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Glioblastoma multiforme (GBM) represents an aggressive tumor type with poor prognosis. The majority of GBM patients cannot be cured. There is high willingness among patients for the compassionate use of non-approved medications, which might occasionally lead to profound toxicity. A 65-year-old patient with glioblastoma multiforme (GBM) has been treated with radiochemotherapy including temozolomide (TMZ) after surgery. The treatment outcome was evaluated as stable disease with a tendency to slow tumor progression. In addition to standard medication (ondansetron, valproic acid, levetiracetam, lorazepam, clobazam), the patient took the antimalarial drug artesunate (ART) and a decoction of Chinese herbs (Coptis chinensis, Siegesbeckia orientalis, Artemisia scoparia, Dictamnus dasycarpus). In consequence, the clinical status deteriorated. Elevated liver enzymes were noted with peak values of 238 U/L (GPT/ALAT), 226 U/L (GOT/ASAT), and 347 U/L (γ-GT), respectively. After cessation of ART and Chinese herbs, the values returned back to normal and the patient felt well again. In the literature, hepatotoxicity is well documented for TMZ, but is very rare for ART. Among the Chinese herbs used, Dictamnus dasycarpus has been reported to induce liver injury. Additional medication included valproic acid and levetiracetam, which are also reported to exert hepatotoxicity. While all drugs alone may bear a minor risk for hepatotoxicity, the combination treatment might have caused increased liver enzyme activities. It can be speculated that the combination of these drugs caused liver injury. We conclude that the compassionate use of ART and Chinese herbs is not recommended during standard radiochemotherapy with TMZ for GBM.

Background: Radiation therapy is an established cornerstone in the treatment of prostate cancer. Significant advances in the techniques and therapeutic concepts have been made in recent decades., Objectives: The objective of this article is to provide an overview of current standards of care and recent technical and conceptional developments., Conclusions: Three-dimensional conformal radiotherapy has long been the standard of care for percutaneous radiotherapy. The development of intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) have increased the precision of treatment, thus, reducing side effects and allowing dose escalation. LDR (low dose rate) and HDR (high dose rate) brachytherapy alone or in combination are a treatment option in localized prostate cancer with a distinct side effect profile. The roles of proton therapy and stereotactic radiotherapy should be further investigated in prospective trials.

Introduction: We report the first case of an intraoperative radiotherapy (IORT) in a patient with recurrent glioblastoma multiforme (GBM) who was followed up with a novel magnetic resonance imaging (MRI) method-(23)Na-MRI-in comparison to a standard contrast-enhanced (1)H-MRI and (18)F-FET-PET., Methods: A 56-year-old female patient with diagnosed GBM in July 2012 underwent tumor resection, radiochemotherapy, and three cycles of chemotherapy. After a relapse, 6 months after the initial diagnosis, an IORT was recommended which was performed in March 2013 using the INTRABEAM system (Carl Zeiss Meditec AG, Germany) with a 3-cm applicator and a surface dose of 20 Gy. Early post-operative contrast-enhanced and 1-month follow-up (1)H-MRI and a (18)F-FET-PET were performed. In addition, an IRB-approved (23)Na-MRI was performed on a 3.0-T MR scanner (MAGNETOM TimTrio, Siemens Healthcare, Germany)., Results: After re-surgery and IORT in March 2013, only a faint contrast enhancement but considerable surrounding edema was visible at the medio-posterior resection margins. In April 2013, new and progressive contrast enhancement, edema, (23)Na content, and increased uptake in the (18)F-FET-PET were visible, indicating tumor recurrence. Increased sodium content within the area of contrast enhancement was found in the (23)Na-MRI, but also exceeding this area, very similar to the increased uptake depicted in the (18)F-FET-PET. The clearly delineable zone of edema in both examinations exhibits a lower (23)Na content compared to areas with suspected proliferating tumor tissue., Conclusion: (23)Na-MRI provided similar information in the suspicious area compared to (18)F-FET-PET, exceeding conventional (1)H-MRI. Still, (23)Na-MRI remains an investigational technique, which is worth to be further evaluated.

Background: Operative and radiotherapeutic procedures are available for the treatment of symptomatic vertebral metastases. The method for treatment of vertebral metastases presented in this article involves a combination of intraoperative radiotherapy (IORT) and kyphoplasty., Methods and Results: Kyphoplasty-IORT allows treatment of symptomatic vertebral metastases between vertebrae T3 and L5. With the patient under intubation narcosis an extrapedicular or bipedicular access to the vertebra is selected as for conventional kyphoplasty. This is followed by insertion of special sheaths of the radiation applicator and radiation therapy is intraoperatively administered via a radiation generator (Intrabeam®, Carl Zeiss Surgical, Oberkochen, Germany). The radiation dose is 8 Gy at a depth of 5-10 mm depending on the study protocol (50 kV X-radiation). Following radiation a conventional kyphoplasty procedure (Medtronic, USA) is carried out and the vertebra stabilized with cement., Conclusions: The procedure presented demonstrates a new approach to treatment of vertebral metastases and represents a valuable alternative to previously established methods.

