Search

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

The treatment of locally recurrent lung cancer is a major challenge for radiation-oncologists, especially with data on high-dose reirradiation being limited to small retrospective studies. The aim of the present study is to assess overall survival (OS) for patients with locally recurrent lung cancer after high-dose thoracic reirradiation. Thirty-nine patients who were re-irradiated for lung cancer relapse between October 2013 and February 2019 were eligible for the current retrospective analysis. All patients were re-irradiated with curative intent for in-field tumor recurrence. The diagnostic work-up included a mandatory 18F-FDG-PET-CT scan and—if possible—histological verification. The ECOG was ≤2, and the interval between initial and second radiation was at least nine months. Thirty patients (77%) had non-small cell lung cancer (NSCLC), eight (20%) had small cell lung cancer (SCLC), and in one patient (3%) histological confirmation could not be obtained. More than half of the patients (20/39, 51%) received re-treatment with dose differentiated accelerated re-irradiation (DART) at a median interval of 20.5 months (range: 6–145.3 months) after the initial radiation course. A cumulative EQD2 of 131 Gy (range: 77–211 Gy) in a median PTV of 46 mL (range: 4–541 mL) was delivered. Patients with SCLC had a 3 mL larger median re-irradiation volume (48 mL, range: 9–541) compared to NSCLC patients (45 mL, range: 4–239). The median cumulative EQD2 delivered in SCLC patients was 84 Gy (range: 77–193 Gy), while NSCLC patients received a median cumulative EQD2 of 135 Gy (range: 98–211 Gy). The median OS was 18.4 months (range: 0.6–64 months), with tumor volume being the only predictor (p &lt, 0.000, HR 1.007, 95%-CI: 1.003–1.012). In terms of toxicity, 17.9% acute and 2.6% late side effects were observed, with a toxicity grade &gt, 3 occurring in only one patient. Thoracic high dose reirradiation plays a significant role in prolonging survival, especially in patients with small tumor volume at recurrence.

Background Given the limited curative treatment options for recurrent lung cancer patients, the aim of our retrospective study was to investigate whether these patients would benefit in terms of overall survival (OS) by adding immunotherapy to high‐dose reirradiation. Materials and methods Between 2013 and 2019, 47 consecutive patients with in‐field tumor recurrence underwent high‐dose thoracic reirradiation at our institute. Twenty patients (43%) received high‐dose reirradiation only, while 27/47 (57%) additionally had systemic therapy (immunotherapy and/or chemotherapy). With the exception of one patent, the interval between first and second radiation was at least 9 months. All patients had an Eastern cooperative oncology group ≤2. The diagnostic work‐up included a mandatory fluorodeoxyglucose‐positron emission tomography‐computed tomography scan and histological verification. The primary endpoint was OS after completion of the second course of irradiation. Results In the whole cohort of 47 patients, the median overall survival (mOS) after reirradiation was 18.9 months (95% confidence interval [CI] 16.5–21.3 months), while in the subgroup of 27 patients who received additional systemic treatment after reirradiation, mOS amounted to 21.8 months (95% CI 17.8–25.8 months). Within this group the comparison between reirradiation combined with either immunotherapy (n = 21) or chemotherapy (n = 6) revealed a difference in OS, which was in favor of the first (log‐rank p value = 0.063). Three patients (11%) experienced acute side effects and one (4%) showed a late hemorrhage grade 3. Conclusion Patients who received immunotherapy and reirradiation lived longer than those who did not receive immunotherapy., The aim of our retrospective study was to investigate whether reccurrent lung patients would benefit in terms of overall survival by adding immunotherapy to high‐dose reirradiation. Between 2013 and 2019, 47 consecutive patients with in‐field tumor recurrence underwent high‐dose thoracic reirradiation at our institute. Twenty patients (43%) received high dose reirradiation only, while 27/47 (57%) additionally had systemic therapy (immunotherapy and/or chemotherapy). Patients who received immunotherapy and reirradiation lived longer than those who did not receive immunotherapy.

