Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Vinorelbine in bladder-preserving multimodality treatment for muscle-invasive bladder cancer-a valid option for cisplatin-unfit patients?

PURPOSE: Treatment of muscle-invasive bladder cancer (MIBC) remains challenging, especially for elderly and/or comorbid patients. Patients who are unfit for or refuse surgery should receive bladder-preserving multimodality treatment (BPMT), consisting of transurethral resection of the bladder tumor (TURB) followed by combined chemoradiotherapy (CRT). We aimed to investigate the effectiveness of vinorelbine, a chemotherapeutic agent not routinely used for MIBC, in patients referred to CRT who are unfit for standard chemotherapy and would thus rely solely on radiotherapy (RT). METHODS: We retrospectively analyzed 52 consecutive patients with MIBC who received standard CRT with cisplatin (n = 14), CRT with vinorelbine (n = 26), or RT alone (n = 12). Primary endpoints were median overall survival (OS) and median cancer-specific survival (CSS). Secondary endpoints were median local control (LC), median distant control (DC), and OS, CSS, LC, and DC after 1, 2, and 3 years, respectively. RESULTS: Median OS and CSS were significantly higher for patients who received vinorelbine as compared to RT alone (OS 8 vs. 22 months, p = 0.003; CSS 11 months vs. not reached, p = 0.001). Median LC and DC did not differ significantly between groups. Vinorelbine was well tolerated with no reported side effects >grade II. CONCLUSION: Our results suggest that CRT with vinorelbine is well tolerated and superior to RT alone in terms of OS and CSS. Therefore, this treatment regime might constitute a new treatment option for patients with MIBC who are unfit for or refuse surgery or standard chemotherapy. This study encourages a randomized controlled trial to compare this new regime to current standard therapies.

Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

Optical Surface Scanning for Patient Positioning in Radiation Therapy: A Prospective Analysis of 1902 Fractions.

PURPOSE/OBJECTIVE: Reproducible patient positioning remains one of the major challenges in modern radiation therapy. Recently, optical surface scanners have been introduced into clinical practice in addition to well-established positioning systems, such as room laser and skin marks. The aim of this prospective study was to evaluate setup errors of the optical surface scanner Catalyst HD (C-RAD AB) in different anatomic regions. MATERIAL/METHODS: Between October 2016 and June 2017 a total of 1902 treatment sessions in 110 patients were evaluated. The workflow of this study included conventional setup procedures using laser-based positioning with skin marks and an additional registration of the 3-dimensional (3D) deviations detected by the Catalyst system. The deviations of the surface-based method were then compared to the corrections of cone beam computed tomography alignment which was considered as gold standard. A practical Catalyst setup error was calculated between the translational deviations of the surface scanner and the laser positioning. Two one-sided t tests for equivalence were used for statistical analysis. RESULTS: Data analysis revealed total deviations of 0.09 mm ± 2.03 mm for the lateral axis, 0.07 mm ± 3.21 mm for the longitudinal axis, and 0.44 mm ± 3.08 mm vertical axis for the Catalyst system, compared to -0.06 ± 3.54 mm lateral, 0.53 ± 3.47 mm longitudinal, and 0.19 ± 3.49 mm vertical for the laser positioning compared to cone beam computed tomography. The lowest positional deviations were found in the cranial region, and larger deviations occurred in the thoracic and abdominal sites. A statistical comparison using 2 one-sided t tests showed a general concordance of the 2 methods ( P ≤ 0.036), excluding the vertical direction of the abdominal region ( P = 0.198). CONCLUSION: The optical surface scanner Catalyst HD is a reliable and feasible patient positioning system without any additional radiation exposure. From the head to the thoracic and abdominal region, a decrease in accuracy was observed within a comparable range for Catalyst and laser-assisted positioning.

Real-time intra-fraction motion management in breast cancer radiotherapy: analysis of 2028 treatment sessions.

