Evaluation of 4-Hz log files and secondary Monte Carlo dose calculation as patient-specific quality assurance for VMAT prostate plans.

PURPOSE: In this study, 4-Hz log files were evaluated with an independent secondary Monte Carlo dose calculation algorithm to reduce the workload for patient-specific quality assurance (QA) in clinical routine. MATERIALS AND METHODS: A total of 30 randomly selected clinical prostate VMAT plans were included. The used treatment planning system (TPS) was Monaco (Elekta, Crawley), and the secondary dose calculation software was SciMoCa (Scientific-RT, Munich). Monaco and SciMoCa work with a Monte Carlo algorithm. A plausibility check of Monaco and SciMoCa was performed using an ionization chamber in the BodyPhantom (BP). First, the original Monaco RT plans were verified with SciMoCa (pretreatment QA). Second, the corresponding 4-Hz log files were converted into RT log file plans and sent to SciMoCa as on-treatment QA. MLC shift errors were introduced for one prostate plan to determine the sensitivity of on-treatment QA. For pretreatment and on-treatment QA, a gamma analysis (2%/1mm/20%) was performed and dosimetric values of PTV and OARs were ascertained in SciMoCa. RESULTS: Plausibility check of TPS Monaco vs. BP measurement and SciMoCa vs. BP measurement showed valid accuracy for clinical VMAT QA. Using SciMoCa, there was no significant difference in PTV Dmean between RT plan and RT log file plan. Between pretreatment and on-treatment QA, PTV metrics, femur right and left showed no significant dosimetric differences as opposed to OARs rectum and bladder. The overall gamma passing rate (GPR) ranged from 96.10% to 100% in pretreatment QA and from 93.50% to 99.80% in on-treatment QA. MLC shift errors were identified for deviations larger than -0.50 mm and +0.75 mm using overall gamma criterion and PTV Dmean. CONCLUSION: SciMoCa calculations of Monaco RT plans and RT log file plans are in excellent agreement to each other. Therefore, 4-Hz log files and SciMoCa can replace labor-intensive phantom-based measurements as patient-specific QA.

Error sensitivity of a log file analysis tool compared with a helical diode array dosimeter for VMAT delivery quality assurance.

PURPOSE: Integrating log file analysis with LINACWatch® (LW) into clinical routine as part of the quality assurance (QA) process could be a time-saving strategy that does not compromise on quality. The purpose is to determine the error sensitivity of log file analysis using LINACWatch® compared with a measurement device (ArcCHECK®, AC) for VMAT delivery QA. MATERIALS AND METHODS: Multi-leaf collimator (MLC) errors, collimator angle errors, MLC shift errors and dose errors were inserted to analyze error detection sensitivity. A total of 36 plans were manipulated with different magnitudes of errors. The gamma index protocols for AC were 3%/3 mm/Global and 2%/2 mm/Global, as well as 2%/2 mm/Global, and 1.5%/1.5 mm/Global for LW. Additionally, deviations of the collimator and monitor units between TPS and log file were calculated as RMS values. A 0.125 cm3 ionization chamber was used to independently examine the effect on dose. RESULTS: The sensitivity for AC was 20.4% and 49.6% vs 63.0% and 86.5% for LW, depending on the analysis protocol. For MLC opening and closing errors, the detection rate was 19.0% and 47.7% for AC vs 50.5% and 75.5% for LW. For MLC shift errors, it was 29.6% and 66.7% for AC vs 66.7% and 83.3% for LW. AC could detect 25.0% and 44.4% of all collimator errors. Log file analysis detected all collimator errors using 1° detection level. 13.2% and 42.4% of all dose errors were detected by AC vs 59.0% and 92.4% for LW using gamma analysis. Using RMS value, all dose errors were detected by LW (1% detection level). CONCLUSION: The results of this study clearly show that log file analysis is an excellent complement to phantom-based delivery QA of VMAT plans. We recommend a 1.5%/1.5 mm/Global criteria for log file-based gamma calculations. Log file analysis was implemented successfully in our clinical routine for VMAT delivery QA.

Long-term surveillance of locally advanced rectal cancer patients with neoadjuvant chemoradiation and aggressive surgical treatment of recurrent disease: a consecutive single-centre experience.

