Forest tree growth is linked to mycorrhizal fungal composition and function across Europe.

Most trees form symbioses with ectomycorrhizal fungi (EMF) which influence access to growth-limiting soil resources. Mesocosm experiments repeatedly show that EMF species differentially affect plant development, yet whether these effects ripple up to influence the growth of entire forests remains unknown. Here we tested the effects of EMF composition and functional genes relative to variation in well-known drivers of tree growth by combining paired molecular EMF surveys with high-resolution forest inventory data across 15 European countries. We show that EMF composition was linked to a three-fold difference in tree growth rate even when controlling for the primary abiotic drivers of tree growth. Fast tree growth was associated with EMF communities harboring high inorganic but low organic nitrogen acquisition gene proportions and EMF which form contact versus medium-distance fringe exploration types. These findings suggest that EMF composition is a strong bio-indicator of underlying drivers of tree growth and/or that variation of forest EMF communities causes differences in tree growth. While it may be too early to assign causality or directionality, our study is one of the first to link fine-scale variation within a key component of the forest microbiome to ecosystem functioning at a continental scale.

Establishing stereotactic body radiotherapy with flattening filter free techniques in the treatment of pulmonary lesions - initial experiences from a single institution.

BACKGROUND: Stereotactic body radiotherapy (SBRT) using flattening filter free (FFF)-techniques has been increasingly applied during the last years. However, clinical studies investigating this emerging technique are still rare. Hence, we analyzed toxicity and clinical outcome of pulmonary SBRT with FFF-techniques and performed dosimetric comparison to conventional techniques using flattening filters (FF). MATERIALS AND METHODS: Between 05/2014 and 06/2015, 56 consecutive patients with 61 pulmonary lesions were treated with SBRT in FFF-mode. Central lesions received 8 × 7.5 Gy delivered to the conformally enclosing 80 %-isodose, while peripheral lesions were treated with 3 × 15 Gy, prescribed to the 65 %-isodose. Early and late toxicity (after 6 months) as well as initial clinical outcomes were evaluated. Furthermore, [deleted] plan quality and efficiency were evaluated by analyzing conformity, beam- on and total treatment delivery times in comparison to plans with FF-dose application. RESULTS: Median follow-up time was 9.3 months (range 1.5-18.0 months). Early toxicity was low with only 5 patients (8.9 %) reporting CTCAE 2° or higher side-effects. Only one patient (1.8 %) was diagnosed with radiation-induced pneumonitis CTCAE 3°, while 2 (3.6 %) patients suffered from pneumonitis CTCAE 2°. After 6 months, no toxicity greater than CTCAE 2° was reported. 1-year local progression-free survival, distant progression-free survival and overall survival were 92.8 %, 78.0 %, and 94.4 %, respectively. While plan quality was similar for FFF- and FF-plans in respect to conformity (p = 0.275), median beam-on time as well as total treatment time were significantly reduced for SBRT in FFF-mode compared to FF-mode (p ≤ 0.001, p ≤ 0.001). CONCLUSIONS: Patient treatment with SBRT using FFF-techniques is safe and provides promising clinical results with only modest toxicity at significantly increased dose delivery speed.

Long-term outcome after highly advanced single-dose or fractionated radiotherapy in patients with vestibular schwannomas - pooled results from 3 large German centers.

PURPOSE: To evaluate long-term clinical outcome and determine prognostic factors for local-control, hearing preservation and cranial nerve toxicity in 449 patients treated for 451 vestibular schwannomas (VS) with radiosurgery (n=169; 38%) or fractionated stereotactic radiotherapy (FSRT; n=291; 62%). METHODS AND MATERIALS: 245 patients were male (55%), and 204 were female (45%). Median age was 60 years (range 17-88 years). Median tumor diameter was 15mm. For FSRT, a median dose of 57.6Gy in median single doses of 1.8Gy was applied. For SRS, median dose was 13Gy. The median follow-up time was 67 months. RESULTS: Local control was 97% at 36 months, 95% at 60 months, and 94% at 120 months with no difference between FSRT and SRS (p=0.39). "Useful hearing" was present 46%. After RT, "useful hearing" was preserved in 85% of the patients. Loss of useful hearing was observed in the FSRT group in 14%, and in the SRS group in 16% of the patients. For patients treated with SRS ⩽13Gy, useful hearing deterioration was 13%. For trigeminal and facial nerve toxicity, there was no difference between FSRT and SRS. CONCLUSION: Supported by this large multicentric series, both SRS and FSRT can be recommended for the treatment of VS. SRS application is limited by tumor size, and is associated with a steep dose-response-curve. When chosen diligently based on tumor volume, pre-treatment characteristics and volume-dependent dose-prescription in SRS (⩽13Gy), both treatments may be considered equally effective.

Accuracy quantification of a deformable image registration tool applied in a clinical setting.

