Search

Background: Chemo-radioimmunotherapy with total radiation doses of 60-66 Gy in 2 Gy fractions is the standard of care for non-small cell lung cancer (NSCLC) UICC stage III. The Austrian radio-oncological lung cancer study association registry (ALLSTAR) is a prospective multicentre registry intended to document clinical practice at the beginning of the Durvalumab era., Patients and Methods: Patients were eligible if they had pathologically verified unresectable NSCLC stage III with a curative treatment option. Chemo-radiation combined with immunotherapy was performed according to local treatment practices. The endpoints were local control (LC), progression-free survival (PFS) and toxicity., Results: Between 2020/03 and 2023/04, 12/14 (86 %) Austrian radiation-oncology centres recruited 188 patients (median 17, range: 1-89). PD-L1 testing was performed in 173/188 (93 %) patients. The median interval between the end of chemoradiotherapy and start of Durvalumab was 14 days (range: 1-65). About 40 % (75/188) of the patients received a total radiation dose of > 66 Gy (range: 67.1-100), which improved 2-year LC (86 % versus 60 %, HR = 0.41; 95 %-CI: 0.17-0.98; log-rank p-value < 0.05). Median PFS for patients with Durvalumab was 25.8 months (95 %-CI: 21.9-not reached) compared to 15.7 months (95 %-CI: 13.2-27.8) for those without (HR = 1.88; 95 %-CI: 1.16-3.05; log-rank p-value < 0.01). The rates of esophageal and pulmonary toxicities were 34.6 % and 23.9 %, respectively, including one case of grade 4 pneumonitis. In the subcohort of 75 patients who received > 66 Gy, 19 (25 %) cases of pulmonary toxicity grades 1-3 were observed., Conclusion: While Durvalumab impacts PFS, LC can be improved by total radiation doses > 66 Gy without excess toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification., Objective: This study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging., Materials and Methods: A retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes., Results: Of 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common., Conclusion: New nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important., (© 2024. The Author(s).)

Purpose: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes., Methods: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS)., Results: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression., Conclusion: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA., (© 2023. The Author(s).)

Background: There is lack of consensus whether neoadjuvant chemoradiotherapy (CHT/RT) is superior to neoadjuvant chemotherapy (CHT) alone in patients with potentially resectable stage III/N2 non-small-cell lung cancer (NSCLC)., Patients and Methods: We retrospectively evaluated clinical parameters and outcomes in patients with clinical stage III/N2 NSCLC treated with neoadjuvant CHT/RT versus CHT followed by surgery. Nearest-neighbor propensity score (PS) matching was used to correct for pretreatment differences., Results: A total of 84 patients were enrolled. Thirty-four (40%) and 50 (60%) patients received CHT/RT or CHT followed by curative-intent surgery, respectively. Overall 90-day mortality and morbidity were 0% versus 0.04% and 21% versus 18%, respectively, with no significant difference between the CHT/RT and the CHT-alone cohorts (P = 0.51 and P = 0.70). In the PS-matched cohort, complete pathological response was recorded in 25% after CHT/RT versus 0% after CHT at the time of surgery. Patients receiving neoadjuvant CHT/RT exhibited significantly better 5-year disease-free survival (DFS) [45% versus 16% CHT group; hazard ratio (HR) 0.43, P = 0.04]; 5-year overall survival (OS) was 75% after CHT/RT and 21% after CHT (HR 0.37, P = 0.001). CHT/RT more often induced pathological mediastinal downstaging (P = 0.007), but CHT/RT remained the only independent factor for DFS and OS and did not depend on mediastinal downstaging., Conclusions: In this retrospective PS-matched long-term analysis, neoadjuvant CHT/RT conferred improved DFS and OS compared with CHT alone in stage III/N2 NSCLC. These highly challenging results require confirmation in well-designed randomized controlled trials conducted at highly specialized thoracic oncology centers., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: An accurate classification of patients with brain metastases (BMs) is an important foundation to guide individualised treatment decisions and to formulate