Surgery vs. radiotherapy in localized prostate cancer. Which is best?

Surgery and radiotherapy are currently accepted alternatives for the treatment of localized prostate cancer. In the absence of relevant randomized trials no decision regarding the superiority of any of the given approaches can be made. Up to now several cohort-based approaches indicate similar outcomes for both treatments. Based on a new population based approach, Merglen and co-workers recently concluded that surgery would offer the best chance of long-term control in terms of 10-year survival for T1–T3 prostate cancer patients. Unfortunately the strength of this trial is limited by several shortcomings. Most importantly, issues of radiation dosage have not been taken into account. In addition, several relevant parameters including Gleason score and PSA are not well balanced between the arms and the assignment to arbitrary risk groups does not reflect the real biological behaviour. Thus, the data provided do not support the strong conclusion issued by the authors. Based on the data available, surgery and radiotherapy still have to be considered as equally effective

Choline PET based dose-painting in prostate cancer - Modelling of dose effects

Background: Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Methods: Based on different assumptions for alpha/beta, gamma 50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Results: Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high gamma 50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Discussion: Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the assumption of high detection rates and low initial TCP values the TCP gain has been shown to be relevant. Conclusions: Based on the employed assumptions, specific dose escalation to choline PET positive areas within the prostate may increase the local control rates. Due to the lack of exact PET sensitivity and prostate alpha/beta parameter, no firm conclusions can be made. Small variations may completely abrogate the clinical benefit of a SIB based on choline PET imaging

Intra-fraction motion of the prostate is not increased by patient couch shifts

Background: During a fraction of external beam radiotherapy for prostate cancer, a mismatch between target volume and dose coverage may accumulate over time due to intra-fraction motion. One way to remove the residual error is to perform a couch shift in opposite direction. In principle, such couch shifts could cause secondary displacements of the patient and prostate. Hence it is interesting to investigate if couch shifts might amplify intra-fraction motion. Findings: Intra-fraction motion of the prostate and patient couch position were simultaneously recorded during 359 fractions in 15 patients. During this time, a total of 22 couch shifts of up to 31.5 mm along different axes were recorded. Prostate position and couch position were plotted before, during and after each couch shift. There was no visible impact of couch shifts on prostate motion. The standard deviation of prostate position was calculated before, during and after each couch shift. The standard deviation did not significantly increase during couch shifts (by 3 % on average, p = 0.88) and even slightly decreased after a couch shift (by 37 % on average;p = 0.02). Conclusions: Shifts of the patient couch did not adversely affect the motion of the prostate relative to the patient couch. Hence, shifts of the patient couch may be a viable way to correct the position of the prostate relative to the dose distribution

Post-processing sets of tilted CT volumes as a method for metal artifact reduction

Background: Metal implants, surgical clips and other foreign bodies may cause `streaking' or `star' artifacts in computed tomography (CT) reconstructions, for example in the vicinity of dental restorations or hip implants. The deteriorated image quality complicates contouring and has an adverse effect on quantitative planning in external beam therapy. Methods: The potential to reduce artifacts by acquisition of tilted CT reconstructions from different angles of the same object was investigated. While each of those reconstructions still contained artifacts, they were not necessarily in the same place in each CT. By combining such CTs with complementary information, a reconstructed volume with less or even without artifacts was obtained. The most straightforward way to combine the co-registered volumes was to calculate the mean or median per voxel. The method was tested with a calibration phantom featuring a titanium insert, and with a human skull featuring multiple dental restorations made from gold and steel. The performance of the method was compared to established metal artifact reduction (MAR) algorithms. Dose reduction was tested. Results: In a visual comparison, streaking artifacts were strongly reduced and details in the vicinity of metal foreign bodies became much more visible. In case of the calibration phantom, average bias in Hounsfield units was reduced by 94% and per-voxel-errors and noise were reduced by 83%. In case of the human skull, bias was reduced by 95% and noise was reduced by 94%. The performance of the method was visually superior and quantitatively compareable to established MAR algorithms. Dose reduction was viable. Conclusions: A simple post-processing method for MAR was described which required one or more complementary scans but did not rely on any a priori information. The method was computationally inexpensive. Performance of the method was quantitatively comparable to established algorithms and visually superior in a direct comparison. Dose reduction was demonstrated, artifacts could be reduced without compromising total dose to the patient

Validation of the prognostic Heidelberg re-irradiation score in an independent mono-institutional patient cohort

Purpose: Re-irradiation has been shown to be a valid option with proven efficacy for recurrent high-grade glioma patients. Overall, up to now it is unclear which patients might be optimal candidates for a second course of irradiation. A recently reported prognostic score developed by Combs et al. may guide treatment decisions and thus, our mono-institutional cohort served as validation set to test its relevance for clinical practice. Patients and methods: The prognostic score is built upon histology, age (< 50 vs. >= 50 years) and the time between initial radiotherapy and re-irradiation (<= 12 vs. > 12 months). This score was initially introduced to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3-4 points) post-recurrence survival (PRS) after re-irradiation. Median prescribed radiation dose during re-treatment of recurrent malignant glioma was 36 Gy in 2 Gy single fractions. A substantial part of the patients was additionally treated with bevacizumab (10 mg/kg intravenously at d1 and d15 during re-irradiation). Results: 88 patients (initially 61 WHO IV, 20 WHO III, 7 WHO II) re-irradiated in a single institution were retrospectively analyzed. Median follow-up was 30 months and median PRS of the entire patient cohort 7 months. Seventy-one patients (80.7%) received bevacizumab. PRS was significantly increased in patients receiving bevacizumab (8 vs. 6 months, p = 0.027, log-rank test). KPS, age, MGMT methylation status, sex, WHO grade and the Heidelberg score showed no statistically significant influence on neither PR-PFS nor PRS. Conclusion: In our cohort which was mainly treated with bevacizumab the usefulness of the Heidelberg score could not be confirmed probably due to treatment heterogeneity; it can be speculated that larger multicentric data collections are needed to derive a more reliable score