PURPOSE: The aim of this study was to analyse the long-term outcome of rectal cancer patients who submitted to preoperative chemoradiation with consecutive intensive follow-up and aggressive surgical treatment of recurrent disease. METHODS: Patients with locally advanced (cT3-4 Nx M0-1) mid/low rectal cancer were treated at a tertiary university hospital with preoperative long-course chemoradiation followed by resection (according to a prospective study protocol). After resection, all patients were urged to participate in a standardised, risk-independent intensive follow-up program. All curatively treated patients (n = 153, 96 %) were included in our long-term analysis with respect to curative re-resection of recurrent disease. RESULTS: Of 153 patients, 143 (93 %) participated in our follow-up program: 63 % were surveyed longer than 5 years after primary therapy (mean follow-up 75 months, 95 % CI 67.8-82.2). Fifty-five (36 %) patients developed cancer recurrence (mean 27.8 months, 95 % CI 20.6-34.9, range 3-108), giving a disease-free survival rate of 68.5 and 60.7 % at 5 and 10 years; 21 (38 %) patients were re-resected curatively and 58 (38 %) patients died during the observation period, giving an overall survival rate of 70.8 and 57.5 % at 5 and 10 years. Multivariate analysis found tumour differentiation (P < 0.01), operative procedure (P < 0.05) and downstaging (P < 0.01) to be independent variables influencing overall survival. CONCLUSIONS: The combination of multimodal therapy and aggressive surgical treatment of metastases including repeated re-resections in curative intention is relevant in order to chronify the disease. Thus, both intensive and extended follow-up beyond 5 years appear to be mandatory.

Pretreatment evaluation of microcirculation by dynamic contrast-enhanced magnetic resonance imaging predicts survival in primary rectal cancer patients.

PURPOSE: To investigate the prognostic value of the perfusion index (PI), a microcirculatory parameter estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), which integrates information on both flow and permeability, to predict overall survival and disease-free survival in patients with primary rectal cancer. METHODS AND MATERIALS: A total of 83 patients with stage cT3 rectal cancer requiring neoadjuvant chemoradiation were investigated with DCE-MRI before start of therapy. Contrast-enhanced dynamic T1 mapping was obtained, and a simple data analysis strategy based on the calculation of the maximum slope of the tissue concentration-time curve divided by the maximum of the arterial input function was used as a measure of tumor microcirculation (PI), which integrates information on both flow and permeability. RESULTS: In 39 patients (47.0%), T downstaging (ypT0-2) was observed. During a mean (±SD) follow-up period of 71 ± 29 months, 58 patients (69.9%) survived, and disease-free survival was achieved in 45 patients (54.2%). The mean PI (PImean) averaged over the group of nonresponders was significantly higher than for responders. Additionally, higher PImean in age- and gender-adjusted analyses was strongly predictive of therapy nonresponse. Most importantly, PImean strongly and significantly predicted disease-free survival (unadjusted hazard ratio [HR], 1.85 [ 95% confidence interval, 1.35-2.54; P<.001)]; HR adjusted for age and sex, 1.81 [1.30-2.51]; P<.001) as well as overall survival (unadjusted HR 1.42 [1.02-1.99], P=.040; HR adjusted for age and sex, 1.43 [1.03-1.98]; P=.034). CONCLUSIONS: This analysis identifies PImean as a novel biomarker that is predictive for therapy response, disease-free survival, and overall survival in patients with primary locally advanced rectal cancer.

Overall survival and extent of surgery in adult versus elderly glioblastoma patients: A population based retrospective study.

INTRODUCTION: The purpose of this retrospective population based study was to investigate the effect of the extent of surgery on overall survival in young versus adult glioblastoma patients in Vorarlberg/Austria during the last 4 years. METHODS: Forty-eight patients (median age 62.5 years, ranging from 25-82 years, 19 female and 29 male) with histologically proven glioblastoma received surgery (16 biopsies, 18 partial and 14 complete resections) and postoperative chemo-irradiation with concomitant and adjuvant temozolomide. The median follow up of the patient population was 11.7 months (ranging from 3 to 36 months). Postoperative temporary morbidity was found in 5 out of 48 (10.4%) patients, and no mortality or permanent morbidity occurred. One infection led to revision surgery. FINDINGS: Altogether, the 12/24 months overall survival was 54/20.2% with a median survival of 13.7 months. In younger patients (<65 yrs, median 57.5 yrs, 28 patients), the 12/24 months overall survival was 68.4/34.3% with 16.9 months median survival, in the elderly patients (>65 yrs, median 73 yrs, 20 patients) the 12/24 months overall survival was 28.8/5.8%, with 7.7 months median survival (Log-rank, p = 0.0005). Extent of surgery influenced overall survival of the adult group nearly significantly (biopsy versus complete resection: p = 0.06), but did not affect overall survival of the elderly (p = 0.5). CONCLUSIONS: Overall survival of elderly glioblastoma patients treated with surgery and chemo-irradiation with concomitant and adjuvant temozolomide is significantly reduced compared to the younger patients. In addition, in the elderly the extent of surgery did not influence the prognosis in our population.

Preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with newly diagnosed, primary operable, cT3NxM0, low rectal cancer: a phase II study.

PURPOSE: In patients with locally advanced rectal cancer (LARC), preoperative chemoradiation is known to improve local control, and down-staging of the tumor serves as a surrogate for survival. Intensification of the systemic therapy may lead to higher downstaging rates and, thus, enhance survival. This phase II study investigated the efficacy and safety of preoperative capecitabine and oxaliplatin in combination with radiotherapy. PATIENTS AND METHODS: Patients with LARC of the mid and lower rectum, T3NxM0 staged by MRI received radiotherapy (total dose 45 Gy) in combination with oral capecitabine (825 mg/m² twice a day on radiotherapy days; weeks 1-4) and oxaliplatin 50 mg/m² intravenously (days 1, 8, 15, and 22). Efficacy was evaluated as rate of tumor down-categorization at the T level. RESULTS: A total of 59 patients were enrolled (19 women, 40 men; median age of 61 years) and all were evaluable for efficacy and toxicity. Down-categorization at the T level was observed in 53% with pathological complete response in 6 patients (10%). Actual total radiotherapy, oxaliplatin and capecitabine doses received were 97%, 90%, and 93% of the protocol-specified preplanned doses, respectively. Grade 3/4 toxicity was observed in 15 patients (25%). The most frequent was diarrhea (12%). CONCLUSIONS: Preoperative chemoradiation with capecitabine and oxaliplatin is feasible in patients with MRI-proven cT3 LARC. The only clinically relevant toxicity was diarrhea. Overall, efficacy of the multimodality treatment was good, but not markedly exceeding that of 5-FU- or capecitabine-based chemoradiation approaches.

Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology.

PURPOSE: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. METHODS AND MATERIALS: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84µg/L were randomized before RT either to receive 500 µg of selenium (in the form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 µg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. RESULTS: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. CONCLUSIONS: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.

Circulating cell-free DNA in plasma of locally advanced rectal cancer patients undergoing preoperative chemoradiation: a potential diagnostic tool for therapy monitoring.

Circulating cell-free DNA opens up an interesting field for therapy monitoring, in particular during multimodal therapy protocols. The objective of this proof of principle study was to evaluate whether the amount of circulating plasma DNA has the potential to serve as a marker for therapy monitoring during the treatment course of locally advanced rectal cancer patients. We especially focused on kinetics of circulating DNA to assess whether variances in kinetics have the potential to discriminate between therapy responders and nonresponders. The amount of circulating DNA in plasma of rectal cancer patients undergoing preoperative chemoradiation was determined using real-time PCR before chemoradiation, after the end of chemoradiation and at the end of treatment. The study population was divided into responders (ypT0-T2 stage) and nonresponders (ypT3-T4 stage). Both groups showed comparable median plasma DNA values before and after the end of chemoradiation. At the end of treatment responders showed a further decrease in circulating DNA, whereas in nonresponders the circulating DNA manifestly increased (P = 0.006). This study demonstrates that circulating DNA in plasma of rectal cancer patients undergoing preoperative chemoradiation might serve as a surrogate marker to discriminate between responders and nonresponders. Therefore, we hypothesize that quantification of plasma DNA could be of use as an easily accessible tool for therapy monitoring in these patients.

Chemotherapy in gastric cancer.

Although treatment of gastric cancer has improved substantially during the last decade there is still controversy about the best way and sequence of treatment. An early interdisciplinary treatment plan is mandatory before therapy is started. In this multidisciplinary expert statement we review current literature and give treatment recommendations for neoadjuvant, adjuvant, and palliative treatment of gastric cancer.