BM cohorts for modern clinical trials., Methods: Six thousand and thirty-one patients with newly diagnosed BM from different solid tumours treated between 1986 and 2020 were identified from the Vienna Brain Metastasis Registry., Results: A rising fraction of patients presented with asymptomatic BM during the observation period (1986-1999: 20.2% vs 2010-2020: 30.6%; p < 0.001). Especially, oncogene-addicted non-small-cell lung cancer (NSCLC) and BRAF (v-Raf murine sarcoma viral oncogene homolog)-positive melanoma had a higher rate of asymptomatic BM presentation compared with wild-type tumours (p < 0.05). Significant changes of initial BM treatment approaches were observed with a decrease of neurosurgical procedures (1986-1999: 30.8% vs 2010-2020: 19.5%) and an increase of radiation treatments (1986-1999: 65.0% vs 2010-2020: 73.3%) and systemic therapies (1986-1999: 1.0% vs 2010-2020: 2.0%; p < 0.001). Median overall survival (OS) was heterogeneous between primary tumour entities but with an overall increase over the decades (median OS 1986-1999: 5 months vs 2010-2020: 7 months; p = 0.001). Survival times were longer in patients with oncogene-addicted NSCLC, BRAF-positive melanoma and hormone receptor-positive breast cancer compared with the other cancer subtypes (p > 0.05)., Conclusion: Our data highlight shifting trends in the symptomatic presentation and in treatment strategies of patients with BM over the last decades. Entity specific aspects and, in particular, the presence of targetable driver mutation impact the clinical presentation and prognosis. Future BM specific trials need to address the modern composition of BM cohorts and the distinct clinical course of patients with targetable driver mutations., Competing Interests: Conflict of interest statement ASB has research support from Daiichi Sankyo (≤10,000€), Roche (>10,000€) and honoraria for lectures, consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo (all <5000€) as well as travel support from Roche, Amgen and AbbVie. GW received restricted travel grants from NX Development Corp. MP has received research support from Böhringer-INgelheim, GlaxoSmithKline, Merck Sharp & Dome and Roche and honoraria for lectures, consultation or advisory board participation from Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome. AMS has received travel support from PharmaMar. All other authors report no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer., Methods: Twenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed., Results: Following decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors., Conclusion: After presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The success of intensification and personalisation of the curative treatment of non-small cell lung cancer (NSCLC) is strongly associated with the precision in radiotherapy. Here, we evaluate the impact of radiotherapy protocol adherence in a prospective multicentre trial., Methods: In the open-label, randomised, controlled PET-Plan trial, patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume delineation informed by 1 F-FDG PET and CT plus elective nodal irradiation (arm A) or target volumes informed by PET alone (arm B) and received iso-toxically dose-escalated concurrent chemoradiation. The prospectively organised quality assurance program (RTQA) included individual case review by predefined criteria. For evaluation, protocol adherence was scored as per protocol (pP), with minor (miD), intermediate (inD) and major (maD) deviations. In order to exclude biases through patients who discontinued treatment, patients who received ≥60 Gy were additionally analysed., Results: Between 05/2009-11/2016, 205 patients were randomized, 204 patients started treatment according to protocol of which 31 (15%) patients had maD. Patients with maD had an inferior overall survival (OS) (HR 2.9, 95% CI 1.8-4.4, p < 0.0001) and a higher risk of loco-regional progression (HR 5.7, 95% CI 2.7-11.1, p < 0.0001). These results were significant also in the subgroup of patients receiving ≥ 60 Gy. Patients with maD concerning normal tissue delineation and/or dose constraints had a worse OS (p = 0.006) although no higher incidence of grade ≥ 3 toxicities., Conclusions: Non-adherence to the radiotherapy protocol was associated with an inferior OS and loco-regional control. These results underline the importance of RTQA., (Copyright © 2021. Published by Elsevier B.V.)