Recurrence pattern analysis after re-irradiation with bevacizumab in recurrent malignant glioma patients

Background: The aim of the present analysis was to evaluate the recurrence pattern in patients with recurrent malignant glioma after re-irradiation in combination with bevacizumab as there is limited data on how to optimally choose dose, fractionation and delineation margins. Methods: Thirty-one patients with recurrent malignant glioma treated with re-irradiation and bevacizumab after previous chemoradiotherapy (concurrent temozolomide 75 mg/m(2)/d according to the EORTC/NCIC trial) and [F-18]FET-PET and/or MRI confirmed recurrence were retrospectively analyzed. Bevacizumab was applied twice during fractionated re-irradiation (10 mg/kg, d1 + d15, median 36 Gy, conventionally fractionated). Recurrence patterns were assessed by means of [F-18]FET-PET and/or MRI. Results: Median follow-up was 34.0 months for all patients [95%-CI, 27.7-40.3] and median post-recurrence survival 10.8 months [95%-CI, 9.2-12.4]. Concerning the recurrence patterns, 61.3% of these were located in-field (19 patients), 22.6% were marginal (7 patients) and 16.1% ex-field (5 patients). No influence on the recurrence pattern was observed according to sex, WHO grade, maintenance chemotherapy or MGMT methylation status whereas planning target volume (PTV) size had a significant influence on the recurrence pattern (p = 0.032). PTV sizes >75 ml were associated with a higher in-field recurrence rate and lower median post-recurrence progression-free survival (8.5 vs. 4.9 months, p = 0.016). Conclusions: After the administration of re-irradiation with bevacizumab the recurrence pattern seems to be mainly centrally located. The PTV size was the main predictor for a marginal/ex-field recurrence

Spinal radiosurgery - efficacy and safety after prior conventional radiotherapy

<p>Abstract</p> <p>Background</p> <p>Conventional external beam radiotherapy is a standard procedure for treatment of spinal metastases. In case of progression spinal cord tolerance limits further radiotherapy in pre-irradiated areas. Spinal stereotactic radiotherapy is a non-invasive option to re-treat pre-irradiated patients. Nevertheless, spinal radiosurgery results in relevant dose deposition within the myelon with potential toxicity. Aim of the study was to retrospectively analyse the efficacy and feasibility for salvage radiosurgery of spinal metastases.</p> <p>Methods</p> <p>During a period of 4 years (2005-2009) 70 lesions in 54 patients were treated in 60 radiosurgery sessions and retrospectively analysed. Clinical (pain, sensory and motor deficit) and radiological (CT/MRI) follow-up data were collected prospectively after radiosurgery. Pain - as main symptom - was classified by the Visual Analogue Scale (VAS) score. Every patient received single session radiosurgery after having been treated first-line with conventionally fractionated radiotherapy. Kaplan-Meier method and life tables were used to analyse freedom from local failure and overall survival.</p> <p>Results</p> <p>At a median follow-up of 14.5 months the actuarial rates of freedom from local failure at 6/12/18 months were 93%, 88% and 85%, respectively. The median radiosurgery dose was 1 × 18 Gy (range 10-28 Gy) to the median 70% isodose. The VAS score of patients with pain (median 6) dropped significantly (median 4, p = 0.002). In 6 out of 7 patients worse sensory or motor deficit after SRS was caused by local or distant failures (diagnosed by CT/MRI). One patient with metastatic renal cell carcinoma developed a progressive complete paraparesis one year after the last treatment at lumbar level L3. Due to multiple surgery and radiosurgery treatments at the lumbar region and further local progression, the exact reason remained unclear. Apart from that, no CTC grade III or higher toxicity has been observed.</p> <p>Conclusions</p> <p>By applying spinal radiosurgery relevant radiation doses can be limited to small parts of the myelon. This prevents myelopathic side effects and makes it an effective and safe treatment option for well-suited patients. Especially for previously irradiated patients with local failure or pain salvage SRS represents a valuable treatment option with high local control rates, low toxicity and significant pain reduction.</p

State-of-the-art treatment alternatives for base of skull meningiomas: complementing and controversial indications for neurosurgery, stereotactic and robotic based radiosurgery or modern fractionated radiation techniques

For skull base meningiomas, several treatment paradigms are available: Observation with serial imaging, surgical resection, stereotactic radiosurgery, radiation therapy or some combination of both. The choice depends on several factors. In this review we evaluate different treatment options, the outcome of modern irradiation techniques as well as the clinical results available, and establish recommendations for the treatment of patients with skull-base meningiomas

Hypofractionated radiotherapy for prostate cancer

In the last few years, hypofractionated external beam radiotherapy has gained increasing popularity for prostate cancer treatment, since sufficient evidence exists that prostate cancer has a low alpha/beta ratio, lower than the one of the surrounding organs at risk and thus there is a potential therapeutic benefit of using larger fractionated single doses. Apart from the therapeutic rationale there are advantages such as saving treatment time and medical resources and thereby improving patient's convenience. While older trials showed unsatisfactory results in both standard and hypofractionated arm due to insufficient radiation doses and non-standard contouring of target volumes, contemporary randomized studies have reported on encouraging results of tumor control mostly without an increase of relevant side effects, especially late toxicity. Aim of this review is to give a detailed analysis of relevant, recently published clinical trials with special focus on rationale for hypofractionation and different therapy settings