Symptom relief, prognostic factors, and outcome in patients receiving urgent radiation therapy for superior vena cava syndrome : A single-center retrospective analysis of 21 years' practice.

PURPOSE: Superior vena cava syndrome (SVCS) often results from external vessel compression due to tumor growth. Urgent symptom-guided radiotherapy (RT) remains a major treatment approach in histologically proven, rapidly progressive disease. Despite several publications, recent data concerning symptom relief and oncological outcome as well as potential confounders in treatment response are still scarce. METHODS: We performed a retrospective single-center analysis of patients receiving urgent RT between 2000 and 2021 at the University Medical Center Göttingen. Symptom relief was evaluated by CTCAE score during the RT course. Effects of variables on symptom relief were assessed by logistic regression. The impact of parameters on overall survival (OS) was evaluated using Kaplan-Meier plot along with the log-rank test and by Cox regression analyses. Statistically significant (p-value < 0.05) confounders were tested in multivariable analyses. RESULTS: A total of 79 patients were included. Symptom relief was achieved in 68.4%. Mean OS was 59 days, 7.6% (n = 6) of patients showed long-term survival (> 2 years). Applied RT dose > 39 Gy, clinical target volume (CTV) size < 387 ml, concomitant chemotherapy, and completion of the prescribed RT course were found to be statistically significant for OS; applied RT dose and completion of the prescribed RT course were found to be statistically significant for symptom relief. CONCLUSION: Symptom relief by urgent RT for SVCS was achieved in the majority of patients. RT dose and completion of the RT course were documented as predictors for OS and symptom relief, CTV < 387 ml and concomitant chemotherapy were predictive for OS.

Comparison of non-myeloablative and reduced-intensity allogeneic stem cell transplantation in older patients with myelodysplastic syndromes.

Allogeneic stem cell transplantation (HSCT) remains the only curative treatment for myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. The introduction of reduced intensity (RIC) and non-myeloablative (NMA) conditioning enabled HSCT in older or comorbid individuals representing the majority of patients. Studies comparing RIC and NMA conditioning are limited. We retrospectively analyzed 151 MDS or MDS/MPN patients older than 50 years who received NMA- or RIC-HSCT. Patients younger or older than 65 years at HSCT were analyzed separately. Patients receiving RIC-HSCT or NMA-HSCT were balanced in factors reflecting disease aggressiveness and the HCT-CI comorbidity score. The NMA conditioned patients had a higher incidence of graft rejection and chronic graft-vs-host disease. Cumulative incidence of relapse (CIR), non-relapse mortality (NRM) and overall survival (OS), did not differ significantly with regard to the conditioning regime in the whole cohort. In patients <65 years at HSCT, NMA conditioning associated with higher NRM and shorter OS by trend, while CIR was similar in both groups. In multivariable analyzes, the conditioning regimen remained a prognostic factor for NRM and OS in patients <65 years at HSCT. In MDS patients NMA and RIC conditioning result in similar disease control, but especially patients <65 years may benefit from RIC-HSCT.

Outcomes of Multimodal Treatment in Elderly Patients with Localized Non-Small Lung Cancer from a Radiation Oncology Point of View: Special Focus on Low-Dose Cisplatin.

Identification of the optimal treatment strategy is challenging in elderly with localized non-small cell lung cancer (NSCLC). Concurrent chemotherapy with low-dose cisplatin represents an option for elderly. Outcomes (1) in elderly (≥70 years, n = 158) vs. younger patients (n = 188) and (2), independently of age, in definitive radiochemotherapy, with low-dose cisplatin (n = 125) vs. cisplatin/vinorelbine (n = 76) were studied. Elderly included more males, had a lower Karnofsky index, more comorbidities, and lower stages. Low-dose cisplatin patients (vs. cisplatin/vinorelbine) had higher age, more comorbidities, and lower stages. We observed reduced dermatitis and dysphagia and increased anemia and thrombocytopenia in elderly vs. younger patients, without increased ≥grade 3 toxicities. Low-dose cisplatin was less toxic than cisplatin/vinorelbine. Survival outcomes were lower in elderly vs. younger and comparable between low-dose cisplatin and cisplatin/vinorelbine. In elderly, gender, Karnofsky index, stage, and multimodal treatment (including additional surgery/systemic therapy) were identified as prognostic factors. In conclusion, we found evidence for an acceptable toxicity profile and the need for improvement of outcomes in elderly with localized NSCLC. Multimodal strategies (including additional surgery/systemic treatment) showed favorable outcomes and should be reasonably considered in elderly who are deemed fit enough. Low-dose cisplatin should be discussed on an individual basis due to favorable toxicity and outcomes.

