A tool to automatically analyze electromagnetic tracking data from high dose rate brachytherapy of breast cancer patients.

During High Dose Rate Brachytherapy (HDR-BT) the spatial position of the radiation source inside catheters implanted into a female breast is determined via electromagnetic tracking (EMT). Dwell positions and dwell times of the radiation source are established, relative to the patient's anatomy, from an initial X-ray-CT-image. During the irradiation treatment, catheter displacements can occur due to patient movements. The current study develops an automatic analysis tool of EMT data sets recorded with a solenoid sensor to assure concordance of the source movement with the treatment plan. The tool combines machine learning techniques such as multi-dimensional scaling (MDS), ensemble empirical mode decomposition (EEMD), singular spectrum analysis (SSA) and particle filter (PF) to precisely detect and quantify any mismatch between the treatment plan and actual EMT measurements. We demonstrate that movement artifacts as well as technical signal distortions can be removed automatically and reliably, resulting in artifact-free reconstructed signals. This is a prerequisite for a highly accurate determination of any deviations of dwell positions from the treatment plan.

On the use of particle filters for electromagnetic tracking in high dose rate brachytherapy.

Modern radiotherapy of female breast cancers often employs high dose rate brachytherapy, where a radioactive source is moved inside catheters, implanted in the female breast, according to a prescribed treatment plan. Source localization relative to the patient's anatomy is determined with solenoid sensors whose spatial positions are measured with an electromagnetic tracking system. Precise sensor dwell position determination is of utmost importance to assure irradiation of the cancerous tissue according to the treatment plan. We present a hybrid data analysis system which combines multi-dimensional scaling with particle filters to precisely determine sensor dwell positions in the catheters during subsequent radiation treatment sessions. Both techniques are complemented with empirical mode decomposition for the removal of superimposed breathing artifacts. We show that the hybrid model robustly and reliably determines the spatial positions of all catheters used during the treatment and precisely determines any deviations of actual sensor dwell positions from the treatment plan. The hybrid system only relies on sensor positions measured with an EMT system and relates them to the spatial positions of the implanted catheters as initially determined with a computed x-ray tomography.

Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells.

Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory cells in anal squamous cell carcinoma and a possible association with survival data. Thirty-eight patients suffering from anal carcinoma were studied using tissue microarrays, double staining immunohistochemistry, whole slide scanning and image analysis software. Therapy consisted of concurrent radiochemotherapy. Numbers of stromal and intraepithelial tumor-infiltrating inflammatory cells (TIC) and the distances between cells were quantified. Double-staining of FoxP3(+) cells with either CD8(+), CD1a(+) or CD20(+) cells was performed. Measured cell-to-cell distances were compared to computer simulated cell-to-cell distances leading to the assumption of non-randomly distributed and therefore functional immune cells. Intraepithelial CD1a(+) and CD20(+) cells were randomly distributed and therefore regarded as non-functional. In contrary, stromal CD20(+) cells had a non-random distribution pattern. A non-random distance between CD20(+) and FoxP3(+) cells was associated with a clearly unfavorable outcome. Measured distances between FoxP3(+) cells were distinctly shorter than expected and indicate a functional active state of the regulatory T cells (Treg). Analysis of cell-to-cell distances between TIC has the potential to distinguish between suppressed non-functional and functionally active inflammatory cells. We conclude that in this tumor model most of the CD1a(+) cells are non-functional as are the intraepithelial CD20(+) cells, while stromal CD20(+) cells and FoxP3(+) cells are functional cells.

Protocol-based image-guided salvage brachytherapy. Early results in patients with local failure of prostate cancer after radiation therapy.

PURPOSE: To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects. PATIENTS AND METHODS: Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005-2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V100 > 95 %) simultaneously respecting the protocol-based dose volume constraints for the urethra (D0.1 cc < 130 %) and the rectum (D2 cc < 50-60 %) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities--particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival. RESULTS: We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1 % (2/18) and 16.7 % (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17 % (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1 %. The overall survival at 3 years was 88.9 %; 22 % (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8-77 months). CONCLUSION: Salvage PDR-brachytherapy of the prostate following local failure after radiation therapy is a treatment option with a low rate of genitourinary side effects and no late gastrointestinal side effects. The treatment efficacy in the first 3 years is promising.

[Neoadjuvant radiochemotherapy for rectal cancer]. / Neoadjuvante Radiochemotherapie des Rektumkarzinoms.

Neoadjuvant radiochemotherapy has become established treatment for rectal cancer. It is indicated when primary R0 resection is not an option, in cases of higher risk of locoregional relapse following surgical treatment alone, and when initially impossible conservation of the anal sphincter becomes possible in conjunction with neoadjuvant radiochemotherapy. The indication for radiochemotherapy in the upper third of the rectum is still controversial. Reevaluation of the tumor situation following neoadjuvant treatment is necessary before decisions on operative strategy. Modern imaging techniques are limited in this respect, as they hardly allow differentiation between living tumor tissue and lesions. In case of doubt clarity is possible only through surgical exploration, taking R1 resection into account. Overall the recognition of lymph node metastasis is not a sufficient indicator of local relapse. The frequency of postoperative complications following neoadjuvant radiochemotherapy is independent of the operative method. The effect of neoadjuvant radiochemotherapy on long-term survival and formation of distant metastases is still not clarified. Current studies seek clarification through the use of new chemotherapies and modified treatment regimes. Further, the correct time interval between the end of neoadjuvant radiochemotherapy and the following surgical therapy has yet to be determined. This applies also to the management of patients following complete remission.

Wollack titration of thiosulphate.

The Wollack titration for the determination of thiosulphate has been reinvestigated. Various modifications are proposed and the conditions necessary for satisfactory results are discussed.