Background: Whole brain radiotherapy (WBRT) is a common treatment option for brain metastases secondary to non-small cell lung cancer (NSCLC). Data from the QUARTZ trial suggest that WBRT can be omitted in selected patients and treated with optimal supportive care alone. Nevertheless, WBRT is still widely used to treat brain metastases secondary to NSCLC. We analysed decision criteria influencing the selection for WBRT among European radiation oncology experts., Methods: Twenty-two European radiation oncology experts in lung cancer as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) for previous projects and by the Advisory Committee on Radiation Oncology Practice (ACROP) for lung cancer were asked to describe their strategies in the management of brain metastases of NSCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies., Results: Eight decision criteria (suitability for SRS, performance status, symptoms, eligibility for targeted therapy, extra-cranial tumour control, age, prognostic scores and "Zugzwang" (the compulsion to treat)) were identified. WBRT was recommended by a majority of the European experts for symptomatic patients not suitable for radiosurgery or fractionated stereotactic radiotherapy. There was also a tendency to use WBRT in the ALK/EGFR/ROS1 negative NSCLC setting., Conclusion: Despite the results of the QUARTZ trial WBRT is still widely used among European radiation oncology experts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Brain metastases (BM) are a frequent complication of advanced cancer and are characterized by a variety of neurological symptoms. Although the presence of neurological symptoms is included in the response assessment in patients with primary brain tumors, to the authors' knowledge little is known regarding the prognostic impact of neurological symptoms in patients with BM., Methods: Patients with newly diagnosed BM from non-small cell lung cancer were identified from the Vienna Brain Metastasis Registry and were evaluated according to the incidence, distribution, and prognostic impact of neurological symptoms at the time of diagnosis of BM., Results: A total of 1608 patients (57.3% male and 42.7% female; median age, 62 years) were available for further analyses. Neurological symptoms including focal deficits (985 patients; 61.3%), signs of increased intracranial pressure (483 patients; 30.0%), epileptic seizures (224 patients; 13.9%), and neuropsychological symptoms (233 patients; 14.5%) were documented in 1186 of the 1608 patients (73.8%). Patients with asymptomatic BM presented with a longer median overall survival after the diagnosis of BM compared with patients with symptomatic BM (11 months vs 7 months; P < .001). In multivariate analysis with a diagnosis-specific graded prognostic assessment (hazard ratio, 1.41; 95% CI, 1.33-1.50 [P < .001]), the presence of neurological symptoms (hazard ratio, 1.39; 95% CI, 1.23-1.57 [P < .001]) was found to be independently associated with survival prognosis from the time of diagnosis of BM., Conclusions: Neurological symptoms at the time of BM diagnosis demonstrated a strong and independent association with survival prognosis. The results of the current study have highlighted the need for the integration of the presence of neurological symptoms into the prognostic assessment of patients with BM from non-small cell lung cancer., Lay Summary: Neurological symptom evaluation is included regularly in the assessment of patients with primary brain tumors. However, to the authors' knowledge, little is known regarding the prognostic impact in patients with newly diagnosed brain metastases (BM). The current study has provided a detailed clinical characterization of the incidence, distribution, and prognostic impact of neurological symptoms in a large, real-life cohort of patients with BM from non-small cell lung cancer. In this cohort, neurological symptoms at the time of diagnosis of BM demonstrated a strong, independent prognostic impact on the survival prognosis. The results of the current study have highlighted the need for the integration of neurological symptom burden into the prognostic assessment of patients with BM from non-small cell lung cancer., (© 2020 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Large variation regarding prescription and dose inhomogeneity exists in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. The aim of this modeling study was to identify which dose metric correlates best with local tumor control probability to make recommendations regarding SBRT prescription., Methods and Materials: We combined 2 retrospective databases of patients with non-small cell lung cancer, yielding 1500 SBRT treatments for analysis. Three dose parameters were converted to biologically effective doses (BEDs): (1) the (near-minimum) dose prescribed to the planning target volume (PTV) periphery (yielding BED min ); (2) the (near-maximum) dose absorbed by 1% of the PTV (yielding BED max ); and (3) the average between near-minimum and