Hemostatic radiotherapy in clinically significant tumor-related bleeding: excellent palliative results in a retrospective analysis of 77 patients.

BACKGROUND: Significant bleeding of tumor sites is a dreaded complication in oncological diseases and often results in clinical emergencies. Besides basic local and interventional procedures, an urgent radiotherapeutic approach can either achieve a bleeding reduction or a bleeding stop in a vast majority of patients. In spite of being used regularly in clinical practice, data reporting results to this therapy approach is still scarce. METHODS: We retrospectively analyzed 77 patients treated for significant tumor-related bleeding at our clinic between 2000 and 2021, evaluating treatment response rate, hemoglobin levels, hemoglobin transfusion necessity, administered radiotherapy dose and overall survival. RESULTS: Response rate in terms of bleeding stop was 88.3% (68/77) in all patients and 95.2% (60/63) in the subgroup, wherein radiotherapy (RT) was completed as intended. Hemoglobin transfusions decreased during treatment in a further subgroup analysis. Median overall survival (OS) was 3.3 months. Patients with primary tumors (PT) of the cervix (carcinoma of the cervix, CC) or endometrium (endometrioid carcinoma, EDC) and patients receiving the full intended RT dose showed statistically significant better OS in a multivariable cox regression model. Median administered dose was 39 Gy, treatment related acute toxicity was considerably low. CONCLUSIONS: Our data show an excellent response rate with a low toxicity profile when administering urgent radiotherapy for tumor related clinically significant bleeding complications. Nonetheless, treatment decisions should be highly individual due to the low median overall survival of this patient group.

Patterns of Pretreatment Diagnostic Assessment in Patients Treated with Stereotactic Body Radiation Therapy (SBRT) for Non-Small Cell Lung Cancer (NSCLC): Special Characteristics in the COVID Pandemic and Influence on Outcomes.

The pandemic raised a discussion about the postponement of medical interventions for non-small cell lung cancer (NSCLC). We analyzed the characteristics of pretreatment diagnostic assessment in the pandemic and the influence of diagnostic assessment on outcomes. A total of 96 patients with stereotactic body radiation therapy (SBRT) for NSCLC were included. The number of patients increased from mean 0.9 (2012-2019) to 1.45 per month in the COVID era (p < 0.05). Pandemic-related factors (contact reduction, limited intensive care unit resources) might have influenced clinical decision making towards SBRT. The time from pretreatment assessment (multidisciplinary tumor board decision, bronchoscopy, planning CT) to SBRT was longer during the COVID period (p < 0.05). Reduced services, staff shortage, or appointment management to mitigate infection risks might explain this finding. Overall survival, progression-free survival, locoregional progression-free survival, and distant progression-free survival were superior in patients who received a PET/CT scan prior to SBRT (p < 0.05). This supports that SBRT guidelines advocate the acquisition of a PET/CT scan. A longer time from PET/CT scan/conventional staging to SBRT (<10 vs. ≥10 weeks) was associated with worse locoregional control (p < 0.05). The postponement of diagnostic or therapeutic measures in the pandemic should be discussed cautiously. Patient- and tumor-related features should be evaluated in detail.

Analysis of chemokine and chemokine receptor expression in squamous cell carcinoma of the head and neck (SCCHN) cell lines.