BACKGROUND: Intra-fraction motion represents a crucial issue in the era of precise radiotherapy in several settings, including breast irradiation. To date, only few data exist on real-time measured intra-fraction motion in breast cancer patients. Continuous surface imaging using visible light offers the capability to monitor patient movements in three-dimensional space without any additional radiation exposure. The aim of the present study was to quantify the uncertainties of possible intra-fractional motion during breast radiotherapy. MATERIAL AND METHODS: One hundred and four consecutive patients that underwent postoperative radiotherapy following breast conserving surgery or mastectomy were prospectively evaluated during 2028 treatment sessions. During each treatment session the patients' motion was continuously measured using the Catalyst™ optical surface scanner (C-RAD AB, Sweden) and compared to a reference scan acquired at the beginning of each session. The Catalyst system works through an optical surface imaging with light emitting diode (LED) light and reprojection captured by a charge coupled device (CCD) camera, which provide target position control during treatment delivery with a motion detection accuracy of 0.5 mm. For 3D surface reconstruction, the system uses a non-rigid body algorithm to calculate the distance between the surface and the isocentre and using the principle of optical triangulation. Three-dimensional deviations and relative position differences during the whole treatment fraction were calculated by the system and analyzed statistically. RESULTS: Overall, the maximum magnitude of the deviation vector showed a mean change of 1.93 mm ± 1.14 mm (standard deviation [SD]) (95%-confidence interval: [0.48-4.65] mm) and a median change of 1.63 mm during dose application (beam-on time only). Along the lateral and longitudinal axis changes were quite similar (0.18 mm ± 1.06 mm vs. 0.17 mm ± 1.32 mm), on the vertical axis the mean change was 0.68 mm ± 1.53 mm. The mean treatment session time was 154 ± 53 (SD) seconds and the mean beam-on time only was 55 ± 16 s. According to Friedman's test differences in the distributions of the three possible directions (lateral, longitudinal and vertical) were significant (p < 0.01), in post-hoc analysis there were no similarities between any two of the three directions. CONCLUSION: The optical surface imaging system is an accurate and easy tool for real-time motion management in breast cancer radiotherapy. Intra-fraction motion was reported within five millimeters in all directions. Thus, intra-fraction motion in our series of 2028 treatment sessions seems to be of minor clinical relevance in postoperative radiotherapy of breast cancer.

[Radiation therapy of locally advanced prostate cancer]. / Radiotherapie beim lokal fortgeschrittenen Prostatakarzinom.

The risk classification for localized prostate cancer is based on the groups "low", "intermediate", and "high-risk" prostate cancer. Following this established risk group definition, locally advanced prostate cancer (cT3/4N0M0) has to be classified as "high-risk" prostate cancer. Radical prostatectomy or high-dose radiotherapy, which is combined with androgen deprivation, are the only curative standard treatments for locally advanced prostate cancer. Particularly adequate radiation doses, modern radiotherapy techniques like IMRT/IGRT, as well as long-term androgen suppression are essential for an optimal treatment outcome. In combination with definitive radiotherapy, androgen deprivation therapy should be started neoadjuvant/simultaneous to radiotherapy and is recommended to be continued after radiotherapy. Previous data suggest that 2­year long-term androgen deprivation in this setting may not be inferior to 3­year long-term androgen deprivation in high-risk patients. An additional radiation therapy of the lymphatic pathways in men with cN0 locally advanced/high-risk prostate cancer is still a matter of research. Ongoing trials may define selected subgroups with a suggested benefit at its best.

[Localized intermediate- to high-risk prostate cancer]. / Lokal begrenztes Intermediate- bis High-risk-Prostatakarzinom.

BACKGROUND: National and international guidelines recommend radical prostatectomy (RP) and radiotherapy (EBRT) as standard treatment for intermediate- and high-risk prostate cancer. Survival benefit of RP in prostate cancer has been proven in prospectively randomized trials. In contrast, the benefit of EBRT as well as the direct comparison of EBRT and RP have been investigated in several retrospective analyses, but are limited by typical problems associated with retrospective studies. RESULTS: Most of the studies comparing RP with EBRT favor RP with regard to overall survival and cancer-specific survival. Especially in young patients with high-grade prostate cancer, RP seems to be superior in comparison with EBRT. These patient are at high risk of a PSA recurrence and subsequently need an additional radiotherapy. Mortality and morbidity related to these both methods are low. Main complications of RP are urinary incontinence and erectile dysfunction. In contrast, rectal sequelae, erectile dysfunction, and irritative urinary symptoms are the main cause for postinterventional morbidity in patients after EBRT.

