Practice of radiation therapy for anal cancer in Austria-a survey on behalf of the Austrian radiation oncology society gastrointestinal tumor group (ÖGRO-GIT).

PURPOSE: We conducted a patterns-of-care survey on chemoradiation for locoregionally confined anal cancer in Austria to evaluate areas of disagreement and to identify possible targets for further standardization. METHODS: An anonymous questionnaire comprising 38 questions was sent to all Austrian radiation oncology departments. Results were analyzed descriptively and compared to two international guidelines. RESULTS: The response rate was 93%. Work-up generally includes DRE, endoscopy, and cross-sectional imaging of chest/abdomen and pelvis. PET-CT is used by 38%. Screening for HIV and biopsies of suspicious lymph nodes are infrequently used. All centers perform IMRT, mainly with daily IGRT. Median doses to the primary are 54.7 Gy (T1-2) and 59.4 Gy (T3-4). Suspicious nodes receive a boost (median dose 54 Gy), while elective nodal areas are mainly treated with 45-50.4 Gy. Target delineation of elective nodal areas seems generally uniform, although disagreement exists regarding inclusion of the common iliac nodes. No agreement was found for OAR-delineation and dose constraints. Concurrent chemotherapy is mitomycin and 5­FU/capecitabine. Supportive care beyond skin care is infrequently offered. Intensive follow-up is performed for at least 5 years. Treatment of T1N0 shows considerable disagreement. CONCLUSION: We found a high rate of agreement between the centers and concordance with major guidelines. PET-CT, routine HIV testing, and biopsies of suspicious LN seem underrepresented. The largest controversy regarding target volumes concerns inclusion of the common iliac nodes. Prescribed doses are generally in line with the recommendations or higher. OAR delineation, dose constraints, supportive care, and treatment of early anal cancer represent areas for further standardization.

THz generation by optical rectification of intense near-infrared pulses in organic crystal BNA.

Generation of terahertz radiation by optical rectification of intense near-infrared laser pulses in N-benzyl-2-methyl-4-nitroaniline (BNA) is investigated in detail by carrying out a complete characterization of the terahertz radiation. We studied the scaling of THz yield with pump pulse repetition rate and fluence which enabled us to predict the optimal operating conditions for BNA crystals at room temperature for 800 nm pump wavelength. Furthermore, recording the transmitted laser spectrum allowed us to calculate the nonlinear refractive index of BNA at 800 nm.

Recent advances in (chemo-)radiation therapy for rectal cancer: a comprehensive review.

The role of radiation therapy in the treatment of (colo)-rectal cancer has changed dramatically over the past decades. Introduced with the aim of reducing the high rates of local recurrences after conventional surgery, major developments in imaging, surgical technique, systemic therapy and radiation delivery have now created a much more complex environment leading to a more personalized approach. Functional aspects including reduction of acute or late treatment-related side effects, sphincter or even organ-preservation and the unsolved problem of still high distant failure rates have become more important while local recurrence rates can be kept low in the vast majority of patients. This review summarizes the actual role of radiation therapy in different subgroups of patients with rectal cancer, including the current standard approach in different subgroups as well as recent developments focusing on neoadjuvant treatment intensification and/or non-operative treatment approaches aiming at organ-preservation.

Evaluation of daily patient positioning for radiotherapy with a commercial 3D surface-imaging system (Catalyst™).

BACKGROUND: To report our initial clinical experience with the novel surface imaging system Catalyst™ (C-RAD AB, Sweden) in connection with an Elekta Synergy linear accelerator for daily patient positioning in patients undergoing radiation therapy. METHODS: We retrospectively analyzed the patient positioning of 154 fractions in 25 patients applied to thoracic, abdominal, and pelvic body regions. Patients were routinely positioned based on skin marks, shifted to the calculated isocenter position and treated after correction via cone beam CT which served as gold standard. Prior to CBCT an additional surface scan by the Catalyst™ system was performed and compared to a reference surface image cropped from the planning CT to obtain shift vectors for an optimal surface match. These shift vectors were subtracted from the vectors obtained by CBCT correction to assess the theoretical setup error that would have occurred if the patients had been positioned using solely the Catalyst™ system. The mean theoretical set up-error and its standard deviation were calculated for all measured fractions and the results were compared to patient positioning based on skin marks only. RESULTS: Integration of the surface scan into the clinical workflow did not result in a significant time delay. Regarding the entire group, the mean setup error by using skin marks only was 0.0 ± 2.1 mm in lateral, -0.4 ± 2.4 mm in longitudinal, and 1.1 ± 2.6 mm vertical direction. The mean theoretical setup error that would have occurred using solely the Catalyst™ was -0.1 ± 2.1 mm laterally, -1.8 ± 5.4 mm longitudinally, and 1.4 ± 3.2 mm vertically. No significant difference was found in any direction. For thoracic targets the mean setup error based on the Catalyst™ was 0.6 ± 2.6 mm laterally, -5.0 ± 7.9 mm longitudinally, and 0.5 ± 3.2 mm vertically. For abdominal targets, the mean setup error was 0.3 ± 2.2 mm laterally, 2.6 ± 1.8 mm longitudinally, and 2.1 ± 5.5 mm vertically. For pelvic targets, the setup error was -0.9 ± 1.5 mm laterally, -1.7 ± 2.8 mm longitudinally, and 1.6 ± 2.2 mm vertically. A significant difference between Catalyst™ and skin mark based positioning was only observed in longitudinal direction of pelvic targets. CONCLUSION: Optical surface scanning using Catalyst™ seems potentially useful for daily positioning at least to complement usual imaging modalities in most patients with acceptable accuracy, although a significant improvement compared to skin mark based positioning could not be derived from the evaluated data. However, this effect seemed to be rather caused by the unexpected high accuracy of skin mark based positioning than by inaccuracy using the Catalyst™. Further on, surface registration in longitudinal axis seemed less reliable especially in pelvic localization. Therefore further prospective evaluation based on strictly predefined protocols is needed to determine the optimal scanning approaches and parameters.

