Biologically effective dose-response relationship for breast cancer treated by conservative surgery and postoperative radiotherapy.

Department of Oncology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
International journal of radiation oncology, biology, physics (Impact Factor: 4.59). 08/2009; 75(2):512-7. DOI: 10.1016/j.ijrobp.2009.05.013
Source: PubMed

ABSTRACT To find a biologically effective dose (BED) response for adjuvant breast radiotherapy (RT) for initial-stage breast cancer.
Results of randomized trials of RT vs. non-RT were reviewed and the tumor control probability (TCP) after RT was calculated for each of them. Using the linear-quadratic formula and Poisson statistics of cell-kill, the average initial number of clonogens per tumor before RT and the average tumor cell radiosensitivity (alpha-value) were calculated. An alpha/beta ratio of 4 Gy was assumed for these calculations.
A linear regression equation linking BED to TCP was derived: -ln[-ln(TCP)] = -ln(No) + alpha(*) BED = -4.08 + 0.07 (*) BED, suggesting a rather low radiosensitivity of breast cancer cells (alpha = 0.07 Gy(-1)), which probably reflects population heterogeneity. From the linear relationship a sigmoid BED-response curve was constructed.
For BED values higher than about 90 Gy(4) the radiation-induced TCP is essentially maximizing at 90-100%. The relationship presented here could be an approximate guide in the design and reporting of clinical trials of adjuvant breast RT.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Radiotherapy (RT) after tumorectomy in early breast cancer patients is an established treatment modality which conventionally takes 6-7 wk to complete. Shorter RT schedules have been tested in large multicentre randomized trials and have shown equivalent results to that of standard RT (50 Gy in 25 fractions) in terms of local tumor control, patient survival and late post-radiation effects. Some of those trials have now completed 10 years of follow-up with encouraging results for treatments of 3-4 wk and a total RT dose to the breast of 40-42.5 Gy with or without boost. A reduction of 50% in treatment time makes those RT schedules attractive for both patients and health care providers and would have a significant impact on daily RT practice around the world, as it would accelerate patient turnover and save health care resources. However, in hypofractionated RT, a higher (than the conventional 1.8-2 Gy) dose per fraction is given and should be managed with caution as it could result in a higher rate of late post-radiation effects in breast, heart, lungs and the brachial plexus. It is therefore advisable that both possible dose inhomogeneity and normal tissue protection should be taken into account and the appropriate technology such as three-dimensional/intensity modulated radiation therapy employed in clinical practice, when hypofractionation is used.
    World journal of radiology. 06/2010; 2(6):197-202.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The continuous increase of breast cancer (BC) incidence, the logistic constraints of the protracted standard 5-week radiations regimen have led to test short hypofractionated whole breast radiation therapy schemes. Three prospective randomized trials and a pilot trial have been published. Large numbers of patients were included, with follow-up duration ranging from 5 to 12 years. The conclusions of these trials were similar, showing local control and toxicity equivalent to those of the standard regimen, and supporting the use of three schemes: 42.5 Gy/16 fractions/3 weeks, 40 Gy/15 fractions/3 weeks or 41.6 Gy/13 fractions/5 weeks. However, the patients in these trials had favourable prognostic factors, were treated to the breast only and the boost dose, when indicated, was delivered with a standard fractionation. Hypofractionated treatment can only be recommended in patients treated to the breast only, without nodal involvement, with grade<3 tumours and who are not candidate to chemotherapy. If a boost is to be given, a standard fractionation should be used. Particular care should be taken to avoid heterogeneities leading to high fractional doses to organs at risk (lung and heart).
    Cancer/Radiothérapie 09/2011; 15(6-7):445-9. · 1.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim-Background Patients with invasive ductal breast cancer undergoing breast-conserving surgery with lymphectomy, with negative or 3(+) LN (lymph nodes), T<5cm, and excellent expectant survival are submitted to either conformal fractionated irradiation (50Gy in 25 fractions, at 2Gy/fraction) or hypofractionated conformal 3D irradiation (fewer fractions at higher doses per fraction). Patients may or may not undergo chemotherapy, and irradiation commences ≤ 16 weeks after surgery. Methods From 2009 to 2010, 11 patients aged between 30 and 50 years, who matched the above criteria and had undergone invasive breast cancer and breast-conserving surgery, received hypofractionated radiotherapy. All patients received 42.5Gy in 16 fractions of 2.66Gy/fraction five times per week. Computed tomography simulation was used to design 3D conformal treatment planning with two tangentional fields and a multileaf collimator linear accelerator. Results After completion of radiotherapy, all patients showed Grade 0-1 skin reaction and no cosmetic impairment (oedema, fibrosis, telangiectasia). No side effects were observed in normal tissue structures and at-risk organs, such as the heart and lung. At 3, 6, 12, 18, 24, 30, and 36-month follow-up, none of the patients displayed post-radiation pneumonitis, pericarditis or dermatitis, nor did any patient develop a recurrence or regional distant metastases. Cosmetic assessment of the irradiated breast showed excellent results in terms of skin reaction compared with the healthy breast. Furthermore, the size and shape of the irradiated breast remained unchanged during and after irradiation. Conclusions Hypofractionated conformal irradiation in invasive breast cancer achieves optimal disease control and an excellent cosmetic result. Patients can be treated in fewer days with a safe and biological effective dose (BED), as that given by conformal fractionated irradiation. This development results in improved safety and enhanced quality of life for breast cancer patients.
    Hellēnikē cheirourgikē. Acta chirurgica Hellenica 03/2013; 85(2).


Available from
Nov 10, 2014