Background Target volume definition of the primary tumor in esophageal cancer is usually based on computed tomography (CT) supported by endoscopy and/or endoscopic ultrasound and can be difficult given the low soft-tissue contrast of CT resulting in large interobserver variability. We evaluated the value of a dedicated planning [F18] FDG-Positron emission tomography/computer tomography (PET/CT) for harmonization of gross tumor volume (GTV) delineation and the feasibility of semiautomated structures for planning purposes in a large cohort. Methods Patients receiving a dedicated planning [F18] FDG-PET/CT (06/2011–03/2016) were included. GTV was delineated on CT and on PET/CT (GTVCT and GTVPET/CT, respectively) by three independent radiation oncologists. Interobserver variability was evaluated by comparison of mean GTV and mean tumor lengths, and via Sørensen–Dice coefficients (DSC) for spatial overlap. Semiautomated volumes were constructed based on PET/CT using fixed standardized uptake values (SUV) thresholds (SUV30, 35, and 40) or background- and metabolically corrected PERCIST-TLG and Schaefer algorithms, and compared to manually delineated volumes. Results 45 cases were evaluated. Mean GTVCT and GTVPET/CT were 59.2/58.0 ml, 65.4/64.1 ml, and 60.4/59.2 ml for observers A–C. No significant difference between CT- and PET/CT-based delineation was found comparing the mean volumes or lengths. Mean Dice coefficients on CT and PET/CT were 0.79/0.77, 0.81/0.78, and 0.8/0.78 for observer pairs AB, AC, and BC, respectively, with no significant differences. Mean GTV volumes delineated semiautomatically with SUV30/SUV35/SUV40/Schaefer’s and PERCIST-TLG threshold were 69.1/23.9/18.8/18.6 and 70.9 ml. The best concordance of a semiautomatically delineated structure with the manually delineated GTVCT/GTVPET/CT was observed for PERCIST-TLG. Conclusion We were not able to show that the integration of PET/CT for GTV delineation of the primary tumor resulted in reduced interobserver variability. The PERCIST-TLG algorithm seemed most promising compared to other thresholds for further evaluation of semiautomated delineation of esophageal cancer.

Purpose In photon radiotherapy, respiratory‐induced target motion can be accounted for by internal target volumes (ITV) or mid‐ventilation target volumes (midV) defined on the basis of four‐dimensional computed tomography (4D‐CT). Intrinsic limitations of these approaches can result in target volumes that are not representative for the gross tumor volume (GTV) motion over the course of treatment. To address these limitations, we propose a novel patient‐specific ITV definition method based on real‐time 4D magnetic resonance imaging (rt‐4DMRI). Methods Three lung cancer patients underwent weekly rt‐4DMRI scans. A total of 24 datasets were included in this retrospective study. The GTV was contoured on breath‐hold MR images and propagated to all rt‐4DMRI images by deformable image registration. Different targets were created for the first (reference) imaging sessions: ITVs encompassing all GTV positions over the complete (ITVurn:x-wiley:00942405:media:mp14023:mp14023-math-0001) or partial acquisition time (urn:x-wiley:00942405:media:mp14023:mp14023-math-0002), ITVs including only voxels with a GTV probability‐of‐presence (POP) of at least 5% (urn:x-wiley:00942405:media:mp14023:mp14023-math-0003) or 10% (urn:x-wiley:00942405:media:mp14023:mp14023-math-0004), and the mid‐ventilation GTV position. Reference planning target volumes (urn:x-wiley:00942405:media:mp14023:mp14023-math-0005) were created by adding margins around the ITVs and midV target volumes. The geometrical overlap of the urn:x-wiley:00942405:media:mp14023:mp14023-math-0006 with urn:x-wiley:00942405:media:mp14023:mp14023-math-0007 from the six to eight subsequent imaging sessions on days n was quantified in terms of the Dice similarity coefficient (DSC), sensitivity [SE: (urn:x-wiley:00942405:media:mp14023:mp14023-math-0008)/urn:x-wiley:00942405:media:mp14023:mp14023-math-0009] and precision [PRE: (urn:x-wiley:00942405:media:mp14023:mp14023-math-0010)/urn:x-wiley:00942405:media:mp14023:mp14023-math-0011] as surrogates for target coverage and normal tissue sparing. Results Patient‐specific analysis yielded a high variance of the overlap values of urn:x-wiley:00942405:media:mp14023:mp14023-math-0012, when different periods within the reference imaging session were sampled. The mid‐ventilation‐based PTVs were smaller than the ITV‐based PTVs. While the SE was high for patients with small breathing pattern variations, changes of the median breathing amplitudes in different imaging sessions led to inferior SE values for the mid‐ventilation PTV for one patient. In contrast, urn:x-wiley:00942405:media:mp14023:mp14023-math-0013 and urn:x-wiley:00942405:media:mp14023:mp14023-math-0014 showed higher SE values with a higher robustness against interfractional changes, at the cost of larger target volumes. Conclusions The results indicate that rt‐4DMRI could be valuable for the definition of target volumes based on the GTV POP to achieve a higher robustness against interfractional changes than feasible with today’s 4D‐CT‐based target definition concepts.

Background This study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results. Methods A total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan–Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors. Results During the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8–53.8; reverse Kaplan–Meier median follow-up time 56.3 months, 95% CI: 51.9–60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1‑year, 3‑year, and 5‑year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation. Conclusion Outcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation.