The purpose of this work was to analyze chemokine and chemokine receptor expression in untreated and in irradiated squamous cell carcinoma of the head and neck (SCCHN) tumor cell lines, aiming at the establishment of assays to test for the relevance of chemokine and chemokine receptor expression in the response of SCCHN to radiotherapy and radiochemotherapy. Five low passage and 10 established SCCHN lines, as well as two normal cell lines, were irradiated at 2 Gy or sham-irradiated, and harvested between 1 and 48 h after treatment. For chemokines with CC and CXC structural motifs and their receptors, transcript levels of target and reference genes were quantified relatively by real-time PCR. In addition, CXCL1 and CXCL12 protein expression was analyzed by ELISA. A substantial variation in chemokine and chemokine receptor expression between SCCHN was detected. Practically, all cell lines expressed CCL5 and CCL20, while CCL2 was expressed in normal cells and in some of the tumor cell lines. CXCL1, CXCL2, CXCL3, CXCL10, and CXCL11 were expressed in the vast majority of the cell lines, while the expression of CXCL9 and CXCL12 was restricted to fibroblasts and few tumor cell lines. None of the analyzed cell lines expressed the chemokines CCL3, CCL4, or CCL19. Of the receptors, transcript expression of CCR1, CCR2, CCR3, CCR5, CCR7, CCXR2, and CCXR3 was not detected, and CCR6, CXCR1, and CXCR4 expression was restricted to few tumor cells. Radiation caused up- and down-regulation with respect to chemokine expressions, while for chemokine receptor expressions down-regulations were prevailing. CXCL1 and CXCL12 protein expression corresponded well with the mRNA expression. We conclude that the substantial variation in chemokine and chemokine receptor expression between SCCHN offer opportunities for the establishment of assays to test for the relevance of chemokine and chemokine receptor expression in the response of SCCHN to radiotherapy and radiochemotherapy.

Identification of Risk Loci for Radiotoxicity in Prostate Cancer by Comprehensive Genotyping of TGFB1 and TGFBR1.

Genetic variability in transforming growth factor beta pathway (TGFB) was suggested to affect adverse events of radiotherapy. We investigated comprehensive variability in TGFB1 (gene coding for TGFß1 ligand) and TGFBR1 (TGFß receptor-1) in relation to radiotoxicity. Prostate cancer patients treated with primary radiotherapy (n = 240) were surveyed for acute and late toxicity. Germline polymorphisms (n = 40) selected to cover the common genetic variability in TGFB1 and TGFBR1 were analyzed in peripheral blood cells. Human lymphoblastoid cell lines (LCLs) were used to evaluate a possible impact of TGFB1 and TGFBR1 genetic polymorphisms to DNA repair capacity following single irradiation with 3 Gy. Upon adjustment for multiplicity testing, rs10512263 in TGFBR1 showed a statistically significant association with acute radiation toxicity. Carriers of the Cytosine (C)-variant allele (n = 35) featured a risk ratio of 2.17 (95%-CI 1.41-3.31) for acute toxicity ≥ °2 compared to Thymine/Thymine (TT)-wild type individuals (n = 205). Reduced DNA repair capacity in the presence of the C-allele of rs10512263 might be a mechanistic explanation as demonstrated in LCLs following irradiation. The risk for late radiotoxicity was increased by carrying at least two risk genotypes at three polymorphic sites, including Leu10Pro in TGFB1. Via comprehensive genotyping of TGFB1 and TGFBR1, promising biomarkers for radiotoxicity in prostate cancer were identified.

CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system.

The chemokine receptor CCR2 plays a vital role for the induction of autoimmunity in the central nervous system. However, it remains unclear how the pathogenic response is mediated by CCR2-bearing cells. By combining bone marrow chimerism with gene targeting we detected a mild disease-modulating role of CCR2 during experimental autoimmune encephalomyelitis, a model for central nervous system autoimmunity, on radio-resistant cells that was independent from targeted CCR2 expression on endothelia. Interestingly, absence of CCR2 on lymphocytes did not influence autoimmune demyelination. In contrast, engagement of CCR2 on accessory cells was required for experimental autoimmune encephalomyelitis induction. CCR2+Ly-6Chi monocytes were rapidly recruited to the inflamed central nervous system and were crucial for the effector phase of disease. Selective depletion of this specific monocyte subpopulation through engagement of CCR2 strongly reduced central nervous system autoimmunity. Collectively, these data indicate a disease-promoting role of CCR2+Ly-6Chi monocytes during autoimmune inflammation of the central nervous system.