Monte Carlo study on the sensitivity of prompt gamma imaging to proton range variations due to interfractional changes in prostate cancer patients.

Proton range verification based on prompt gamma imaging is increasingly considered in proton therapy. Tissue heterogeneity normal to the beam direction or near the end of range may considerably degrade the ability of prompt gamma imaging to detect proton range shifts. The goal of this study was to systematically investigate the accuracy and precision of range detection from prompt gamma emission profiles for various fractions for intensity modulated proton therapy of prostate cancer, using a comprehensive clinical dataset of 15 different CT scans for 5 patients. Monte Carlo simulations using Geant4 were performed to generate spot-by-spot dose distributions and prompt gamma emission profiles for prostate treatment plans. The prompt gammas were scored at their point of emission. Three CT scans of the same patient were used to evaluate the impact of inter-fractional changes on proton range. The range shifts deduced from the comparison of prompt gamma emission profiles in the planning CT and subsequent CTs were then correlated to the corresponding range shifts deduced from the dose distributions for individual pencil beams. The distributions of range shift differences between prompt gamma and dose were evaluated in terms of precision (defined as half the 95% inter-percentile range IPR) and accuracy (median). In total about 1700 individual proton pencil beams were investigated. The IPR of the relative range shift differences between the dose profiles and the prompt gamma profiles varied between ±1.4 mm and ±2.9 mm when using the more robust profile shifting analysis. The median was found smaller than 1 mm. Methods to identify and reject unreliable spots for range verification due to range mixing were derived and resulted in an average 10% spot rejection, clearly improving the prompt gamma-dose correlation. This work supports that prompt gamma imaging can offer a reliable indicator of range changes due to anatomical variations and tissue heterogeneity in scanning proton treatment of prostate cancer patients when considering prompt gamma emission profiles.

The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

PURPOSE: To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy. METHODS: A multicenter data analysis of 956 patients with pT2R1N0/Nx tumors was performed. Patients underwent radical prostatectomy between 1994 and 2009. No patients received neoadjuvant or adjuvant therapy. All prostate specimens were re-evaluated according to a well-defined protocol. The association of pathological and clinical features, in regard to BCR, was calculated using various statistical tests. RESULTS: With a mean follow-up of 48 months, BCR was found in 25.4 %. In univariate analysis, multiple parameters such as tumor volume, PSA, Gleason at positive margin were significantly associated with BCR. However, in multivariate analysis, Gleason score (GS) of the prostatectomy specimen was the only significant parameter for BCR. Median time to recurrence for GS ≤ 6 was not reached; 5-year BCR-free survival was 82 %; and they were 127 months and 72 % for GS 3+4, 56 months and 54 % for GS 4 + 3, and 27 months and 32 % for GS 8-10. The retrospective approach is a limitation of our study. CONCLUSIONS: Our study provides data on the BCR in pT2R1-PCa without adjuvant/neoadjuvant therapy and thus a rationale for an individual's risk stratification. The data support patients and physicians in estimating the individual risk and timing of BCR and thus serve to personalize the management in pT2R1-PCa.

Intra-fraction motion of the prostate is a random walk.

