Assessing advantages of sequential boron neutron capture therapy (BNCT) in an oral cancer model with normalized blood vessels

Background. We previously demonstrated the therapeutic success of sequential boron neutron capture therapy (SeqBNCT) in the hamster cheek pouch oral cancer model. It consists of BPA-BNCT followed by GB-10-BNCT 24 or 48 hours later. Additionally, we proved that tumor blood vessel normalization with thalidomide prior to BPA-BNCT improves tumor control. The aim of the present study was to evaluate the therapeutic efficacy and explore potential boron microdistribution changes in Seq-BNCT preceded by tumor blood vessel normalization. Material and Methods. Tumor bearing animals were treated with thalidomide for tumor blood vessel normalization, followed by Seq-BNCT (ThSeq-BNCT) or Seq-Beam Only (ThSeq-BO) in the window of normalization. Boron microdistribution was assessed by neutron autoradiography. Results. ThSeq-BNCT induced overall tumor response of 100%, with 87 (4)% complete tumor response. No cases of severe mucositis in dose-limiting precancerous tissue were observed. Differences in boron homogeneity between tumors pre-treated and not pre-treated with thalidomide were observed. Conclusion. ThSeq-BNCT achieved, for the first time, response in all treated tumors. Increased homogeneity in tumor boron microdistribution is associated to an improvement in tumor control

Boron neutron capture therapy (BNCT) for liver metastasis in an experimental model: dose–response at five-week follow-up based on retrospective dose assessment in individual rats

Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal liver metastases. Employing an experimental model of liver metastases in rats, we recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13 Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of the present study was to evaluate dose–response at 5-week follow-up, based on retrospective dose assessment in individual rats. BDIX rats were inoculated with syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched manipulation, no treatment). For each rat, neutron flux was measured in situ and boron content was measured in a pre-irradiation blood sample for retrospective individual dose assessment. For statistical analysis (ANOVA), individual data for the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5–8.9 Gy and BPA-BNCT II: 9.2–16 Gy. At 5 weeks postirradiation, the tumor surface area post-treatment/pre-treatment ratio was 12.2 ± 6.6 for Sham, 7.8 ± 4.1 for Beam only, 4.4 ± 5.6 for BPA-BNCT I and 0.45 ± 0.20 for BPABNCT II; tumor nodule weight was 750 ± 480 mg for Sham, 960 ± 620 mg for Beam only, 380 ± 720 mg for BPABNCT I and 7.3 ± 5.9 mg for BPA-BNCT II. The BPABNCT II group exhibited statistically significant tumor control with no contributory liver toxicity. Potential threshold doses for tumor response and significant tumor control were established at 6.1 and 9.2 Gy, respectively.Fil: Pozzi, Emiliano César Cayetano. Comisión Nacional de Energía Atómica. Centro Atómico Ezeiza; Argentina;Fil: Trivillin, Verónica Andrea. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina;Fil: Colombo, Lucas Luis. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina;Fil: Monti Hughes, Andrea. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina;Fil: Thorp, Silvia Inés. Comisión Nacional de Energía Atómica; Argentina;Fil: Cardoso, Jorge E.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; Argentina;Fil: Garabalino, Marcela Alejandra. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina;Fil: Molinari, Ana Julia. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina;Fil: Heber, Elisa Mercedes. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina;Fil: Curotto, Paula. Comisión Nacional de Energía Atómica; Argentina;Fil: Miller, Marcelo Eduardo. Comisión Nacional de Energía Atómica; Argentina;Fil: Itoiz, Maria Elina. Universidad de Buenos Aires. Facultad de Odontología; Argentina; Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina;Fil: Aromando, Romina Flavia. Universidad de Buenos Aires. Facultad de Odontología; Argentina; Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina;Fil: Nigg, David W.. Idaho National Laboratory; Estados Unidos de América;Fil: Schwint, Amanda Elena. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Departamento de Radiobiología; Argentina