The purpose of this study was to test the accuracy of a commercially available deformable image registration tool in a clinical situation. In addition, to demonstrate a method to evaluate the resulting transformation of such a tool to a reference defined by multiple experts. For 16 patients (seven head and neck, four thoracic, five abdominal), 30-50 anatomical landmarks were defined on recognizable spots of a planning CT and a corresponding fraction CT. A commercially available deformable image registration tool, Velocity AI, was used to align all fraction CTs with the respective planning CTs. The registration accuracy was quantified by means of the target registration error in respect to expert-defined landmarks, considering the interobserver variation of five observers. The interobserver uncertainty of the landmark definition in our data sets is found to be 1.2 ± 1.1 mm. In general the deformable image registration tool decreases the extent of observable misalignments from 4-8 mm to 1-4 mm for nearly 50% of the landmarks (to 77% in sum). Only small differences are observed in the alignment quality of scans with different tumor location. Smallest residual deviations were achieved in scans of the head and neck region (79%, ≤ 4 mm) and the thoracic cases (79%, ≤ 4 mm), followed by the abdominal cases (59%, ≤ 4 mm). No difference is observed in the alignment quality of different tissue types (bony vs. soft tissue). The investigated commercially available deformable image registration tool is capable of reducing a mean target registration error to a level that is clinically acceptable for the evaluation of retreatment plans and replanning in case of gross tumor change during treatment. Yet, since the alignment quality needs to be improved further, the individual result of the deformable image registration tool has still to be judged by the physician prior to application.

Hearing preservation after radiotherapy for vestibular schwannomas is comparable to hearing deterioration in healthy adults and is accompanied by local tumor control and a highly preserved quality of life (QOL) as patients' self-reported outcome.

PURPOSE: To evaluate long-term results and patients' self-reported outcome of high-precision photon radiotherapy for the treatment of patients with vestibular schwannoma (VS). METHODS AND MATERIALS: We treated 246 patients with 248 VS with fractionated stereotactic radiotherapy (FSRT) or stereotactic radiosurgery (SRS). For FSRT, a median total dose of 57.6 Gy was prescribed in median single doses of 1.8 Gy, for SRS, a median dose of 13 Gy/80% isodose was applied. Of all patients, 51 patients died during follow-up. To evaluate long-term toxicity and QOL, we sent out a questionnaire to all living patients; of these, 81 patients (42%) sent back the questionnaire. RESULTS: Median local control was 84 months, actuarial local control rates for both groups (SRS and FSRT) were 98% after 2, 95% after 5, and 93% after 10 years; there was no statistical difference between FSRT and SRS. Hearing deterioration was significantly higher in the SRS group than the FSRT group. However, when comparing FSRT to SRS with doses ≤ 13 Gy, hearing preservation is comparable. In patients with useful hearing, hearing preservation was 89.7% at 1 year, 84.7% at 3 years, 76.5% at 5 years, and 68.6% at 10 years. After 10 years of follow-up, hearing deterioration can be observed in both subgroups. In the FSRT group, facial nerve toxicity rate was 1.6%. Trigeminal nerve toxicity was observed in 2.1% after FSRT. Overall QOL was unchanged in 47% of the patients after RT, and 31% reported an improvement in QOL during follow-up. CONCLUSION: Patients' self-reported outcome confirms good results with respect to tumor control and QOL after FSRT or SRS in patients with VS. SRS can be associated with higher side effect following a dose-dependency. In long-term follow-up, hearing deterioration is most likely attributed to normal aging, but not treatment-related.

Definitive Radiotherapy versus Postoperative Radiotherapy of Patients with Oro- and Hypopharyngeal Cancer: Impact of Prognostic Factors.

Purpose. To compare the impact of prognostic factors of patients treated with definitive radio(chemo)therapy versus patients treated with surgery and postoperative radiotherapy for squamous cell carcinoma of the oro- and hypopharynx. Patients and Methods. 162 patients treated with definitive radiotherapy and 126 patients treated with postoperative radiotherapy were retrospectively analysed. The impact of the prognostic factors gender, age, total tumor volume (TTV), pre-radiotherapy hemoglobin level (Hb-level), tumor site, T- and N-classification, radiotherapy interruptions >5 days, radiotherapy versus simultaneous radiochemotherapy, R-status and time interval between surgery and radiotherapy were investigated. Results. The median follow-up time for the censored patients treated with definitive radio(chemo)therapy was 28.5 months and for postoperative radiotherapy 36.5 months. On univariate analysis, the TTV, Hb-level, and simultaneous radiochemotherapy had a significant impact on the survival of patients treated with definitive radio(chemo)therapy. For patients treated with postoperative radiotherapy, only the TTV showed a statistical trend for the survival (P = 0.13). On multivariate analysis, the TTV and simultaneous radiochemotherapy maintained their statistical significance for patients treated with definitive raditherapy, and the TTV, the statistical trend for patients treated with postoperative radiotherapy (P = 0.19). Conclusions. The TTV was the predominant prognostic factor for both, patients treated with definitive or postoperative radiotherapy.

Influence of intravenous contrast agent on dose calculation in 3-D treatment planning for radiosurgery of cerebral arteriovenous malformations.