The Kypho-IORT procedure is a recently developed surgical technique to combine intraoperative radiotherapy with cement augmentation of the vertebra for spinal metastases. The technical feasibility and the operation principle of this new method have been described. In the following article the refinement of the standard operation procedure and the technical development of the method are described. Not only the procedural improvements but also the learning curves of the inaugurators are pointed out. Moreover, the article presents the measures which were necessary to educate trainees during surgical master classes in this new method and to transfer the method. The learning success was quantified by recording the accuracy reached by the trainees in the key procedure during hands-on cadaver exercises. Improvements of the standard operation procedure could be successfully transferred in a second master class. The method of Kypho-IORT and the demonstrated way of postgraduate education is feasible to instruct trainees. The Kypho-IORT procedure can be learnt and performed safely by running through the surgical master class.

Purpose: Long-term administration of adjuvant temozolomide is common practice in many institutions, especially when treatment is well tolerated and stable disease is achieved. In this study, we evaluate the feasibility and efficacy of long-term temozolomide in patients with glioblastoma multiforme treated at a single institution., Methods: One hundred and fourteen patients with newly diagnosed glioblastoma were followed for the course of their disease. Treatment consisted of surgery [gross total resection (GTR) subtotal resection (STR) or biopsy] followed by radiotherapy and concomitant temozolomide. Adjuvant temozolomide was administered until evidence for progressive disease or serious side effects occurred. Follow-up was routinely performed every 3 months., Results: One hundred and fourteen patients with glioblastoma multiforme received a median of 6 cycles of adjuvant first-line temozolomide (range 1-57). For patients with less than 6 cycles, chemotherapy was stopped in 60% for reasons other than progression, while only in 17% of patients receiving 6 or more (P < 0.0001). Median TTP was 7 months (95% CI: 6-10 months). PFS after 6 months was 53%. Median OS in all patients was 15 months (95% CI: 13-18 months). TTP and OS directly correlate with the amount of chemotherapy cycles (each P < 0.0001). No significant influence of the extent of surgical treatment on PFS (P = 0.2141) and OS (P = 0.4308) could be detected., Conclusion: This data set suggests that long-term administration of temozolomide is safe and efficacious. Side effects occur more frequently in the early phase of drug administration (<6 cycles). There is a strong correlation of long-term temozolomide on PFS and OS regardless of the extent of surgery and other factors.

Prostate cancer is the most common malignancy of men with approximately 32,000 new cases of prostate cancer in Germany and approximately 11,000 men who would die of the disease each year. For early diagnosis of prostate cancer PSA testing is used, whereas at present screening cannot be recommended due to the lack of confirmed medical and economic benefits. Regarding the imaging modalities, ultrasound of the prostate, currently performed in combination with elastography and histoscanning, magnetic resonance imaging of the prostate in combination with endorectal coils and positron emission tomography combined with computed tomography (PET-CT) are the methods of choice. Using these methods benign prostatitis can be differentiated from prostate cancer and staging of the tumor can be accomplished. On the other hand using these imaging methods it is possible to define the dominant intraprostatic lesion with different sensitivities and specificities, which is important for minimally invasive therapeutic strategies.

Postoperative adjuvant radiation therapy has achieved special significance based on the results of three randomized studies on stage pT3R1 prostate cancer which provided evidence for prolonged survival in comparison to the "wait and see" strategy. When PSA levels persist or increase after radical prostatectomy, irradiation represents an alternative. In this instance, salvage radiotherapy should be initiated as early as possible, most suitably when the PSA level is <0.5 ng/ml. Side effects of percutaneous radiotherapy using modern techniques are minimal in this stage; severe grade 3 or 4 late sequelae occur in <3% of cases. Low dose rate (LDR) brachytherapy as monotherapy is a primary treatment option for low-risk tumors. In patients with intermediate-risk tumors, data are controversial and cannot be assessed conclusively. LDR brachytherapy should not be administered in high-risk tumors. High dose rate (HDR) brachytherapy combined with percutaneous radiotherapy as an example of a typical dose escalation approach is a primary option for intermediate- and high-risk prostate cancer. Whether additional hormone therapy is needed with HDR brachytherapy is unclear. HDR monotherapy can only be recommended in the clinical trial setting.