Anatomical considerations in TNM staging and therapeutical procedures for low rectal cancer.

BACKGROUND: Separation of the mesoderm-derived muscular structures and the endoderm-derived structures of the hindgut and reclassification of their involvement based on their embryological origin may be of clinical importance in providing anatomical support for a more standardized perineal resection during abdominoperineal resection. The aim of this study was to utilize magnetic resonance images and histological studies of fetal and neonatal specimens to redefine the T3/T4 distinction by reassessment of the intersphincteric plane and the pelvic diaphragm as they pertain to cancer infiltration and as part of the embryological development of the pelvic floor muscles and their connective tissue compartments. MATERIALS AND METHODS: Pelvic floor anatomy was studied in seven newborn children and 120 embryos and fetuses. Anatomical data were completed by magnetic resonance imaging in 82 patients with T3 and T4 rectal cancers (64 T3, 18 T4; 35 women and 47 men) undergoing neoadjuvant chemoradiation for locally advanced (T3 or T4) rectal cancers. RESULTS: Clear demarcation between mesodermal and endodermal structures of the pelvic floor, which is equally evident in plastinated sections and magnetic resonance images, is already visible in early fetal stages. There is a constitutive overlap between the endoderm- and the ectoderm-derived components of the pelvic floor. CONCLUSION: Our data suggest that the current classification of rectal cancer staging is confusing, where the routinely used TNM classification system unnecessarily differentiates between embryologically identical muscular structures. Tumor spread along the musculature of the hindgut beyond the dentate line could possibly explain the occasional involvement of lymph nodes outside the conventional mesorectum.

Results and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy.

UNLABELLED: In locally advanced carcinoma of the exocrine pancreas combined radiochemotherapy has been established as a standard treatment. MATERIALS AND METHODS: Two different treatment schemes have been consecutively used. Between 1/1994 and 12/2001, a total of 110 patients with locally advanced adenocarcinoma of the pancreas were treated with hyperfractionated accelerated radiotherapy to a total dose of 44.8 Gy combined with 5-fluorouracil (5-FU) (600 mg/m2) and folinic acid (FA) (300 mg/m2) injection. Chemotherapy was repeated monthly in non-progressive disease. From 1/2002 to 11/2003, in another 15 consecutive patients, chemotherapy was changed to gemcitabine (Gem) (300 mg/m2) and cisplatinum (Cis) (30 mg/m2), followed by gemcitabine (1000 mg/m2) every 2 weeks in non-progressive patients. RESULTS: Median survival in the 5-FU/FA group was 10.3 months with a 1-year survival of 46.6% and a 2-year survival of 20.1%. Median time to progression was 8.6 months. Treatment was well tolerated with nausea/vomiting grade I/II in 58.2%, grade III/IV in 14.5%, diarrhea grade I/II in 27.3%, leucopenia/thrombopenia grade I/II in 21.8%, grade III/IV in 7.2%, and mucositis grade III/IV in 7.2%. In the Gem/Cis group, median survival was 13.8 months with a 1-year survival of 54.9% and a 2-year survival of 24.4%. The toxicity data also revealed comparable feasibility: nausea/vomiting grade I/II in 46.7%, grade III/IV in 20%, diarrhea grade I/II in 20%, leucopenia/thrombopenia grade I/II in 26. 7%, and grade III/IV in 13.3%. CONCLUSION: Radiochemotherapy in locally advanced pancreatic cancer is an effective and well-tolerated treatment. The long-term efficacy concerning survival is limited. The integration of predictive factors and new chemotherapeutic agents like gemcitabine in the multimodality treatment may give a more promising perspective. Because of the narrow therapeutic index of gemcitabine-based radiochemotherapy schemes, a feasible combination of radiotherapy treatment volume and gemcitabine dose must be found.

Irradiation causes biphasic neutrophilic granulocyte phagocytic function.