PURPOSE: To investigate the influence of local density increase by i.v. contrast agent on dose calculation in linac-based radiosurgery (RS) of cerebral arteriovenous malformations (AVMs). MATERIAL AND METHODS: RS was performed after three-dimensional (3-D) treatment planning using a total number of nine to 14 beams. Mean target volume was 5.3 cm(3) (range, 0.1-41.2 cm(3)). Mean maximum diameter was 23.2 mm (range, 8-51 mm). Dose deviation was estimated and calculated from the enhanced and unenhanced datasets of 30 patients. Dose calculation was performed using the same RS treatment plan on both datasets. Both plans were standardized to 1 Gy at isocenter with the same dose weight for all beams. RESULTS: Mean difference of Hounsfield units (DeltaHU) between enhanced and unenhanced CT was 152 HU (range, 50-350 HU). The estimated dose deviation was

Contrast-enhanced color duplex sonography (CDS): an alternative for the evaluation of therapy-relevant tumor oxygenation?

PURPOSE: To evaluate the predictive value of radiotherapeutically relevant tumor hypoxia by contrast-enhanced color duplex sonography (CDS). The objectification was based on pO(2) histography. MATERIAL AND METHODS: 25 patients with metastatic neck lymph node from a primary squamous carcinoma of the head and neck were examined. To visualize as many vessels as possible, a contrast enhancer (Levovist), Schering Corp., Germany) was administered. Horizontal and longitudinal sonographic scans with a thickness of 5 mm were performed on the metastatic neck lymph node. Color pixel density (CPD) was defined as the ratio of colored to gray pixels in a region of interest. It represents the extent of vascularization in the investigated slice. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO(2) readings < or = 2.5, 5.0, and 10.0 mmHg, as well as mean and median pO(2), were documented. RESULTS: In order to investigate the degree of linear association, the Pearson correlation coefficient was calculated. Moderate (/r/ > 0.5) to high (/r/ > 0.7) correlation was found between the CPD and the parameters of hypoxic fraction (pO(2) readings with values < or = 5.0 and 10.0 mmHg, as well as mean and median). There was only a slight correlation between CPD and the fraction of pO(2) values < or = 2.5 mmHg (r = -0.479). CONCLUSION: CPD represents the mean degree of vascularization. As a noninvasive measurement, this method seems feasible for evaluating the state of global oxygenation in superficial tumors. Nevertheless, this method is limited through its deficiency in describing the vascular heterogeneity of tumors.

Evaluation of tumor oxygenation by color duplex sonography: a new approach.

OBJECTIVE: Description of a new noninvasive method for the evaluation of tissue oxygenation in head and neck cancer. STUDY DESIGN AND SETTING: Prospective nonrandomized controlled study in an academic medical center on 20 patients with neck metastases of head and neck cancer. Metastases were investigated using color duplex sonography and pO2 histography. The vascularization in sonography was quantitatively evaluated by color pixel density and compared to the pO2 values of the same nodes. RESULTS: The correlation between vascularization and flow velocity was 0.71. For the mean/median pO2 -values and for the pO2 readings <10.0 mmHg correlations were r = 0.65 / 0.76 and 0.71. CONCLUSION: This sonographic method allows a safe and reliable evaluation of oxygenation in metastases of head and neck cancer. SIGNIFICANCE: The new approach is an alternative to pO2 histography and may play a future role in the planning of radiotherapy in the neck.

The electronic portal imaging system Siemens Beamview Plus versus the conventional verification films CEA-TVS and DuPont COL-7. A critical appraisal of visual image quality.

AIM: The aim of this study was the validation of the visual image quality of electronic portal imaging devices (EPID) and conventional verification films from the point of view of the end-viewers of portal films, the radiotherapists. MATERIAL AND METHODS: The verification image was represented in two different forms, viz. an electronic portal image employing Siemens Beamview Plus (on a computer monitor) and two different portal films using the conventional verification films CEA-TVS and DuPont CQL-7 (on a negatoscope). A total of 270 image sets (simulation film and portal image) were evaluated by each radiotherapist, evaluation extending to 90 sets of each type of verification film. Each set was evaluated by three specialists in radiotherapy examining subjective visual image quality whereby the following aspects served as evaluation criteria: contrast, artifacts, determination of actual radiation field edge position, anatomical structures and main structural feature for the determination of treatment field position. In addition, the anatomical structures employed for visual feature correlation between reference and portal films were classified according to their importance. RESULTS: In general the electronic portal image was rated significantly "visible" or better. Only the evaluation of artifacts showed an appreciable disadvantage for electronic portal imaging caused by physical artifacts due to radiographic technique and data processing aspects peculiar to the Siemens Beamview Plus 1.1. and also caused by different image processing tools reducing physical artifacts and enhancing the visibility of anatomical structures and likewise of anatomical artifacts (e.g. intestinal gas). By calculating the Spearman correlation coefficient to detect a possible relationship between the different criteria of subjective visual image quality, the research demonstrated that artifacts when limited to a tolerable proportion had no significant impact on the other criteria. CONCLUSIONS: As data of EPIDS are digital, images can be postprocessed and enhanced in a wide variety of ways. Using this tool the electronic portal imaging device provides images that, in terms of visual image quality, are at least comparable to the two evaluated types of radiographic films and also have the added advantage that such images are stored and can be transferred electronically being presupposition for digital patient documentation.