near-maximum doses (yielding BED ave ). These BED parameters were then correlated to the risk of local recurrence through Cox regression. Furthermore, BED-based prediction of local recurrence was attempted by logistic regression and fast and frugal trees. Models were compared using the Akaike information criterion., Results: There were 1500 treatments in 1434 patients; 117 tumors recurred locally. Actuarial local control rates at 12 and 36 months were 96.8% (95% confidence interval, 95.8%-97.8%) and 89.0% (87.0%-91.1%), respectively. In univariable Cox regression, BED ave was the best predictor of risk of local recurrence, and a model based on BED min had substantially less evidential support. In univariable logistic regression, the model based on BED ave also performed best. Multivariable classification using fast and frugal trees revealed BED max to be the most important predictor, followed by BED ave ., Conclusions: BED ave was generally better correlated with tumor control probability than either BED max or BED min . Because the average between near-minimum and near-maximum doses was highly correlated to the mean gross tumor volume dose, the latter may be used as a prescription target. More emphasis could be placed on achieving sufficiently high mean doses within the gross tumor volume rather than the PTV covering dose, a concept needing further validation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements. Patients and methods This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally. Results Between March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokers; ECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively; 21% prior weight loss; 53% squamous carcinoma, 38% adenocarcinoma; 10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy (9%). Stages IIIA/IIIB were diagnosed in 55%/45% of patients, respectively. N2/N3 nodes were diagnosed in 60%/23% and pathologically confirmed in 29% of patients. Most patients (56%) were treated by combined modalities. Surgery plus chemotherapy was administered to 20%, definitive chemoradiotherapy to 34%, chemotherapy only to 26%, radiotherapy only to 12% and best supportive care (BSC) to 5% of patients. Median survival and progression-free survival times were 16.8 (15.3;18.5) and 11.2 (10.2;12.2) months, respectively. Stage IIIA, female gender, no weight loss, pathological mediastinal lymph node verification, surgery and combined modality therapy were associated with longer survival. Conclusions The real-world study demonstrated a broad heterogeneity in the management o f stage III NSCLC in Central European countries and suggested to increase the rates of PET-CT imaging, brain imaging and invasive mediastinal staging.

Background: With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer., Methods: We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18 F-fluorodeoxyglucose ( 18 F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18 F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone ( 18 F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60-74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18 F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT00697333., Findings: From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18 F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18 F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9-54), the risk of locoregional progression in the 18 F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% [95% CI 5-21] vs 29% [17-38] at 1 year; HR 0·57 [95% CI 0·30-1·06]). The risk of locoregional progression in the 18 F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% [95% CI 9-24] vs 30% [20-39] at 1 year; HR 0·64 [95% CI 0·37-1·10]). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 [16%] of 99 patients in the conventional target group vs 17 [16%] of 105 patients in the 18 F-FDG PET-based target group); the most common late toxicities were lung-related (12 [12%] vs 11 [10%]). 20 deaths potentially related to study treatment were reported (seven vs 13)., Interpretation: 18 F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours., Funding: German Cancer Aid (Deutsche Krebshilfe)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Purpose: In 2017 the ACROP guideline on SBRT for peripherally located early stage NSCLC was published. Later that year ICRU-91 about prescribing, recording and reporting was published. The purpose of this study is to quantify the current variation in prescription practice in the institutions that contributed to the ACROP guideline and to establish the link between the ACROP and ICRU-91 recommendations., Material and Methods: From each of the eight participating centres, 15 SBRT plans for stage I NSCLC were analyzed. Plans were generated following the institutional protocol, centres prescribed 3 × 13.5 Gy, 3 × 15 Gy, 3 × 17 Gy or 3 × 18 Gy. Dose parameters of the target volumes were reported as recommended by ICRU-91 and also converted to BED 10Gy ., Results: The intra-institutional variance in