Spontaneous and radiation-induced chromosomal instability and persistence of chromosome aberrations after radiotherapy in lymphocytes from prostate cancer patients.

The aim of the study was to compare the spontaneous and ex vivo radiation-induced chromosomal damage in lymphocytes of untreated prostate cancer patients and age-matched healthy donors, and to evaluate the chromosomal damage, induced by radiotherapy, and its persistence. Blood samples from 102 prostate cancer patients were obtained before radiotherapy to investigate the excess acentric fragments and dicentric chromosomes. In addition, in a subgroup of ten patients, simple exchanges in chromosomes 2 and 4 were evaluated by fluorescent in situ hybridization (FISH), before the onset of therapy, in the middle and at the end of therapy, and 1 year later. Data were compared to blood samples from ten age-matched healthy donors. We found that spontaneous yields of acentric chromosome fragments and simple exchanges were significantly increased in lymphocytes of patients before onset of therapy, indicating chromosomal instability in these patients. Ex vivo radiation-induced aberrations were not significantly increased, indicating proficient repair of radiation-induced DNA double-strand breaks in lymphocytes of these patients. As expected, the yields of dicentric and acentric chromosomes, and the partial yields of simple exchanges, were increased after the onset of therapy. Surprisingly, yields after 1 year were comparable to those directly after radiotherapy, indicating persistence of chromosomal instability over this time. Our results indicate that prostate cancer patients are characterized by increased spontaneous chromosomal instability. This instability seems to result from defects other than a deficient repair of radiation-induced DNA double-strand breaks. Radiotherapy-induced chromosomal damage persists 1 year after treatment.

Effect of tumour-cell-derived or recombinant keratinocyte growth factor (KGF) on proliferation and radioresponse of human epithelial tumour cells (HNSCC) and normal keratinocytes in vitro.

Purpose of this work was to test the effect of tumour-cell-derived keratinocyte growth factor (KGF) or recombinant KGF (palifermin) on cell proliferation and radiation response of human HNSCC cells and normal keratinocytes in vitro. Four tumour cell cultures derived from head and neck squamous cell carcinomas, primary keratinocytes, and immortalized keratinocytes were analysed. Fibroblasts, the natural source of KGF protein, served as controls. KGF expression was observed in primary and immortalized keratinocytes, fibroblasts, and in tumour cells, while significant KGF receptor expression was only found in keratinocytes. Recombinant KGF as well as tumour-cell-derived KGF caused a significant growth stimulation and radioprotection in keratinocytes, which was abolished by a neutralizing anti-KGF antibody. This indicates that tumour-cell-derived KGF is biologically active. In the tumour cell lines, no significant growth stimulation was induced by recombinant KGF, and the neutralizing antibody did not influence tumour cell growth or radiation response. Our results indicate that the normal, paracrine KGF regulatory mechanisms, which are based on KGF receptor expression, are lost in malignant cells, with the consequence of irresponsiveness of the tumour cells to exogenous KGF. In face of the amelioration of the radiation response of normal epithelia, demonstrated in various clinical and various preclinical animal studies, recombinant KGF represents a candidate for the selective protection of normal epithelia during radio(chemo) therapy of squamous cell carcinoma.

Evaluation of Prognosticators and Treatment-Related Side Effects in Patients Irradiated Postoperatively for Endometrial Cancer.