Radiation therapy is a treatment option for curative management of localized and locally advanced prostate cancer. Depending on tumor stage and constellation of risk factors (PSA level, findings on digital rectal examination, and Gleason score), various forms of radiotherapy are applied. In addition to the sole use of external beam radiotherapy, brachytherapy with radioactive seeds is also employed as stand-alone treatment in patients with low risk factors and in early clinical stages. Increasing risk of recurrence requires more intensive therapies which can be accomplished by adding hormone deprivation therapy and/or intensifying radiation therapy (dose escalation). Combined approaches using brachytherapy and percutaneous radiotherapy are also initiated in these cases. If hormone ablation therapy is administered, this should occur over a course of 3-36 months as neoadjuvant, concommitant and/or adjuvant treatment, depending on the risk of recurrence.

Purpose: Glioblastoma multiforme is the prototype of an angiogenic tumour. Under experimental conditions, anti-angiogenic therapy strategies lead to an increased invasion. Here we report on the pattern of tumour recurrence in glioblastoma patients treated with an anti-angiogenic chemotherapy., Patients and Methods: A total of 32 patients with glioblastoma multiforme and a residual tumour mass after operation were treated with a continuous low-dose chemotherapy with temozolomide and a COX-II inhibitor, a presumably anti-angiogenic therapy., Results: While anti-tumour activity of this therapy regimen was excellent with a mean overall time to progression of 10.4 (+/-0.9) months and a mean overall survival of 17.8 (+/-1.5) months, an unusually high rate of distant recurrences was observed (62.5%)., Conclusion: Patients treated with an anti-angiogenic chemotherapy experience distant recurrences at a higher rate than reported for conventional therapies. This may reflect an anti-angiogenic therapy-induced activation of glioma invasion confirming similar recently published experimental results.

Background: Brachytherapy (BT) is an established treatment option for low risk prostate cancer. The aim of this study was to determine the long-term complications and side effects of the procedure in an up to 13 year long single center follow-up analysis., Material: A total of 505 patients were treated by BT for prostate cancer between May 1991 and August 2005. Cohort I (n=412; May 1991 to November 2003) was evaluated by written questionnaire (modified ICS male) and patient chart evaluation in terms of side effects and secondary interventions. In cohort II (n=148; January 2002 to August 2005) perioperative complications were investigated., Results: The mean follow-up was 5.5 years. Perioperative complications were present in 5.4% of patients. Transurethral resection of the prostate was a common secondary intervention, performed in 7% of cases. The rate of incontinence was 6.3% in the long-term follow-up, the rate of potency was 43.5% in those patients who were potent before BT and no hormonal manipulation was performed at any time., Conclusion: BT is a minimally invasive procedure for the treatment of localised "low risk" prostate cancer. Perioperative complications are rare, secondary intervention may be necessary and the patient has to be informed of possible impotence, incontinence and lack of ejaculation.

Purpose: Glioblastoma multiforme (GBM) represents the prototype of an angiogenic tumor. Recently, the continuous low-dose scheduling of chemotherapeutic drugs in combination with an inhibition of cyclooxygenase-2 (COX-2) has been suggested as a novel anti-angiogenic approach. The aim of this study was to evaluate the safety and activity of continuous low-dose temozolomide (TMZ) plus the COX-2 inhibitor rofecoxib in patients with newly diagnosed GBM., Methods: In vitro, endothelial cells were characterized by a tenfold higher sensitivity to TMZ than glioma cells. Consequently, a subgroup of patients with incompletely resected GBM (n=13) was divided into three groups aiming at a dose escalation to 1/10 of the daily MTD for TMZ: (A) TMZ 10 mg/m2 every third day and rofecoxib 25 mg/d; (B) TMZ 10 mg/m2/d and rofecoxib 25 mg/d; (C) TMZ 5 mg/m2 twice a day and rofecoxib 12.5 mg twice a day. COX-2, VEGF, VEGF Receptor-2, and CD34 were assessed immunohistochemically, in the clinical setting., Results: The mean follow-up period was 15 months. We observed no severe toxicity attributable to the therapy. Quality of life was not impaired. For the whole study population, median time to progression and overall survival were 8 months and 16 months, respectively. Immunohistochemistry suggested that tumors with higher vessel densities were characterized by a significantly better control than those with lower vessel densities., Conclusions: Continuous low-dose TMZ plus rofecoxib is feasible, safe, and maintains good quality of life. This study is indicative of an anti-angiogenic efficacy of continuous low-dose TMZ plus rofecoxib in GBMs, especially in those tumors that are characterized by a high angiogenic activity.