A random walk model for intra-fraction motion has been proposed, where at each step the prostate moves a small amount from its current position in a random direction. Online tracking data from perineal ultrasound is used to validate or reject this model against alternatives. Intra-fraction motion of a prostate was recorded by 4D ultrasound (Elekta Clarity system) during 84 fractions of external beam radiotherapy of six patients. In total, the center of the prostate was tracked for 8 h in intervals of 4 s. Maximum likelihood model parameters were fitted to the data. The null hypothesis of a random walk was tested with the Dickey-Fuller test. The null hypothesis of stationarity was tested by the Kwiatkowski-Phillips-Schmidt-Shin test. The increase of variance in prostate position over time and the variability in motility between fractions were analyzed. Intra-fraction motion of the prostate was best described as a stochastic process with an auto-correlation coefficient of ρ = 0.92  ±  0.13. The random walk hypothesis (ρ = 1) could not be rejected (p = 0.27). The static noise hypothesis (ρ = 0) was rejected (p < 0.001). The Dickey-Fuller test rejected the null hypothesis ρ = 1 in 25% to 32% of cases. On average, the Kwiatkowski-Phillips-Schmidt-Shin test rejected the null hypothesis ρ = 0 with a probability of 93% to 96%. The variance in prostate position increased linearly over time (r(2) = 0.9  ±  0.1). Variance kept increasing and did not settle at a maximum as would be expected from a stationary process. There was substantial variability in motility between fractions and patients with maximum aberrations from isocenter ranging from 0.5 mm to over 10 mm in one patient alone. In conclusion, evidence strongly suggests that intra-fraction motion of the prostate is a random walk and neither static (like inter-fraction setup errors) nor stationary (like a cyclic motion such as breathing, for example). The prostate tends to drift away from the isocenter during a fraction, and this variance increases with time, such that shorter fractions are beneficial to the problem of intra-fraction motion. As a consequence, fixed safety margins (which would over-compensate at the beginning and under-compensate at the end of a fraction) cannot optimally account for intra-fraction motion. Instead, online tracking and position correction on-the-fly should be considered as the preferred approach to counter intra-fraction motion.

Primary non-small cell lung cancer in a transplanted lung treated with stereotactic body radiation therapy. A case study.

The first case of primary lung cancer in a transplanted lung was described in 2001. Since then, only 5 cases of lung cancer in donated lung have been reported. We present one more patient with non-small cell cancer in the transplanted lung treated with stereotactic body radiation therapy. In most cases of primary lung cancer in transplanted lung, rapid progression of the cancer was reported. Occurrence of the locoregional failure in our case could be explained by factors related to the treatment protocol and also to underlying immunosuppression.

Hippocampus sparing in whole-brain radiotherapy. A review.

Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing.

Feasibility of 6-month maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck.

BACKGROUND: Close resection margins < 5 mm (CM) or extra capsular extent at the lymph nodes (ECE) impair the prognosis of patients with squamous cell cancer of the head and neck (SCCHN) scheduled for adjuvant radiochemotherapy. We conducted a multicenter phase II study to investigate toxicity and efficacy of additional cetuximab administered concomitantly and as maintenance for the duration of 6 months following adjuvant radiochemotherapy., Ppreliminary results on feasibility and acute toxicity on skin and mucosa are presented in this article. METHODS: Patients with SCCHN following CM resection or with ECE were eligible for the study. In all, 61.6 Gy (1.8/2.0/2.2 Gy, days 1-36) were administered using an integrated boost intensity-modulated radiotherapy (IMRT) technique. Cisplatin (20 mg/m(2), days 1-5 and days 29-33) and 5-fluorouracil (5-FU) as continuous infusion (600 mg/m(2), days 1-5 + days 29-33) were given concurrently. Cetuximab was started 7 days prior to radiochemotherapy at 400 mg/m(2) followed by weekly doses of 250 mg/m(2). Maintenance cetuximab began after radiochemotherapy at 500 mg/m(2) every 2 weeks for 6 months. RESULTS: Of the 55 patients (46 male, 9 female, mean age 55.6, range 29-70 years) who finished radiochemotherapy, 50 were evaluable for acute toxicity concerning grade III/IV toxicities of skin and mucosa. Grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals were documented for 46, 28, and 14 % of patients, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 5 patients due to allergic reactions after the first application. In addition, 22 % of patients discontinued cetuximab within the last 2 weeks or at the end of radiochemotherapy. Of patients embarking on maintenance treatment, 80 % were still on cetuximab at 3 months and 63 % at 5 months. Concurrent and maintenance treatment with cetuximab could be administered as scheduled in 48 % of patients. CONCLUSION: Adjuvant radiochemotherapy with concomitant and maintenance cetuximab is feasible and acute toxicities are within the expected range. Compliance within the first 3-5 months is moderate.