Numerous clinical trials sought to improve outcomes in endometrial cancer patients with multimodal treatment strategies. We tested the hypothesis that specific histopathological and clinical parameters are prognosticators for outcomes at our Gynecological Cancer Center. A total of 203 patients (median age, 69.5 years) was included. They were irradiated postoperatively (n = 184: Brachytherapy, n = 19: Teletherapy) between 05/2007 and 03/2020. The median follow-up was 37.2 months. As statistical methods, we used the univariable Cox proportional hazards regression, and log-rank statistics. First, we found a significant influence of grading and nodal stage on outcomes. These findings underline the recommendations of more intense treatment in these patient groups, as already reflected in current guidelines. Secondly, we found that patient age had a significant influence on survival be it due to comorbidities and/or due to too hesitant treatment regimen in the elderly. Thus, it should be aimed at particular strategies in treatment of these patients. Lastly, we found very low rates of treatment-related side effects in patients treated with brachytherapy and moderate rates of side effects in patients treated with teletherapy. Overall, our study serves as basis for further improvement of treatment strategies and for conceptualization of clinical trials.

The impact of rectal/bladder filling and applicator positioning on in vivo rectal dosimetry in vaginal cuff brachytherapy using an enhanced therapy setting.

PURPOSE: The impact of rectal filling and bladder volume on in vivo rectal dosimetry (IVD) in vaginal cuff brachytherapy (VCBT) is unknown. The purpose of this study was to compare rectal doses from IVD with those calculated from treatment planning and to identify influencing factors. MATERIALS AND METHODS: We collected data of 80 VCBT sessions, four for each of 20 patients. Each was retrospectively compared with doses determined by the treatment planning system. Factors potentially predicting the IVD rectum dose were analyzed. RESULTS: For a series of 80 brachytherapy applications, the calculated mean dose to the rectum was 2.52 Gy. The mean difference between all calculated and measured doses for the 80 applications with five probe positions each was 0.09 Gy (p = 0.952) proving high overall accordance between IVD and calculated doses at the rectum. The mean volume of the rectum was 119 ± 57 cm³. The rectal volume was not statistically significantly associated with the IVD or the calculated rectum doses. At the third and fourth rectal probe position in craniocaudal ordering, increased filling of the urinary bladder resulted in decreased measured and calculated doses (p < 0.05 for both). A rectum pointing position of the applicator significantly increased the maximum rectum dose compared with a bladder-oriented position (p < 0.05). CONCLUSIONS: IVD provided valuable data for rectal exposure in VCBT. Increased bladder filling and vaginal applicator positioning off the rectum elicited related with less rectal radiation exposure, whereas rectal filling did not. Further confirmation including assessment of IVD in bladder is pending to define optimal dosimetric conditions in VCBT.

The impact of prostate volume changes during external-beam irradiation in consequence of HDR brachytherapy in prostate cancer treatment.

PURPOSE: To evaluate prostate volume changes during external-beam irradiation in consequence of high-dose-rate (HDR) brachytherapy in prostate cancer treatment. PATIENTS AND METHODS: 20 patients who underwent radiotherapy for prostate cancer were included in this prospective evaluation. All patients had a computed tomography (CT) scan for planning of the external-beam irradiation and additional scans after each HDR brachytherapy. For the planning target volume (PTV), a safety margin of 10 mm was added to the clinical target volume (CTV) in each direction. The prostate volume measured in the planning CT was compared with the prostate volumes measured after HDR brachytherapy and, subsequently, the change of prostate volume was calculated. Volume changes which resulted in differences of the prostate radius of > 5 mm for the CTV were defined as a reason for a new treatment-planning procedure for the patient. RESULTS: Taking all patients together, prostate volumes before HDR, 1 day and 4-6 days after the first HDR treatment, as well as 1 day and 4-6 days after the second HDR treatment were in median 37.7 cm(3), 37.6 cm(3), 38.2 cm(3), 39.3 cm(3), and 40.5 cm(3), respectively. In none of the patient, a volume change resulted in a change of the prostate radius of > 5 mm for the CTV. Prerequisite for this calculation was the simplification of the complex prostate geometry to a sphere. No new treatment-planning procedure was necessary during external-beam radiotherapy. CONCLUSION: HDR brachytherapy does change the prostate volume. Under the condition of a 10-mm safety margin in each direction added to the CTV for the PTV, no new treatment-planning procedure was necessary after HDR brachytherapy. There is no need for CT scans at regular intervals during external-beam radiotherapy.

