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: 4.18). 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.


Available from: Roger Dale, Nov 10, 2014
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    ABSTRACT: Purpose: The objective of this study is to evaluate toxicity and cosmetic outcome in breast cancer patients treated with adjuvant hypo fractionated radiotherapy to the whole breast, and to identify the risk factors for toxicity.Methods and materials: Two hundred twelve women with early breast cancer underwent conserving surgery were enrolled in the study. The patients received 40.05 Gy in 15 daily fractions, 2.67 Gy per fraction. The boost to the tumor bed was administered with a total dose of 9 Gy in 3 consecutive fractions in 55 women. Physician-rated acute and late toxicity and cosmetic outcome (both subjective and objective ) were prospectively assessed during and after radiotherapy. In our population study the mean age was 63 with the 17% (36 pts) of the women younger than 50 years.The median follow-up was 34 months. By the end of RT, 35 patients out of 212 (16%) no acute toxicity, according to the RTOG criteria, while 145 (68%) and 31 patients (15%) developed grade 1 and grade 2 acute skin toxicity, respectively.Late skin toxicity evaluation was available for all 212 patients with a minimum follow up of 8 months. The distribution of toxicity was : 39 pts (18%) with grade 1 and 2 pts (1%) with grade 2. No worse late skin toxicity was observed.Late subcutaneous grade 0-1 toxicity was recorded in 208 patients (98%) and grade 2 toxicity in 3 patients (2%), while grade 3 was observed in 1 patient only. At last follow up, a subjective and objective good or excellent cosmetic outcome was reported in 93% and 92% of the women, respectively. At univariate and multivariate analysis, the late skin toxicity was correlated with the additional boost delivery (p=0.007 and p=0.023). Regarding the late subcutaneous tissue, a correlation with diabetes was found (p=0.0283). These results confirm the feasibility and safety of the hypofractionated radiotherapy in patients with early breast cancer. In our population the boost administration was resulted to be a significant adverse prognostic factor for acute and late toxicity. Long-term follow up is need to confirm this finding.
    Radiation Oncology 04/2014; 9(1):97. DOI:10.1186/1748-717X-9-97 · 2.36 Impact Factor
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    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). DOI:10.1007/s13126-013-0017-5
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    ABSTRACT: Background To report results in terms of feasibility and early toxicity of hypofractionated simultaneous integrated boost (SIB) approach with Volumetric Modulated Arc Therapy (VMAT) as adjuvant treatment after breast-conserving surgery. Methods Between September 2010 and May 2011, 50 consecutive patients presenting early-stage breast cancer were submitted to adjuvant radiotherapy with SIB-VMAT approach using RapidArc in our Institution (Istituto Clinico Humanitas ICH). Three out of 50 patients were irradiated bilaterally (53 tumours in 50 patients). All patients were enrolled in a phase I-II trial approved by the ICH ethical committee. All 50 patients enrolled in the study underwent VMAT-SIB technique to irradiate the whole breast with concomitant boost irradiation of the tumor bed. Doses to whole breast and surgical bed were 40.5 Gy and 48 Gy respectively, delivered in 15 fractions over 3 weeks. Skin toxicities were recorded during and after treatment according to RTOG acute radiation morbidity scoring criteria with a median follow-up of 12 months (range 8–16). Cosmetic outcomes were assessed as excellent/good or fair/poor. Results The median age of the population was 68 years (range 36–88). According to AJCC staging system, 38 breast lesions were classified as pT1, and 15 as pT2; 49 cases were assessed as N0 and 4 as N1. The maximum acute skin toxicity by the end of treatment was Grade 0 in 20/50 patients, Grade 1 in 32/50, Grade 2 in 0 and Grade 3 in 1/50 (one of the 3 cases of bilateral breast irradiation). No Grade 4 toxicities were observed. All Grade 1 toxicities had resolved within 3 weeks. No significant differences in cosmetic scores on baseline assessment vs. 3 months and 6 months after the treatment were observed: all patients were scored as excellent/good (50/50) compared with baseline; no fair/poor judgment was recorded. No other toxicities or local failures were recorded during follow-up. Conclusions The 3-week course of postoperative radiation using VMAT with SIB showed to be feasible and was associated with acceptable acute skin toxicity profile. Long-term follow-up data are needed to assess late toxicity and clinical outcomes.
    Radiation Oncology 08/2012; 7(1):145. DOI:10.1186/1748-717X-7-145 · 2.36 Impact Factor