The Evolving Strategy of Californium-252 Neutron Intracavitary Brachytherapy in Treating Patients With Low-Lying T2 or T3 Rectal Adenocarcinoma: From Fixed to Individualized Regime With Intrarectal Peritumoral Injection of Amifostine

PurposeTo retrospectively and comparatively evaluate the improvement of the efficacy and safety on the addition of 252Cf neutron intracavitary brachytherapy (ICBT), individualized or individualized with intrarectal peritumoral injection of amifostine (IPIA) to external-beam radiotherapy (EBRT) or concurrent chemo-EBRT in 314 patients with T2N0-1 or T3N0-1 low-lying rectal adenocarcinoma.MethodsPhase I: from 2009 to 2011, 157 patients were treated with additional 252Cf neutron ICBT for four fixed fractions with a total dose of 40–45 Gy-eq during the EBRT. Phase II: from 2011 to 2013, 75 patients were treated with individualized neutron ICBT delivered for two to five fractions with a total dose of 26–45 Gy-eq according to the response of tumor after concurrent chemo-EBRT. Phase III: from 2013 to 2014, 82 patients were treated with individualized ICBT protected by pretreatment IPIA.ResultsThe 4-year local control rates for the entire T2 and T3 patients were 69.4, 72.0, and 79.3%, while the 4-year overall survival rates were 63.1, 54.7, and 72.0% (P=0.08), and the 4-year disease-free survival rates were 55.4, 52.0, and 69.5% (P=0.053) in Phases I, II, and III, respectively. The late complication (LAC, ≥G2) rates were 33.8, 26.7, and 15.9%, respectively (P=0.012), and the serious LAC (≥G3) rates were 4.5, 4.2, and 0%, respectively, in Phases I, II, and III.ConclusionConcurrent chemo-EBRT combined with individualized 252Cf neutron ICBT protected by IPIA shows promising efficacy and safety in treating low-lying T2 and T3 rectal adenocarcinoma patients without surgery opportunity or willing.

Peritumoral administration of IFNβ upregulated mesenchymal stem cells inhibits tumor growth in an orthotopic, immunocompetent rat glioma model

BackgroundImmunotherapy with IFNβ is a promising strategy for treating malignant glioma. However, systemic administration of IFNβ is inadequate because of low intratumoral concentration and major adverse effects. This study aimed to determine whether mesenchymal stem cells (MSCs) can be used as cellular vehicles to locally deliver IFNβ for glioma therapy by using in vivo MRI tracking.MethodsA recombinant lentiviral vector encoding IFNβ and ferritin heavy chain (FTH) reporter genes was constructed to transduce MSCs. The effectiveness and safety of transduction were assessed. After the IFNβ and FTH overexpressed MSCs (IFNβ-FTH-MSCs) were transplanted into intracranial orthotopic rat F98 gliomas via peritumoral, intracerebral, intratumoral or intra-arterial injection, MRI was performed to track IFNβ-FTH-MSCs and to evaluate their therapeutic effect on glioma in vivo, as validated by histologic analysis, quantitative PCR and ELISA assays.ResultsMSCs were efficiently and safely transduced to upregulate their IFNβ secretion and FTH expression by the constructed lentivirus. After peritumoral injection, IFNβ-FTH-MSCs appeared as hypointense signals on MRI, which gradually diminished but remained visible until 11 days. Compared with other administration routes, only peritumoral injection of IFNβ-FTH-MSCs showed a remarkable inhibition on the glioma growth. Nearly 30% of IFNβ-FTH-MSCs survived up to 11 days after peritumoral injection, while most of IFNβ-FTH-MSCs injected via other routes died within 11 days. IFNβ-FTH-MSCs grafted peritumorally secreted IFNβ persistently, leading to pronounced Batf3+dendritic cells and CD8+T lymphocyte infiltration within the glioma.ConclusionsMSCs can be used as cellular vehicles of IFNβ to treat malignant glioma effectively via peritumoral injection.