Long term results of postoperative Intensity-Modulated Radiation Therapy (IMRT) in the treatment of Squamous Cell Carcinoma (SCC) located in the oropharynx or oral cavity.

BACKGROUND: To report our long-term results with postoperative intensity-modulated radiation therapy (IMRT) in patients suffering from squamous-cell carcinoma (SCC) of the oral cavity or oropharynx. METHODS: Seventy five patients were retrospectively analyzed. Median age was 58 years and 84 % were male. 76 % of the primaries were located in the oropharynx. Surgery resulted in negative margins (R0) in 64 % of the patients while 36 % suffered from positive margins (R1). Postoperative stages were as follows: stage 1:4 %, stage 2:9 %, stage 3:17 %, stage 4a:69 % with positive nodes in 84 %. Perineural invasion (Pn+) and extracapsular extension (ECE) were present in 7 % and 29 %, respectively. All patients received IMRT using the step-and-shoot approach with a simultaneously integrated boost (SIB) in 84 %. Concurrent systemic therapy was applied to 53 patients, mainly cisplatin weekly. RESULTS: Median follow-up was 55 months (5-150). 13 patients showed locoregional failures (4 isolated local, 4 isolated neck, 5 combined) transferring into 5-year-LRC rates of 85 %. Number of positive lymph nodes (n > 2) and presence of ECE were significantly associated with decreased LRC in univariate analysis, but only the number of nodes remained significant in multivariate analysis. Overall treatment failures occurred in 20 patients (9 locoregional only, 7 distant only, 4 combined), transferring into 3-and 5-year-FFTF rates of 77 % and 75 %, respectively. The 3-and 5-year-OS rates were 80 % and 72 %, respectively. High clinical stage, high N stage, number of positive nodes (n > 2), ECE and Pn1 were significantly associated with worse FFTF and OS in univariate analysis, but only number of nodes remained significant for FFTF in multivariate analysis. Maximum acute toxicity was grade 3 in 64 % and grade 4 in 1 %, mainly hematological or mucositis/dysphagia. Maximum late toxicity was grade 3 in 23 % of the patients, mainly long-term tube feeding dependency. CONCLUSION: Postoperative IMRT achieved excellent LRC and good OS with acceptable acute and low late toxicity rates. The number of positive nodes (n > 2) was a strong prognostic factor for all endpoints in univariate and the only significant factor for LRC and FFTF in multivariate analysis. Patients with feeding tubes due to postoperative complications had an increased risk for long-term feeding tube dependency.

Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo.

BACKGROUND: Inhibition of pyruvate dehydrogenase kinase (PDK) by dichloroacetate (DCA) can shift tumor cell metabolism from anaerobic glycolysis to glucose oxidation, with activation of mitochondrial activity and chemotherapy-dependent apoptosis. In radiotherapy, DCA could thus potentially enhance the frequently moderate apoptotic response of cancer cells that results from their mitochondrial dysfunction. The aim of this study was to investigate tumor-specific radiosensitization by DCA in vitro and in a human tumor xenograft mouse model in vivo. MATERIALS AND METHODS: The interaction of DCA with photon beam radiation was investigated in the human tumor cell lines WIDR (colorectal) and LN18 (glioma), as well as in the human normal tissue cell lines HUVEC (endothelial), MRC5 (lung fibroblasts) and TK6 (lymphoblastoid). Apoptosis induction in vitro was assessed by DAPI staining and sub-G1 flow cytometry; cell survival was quantified by clonogenic assay. The effect of DCA in vivo was investigated in WIDR xenograft tumors growing subcutaneously on BALB/c-nu/nu mice, with and without fractionated irradiation. Histological examination included TUNEL and Ki67 staining for apoptosis and proliferation, respectively, as well as pinomidazole labeling for hypoxia. RESULTS: DCA treatment led to decreased clonogenic survival and increased specific apoptosis rates in tumor cell lines (LN18, WIDR) but not in normal tissue cells (HUVEC, MRC5, TK6). However, this significant tumor-specific radiosensitization by DCA in vitro was not reflected by the situation in vivo: The growth suppression of WIDR xenograft tumors after irradiation was reduced upon additional DCA treatment (reflected by Ki67 expression levels), although early tumor cell apoptosis rates were significantly increased by DCA. This apparently paradoxical effect was accompanied by a marked DCA-dependent induction of hypoxia in tumor-tissue. CONCLUSION: DCA induced tumor-specific radiosensitization in vitro but not in vivo. DCA also induced development of hypoxia in tumor tissue in vivo. Further investigations relating to the interplay between tumor cell metabolism and tumor microenvironment are necessary to explain the limited success of metabolic targeting in radiotherapy.