Toxicity and outcome of pelvic IMRT for node-positive prostate cancer.

BACKGROUND AND PURPOSE: This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0). PATIENTS AND METHODS: Pelvic IMRT to 45-50.4 Gy was applied in 39 cases either after previous surgery of involved lymph nodes (n = 18) or with a radiation boost to suspicious nodes (n = 21) with doses of 60-70 Gy, usually combined with androgen deprivation (n = 37). The prostate and seminal vesicles received 70-74 Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66-70 Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria. RESULTS: Acute radiation-related toxicity higher than grade 2 occurred in 2 patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1-2) after a median follow-up of 70 months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over 5 years. CONCLUSION: Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort.

[Image-guided radiation therapy]. / Bildgeführte Strahlentherapie.

Radiotherapy technology has improved rapidly over the past two decades. New imaging modalities, such as positron emission (computed) tomography (PET, PET-CT) and high-resolution morphological and functional magnetic resonance imaging (MRI) have been introduced into the treatment planning process. Image-guided radiation therapy (IGRT) with 3D soft tissue depiction directly imaging target and normal structures, is currently replacing patient positioning based on patient surface markers, frame-based intracranial and extracranial stereotactic treatment and partially also 2D field verification methods. On-line 3D soft tissue-based position correction unlocked the full potential of new delivery techniques, such as intensity-modulated radiotherapy, by safely delivering highly conformal dose distributions that facilitate dose escalation and hypofractionation. These strategies have already resulted in better clinical outcomes, e.g. in prostate and lung cancer and are expected to further improve radiotherapy results.

Radiation treatment parameters for re-irradiation of malignant glioma.

BACKGROUND AND PURPOSE: Most patients with malignant glioma ultimately fail locally or loco-regionally after the first treatment, with re-irradiation being a reasonable treatment option. However, only limited data are presently available allowing for a precise selection of patients suitable for re-treatment with regard to safety and efficacy. MATERIAL AND METHODS: Using the department database, 39 patients with a second course of radiation were identified. Doses to gross tumor volume (GTV), planning target volume (PTV), and relevant organs at risk (OARs; brainstem, optic chiasm, optic nerves, brain) were retrospectively analyzed and correlated to outcome parameters. Relevant treatment parameters including D(max), D(min), D(mean), and volume (ml) were obtained. Equivalent uniform dose (EUD) values were calculated for the tumor and OARs. To address the issue of radiation necrosis/leukoencephalopathy posttherapeutic MRI images were routinely examined every 3 months. RESULTS: Median follow-up was 147 days. The time interval between first and second irradiation was regularly greater than 6 months. Median EUDs to the OARs were 11.9 Gy (range 0.7-27.4 Gy) to the optic chiasm, 17.6 Gy (range 0.7-43.0 Gy) to the brainstem, 4.9/2.1 Gy (range 0.3-24.5 Gy) to the right/left optic nerve, and 29.4 Gy (range 25.2-32.5 Gy) to the brain. No correlation between treated volume and survival was observed. Cold spots and dose did not correlate with survival. Re-irradiated volumes were treated with on average lower doses if they were larger and vice versa. CONCLUSION: In general, re-irradiation is a safe and feasible re-treatment option. No relevant toxicity was observed after re-irradiation in our patient cohort during follow-up. In this regard, this analysis provides baseline data for the selection of putative patients. EUD values are derived and may serve as reference for further studies, including intensity-modulated radiotherapy (IMRT) protocols.

[Radiotherapy in prostate cancer]. / Strahlentherapie beim Prostatakarzinom.

Radiotherapy is a well-accepted treatment modality for patients with localised prostate cancer. Provided that radiotherapy is applied with a sufficient radiation dose, it is as effective as radical prostatectomy. Different radiation modalities are available (interstitial brachytherapy, external beam radiotherapy or a combination of both). Various new developments will further increase the value of radiation-based approaches. In this regard, a wider use of intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) will result in higher treatment doses with even lower toxicity rates. Combinations of radiotherapy and hormonal ablation improve local control rates in defined groups of patients. After prostatectomy with positive surgical margins, adjuvant radiotherapy improves disease-free survival rates; in cases of local relapse, salvage radiotherapy is the only potentially curative treatment approach.

