5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1·44% (95% CI 0·51-2·38) with APBI and 0·92% (0·12-1·73) with whole-breast irradiation (difference 0·52%, 95% CI -0·72 to 1·75; p=0·42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3·2% with APBI versus 5·7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7·6% versus 6·3% (p=0·53). The risk of severe (grade 3) fibrosis at 5 years was 0·2% with whole-breast irradiation and 0% with APBI (p=0·46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

Complete protection against P. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing Salmonella type III secretion system and Bordetella adenylate cyclase toxoid

Sterile immunity against malaria can be achieved by the induction of IFNgamma-producing CD8(+) T cells that target infected hepatocytes presenting epitopes of the circumsporozoite protein (CSP). In the present study we evaluate the protective efficacy of a heterologous prime/boost immunization protocol based on the delivery of the CD8(+) epitope of Plasmodium berghei CSP into the MHC class I presentation pathway, by either a type III secretion system of live recombinant Salmonella and/or by direct translocation of a recombinant Bordetella adenylate cyclase toxoid fusion (ACT-CSP) into the cytosol of professional antigen-presenting cells (APCs). A single intraperitoneal application of the recombinant ACT-CSP toxoid, as well as a single oral immunization with the Salmonella vaccine, induced a specific CD8(+) T cell response, which however conferred only a partial protection on mice against a subsequent sporozoite challenge. In contrast, a heterologous prime/boost vaccination with the live Salmonella followed by ACT-CSP led to a significant enhancement of the CSP-specific T cell response and induced complete protection in all vaccinated mice.