SU-E-J-147: Dosimetric Consequences of Intrafraction Prostate Motion: Comparison Between Phantom Measurements and Three Different Calculation Methods.

PURPOSE: Evaluation of different calculation methods for dose modification due to intrafraction prostate motion using film measurements as ground truth. METHODS: We acquired intrafraction motion data with the Calypso tumor tracking system by Varian Medical Systems Inc for 4 prostate IMRT patients treated with 35 fractions each. These motion data were transferred to a phantom platform which reproduces the observed motion and has a 20 cm diameter cylindrical solid water phantom mounted. For each patient all fractions were irradiated on one radiochromic MD-V2-55 film placed in the isocentric transversal slice of this phantom. These films serve as ground truth for three calculation Methods: 1) Recalculation of the plan with shifted target point for every segment with the segment's mean Calypso position. 2)+3) Convolution of the static dose distribution with a probability density function of the observed positions. For 2) only Calypso positions with activated beam on signal were used whereas for 3) all Calypso positions between the first and the last beam on signal for all fractions were employed. The comparisons between films and calculated dose distributions were made with the verification software VeriSoft 3.2 (PTW, Freiburg, Germany) where an 8×8 cm̂2 ROI around the isocenter was selected for gamma evaluation. RESULTS: The segment shifted plans reach 3%/3mm gamma values above 90% against the films for all four patients. For both convolution methods three values are above 90%, only for the patient with the largest intrafraction motion they decrease to 89%. CONCLUSIONS: Shifting of the target point for every segment is well suited to estimate the dosimetric consequences of intrafraction prostate motion. This may facilitate the evaluation of different margin sizes or dose prescribing recipes under different motion conditions. If such a lengthy calculation is not possible, a convolution with motion data can be used for acceptable results, too. Our work was partially supported by Siemens Healthcare and Varian Medical Systems Inc.

Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases.

BACKGROUND: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). PATIENTS AND METHODS: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo)radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied. RESULTS: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC. CONCLUSIONS: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.

Indolent stage IE non-Hodgkin's lymphoma of the orbit: results after primary radiotherapy.

AIMS: Primary non-Hodgkin's lymphoma (NHL) of the orbit is uncommon, representing approximately 8% of extranodal NHLs. Twenty-two patients with indolent stage IE NHL were reviewed retrospectively to analyze the outcome and late effects of primary local radiotherapy. MATERIALS AND METHODS: The median age at first diagnosis was 63.5 years (range 24-82 years). Extranodal mucosa-associated lymphoid tissue lymphoma (n = 15) was the most common histological subtype of NHL, followed by follicular (n = 6) and lymphoplasmacytic lymphoma (n = 1). Radiotherapy was performed using a linear accelerator. The median radiation dose was 40 Gy (range 30-46 Gy). None of the patients received chemotherapy before irradiation. The follow-up period was 62 months (range 8-136 months). RESULTS: A complete response was achieved in all patients. The 5-year local control rate was 100%. Distant relapse occurred in 2 patients, resulting in a 5-year distant relapse-free survival rate of 88%. The 5-year overall survival rate was 89%; there were no lymphoma-related deaths. No serious acute complications (grade 3/4) were observed. Grade 1/2 late effects were documented in 44% of patients. Grade 3 complications (cataract: 2, dryness: 2) were observed in 4 patients (18%). CONCLUSIONS: Indolent early stage orbital NHL can be controlled with local radiotherapy. Morbidity is low. Regular follow-up examinations are necessary to detect rare cases of distant relapse.

[Indications for stereotaxic neurosurgery of patients with multiple sclerosis (author's transl)]. / Indikationen zur stereotaktischen Operation bei Patienten mit multipler Sklerose

The long-term results of 12 stereotaxic operations on 11 multiple sclerosis patients with incapacitating intention tremor were evaluated and compared with the experiences of other authors. The selection of the patients, the criteria applied for the success and the length of the follow-up period influenced the reported results. Considering not only the relief of the intention tremor but the overall performance after the operation only a certain group of patients seemed to profit by neurosurgical treatment. Applying this criterion of overall performance and evaluation only 3 out of 11 patients in our series had real benefit from the operation. The reasons for this small number of good or moderate results are given with brief discussion of some of the cases. History, course and fatal outcome of one patient are presented in detail together with the neuropathological findings. According to the literature and the limited number of our own cases the following indications for stereotaxic operations on MS patients can be established: 1. Tremor and hyperkinetic movements should be the dominant features of the symptomatology. 2. The overall performance should be essentially improved by the operation. 3. Patients in the terminal stage of the disease gain little from the procedure, whereas patients with longstanding more benign course are the best candidates.