Introduction: Thoracic re-irradiation for recurrent lung cancer dates back four decades, when the first small series on 29 patients receiving palliative doses was published. With 5-year overall survival rates of 57% in PDL-1 positive patients after primary chemo-radio-immunotherapy, the number of patients who experience loco-regional relapse will increase in the near future. In this context, centrally recurring lung tumors pose a major treatment challenge. Hence, the aim of the current review is to compile the available evidence on curatively intended thoracic re-irradiation for this special clinical situation. Methods: A systematic literature search according to the PRISMA guidelines was performed. A study was included when the following criteria were met: (1) 66% of the patients had NSCLC, (2) a total dose of 50 Gy in the second course and/or a biologically effective dose of at least 100 Gy in both treatment courses was administered, (3) re-irradiation was administered with modern radiation techniques, (4) 50% or more of the patients had a centrally located relapse, (5) the minimum cohort size was 30 patients. Results: Of the initial 227 studies, 11 were analyzed, 1 of which was prospective. Median overall survival (OS) was 18.1 months (range 9.3–25.1), median progression free survival (PFS) was nine months (range 4.5–16), and median loco-regional control (LRC) was 12.1 months (range 6.5–20). Treatment-related mortality rates ranged from 2% to 14%. The total dose at re-irradiation correlated with both LRC (p-value = 0.012) and OS (p-value = 0.007) with a close relation between these two clinical endpoints (p-value = 0.006). The occurrence of acute toxicity grade 1 to 4 depended on the PTV size at re-irradiation (p-value = 0.033). Conclusion: The evidence regarding curative re-irradiation for centrally recurrent NSCLC is primarily based on scarce retrospective data, which are characterized by a high degree of heterogeneity. The OS in this clinically challenging situation is expected to be around 1.5 years after re-treatment. Patients with a good performance score, younger age, small tumors, and a longer interval to recurrence potentially benefit most from re-irradiation. In this context, prospective trials are warranted to achieve substantial advances in the field.

Optimal doses for the treatment of adrenal metastases with stereotactic radiotherapy (SBRT) are unknown. We aimed to identify dose-volume cut-points associated with decreased local recurrence rates (LRR). A multicenter database of patients with adrenal metastases of any histology treated with SBRT (biologically effective dose, BED10 ≥50 Gy, ≤12 fractions) was analyzed. Details on dose-volume parameters were required (planning target volume: PTV-D98%, PTV-D50%, PTV-D2%; gross tumor volume: GTV-D50%, GTV-mean). Cut-points for LRR were optimized using the R maxstat package. One hundred and ninety-six patients with 218 lesions were included, the largest histopathological subgroup was adenocarcinoma (n=101). Cut-point optimization resulted in significant cut-points for PTV-D50% (BED10: 73.2 Gy; P= .003), GTV-D50% (BED10: 74.2 Gy; P= .006), GTV-mean (BED10: 73.0 Gy; P= .007), and PTV-D2% (BED10: 78.0 Gy; P= .02) but not for the PTV-D98% (P= .06). Differences in LRR were clinically relevant (LRR ≥ doubled for cut-points that were not achieved). Further dose-escalation was not associated with further improved LRR. PTV-D50%, GTV-D50%, and GTV-mean cut-points were also associated with significantly improved LRR in the adenocarcinoma subgroup. Separate dose optimizations indicated a lower cut-point for the PTV-D50% (BED10: 69.1 Gy) in adenocarcinoma lesions, other values were similar (73.2 Gy (adenocarcinoma: 69.1 Gy) should be considered.

Total neoadjuvant therapy (TNT)—the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery—may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians—without any claim to general validity.

Retrospective evaluation of stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC). We retrospectively analyzed 36 patients (45 lesions) treated between 2011 and 2017. Twenty-seven had previous treatments. Current treatment consisted of SBRT alone (n = 15) or selective transarterial chemoembolization (TACE) followed by SBRT to the same lesions (n = 21). Eight patients received additional local treatments to different lesions. Liver function was predominantly moderately restricted (Child A: 29, Child B: 6, Child C: 1). Treatment planning was based on 4D-computed tomography, dose/fractionation varied depending on location and size, most commonly 3 fractions of 12.5 Gy (65% isodose) and 5 fractions of 8 Gy (80% isodose). Median follow-up was 15 months. Local recurrence was observed in 3 lesions (7%), resulting in 1‑and 2‑year local control rates of 93%. The only significantly predicting factor was the use of abdominal compression. New hepatic lesions occurred in 19 patients (52%), 1‑ and 2‑year freedom-from-hepatic-failure (FFHF) was 39% and 32%, respectively. Only the number of treated lesions was predictive for FFHF. Sixteen patients have died, resulting in 1‑ and 2‑year overall survival (OS) of 64% and 41%, respectively, significantly impacted by the number of treated lesions and Child–Pugh class. Severe acute and late toxicity (≥grade 3) was observed in 3% and 8%, respectively. 6 patients (17%) received liver transplantation (OLT) after SBRT, of whom 5 showed pathological complete remission. SBRT (±TACE) in highly pretreated HCC is effective and associated with excellent LC and low toxicity. SBRT may be used as definitive or bridging treatment prior to OLT. Patients with multifocal lesions have significantly decreased 1‑ and 2‑year FFHF and OS.

This multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non-small-cell lung cancer (NSCLC).This analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT.The median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed.SBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.

Purpose The need for four-dimensional (4D) treatment planning becomes indispensable when it comes to radiation therapy for moving tumors in the thoracic and abdominal regions. The primary purpose of this study is to combine the actual breathing trace during each individual treatment fraction with the Linac's log file information and Monte Carlo 4D dose calculations. We investigated this workflow on multiple computed tomography (CT) datasets in a clinical environment for stereotactic body radiation therapy (SBRT) treatment planning. Methods We have developed a workflow, which allows us to recalculate absorbed dose to a 4DCT dataset using Monte Carlo calculation methods and accumulate all 4D doses in order to compare them to the planned dose using the Linac's log file, a 4DCT dataset, and the patient's actual breathing curve for each individual fraction. For five lung patients, three-dimensional-conformal radiation therapy (3D-CRT) and volumetric modulated arc treatment (VMAT) treatment plans were generated on four different CT image datasets: a native free-breathing 3DCT, an average intensity projection (AIP) and a maximum intensity projection (MIP) CT both obtained from a 4DCT, and a 3DCT with density overrides based on the 3DCT (DO). The Monte Carlo 4D dose has been calculated on each 4DCT phase using the Linac's log file and the patient's breathing trace as a surrogate for tumor motion and dose was accumulated to the gross tumor volume (GTV) at the 50% breathing phase (end of exhale) using deformable image registration. Results Δ D 98 % and Δ D 2 % between 4D dose and planned dose differed largely for 3DCT-based planning and also for DO in three patients. Least dose differences between planned and recalculated dose have been found for AIP and MIP treatment planning which both tend to be superior to DO, but the results indicate a dependency on the breathing variability, tumor motion, and size. An interplay effect has not been observed in the small patient cohort. Conclusions We have developed a workflow which, to our best knowledge, is the first incorporation of the patient breathing trace over the course of all individual treatment fractions with the Linac's log file information and 4D Monte Carlo recalculations of the actual treated dose. Due to the small patient cohort, no clear recommendation on which CT can be used for SBRT treatment planning can be given, but the developed workflow, after adaption for clinical use, could be used to enhance a priori 4D Monte Carlo treatment planning in the future and help with the decision on which CT dataset treatment planning should be carried out.

Stereotactic body radiation therapy (SBRT) is an emerging treatment for hepatocellular carcinoma. This technique results in excellent local control rates with favorable toxicity profile despite being predominantly used in heavily pretreated patients or those unsuitable for other local therapies. SBRT may be used as a sole treatment or in combination with other local therapies as well as a bridging strategy for patient awaiting liver transplants. This brief review describes current practice of SBRT with respect to radiation technique, patient selection and treatment concepts. It summarizes available evidence from retro- and prospective studies evaluating SBRT alone, SBRT in combination with other treatments and SBRT compared to other local treatment approaches.

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

Background To analyse the outcome of elderly patients (≥70 years) with esophageal cancer treated with curative intent radio(chemo)therapy. Methods Fifty five patients (median 75 years) receiving curative intent radio(chemo)therapy for esophageal cancer from 1999 to 2015 were retrospectively analyzed. Most patients showed locally advanced disease (T3/4:78%, N+:58%) with squamous cell histology (74%). Charlson comorbidity score was > 1 in 27%. 48 patients (87%) received definitive treatment while 7 patients were treated neoadjuvantly. RT was carried out as 3D-conformal treatment or IMRT. Concurrent chemotherapy was applied in 85%, mainly cisplatin/5-FU or mitomycin/5-FU. 18FDG-PET/CT staging was used in 65%. Results Median follow-up was 11 months (1–68) and 21 months in survivors. 1- and 2-year rates of LRC, DC, FFTF and OS were 60%/45, 81%/72, 55%/41 and 46%/26% for the entire cohort. In univariate analysis, addition of surgery was associated with improved LRC and FFTF, nodal involvement with improved DC and lower T stage, lower Charlson score and use of PET-CT with improved OS. In multivariate analysis, lower T stage and lower Charlson score remained significant for OS. Patients treated after 2008 showed a significantly improved FFTF (1-year FFTF 64% vs 35%) and OS (1-year OS 66% vs 24%). Maximum (chemo)radiation related grade3+ toxicity was observed in 80% including 7 deaths (13%). Grade5 toxicity was significantly associated with Charlson score (CS > 1:33% vs CS ≤ 1:5%) and treatment period (24% before vs 3% after 2008). The patients treated after 2008 included significantly more SCCs, less T4 stages, had a higher percentage of PET-CT staging and were treated with smaller field lengths. Trends were also observed for lower Charlson scores and increased use of IMRT. Conclusion Curative intent (chemo)radiation of elderly patients with esophageal cancer may result in considerable toxicity and unfavorable outcome. However, a clear improvement over time was observed in our cohort, probably based on improved patient selection. In patients with less advanced stages and lower comorbidity similar results as in younger cohorts seem achievable with modern staging and treatment approaches. Age per se should not be a decisive factor, but careful attention should be paid regarding patient selection including a structured and tight follow-up strategy.

