Brachytherapy for targeting the immune system in cervical cancer patients.

BACKGROUND: New combinations based on standard therapeutic modalities and immunotherapy require understanding the immunomodulatory properties of traditional treatments. The objective was to evaluate the impact of brachytherapy (BT) on the immune system of cervical cancer and to identify the best modality, High-dose-rate brachytherapy (HDR-BT) vs. Pulsed-dose-rate (PDR-BT), to target it. METHODS: Nineteen patients enrolled in a prospective study received chemoradiation (CRT) and subsequently HDR-BT or PDR-BT. Peripheral blood samples were obtained for immunophenotyping analysis by flow-cytometry before CRT, BT, and two and four weeks after BT. The Friedman one-way ANOVA, Conover post hoc test, and the Wilcoxon signed-rank test were used to compare changes in cell populations at different periods, perform multiple pairwise comparisons and assess differences between treatment groups (PDR and HDR). RESULTS: Natural killer cells (NKs) were the best target for BT. Patients receiving HDR-BT achieved significantly higher values ​​and longer time of the CD56dimCD16 + NK cells with greater cytotoxic capacity than the PDR-BT group, which presented their highest elevation of CD56-CD16 + NK cells. Furthermore, both BT modalities were associated with an increase in myeloid-derived suppressor cells (MDSCs), related to a worse clinical prognosis. However, there was a decrease in the percentage of CD4 + CD25 + Foxp3 + CD45RA + regulatory T cells (Tregs) in patients receiving HDR-BT, although there were no significant differences between BT. CONCLUSIONS: Immune biomarkers are important predictive determinants in cervical cancer. Higher cytotoxic NK cells and a trend toward lower values of Tregs might support the use of HDR-BT to the detriment of PDR-BT and help develop effective combinations with immunotherapy.

Improving radiation oncology through clinical audits: Introducing the IROCA project.

As radiotherapy practice and processes become more complex, the need to assure quality control becomes ever greater. At present, no international consensus exists with regards to the optimal quality control indicators for radiotherapy; moreover, few clinical audits have been conducted in the field of radiotherapy. The present article describes the aims and current status of the international IROCA "Improving Radiation Oncology Through Clinical Audits" project. The project has several important aims, including the selection of key quality indicators, the design and implementation of an international audit, and the harmonization of key aspects of radiotherapy processes among participating institutions. The primary aim is to improve the processes that directly impact clinical outcomes for patients. The experience gained from this initiative may serve as the basis for an internationally accepted clinical audit model for radiotherapy.

Preoperative radiotherapy for rectal cancer: a comparative study of quality control adherence at two cancer hospitals in Spain and Poland.

BACKGROUND: We performed a clinical audit of preoperative rectal cancer treatment at two European radiotherapy centres (Poland and Spain). The aim was to independently verify adherence to a selection of indicators of treatment quality and to identify any notable inter-institutional differences. METHODS: A total of 162 patients, in Catalan Institute of Oncology (ICO) 68 and in Greater Poland Cancer Centre (GPCC) 94, diagnosed with locally advanced rectal cancer and treated with preoperative radiotherapy or radio-chemotherapy were included in retrospective study. A total of 7 quality control measures were evaluated: waiting time, multidisciplinary treatment approach, portal verification, in vivo dosimetry, informed consent, guidelines for diagnostics and therapy, and patient monitoring during treatment. RESULTS: Several differences were observed. Waiting time from pathomorphological diagnosis to initial consultation was 31 (ICO) vs. 8 (GPCC) days. Waiting time from the first visit to the beginning of the treatment was twice as long at the ICO. At the ICO, 82% of patient experienced treatment interruptions. The protocol for portal verification was the same at both institutions. In vivo dosimetry is not used for this treatment localization at the ICO. The ICO utilizes locally-developed guidelines for diagnostics and therapy, while the GPCC is currently developing its own guidelines. CONCLUSIONS: An independent external clinical audit is an excellent approach to identifying and resolving deficiencies in quality control procedures. We identified several procedures amenable to improvement. Both institutions have since implemented changes to improve quality standards. We believe that all radiotherapy centres should perform a comprehensive clinical audit to identify and rectify deficiencies.

Fractionated stereotactic radiotherapy in the treatment of exclusive cavernous sinus meningioma: functional outcome, local control, and tolerance.

BACKGROUND: Fractionated stereotactic radiotherapy (FSRT) combines the precision of stereotactic positioning with the radiobiologic advantage of dose fractionation. METHODS: From June 1997 to June 2001, 30 patients with cavernous sinus meningiomas were treated with FSRT using fixed noncoplanar conformal fields. Patient skull fixation was achieved using the BrainLAB mask (20 patients) or Beverly frame (10 patients). The Cosman-Roberts-Wells coordinate frame was used for stereotactic space definition. In selected cases before 1999, and in all cases afterward, gadolinium-enhanced MRI for image fusion was performed. The median radiation dose was 52 Gy, with a daily fraction of 2 Gy. Patients were regularly followed up analyzing symptoms, tumor progression, and side effects. Neurocognitive function was evaluated retrospectively for 26 patients using Mini-Mental State Examination. RESULTS: Median follow-up period was 50 months (range, 28.2-74.5 months). Preexisting neurologic symptoms improved in 50% of the patients and worsened in 2 patients. Only 2 patients progressed and the actuarial local progression free survival was 93% at 4 years. Tolerance was good with 2 cases of late radiation toxicity which consisted of moderate short-term memory loss and dysphasia in one case and neuropsychologic deficit with seizures in the other. Postradiotherapy Mini-Mental State Examination results showed a median score of 28 (range, 16-30). CONCLUSIONS: Fractionated stereotactic radiotherapy is a high-precision technique. It is safe and feasible in the primary and adjuvant treatment of cavernous sinus meningiomas. Fractionated stereotactic radiotherapy allowed local control in more than 90% of patients.

The use of caspase inhibitors in pulsed-field gel electrophoresis may improve the estimation of radiation-induced DNA repair and apoptosis.

BACKGROUND: Radiation-induced DNA double-strand break (DSB) repair can be tested by using pulsed-field gel electrophoresis (PFGE) in agarose-encapsulated cells. However, previous studies have reported that this assay is impaired by the spontaneous DNA breakage in this medium. We investigated the mechanisms of this fragmentation with the principal aim of eliminating it in order to improve the estimation of radiation-induced DNA repair. METHODS: Samples from cancer cell cultures or xenografted tumours were encapsulated in agarose plugs. The cell plugs were then irradiated, incubated to allow them to repair, and evaluated by PFGE, caspase-3, and histone H2AX activation (γH2AX). In addition, apoptosis inhibition was evaluated through chemical caspase inhibitors. RESULTS: We confirmed that spontaneous DNA fragmentation was associated with the process of encapsulation, regardless of whether cells were irradiated or not. This DNA fragmentation was also correlated to apoptosis activation in a fraction of the cells encapsulated in agarose, while non-apoptotic cell fraction could rejoin DNA fragments as was measured by γH2AX decrease and PFGE data. We were able to eliminate interference of apoptosis by applying specific caspase inhibitors, and improve the estimation of DNA repair, and apoptosis itself. CONCLUSIONS: The estimation of radiation-induced DNA repair by PFGE may be improved by the use of apoptosis inhibitors. The ability to simultaneously determine DNA repair and apoptosis, which are involved in cell fate, provides new insights for using the PFGE methodology as functional assay.