Effect of Whole-abdominal Irradiation on Penetration Depth of Doxorubicin in Normal Tissue After Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in a Post-mortem Swine Model.

BACKGROUND: This study was performed to evaluate the impact of whole-abdominal irradiation on local penetration of doxorubicin into the peritoneum and the abdominal organs in a post-mortem swine model. MATERIALS AND METHODS: Doxorubicin was aerosolized into the abdominal cavity of swine at a pressure of 12 mmHg CO2 at room temperature (25°). One swine was subjected to pressurized intraperitoneal aerosol chemotherapy (PIPAC) using Micropump© without irradiation; the second one received 2 Gy and the third one 7 Gy whole-abdominal irradiation, 15 min prior to PIPAC application. Samples of the peritoneal surface were extracted at different positions from within the abdominal cavity. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: The depth of penetration of doxorubicin was found to be wide-ranging, between 17 µm on the surface of the stomach and 348 µm in the small intestine. The penetration depth into the small intestine was 348 µm, 312 µm and 265 µm for PIPAC alone, PIPAC with 2 Gy irradiation and PIPAC with 7 Gy irradiation, respectively (p<0.05). The penetration into the liver was 64 µm, 55 µm and 40 µm, respectively (p=0.05). CONCLUSION: Irradiation was not found to increase the depth of doxorubicin penetration into normal tissue in the post-mortem swine model. A reduction of doxorubicin penetration was observed after application of higher irradiation doses. Further studies are warranted to determine if irradiation can be used safely as chemopotentiating agent for patients with peritoneal metastases treated with PIPAC.

Effect of Irradiation on Tissue Penetration Depth of Doxorubicin after Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) in a Novel Ex-Vivo Model.

BACKGROUND: This study was performed to assess the impact of irradiation on the tissue penetration depth of doxorubicin delivered during Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC). METHODS: Fresh post mortem swine peritoneum was cut into 10 proportional sections. Except for 2 control samples, all received irradiation with 1, 2, 7 and 14 Gy, respectively. Four samples received PIPAC 15 minutes after irradiation and 4 other after 24 hours. Doxorubicin was aerosolized in an ex-vivo PIPAC model at 12 mmHg/36°C. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections. RESULTS: Doxorubicin penetration after PIPAC (15 minutes after irradiation) was 476 ± 74 µm for the control sample, 450 ± 45µm after 1 Gy (p > 0.05), 438 ± 29 µm after 2 Gy (p > 0.05), 396 ± 32 µm after 7 Gy (p = 0.005) and 284 ± 57 after 14 Gy irradiation (p < 0.001). The doxorubicin penetration after PIPAC (24 hours after irradiation) was 428 ± 77 µm for the control sample, 393 ± 41 µm after 1 Gy (p > 0.05), 379 ± 56 µm after 2 Gy (p > 0.05), 352 ± 53 µm after 7 Gy (p = 0.008) and 345 ± 53 after 14 Gy irradiation (p = 0.001). CONCLUSIONS: Higher (fractional) radiation dose might reduce the tissue penetration depth of doxorubicin in our ex-vivo model. However, irradiation with lower (fractional) radiation dose does not affect the tissue penetration negatively. Further studies are warranted to investigate if irradiation can be used safely as chemopotenting agent for patients with peritoneal metastases treated with PIPAC.

Treatment Results of MammoSite Catheter in Combination with Whole-breast Irradiation.

AIM: To report the initial outcomes of patients treated with the MammoSite brachytherapy device (MSBT) as a boost followed by external whole-breast irradiation (WBI). PATIENTS AND METHODS: From June 2011 to March 2014, 107 patients (typically with pT1-2, pN0-1, M0 disease) were treated with breast-conserving therapy and adjuvant radiotherapy with MSBT (15 Gy in 2.5-Gy fractions) followed by WBI (median=50.4 Gy). Toxicity was classified according to the Common Terminology Criteria for Adverse Events v3.0. The median follow-up was 21 months. RESULTS: To date, no ipsilateral breast-tumor recurrences have been observed; 102 patients (95%) were alive at last follow-up. Two patients (2%) developed distant metastases. Five patients (5%) died during follow-up, only one as a result of breast cancer. The 2-year disease-free survival was 95±3%. The incidence of asymptomatic and symptomatic seroma in 90 days after MSBT was 28% and 10%, respectively. Infectious mastitis was observed in three patients (3%), who were treated successfully with antibiotics. Only three patients (3%) developed RT-induced dermatitis greater than grade 2 after WBI. CONCLUSION: The boost technique used in this study seems to provide excellent local control with acceptable toxicity, similar to the results observed with other forms of interstitial accelerated partial-breast irradiation as a boost. Long-term follow-up is necessary to refine the patient selection criteria and to assess efficacy and late toxicities.