Organ function and quality of life after transoral laser microsurgery and adjuvant radiotherapy for locally advanced laryngeal cancer.

BACKGROUND AND PURPOSE: Transoral laser microsurgery (TLM) and adjuvant radiotherapy are an established therapy regimen for locally advanced laryngeal cancer at our institution. Aim of the present study was to assess value of quality of life (QoL) data with special regard to organ function under consideration of treatment efficacy in patients with locally advanced laryngeal cancer treated with larynx-preserving TLM and adjuvant radiotherapy. PATIENTS AND METHODS: From 1994 to 2006, 39 patients (ten UICC stage III, 29 UICC stage IVA/B) with locally advanced laryngeal carcinomas were treated with TLM and adjuvant radiotherapy. Data concerning treatment efficacy, QoL (using the VHI [Voice Handicap Index], the EORTC QLQ-C30 and QLQ-H&N35 questionnaires) and organ function (respiration, deglutition, voice quality) were obtained for ten patients still alive after long-term follow-up. Correlations were determined using the Spearman rank test. RESULTS: After a median follow-up of 80.8 months, the 5-year overall survival rate was 46.8% and the locoregional control rate 76.5%, respectively. The larynx preservation rate was 89.7% for all patients and 100% for patients still alive after follow-up. Despite some verifiable problems in respiration, speech and swallowing, patients showed a subjectively good QoL. CONCLUSION: TLM and adjuvant radiotherapy is a curative option for patients with locally advanced laryngeal cancer and an alternative to radical surgery. Even if functional deficits are unavoidable in the treatment of locally advanced laryngeal carcinomas, larynx preservation is associated with a subjectively good QoL.

Effect of irradiation on gene expression of rat liver adhesion molecules: in vivo and in vitro studies.

BACKGROUND AND PURPOSE: Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro. MATERIAL AND METHODS: Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology. RESULTS: Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), beta1-integrin, beta2-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, beta1-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), beta2-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-)alpha, interleukin-(IL-)1beta, or IL-6 plus TNF-alpha led to an upregulation of P-selectin, ICAM-1 and VCAM-1. CONCLUSION: The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of inflammation in the irradiated rat liver.

Effect of a prostaglandin--given rectally for prevention of radiation-induced acute proctitis--on late rectal toxicity. Results of a phase III randomized, placebo-controlled, double-blind study.

BACKGROUND AND PURPOSE: To assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. PATIENTS AND METHODS: A total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. RESULTS: The median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). CONCLUSION: Misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended.

Faecal calprotectin and lactoferrin values during irradiation of prostate cancer correlate with chronic radiation proctitis: results of a prospective study.

OBJECTIVE: Acute proctitis and chronic radiation proctitis are relevant complications of pelvic radiation. The purpose of this study was to investigate two markers of gut inflammation during and after irradiation for prostate cancer to evaluate a correlation between acute and chronic proctitis. MATERIAL AND METHODS: Two patient groups were analysed. In group 1, stool samples from 20 patients were collected before therapy, every week during therapy, at the end of therapy, and 13 and 27 months after therapy. Group 2 comprised 47 patients who had undergone irradiation 40 months earlier. Toxicity was determined by common toxicity criteria (CTC) and the LENT soma scale. Calprotectin and lactoferrin values were determined by ELISA. RESULTS: In group 1, acute values for both faecal markers were significantly correlated with chronic proctitis symptoms and all patients with chronic toxicity had acute proctitis symptoms with elevated faecal values. In group 2, where stool samples were solely collected 40 months after irradiation, the Pearson square test showed both a significant correlation between calprotectin and lactoferrin values and toxicity after 40 months. CONCLUSIONS: Within a group of 19 patients followed for two years after irradiation for prostate cancer, and 47 patients tested 40 months after irradiation, increased faecal values of calprotectin and lactoferrin were significantly correlated with the occurrence of chronic proctitis. This observation should be confirmed in an expanded study.