[Recurrence of prostate cancer--value of salvage radiotherapy]. / Strahlentherapie beim Lokalrezidiv des Prostatakarzinoms.

Approximately 25% of patients experience recurrent disease after radical prostatectomy. Most frequently, the only evidence of a relapse is a rising PSA level without clinical evidence. Without further treatment the natural history of PSA progression results in local recurrence or distant metastasis of prostate cancer. Since a proportion of these biochemical failures relate to a local recurrence, radiotherapy offers a potential curative approach. Up to now, no randomized studies are available. Therefore any decision can only be based on prospective observation studies or retrospective data. The data available indicate that optimal results can be obtained in patients with PSA levels below 1-2 ng/ml or even lower, a documented R1 resection, and a PSA doubling time>10 months. Doses of 64-66 Gy seem to be required for adequate control. Side effects are generally well acceptable and importantly no adverse effects on urinary continence have been documented. Taken together, radiotherapy is the only treatment option with curative potential in situations where a local failure is highly likely.

Combination of celecoxib with percutaneous radiotherapy in patients with localised prostate cancer - a phase I study.

BACKGROUND: Current approaches for the improvement of bNED for prostate cancer patients treated with radiotherapy mainly focus on dose escalation. However molecularly targeted approaches may also turn out to be of value. In this regard cyclooxygenase (COX)-2 inhibitors have been shown to exert some anti-tumour activities in human prostate cancer in vivo and in vitro. Although in vitro data indicated that the combination of COX-2 inhibition and radiation was not associated with an increased toxicity, we performed a phase I trial using high dose celecoxib together with percutaneous radiation therapy. METHODS: In order to rule out any increases of more than 20% incidence for a given side effect level 22 patients were included in the trial. Celecoxib was given 400 mg twice daily with onset of the radiation treatment. Risk adapted radiation doses were between 70 and 74 Gy standard fractionation. RTOG based gastrointestinal (GI) and genitourinary (GU) acute toxicity scoring was performed weekly during radiation therapy, at six weeks after therapy and three month after completing radiation treatment. RESULTS: Generally no major increase in the level and incidence of side effects potentially caused by the combined treatment was observed. In two cases a generalised skin rash occurred which immediately resolved upon discontinuation of the drug. No grade 3 and 4 toxicity was seen. Maximal GI toxicity grade 1 and 2 was observed in 85% and 10%, respectively. In terms of GU toxicity 80% of the patients experienced a grade 1 toxicity and 10 % had grade 2 symptoms. CONCLUSION: The combination of irradiation to the prostate with concurrent high dose celecoxib was not associated with an increased level of side effects.

70 Gy or more: which dose for which prostate cancer?

INTRODUCTION: Radical prostatectomy and radiotherapy are currently accepted treatment modalities for localized prostate cancer. Regarding radiotherapy, current evidence suggests that favorable treatment outcome critically depends on adequate radiation doses. However, the exact role of dose in relation to the individual risk profile is complex. In order to evaluate available data on radiation dose response relationships, in prostate cancer, a thorough and critical literature analysis was performed. MATERIAL AND METHODS: Studies on dose response relationships from randomized trials, dose escalation trials, retrospective subgroup analyses and pooled data were identified by Pubmed and ISI web of sciences searches and were critically reviewed. RESULTS AND CONCLUSION: All available data suggest a clear dose response relationship for radiotherapy for localized prostate cancer. In low risk cases, most studies suggest that doses of 70-72 Gy are adequate. Dose escalations up to 78-80 Gy seem to be beneficial for intermediate risk patients. Due to confounding variables, the dose response curves for high-risk patients are less steep. The integration of dose escalation into a more comprehensive treatment protocol is difficult, since trials on the relative impact of either hormonal ablation or inclusion of adjuvant nodal regions on dose escalation are missing.