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.

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.

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.

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.