Infrared fluorescence lymphography in experimental and clinical practice

Introduction. Near infrared (NIR) fluorescent diagnostics is promising due to a deeper penetration into biological tissues. Material and methods. In experiments on rabbits and in clinical studies evaluation the lymphatic system with the use of the instrument complex FLUM-808 was analysed. Results. For visualization of the lymphatic vessels of the skin, the intradermal administration of ICG, dissolved in 20 % albumin in the order of 0.02 mg/ml, is optimal. Peritumoral injection of ICG allows visualizing sentinel lymph nodes in patients with lung cancer. Conclusions. The developed NIR fluorescence diagnostic system FLUM-808 allows to real time visualization of lymphatic vessels and lymph nodes.

Laparoscopic subperitoneal injection of chemo-loaded particles lowers tumor growth on a rabbit model of peritoneal carcinomatosis

The purpose of our study was to assess the effect of controlled-release chemotherapy on the growth and viability of peritoneal carcinomatosis treated by subperitoneal injection in a rabbit VX2 model. A model of peritoneal carcinomatosis was created by laparoscopic injection of VX2 tumor in the left and right broad ligaments of 12 White New Zealand rabbits. At day 12, each tumor was randomly treated with a peritumoral injection of 0.5 mL microspheres loaded with doxorubicin (DEM-DOX) or unloaded (DEM-BLAND). Seven days after treatment, tumor volume, tumor viability in histology, local tumor necrosis in contact with DEM, and doxorubicin concentration profile around the drug eluting microspheres (DEM) were measured. Tumor volume was significantly lower in the DEM-DOX group (3.6 ± 3.2 cm3) compared with the DEM-BLAND group (8.9 ± 5.4 cm3) (p = 0.0425). The percentage of viable tumor tissue was significantly lower in the DEM-DOX group (38% ± 17%) compared with the DEM-BLAND group (56% ± 20%) (p = 0.0202). Tissue necrosis was observed around all DEM-DOX up to a distance of 1.094 ± 0.852 mm and never observed around DEM-BLAND. Drug concentration was above the therapeutic level of 1.0 µM up to a distance of 1.4 mm from the DEM to the tumor. Laparoscopic subperitoneal injection of chemo-loaded particles is feasible and lowers tumor growth and viability in a rabbit model of peritoneal carcinomatosis after 1 week.

Sentinel Lymph Node Detection in Breast Cancer – First Experience/ Детекција На Сентинелни Лимфни Јазли Кај Карцином На Дојка – Први Искуства

Introduction: Breast cancer accouns for 22.9% of all cancers in women and 13.7% of cancer deaths. Positive axillary lymphnodes (ALN) predict the development of distant metastases. The status of the sentinel lymphnode (SLN) is crutial for the treatment selection. Aim: To determine the benefits of SLN detection in patients with breast cancer. Material and methodology: 38 female patients (pts), age 44 ± 12 years, with T1-2 N0 M0 breast cancer, without enlarged ALN on ultrasound (US), were included. SLN detection was performed using gamma camera and gamma detection probe after periareolar subcutaneous and/or peritumoral injection of (99m-Technetium-SENTISCINT). Blue dye was administered 20 min before the operation. SLN was extirpated and ex tempore histopathology was performed. Results: Ex tempore SLN evaluation was negative and the lymphatic pathways preserved in 28/38 (74%) pts. In 10/38 (26%) pts SLN was positive, followed by radical surgery. In 3/28 ex tempore negative patients, histopathological analysis showed metastatic involvement (false negative). In 3/10 ex tempore positive patients micro metastases 0,2-2 mm were detected. 12 pts had 2 SLN, 8/12 (66%) had negative and 4/12 (34%) had positive SLN. 3 pts had a rare double drainage to axilla and a. mammaria int. Conclusion: Our results confirm that SLN detection technique is non-invasive, safe and reliable and should be incorporated into the guidelines for breast cancer pts (T1-2 N0 M0). The most reliable option for colloid application is the combined technique of periareolar and peritumoral injection. Patients with drainage to a. mammaria interna should be selected for adjuvant protocols.