrobp.2004.07.691

}

TY - JOUR

T1 - A challenge to traditional radiation oncology

AU - Fowler, Jack F.

AU - Tome, Wolfgang A.

AU - Fenwick, John D.

AU - Mehta, Minesh P.

PY - 2004/11/15

Y1 - 2004/11/15

N2 - 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. Linear quadratic (LQ) modeling is employed with only the standard assumptions that tumor α/β ratio is 10 Gy, pneumonitis and late complication α/β 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 LQmodeling 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 Gy10 for tumors or Gy3 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. Tumor cell kill varies between 16 and 27 logs to base 10 for schedules from 4F × 12 Gy to 3F × 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 Gy3, equivalent to 2 Gy × 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. 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.

AB - 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. Linear quadratic (LQ) modeling is employed with only the standard assumptions that tumor α/β ratio is 10 Gy, pneumonitis and late complication α/β 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 LQmodeling 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 Gy10 for tumors or Gy3 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. Tumor cell kill varies between 16 and 27 logs to base 10 for schedules from 4F × 12 Gy to 3F × 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 Gy3, equivalent to 2 Gy × 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. 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.

KW - Ablation

KW - Biologically effective dose

KW - Lung cancer

KW - Parallel tissues

KW - Pneumonitis

KW - Stereotactic extracranial

KW - Tumor control

KW - Volume

UR - http://www.scopus.com/inward/record.url?scp=7444254382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7444254382&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2004.07.691

DO - 10.1016/j.ijrobp.2004.07.691

M3 - Article

VL - 60

SP - 1241

EP - 1256

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 4

ER -