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.
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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. 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
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ABSTRACT: Multiple partial breast radiotherapy techniques are available. We have previously presented the technical details of our procedure of delivering partial breast irradiation with a single fraction of intraoperative radiotherapy (IORT) targeting the tumor in situ prior to partial mastectomy. This study details our completed, single-institution trial. An IRB-approved, DSMB-monitored phase II trial was performed with the following inclusion criteria: women age ≥48, ultrasound-visible invasive ductal cancers <3 cm, clinically negative axillary nodes. IORT was delivered using mobile electron irradiator, at least a 1.5-cm radial and 1-cm deep margin; patients received 15 Gy and immediately underwent partial mastectomy. Ipsilateral breast recurrence was classified as true/marginal, elsewhere in the breast or nodal basin. Kaplan-Meier methods were used to estimate survival functions and exact 95% confidence intervals are reported. Between 2003 and 2007, 71 women underwent IORT (median follow-up: 3.5 years). For patients with tumor-involved or close margins, additional therapy was required: 7 patients, total mastectomy; 11, whole breast radiation. Four women experienced invasive ipsilateral breast failures (1 new primary, 3 margin recurrences) for a 3-year local control rate of 49 of 53 (94.8%; 95% confidence interval 92.4% [95% CI] 84.2–98.3%), actuarial three-year in breast recurrence was 8% (95% CI 2–18%), and breast cancer-specific survival was 100%. Intraoperative radiotherapy delivered to an in situ tumor is feasible, but our local control rate at 3.5 years is concerning. Possible changes to this technique to improve local control rates include better preoperative imaging (MRI), routine intraoperative ultrasound, and improved IORT delivery (larger cone, increased dose).Annals of Surgical Oncology 11/2010; 18(4):939-45. · 4.12 Impact Factor
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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.