Biologically effective dose-response relationship for breast cancer treated by conservative surgery and postoperative radiotherapy.
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.
- SourceAvailable from: Antonella Fogliata[Show abstract] [Hide abstract]
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. METHOD: S: 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 (Humanitas). Three out of 50 patients were irradiated bilaterally (53 tumors 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. · 2.11 Impact Factor
- [Show abstract] [Hide abstract]
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. · 2.11 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Radioimmunotherapy of solid tumors remains a challenge despite the tremendous success of ⁹⁰Y ibritumomab tiuxetan (Zevalin) and ¹³¹I Tositumomab (Bexxar) in treating non-Hodgkin's lymphoma. For a variety of reasons, clinical trials of radiolabeled antibodies against solid tumors have not led to responses equivalent to those seen against lymphoma. In contrast, promising responses have been observed with unlabeled antibodies that target solid tumor receptors associated with cellular signaling pathways. These observations suggest that anti-tumor efficacy of the carrier antibody might be critical to achieving clinical responses. Here, we review and compare tumor antigens targeted by radiolabeled antibodies and unlabeled antibodies used in immunotherapy. The review shows that the trend for radiolabeled antibodies under pre-clinical development is to also target antigens associated with signaling pathways that are essential for the growth and survival of the tumor.Current Drug Delivery 11/2010; 8(1):26-44.