Background Stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by an excellent safety profile; however, experiences are mostly based on treatment of one single metastasis. It was the aim of this study to evaluate safety and efficacy of SBRT for multiple pulmonary metastases. Patients and methods This study is based on a retrospective database of the DEGRO stereotactic working group, consisting of 637 patients with 858 treatments. Cox regression and logistic regression were used to analyze the association between the number of SBRT treatments or the number and the timing of repeat SBRT courses with overall survival (OS) and the risk of early death. Results Out of 637 patients, 145 patients were treated for multiple pulmonary metastases; 88 patients received all SBRT treatments within one month whereas 57 patients were treated with repeat SBRT separated by at least one month. Median OS for the total patient population was 23.5 months and OS was not significantly influenced by the overall number of SBRT treatments or the number and timing of repeat SBRT courses. The risk of early death within 3 and 6 months was not increased in patients treated with multiple SBRT treatments, and no grade 4 or grade 5 toxicity was observed in these patients. Conclusions In appropriately selected patients, synchronous SBRT for multiple pulmonary oligometastases and repeat SBRT may have a comparable safety and efficacy profile compared to SBRT for one single oligometastasis.

The increasing use of targeted therapy (TT) has resulted in prolonged disease control and survival in many metastatic cancers. In parallel, stereotactic radiotherapy (SRT) is increasingly performed in patients receiving TT to obtain a durable control of resistant metastases, and thereby to prolong the time to disseminated disease progression and switch of systemic therapy. The aims of this study were to analyze the safety and efficacy of SRT combined with TT in metastatic cancer patients and to assess the influence of continuous vs. interrupted TT during metastasis-directed SRT. The data of 454 SRTs in 158 patients from the international multicenter database (TOaSTT) on metastatic cancer patients treated with SRT and concurrent TT (within 30 days) were analyzed using Kaplan–Meier and log rank testing. Toxicity was defined by the CTCAE v4.03 criteria. The median FU was 19.9 mo (range 1–102 mo), 1y OS, PFS and LC were 59%, 24% and 84%, respectively. Median TTS was 25.5 mo (95% CI 11–40). TT was started before SRT in 77% of patients. TT was interrupted during SRT in 44% of patients, with a median interruption of 7 (range 1–42) days. There was no significant difference in OS or PFS whether TT was temporarily interrupted during SRT or not. Any-grade acute and late SRT-related toxicity occurred in 63 (40%) and 52 (33%) patients, respectively. The highest toxicity rates were observed for the combination of SRT and EGFRi or BRAF/MEKi, and any-grade toxicity was significantly increased when EGFRi (p = 0.016) or BRAF/MEKi (p = 0.009) were continued during SRT. Severe (≥grade 3) acute and late SRT-related toxicity were observed in 5 (3%) and 7 (4%) patients, respectively, most frequently in patients treated with EGFRi or BRAF/MEKi and in the intracranial cohort. There was no significant difference in severe toxicity whether TT was interrupted before and after SRT or not. In conclusion, SRT and continuous vs. interrupted TT in metastatic cancer patients did not influence OS or PFS. Overall, severe toxicity of combined treatment was rare, a potentially increased toxicity after SRT and continuous treatment with EGFR inhibitors or BRAF(±MEK) inhibitors requires further evaluation.