Application of two component biodegradable carriers in a particle-fixed biofilm airlift suspension reactor: development and structure of biofilms.

Two component biodegradable carriers for biofilm airlift suspension (BAS) reactors were investigated with respect to development of biofilm structure and oxygen transport inside the biofilm. The carriers were composed of PHB (polyhydroxybutyrate), which is easily degradable and PCL (caprolactone), which is less easily degradable by heterotrophic microorganisms. Cryosectioning combined with classical light microscopy and CLSM was used to identify the surface structure of the carrier material over a period of 250 days of biofilm cultivation in an airlift reactor. Pores of 50 to several hundred micrometers depth are formed due to the preferred degradation of PHB. Furthermore, microelectrode studies show the transport mechanism for different types of biofilm structures, which were generated under different substrate conditions. At high loading rates, the growth of a rather loosely structured biofilm with high penetration depths of oxygen was found. Strong changes of substrate concentration during fed-batch mode operation of the reactor enhance the growth of filamentous biofilms on the carriers. Mass transport in the outer regions of such biofilms was mainly driven by advection.

Increase of hepcidin plasma and urine levels is associated with acute proctitis and changes in hemoglobin levels in primary radiotherapy for prostate cancer.

PURPOSE: To analyse hepcidin serum and urine levels during radiotherapy for prostate cancer. METHODS: In 18 patients undergoing radiotherapy for prostate cancer, blood, plasma, and urine samples were taken before and during radiotherapy. Complete blood cell count, pro-hepcidin-, ferritin-, transferrin-, IL-1beta-, IL-6-, and TNF-alpha concentration was determined. Pro-hepcidin concentration was additionally measured in urine samples. Toxicity was evaluated weekly. Differences among tested factors were tested by Wilcoxon rank sign test for paired data. RESULTS: In ten patients developing acute radiation-induced proctitis, a significant increase in pro-hepcidin, IL-6, and TNF-alpha plasma levels (p < 0.05) was detected. Pro-hepcidin urine levels also showed a strong trend towards increase (p = 0.06). Concurrently, hemoglobin, and leucocytes were significantly decreased in the patients with acute proctitis (p < 0.05). In eight patients showing no symptoms of proctitis, solely a significant decrease for leucocytes was detected. Additive, these patients showed a significant increase of ferritin, and a decrease of transferrin levels (p < 0.05). CONCLUSIONS: Hepcidin levels are increased and hemoglobin is decreased during radiotherapy for prostate cancer in patients who develop acute proctitis. Radiation-induced expression of cytokines may be responsible for increased hepcidin expression in the liver. Regulation of iron metabolism by hepcidin may be an underestimated response in radiotherapy.

In vivo dosimetry with alanine/electron spin resonance dosimetry to evaluate the urethra dose during high-dose-rate brachytherapy.

PURPOSE: To determine the dose of the urethra during Ir-192 high-dose-rate brachytherapy in 15 patients, a new detector form developed for in vivo measurements was used as described by Anton et al. 2009. METHODS AND MATERIALS: The detector consists of alanine powder with paraffin as binder which was filled in a shrinkable tube for measurements. The alanine strand so produced was inserted in the foley catheter during high-dose-rate brachytherapy of the prostate. The measured dose was compared with the dose calculated by the treatment planning system SWIFT for 15 patients. After 8 patients, a marker was introduced for better positioning of the alanine strand using transrectal ultrasound images. RESULTS: The measurements of the dose of the urethra agreed very well with the dose calculated by SWIFT within the estimated standard uncertainty of the method for 8 patients with a mean absolute deviation of 0.08 Gy. However, for the other 7 patients, a mean absolute deviation between delivered and measured dose of -5.13 Gy was seen. For these patients, the active volume of the alanine dosimeter could not properly be reconstructed on the ultrasound images. CONCLUSION: The method presented in this study is useful for quality control of irradiations in vivo. To reconstruct the active volume on the corresponding ultrasound images, the correct application of the alanine strand in the urethra is very important. This procedure needs a well-trained physician.