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

Hilde Van Parijs, Geertje Miedema, Vincent Vinh-Hung, Sylvia Verbanck, Nele Adriaenssens, Dirk Kerkhove, Truus Reynders, Daniel Schuermans, Katrien Leysen, Shane Hanon, Guy Van Camp, Walter Vincken, Guy Storme, Dirk Verellen, Mark De Ridder, Hilde Van Parijs, Geertje Miedema, Vincent Vinh-Hung, Sylvia Verbanck, Nele Adriaenssens, Dirk Kerkhove, Truus Reynders, Daniel Schuermans, Katrien Leysen, Shane Hanon, Guy Van Camp, Walter Vincken, Guy Storme, Dirk Verellen, Mark De Ridder

Abstract

Background: TomoBreast 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.

Methods: The 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.

Results: By 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).

Conclusions: There 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.

Trial registration: [corrected] ClinicalTrials.gov NCT00459628.

Figures

Figure 1
Figure 1
Dose volume histogram. The average dose volume histograms (DVH) of the CTV's and the most important organs at risk are shown for CR and TT. The average DVH for the heart was generated for left sided irradiation only. The dose is formulated in 2 Gy equivalent dose (EQ2) with an alpha/beta of 3 Gy.
Figure 2
Figure 2
DVHs of the ipsilateral lung for patients who showed consistent DLco-decrease of >10%. The individual DVHs for the patients who had G1 or higher lung toxicity based on DLco, which proved consistent over time, are shown compared to the average DVH for TT and CR. The dose is formulated in 2 Gy equivalent dose (EQ2) with an alpha/beta of 3 Gy.

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