Background: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. Methods: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. Results: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. Conclusion: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Primary aldosteronism (PA), the most common form of secondary hypertension, causes relevant morbidity. The value of salivary measurements of aldosterone in clinical routine in PA so far has not been assessed. First, we analyzed salivary and plasma aldosterone concentrations of 42 patients with PA and 37 hypertensive controls (HC) during a sodium infusion test prospectively. Second, morning salivary and plasma aldosterone concentrations as well as diurnal saliva aldosterone profiles were analyzed in 115 patients treated for PA (46 adrenalectomy, 56 spironolactone, 13 eplerenone). Salivary aldosterone was substantially elevated in PA patients compared to HC at baseline (106±119 vs. 40±21 ng/l, p=0.01), and after 4-h sodium infusion test (60±36 vs. 23±14, p=0.01). Positive correlation between salivary and plasma aldosterone levels was evident, with exception of concentrations in or below the lower normal range. Applying a salivary aldosterone cutoff of 51.2 ng/l, found by ROC curve analysis, rendered a sensitivity of 81% and a specificity of 73% for PA. The diurnal rhythm of aldosterone was preserved in untreated PA patients, but concentrations were higher in the context of PA, and normalized after surgery (118±57 vs. 31±18 ng/l, p0.01). Taken together, salivary aldosterone measurements correlate with plasma levels, allowing simple and cost effective assessments of aldosterone secretion in an outpatient setting. Nevertheless, as this method alone cannot replace other plasma parameters, and as aldosterone profiling would not alter diagnostic or treatment strategies, salivary aldosterone measurements in routine practice are of limited clinical value.

Pancreatic ductal adenocarcinoma (PDAC) is a highly devastating disease with poor prognosis and rising incidence. Late detection and a particularly aggressive biology are the major challenges which determine therapeutic failure. In this review, we present the current status and the recent advances in PDAC treatment together with the biological and immunological hallmarks of this cancer entity. On this basis, we discuss new concepts combining distinct treatment modalities in order to improve therapeutic efficacy and clinical outcome – with a specific focus on protocols involving radio(chemo)therapeutic approaches.

Purpose Non-resectable cholangiocarcinoma (CCC) is a significant therapeutic challenge because of bad prognosis. This study analyzed the outcome after SBRT for intra- and extrahepatic CCC. Material and methods Sixty-four patients with 82 CCC lesions from a retrospective multicenter database were analyzed. Available parameters were analyzed for local control (LC), overall survival (OS) and toxicity. Results Median follow-up time for patients alive was 35 months (range 7–91 months). Median overall survival (OS) time was 15 months; 2-year and 3-year OS rates were 32% and 21%. Median prescribed biological effective radiation dose (BED, α/β = 10) was 67.2 Gy10 (range, 36–115 Gy10; SD: 20 Gy10) in median 8 fractions (range, 3–17; 95% CI: 3–12), median BEDmax was 91 Gy10. BED was the only prognostic factor for LC and OS. Patients receiving BEDmax >91 Gy10 had a median OS of 24 months vs. 13 months for those receiving lower doses (p = 0.008). LC rates at 12 and 24 months were 91% and 80% for BEDmax >91 Gy10 vs. 66% and 39% for lower doses (p = 0.009). Of note, tumor size and PTV were neither predictive nor prognostic for LC and OS. Treatment tolerance was good with 17% of grade 1 gastroduodenitis, 11% of grade 2–3 cholangitis and 4.7% of grade 3 gastrointestinal bleeding. Conclusion This is the largest reported series on SBRT in cholangiocarcinoma. Overall survival and local control were significantly improved after higher doses (BED) and tolerance was excellent.

Background To report our experience with SBRT in primary and secondary liver tumors. Methods We retrospectively analysed 55 patients (70 lesions) with a median follow-up of 10 months (range 1–57) treated from 2011 to 2016. All patients had not been eligible for other local treatment options. Median age was 64 years and 64% were male. 27 patients (36 lesions) suffered from hepatocellular carcinoma (HCC, Child A:78%, Child B:18%, Child C:4%), 28 patients (34 lesions) had oligometastatic liver disease (MD). Treatment planning was based on 4D-CT usually after placement of fiducials. Dose and fractionation varied depending on localization and size, most commonly 3 × 12.5 Gy (prescribed to the surrounding 65%-isodose) in 56% and 5x8Gy (80% isodose) in 20% of the treated lesions. Results Local recurrence was observed in 7 patients (13%) and 8 lesions (11%), resulting in estimated 1- and 2-year local control rates (LC) of 91 and 74%. Estimated 1- and 2-year rates of Freedom from hepatic failure (FFHF) were 42 and 28%. Number of lesions was predictive for LC and FFHF in the entire cohort. Estimated 1- and 2-year overall survival (OS) was 76 and 57%. OS was significantly affected by number of treated lesions and performance status. In the HCC subgroup, pretreatment liver function and gender were also predictive for OS. Maximum acute non-hepatic toxicity was grade 1 in 16% and grade 2 in 10% of the patients. Three HCC patients (11%) developed marked deterioration of liver function (grade 3/4). Conclusions SBRT resulted in high local control and acceptable survival rates in patients with HCC or MD not amendable to other locally-ablative treatment options with limited toxicity. Care should be taken in HCC patients with Child B cirrhosis.