BACKGROUND AND PURPOSE: The anti-inflammatory effect of low-dose radiotherapy is clinically well described. Nevertheless, until now neither the optimal dose nor the background of tissue reactions have been defined. The current study examines the influence of low radiation doses on neutrophilic granulocyte function, which could be helpful in finding the optimal dose for either stimulation or suppression of anti-inflammatory activity. MATERIAL AND METHODS: Lymphoprep density gradient-purified neutrophilic granulocytes of three voluntary, healthy donors were used for all experiments. Granulocytes were incubated 48 h in RPMI 1640 and irradiated with single doses of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, and 12 Gy using a (137)Cs IBL 437L irradiator. Their function was assessed by measuring granulocytic release of reactive oxygen species (ROS) with luminol-enhanced chemiluminescence after stimulation with phorbol myristate acetate (PMA). RESULTS: Relative changes of ROS release (ROS release before stimulation was set to 100%) increased after stimulation with PMA (mean +/- standard deviation [SD]): 0 Gy: 147.6% +/- 60%; 0.5 Gy: 153.6% +/- 70%; 1.0 Gy: 164.9% +/- 63%; 1.5 Gy: 177.8% +/- 66%; 2.0 Gy: 162.5% +/- 57%; 2.5 Gy: 156.2% +/- 60%; 3.0 Gy: 159.2% +/- 60%; 3.5 Gy: 126.9% +/- 55%; 4.0 Gy: 137.9% +/- 71%; 6.0 Gy: 148.3% +/- 65%; 12.0 Gy: 156.1% +/- 52%. The relative ROS release showed a significant increase at 1.5 Gy (p < 0.001) after PMA stimulation and a significant decrease of ROS release at 3.5 Gy (p < 0.005) and less markedly at 4.0 Gy (p < 0.05). 6.0 and 12.0 Gy showed a significant (p < 0.05) increase again. CONCLUSION: This ex vivo in vitro study on native human neutrophilic granulocytes shows an increase at 1.5 Gy and a significant decrease of granulocyte function at 3.5 and 4.0 Gy, as it was described for different other phenomena in low-dose radiotherapy. These results may provide a further explanation for the local anti-inflammatory effect of low-dose ionizing irradiation.

Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue.

PURPOSE: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. MATERIALS AND METHODS: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. RESULTS: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g +/- 2.45 versus 3.56 ml/min/100 g +/- 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. CONCLUSION: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated.

Providing psychosocial support for breast cancer patients based on screening for distress within a consultation-liaison service.

In a consecutive sample of 100 breast cancer patients undergoing radiotherapy, cancer-related distress was assessed with the Hospital Anxiety and Depression Scale and patients' interest in and acceptance of psychosocial support with the Questionnaire for Psychosocial Support and the European Consultation Liaison Workgroup documentation form. 31% of the patients suffered moderate to severe anxiety and/or depression and 42% expressed interest in supportive counselling. The wish for psychosocial support did not correlate with distress (moderate or severe anxiety and/or depression; Kappa = 0.06; P = 0.560). Patients with elevated levels of distress and/or those expressing a wish for psychosocial support were offered counselling by a psychotherapist and a social worker within the framework of a liaison service; 69% of the 58 patients offered such support accepted it. We conclude that screening instruments are helpful in identifying and consequently offering support to patients in need of counselling.

Predictive value of carbohydrate antigen 19-9 in pancreatic cancer treated with radiochemotherapy.

PURPOSE: To determine the predictive value of carbohydrate antigen (CA) 19-9 in pancreatic cancer treated with radiochemotherapy. METHODS AND MATERIALS: Ninety-five patients with locally advanced unresectable adenocarcinoma of the pancreas were treated with hyperfractionated accelerated radiotherapy to a total dose of 44.8 Gy combined with 5-fluorouracil and folinic acid. CA 19-9 was measured before therapy, each week during therapy, and every 4 weeks during the follow-up period. RESULTS: The median CA 19-9 before treatment was 420 U/mL; in the responder group it was 117 U/mL, and in the nonresponder group it was 806 U/mL. Patients with a pretreatment CA 19-9 less than the median had not only a significantly better tumor response (45.8%) but also a better survival prognosis (median survival 12.3 months) than those with a level higher than the median (tumor response 12.8%; median survival 7.1 months). The posttreatment median CA 19-9 for all patients also exhibited prognostic significance. The median survival of patients with a CA 19-9 level lower than the posttreatment median of 293 U/mL was 13.5 months, compared with 7.2 months for those with a CA 19-9 level greater than the median. To detect recurrent disease during follow-up, the sensitivity of CA 19-9 was 100% and the specificity 88%. CONCLUSION: Our results indicate that CA 19-9 is of predictive value for prognosis, response, and detecting recurrence of pancreatic cancer in patients undergoing combined radiochemotherapy. Therefore, we recommend the routine implementation of CA 19-9 observation during the clinical course of treatment for patients with pancreatic cancer undergoing radiochemotherapy.

Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma.

PURPOSE: The aim of our study was to correlate perfusion indices and apparent diffusion coefficients with therapy outcome after chemoradiation. METHODS AND MATERIALS: In 34 patients with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation, pretherapeutic perfusion indices and apparent diffusion coefficients were obtained by dynamic or diffusion-weighted magnetic resonance imaging. Therapy response was defined if the pathologic observation revealed no invasion into the perirectal fat after chemoradiation. RESULTS: In 18 patients, a response and in 16, no response was observed. Statistically significant differences were found for the mean perfusion index (p < 0.001; 7.5 +/- 1.5 mL/min/100 g vs. 10.7 +/- 2.7 mL/min/100 g) and for the intratumoral cumulative fraction of pixels with perfusion-indices > 12 mL/min/100 g (p < 0.001, 3.7 +/- 4.0% vs. 24.7 +/- 17.9%). A three-way ANOVA resulted in significant effects for therapy responder/nonresponder (p < 0.001) and for apparent diffusion coefficient and the individual patients. CONCLUSION: Perfusion indices and apparent diffusion coefficients inside the tumor region seem to be of predictive value for therapy outcome of preoperative therapy in patients with primary rectal carcinoma. Higher parameter levels in the nonresponding group could be explained by increased shunt flow or increased angiogenic activity in aggressive tumor cell clusters resulting in reduced nutrients supply and higher fraction of intratumoral necrosis respectively.

Selenium in the treatment of radiation-associated secondary lymphedema.

PURPOSE: The aim of this explorative study was to evaluate the impact of selenium in the treatment of lymphedema after radiotherapy. MATERIALS AND METHODS: Between June 1996 and June 2001, 12 patients with edema of the arm and 36 patients with edema of the head-and-neck region were treated with selenium for therapy-related lymphedema. Of these 36 patients, 20 had interstitial endolaryngeal edema associated with stridor and dyspnea. All patients received sodium selenite over 4 to 6 weeks. RESULTS: Self-assessment using a visual analog scale (n = 48) showed a reduction of 4.3 points when comparing pre- and posttreatment values (p < 0.05). Of 20 patients with endolaryngeal edema, 13 underwent no tracheostomy, 5 underwent a temporary tracheostomy, and only 2 underwent a permanent tracheostomy. Ten of 12 patients with arm edema showed a circumference reduction of the edematous limb and improvement in the Skin-Fold Index by 23.3 points. An improvement of one stage or more was shown by the Földi or the Miller score (n = 28) in 22 (Földi score) and in 24 (Miller score) patients. CONCLUSIONS: Treatment with sodium selenite is well tolerated and easy to deliver. Additionally, our results suggest that sodium selenite has a positive effect on secondary-developing lymphedema caused by radiation therapy alone or by irradiation after surgery.

Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradiation: preliminary results of a prospective study.

PURPOSE: To evaluate the clinical value of diffusion-weighted magnetic resonance imaging (DW-MRI) to monitor response of primary carcinoma of the rectum to preoperative chemoradiation by measuring tumor apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Diffusion data of nine patients undergoing preoperative combined chemoradiation for clinical staged T3, N(0-2), M(0) carcinoma of the rectum were analyzed. Diffusion-weighted echo-planar MR images were obtained prior to and at specified intervals during chemoradiation and ADCs calculated from acquired tumor images. RESULTS: Comparison of mean ADC and cumulative radiation dose showed a significant decrease of mean ADC at the 2nd (P = 0.028), 3rd (P = 0.012), and 4th (P = 0.008) weeks of treatment. Cytotoxic edema and fibrosis were considered as reasons for ADC decrease. CONCLUSION: This study demonstrated tumor ADC changes via detection of therapy-induced alterations in tumor water mobility. Our results indicate that diffusion-weighted imaging may be a valuable clinical tool to diagnose the early stage of radiation-induced fibrosis.