Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial

Abstract

BackgroundTomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR) vs. hypofractionated Tomotherapy (TT) for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities.MethodsThe trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS) or by mastectomy (MA) who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks), versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks). Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test.ResultsBy May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA), 37 to TT (20 BCS, 17 MA). Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05).ConclusionsThere were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need confirmation with longer follow-up of patients.Trail registrationClinicalTrials.gov NCT00459628

Is the simultaneously integrated boost (SIB) technique for early breast cancer ready to be adopted for routine adjuvant radiotherapy?

“…A recent prospective randomized study from Belgium [20] compares a standard WBI (25 fractions of 2 Gy tangential fields, 8 fractions of 2 Gy electron boost) to a hypofractionated tomotherapy comprising a SIB (15 fractions of 2.8 Gy WBI; 3.4 Gy SIB). Included were 41 patients after BCS and 28 patients following mastectomy.…”

Comparison of Breast Sequential and Simultaneous Integrated Boost Using the Biologically Effective Dose Volume Histogram (BEDVH)

“…This limitation may be important when comparing treatment schemes differing on overall treatment time in terms of acute toxicity [10,18]. Therefore, the assumption of overall treatment time independency may become inaccurate when comparing widely different overall treatment times such as in hypofractionated schemes [1,5,6,24]. Generally, it is considered that the limitations of using the LQ model are mainly due to inaccuracies of accounting for repopulation, bi-fractionated treatments and high-dose fractions [25].…”

“…Recent clinical trials [1,5,6] were published proving the feasibility and well-tolerated toxicity of hypofractionation with SIB in early breast cancer. The comparison done here was based on the BED and hence it is important to consider the limitations of the LQ model and the BED calculations.…”

“…Recently, many authors suggested the use of simultaneously integrated boost (SIB) using doses of 2.3-2.4 Gy to the tumor bed as it showed to be dosimetrically better, more convenient due to the shorter treatment time and well tolerated [3,4]. Moreover, hypofractionation with SIB has been evaluated in a few trials and appears to be feasible with no severe adverse events [1,[3][4][5][6].…”

Prospective evaluation of weekly concomitant tumor bed boost with three-week hypofractionated whole breast irradiation in early breast cancer

“…Similarly, the ongoing phase III IMPORT-HIGH, IMRT MC-2 and UZB trials also investigate HF-WBI with concomitant tumour bed boosts, and will also help determine the optimal way to deliver breast and tumour bed radiotherapy [42][43][44].…”