Background The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. Methods From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. Results In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. Conclusion After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

Background and Aims: Stereotactic body radiation therapy (SBRT) has emerged as a safe and effective treatment for patients with hepatocellular carcinoma (HCC), but its role in patients with advanced HCC is not yet defined. In this study, we aim to assess the efficacy and safety of SBRT in comparison to sorafenib treatment in patients with advanced HCC. Methods: We included 901 patients treated with sorafenib at six tertiary centers in Europe and Asia and 122 patients treated with SBRT from 13 centers in Germany and Switzerland. Medical records were reviewed including laboratory parameters, treatment characteristics and development of adverse events. Propensity score matching was performed to adjust for differences in baseline characteristics. The primary endpoint was overall survival (OS) and progression-free survival. Results: Median OS of SBRT patients was 18.1 (10.3–25.9) months compared to 8.8 (8.2–9.5) in sorafenib patients. After adjusting for different baseline characteristics, the survival benefit for patients treated with SBRT was still preserved with a median OS of 17.0 (10.8–23.2) months compared to 9.6 (8.6–10.7) months in sorafenib patients. SBRT treatment of intrahepatic lesions in patients with extrahepatic metastases was also associated with improved OS compared to patients treated with sorafenib in the same setting (17.0 vs. 10.0 months, p = 0.012), whereas in patients with portal vein thrombosis there was no survival benefit in patients with SBRT. Conclusions: In this retrospective comparative study, SBRT showed superior efficacy in HCC patients compared to patients treated with sorafenib.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all pBACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases.PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases.RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all pCONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Introduction Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. Methods 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BED max ). Results After adjusting for histology, BED max was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy 10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy 10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BED max of 157±80Gy 10 or 80±62Gy 10 with and without prior chemotherapy, respectively. Conclusions Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Respiratory motion remains a source of major uncertainties in radiotherapy. Respiratory correlated computed tomography (referred to as 4DCT) serves as one way of reducing breathing artifacts in 3D-CTs and allows the investigation of tumor motion over time. The quality of the 4DCT images depends on the data acquisition scheme, which in turn is dependent on the vendor. Specifically, the only way Toshiba Aquilion LB CT scanners can reconstruct 4DCTs is a cycle-based reconstruction using triggers provided by an external surrogate signal. The accuracy is strongly dependent on the method of trigger generation. Two consecutive triggers are used to define a breathing cycle which is divided into respiratory phases of equal duration. The goal of this study is to identify if there are advantages in the usage of local-amplitude based sorting (LAS) of the respiration motion states, in order to reduce image artifacts and improve 4DCT quality. Furthermore, this study addresses the generation and optimization of a clinical workflow using as surrogate motion monitoring system the Sentinel™ (C-RAD AB, Sweden) optical surface scanner in combination with a Toshiba Aquilion LB CT scanner. For that purpose, a phantom study using 10 different breathing waveforms and a retrospective patient study using the 4DCT reconstructions of 10 different patients has been conducted. The error in tumor volume has been reduced from 2.9±3.7% to 2.7±2.6% using optimal cycle-based triggers (manipulated CBS) and to 2.7±2.2% using LAS in the phantom study. Moreover, it was possible to decrease the tumor volume variability from 5.0±3.6% using the original cycle-based triggers (original CBS) to 3.5±2.5% using the optimal triggers and to 3.7±2.7% using LAS in the patient data analysis. We therefore propose the usage of the manipulated CBS, also with regard to an accurate and safe clinical workflow.

Purpose Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS). Methods and Materials A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS. Results Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval [CI] 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively ( P =.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers ( P ≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC. Conclusion Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center.

Psychopathological symptoms in patients with primary aldosteronism (PA) have been reported. In a cross-sectional design the self-reported physical and mental condition among patients with PA of the German Conn's Registry differently treated during the course of the disease were analysed. 27 patients were investigated before initiation of specific therapy (U), 56 patients were on chronic mineralocorticoid antagonist treatment (MRA) and 49 patients had undergone adrenalectomy (ADX). Patient's quality of life was analysed with the SF-12 for a Physical (PCS) and a Mental Component (MCS). Statistically significant lower scores for PCS were found for female PA patients treated with MRA in comparison to ADX patients and the German reference population (36.4 ± 11.1 vs. 49.1 ± 10.9 (p = 0.024) vs. 47.9 ± 9.7 (p = 0.001)), respectively. Concerning MCS, untreated female patients scored significantly lower (36.5 ± 7.4) than females from the German population (51.3 ± 8.4, p = 0.000). Furthermore, untreated females appear to differ significantly from MRA and ADX females, scoring the lowest reading (U vs. MRA: p = 0.029; U vs. ADX: p = 0.005). Significant correlations were found between plasma aldosterone (r = -0.819, p = 0.013) and the MCS and between plasma renin concentration and MCS (r = -0.938, p = 0.001) in female MRA patients. In summary, PA patients report a worse physical and mental condition than the one reported for the German reference population. Untreated and mineralocorticoid antagonist treated patients report the lowest readings. Females were found to be more impaired than males in QoL. MRA treatment seems to affect the MCS of female patients.

Objectives The current literature on stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by small patient cohorts with heterogeneous primary tumors, metastases location and dose regimes. Hence, this study established a multi-institutional database of 700 patients treated with SBRT for pulmonary metastases to identify prognostic factors influencing survival and local control. Materials and methods All German radiotherapy departments were contacted and invited to participate in this analysis. A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in a database. Primary and metastatic tumor characteristics, treatment characteristics and follow-up data including survival, local control, distant metastases, and toxicity were evaluated. Lung metastases were treated with median PTV-encompassing single doses of 12.5 Gy (range 3.0–33.0 Gy) in a median number of 3 fractions (range 1–13). Results After a median follow-up time of 14.3 months, 2-year local control (LC) and overall survival (OS) were 81.2% and 54.4%, respectively. In multivariate analysis, OS was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases. For LC, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter (BEDISO) and single fraction (PTV-encompassing) dose in multivariate analysis. Radiation-induced pneumonitis grade 2 or higher was observed in 6.5% of patients. The only factor significantly influencing toxicity was BEDISO (p = 0.006). Conclusion SBRT for medically inoperable patients with pulmonary metastases achieved excellent local control and promising overall survival. Important prognostic factors were identified for selecting patients who might benefit most from this therapy approach.

Background Fiducial markers are the superior method to compensate for interfractional motion in liver SBRT. However this method is invasive and thereby limits its application range. In this retrospective study, the compensation method for the interfractional motion using fiducial markers (gold standard) was compared to a new non-invasive approach, which does rely on the organ motion of the liver and the relative tumor position within this volume. Methods We analyzed six patients (3 m, 3f) treated with SBRT in 2014. After fiducial marker implantation, all patients received a treatment CT (free breathing, without abdominal compression) and a 4D-CT (consisting of 10 respiratory phases). For all patients the gross tumor volumes (GTVs), internal target volume (ITV), planning target volume (PTV), internal marker target volumes (IMTVs) and the internal liver target volume (ILTV) were delineated based on the CT and 4D-CT images. CBCT imaging was used for the standard treatment setup based on the fiducial markers. According to the patient coordinates the 3 translational compensation values (tx, ty, tz) for the interfractional motion were calculated by matching the blurred fiducial markers with the corresponding IMTV structures. 4 observers were requested to recalculate the translational compensation values for each CBCT (31) based on the ILTV structures. The differences of the translational compensation values between the IMTV and ILTV approach were analyzed. Results The magnitude of the mean absolute 3D registration error with regard to the gold standard overall patients and observers was 0.50 cm ± 0.28 cm. Individual registration errors up to 1.3 cm were observed. There was no significant overall linear correlation between the respiratory motion and the registration error of the ILTV approach. Conclusions Two different methods to calculate the translational compensation values for interfractional motion in stereotactic liver therapy were evaluated. The registration accuracy of the ILTV approach is mainly limited by the non-rigid behavior of the liver and the individual registration experience of the observer. The ILTV approach lacks the accuracy that would be desired for stereotactic radiotherapy of the liver.

Recent evidence demonstrates an increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population, making noninvasive and simple screening methods necessary. The aim of the present study was to apply a time-resolved fluorescence immunoassay for the measurement of aldosterone in saliva and the establishment of a cut-off to identify patients with a high likelihood for PA requiring subsequent screening with the aldosterone to renin ratio. Saliva was collected (AM and PM) to ascertain an optimum time with best discriminating power between healthy and disease states. Plasma aldosterone, after overnight recumbency and 4 h later, was collected for posture testing. The participants included 53 PA patients (aged 14-78), 54 with essential hypertension (EH, aged 19-82), and 38 healthy volunteers (aged 19-56). Saliva aldosterone (SA) (median, 25-75 th %) in PA was found at 90 pg/ml (61-139) compared to 53 pg/ml (40-85) in EH, with discrimination between PA versus EHs best in the morning (cutoff: 81 pg/ml, 77% sensitivity, 82% specificity). Saliva aldosterone decreases throughout the day in patients with adenomas [APA AM: 123 pg/ml (92-213) vs. PM: 79 pg/ml (41-116)], but not in those with bilateral hyperplasia [BAH AM: 85 pg/ml (59-115)] vs. pm 69 pg/ml (57-114). Morning SA alone allows discrimination between PA and controls, though with significant overlap against EHs, leading to a high number of false positives. More promising is the use of diurnal variation in SA in distinguishing between APA and BAH. The decline in SA seen in patients with APA presents a more constant finding compared to posture testing, which fails to correctly classify a large number of patients.