D98%, Dmean and D2% of the PTV and GTV/ITV is substantially smaller than the inter-institutional spread, indicating well protocollised planning procedures are followed. The median values per centre ranged from 56.1 Gy to 73.1 Gy (D2%), 50.4 Gy to 63.3 Gy (Dmean) and 40.5 Gy to 53.6 Gy (D98%) for the PTV and from 57.1 Gy to 73.6 Gy (D2%), 53.7 Gy to 68.7 Gy (Dmean) and 48.5 Gy to 62.3 Gy (D98%) for the GTV/ITV. Comparing the variance in PTV D98% with the variance in GTV Dmean per centre, using an F-test, shows that four centres have a larger variance in GTV Dmean, while one centre has a larger variance in PTV D98% (p values <0.01). This shows some centres focus on achieving a constant PTV coverage while others aim at a constant GTV coverage., Conclusion: More detailed recommendations for dose planning and reporting of lung SBRT in line with ICRU-91 were formulated, including a minimum PTV D98% of 100 Gy BED 10Gy and minimum GTV/ITV mean dose of 150 Gy BED 10Gy and a D2% in the range of 60-70 Gy., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data., Materials and Methods: We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size., Results: A total of 109 local progressions were observed after a median of 17.7 months (range 0.6-76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12-16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy., Conclusions: Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12-16 Gy are more probable, consistent with recent meta-regression analyses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purposes: Brain metastases (BM) are a frequent complication in small cell lung cancer (SCLC), resulting in a reduced survival prognosis. Precise prognostic assessment is an important foundation for treatment decisions and clinical trial planning., Methods: Patients with newly diagnosed SCLC BM were identified from the Vienna Brain Metastasis Registry and evaluated concerning prognostic factors., Results: 489 patients (male 62.2%, female 37.8%; median age 61 years) were included. Neurological symptoms were present in 297/489 (60.7%) patients. A- to oligosymptomatic patients (5 vs. 9 months, p = 0.030) as well as patients with synchronous diagnosis of BM and primary tumor (5 vs. 9 months, p = 0.008) presented with improved overall survival (OS) prognosis. RPA (HR 1.66; 95% CI 1.44-1.91; p < 0.001), GPA (HR 1.65; p < 0.001), DS-GPA (HR 1.60; p < 0.001) and LabBM score (HR 1.69; p < 0.001) were statistically significantly associated with OS. In multivariate analysis, DS-GPA (HR 1.59; p < 0.001), neurological deficits (HR 1.26; p = 0.021) and LabBM score (HR 1.57; p < 0.001) presented with statistical independent association with OS., Conclusion: A- to oligosymptomatic BM as well as synchronous diagnosis of SCLC and BM were associated with improved OS. Established prognostic scores could be validated in this large SCLC BM real-life cohort.

Background: Stereotactic body radiotherapy (SBRT) has become the standard of care for medically inoperable patients with peripherally located, early stage non-small cell lung cancer (NSCLC), and for those refusing surgical resection. Despite the availability of national and international guidelines, there exists substantial variability in many aspects of SBRT practice., Methods: The ESTRO ACROP guideline is based on a questionnaire covering all aspects of SBRT implementation and practice (n=114 items). The questionnaire was answered by the 11 faculty members of the ESTRO course "Clinical practice and implementation of image-guided SBRT" and their 8 institutions., Results: Agreement by >50% of the institutions was achieved in 72% of all items. Only 8/57 technologies and techniques were identified as mandatory for SBRT while 32/57 were considered as optional. In contrast, quality-assurance related elements were considered as mandatory in 12/24 items. A consensus of risk-adapted SBRT fractionation was achieved with 3×15Gy for peripherally located lesions and 4×12Gy (PTV D95-D99; D max <125% to <150%) for lesions with broad chest wall contact. For patients free from severe comorbidities and with favourable long-term OS expectancy, use of the maximum tolerated dose of 3×18Gy should be considered., Conclusions: This ACROP guideline achieved detailed recommendations in all aspects of SBRT implementation and practice, which will contribute to further standardization of SBRT for peripherally located early stage NSCLC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Brain metastases (BM) are frequent in small cell lung cancer (SCLC). Novel insights into their pathobiology are needed for development of better therapies. We investigated tumor-infiltrating lymphocyte (TIL) subsets (CD3+, CD8+, CD45RO+, FOXP3+ and PD-1+) and expression of PD-L1 in a series of 32 SCLC BM specimens and four matched primary tumor specimens using immunohistochemistry. 30/32 (93.8 %) BM specimens showed TIL infiltration. CD3+ TILs were observed in 30/32 (93.8 %) BM specimens, CD8+ TILs in 25/32 (78.1 %), CD45RO+ TILs in 15/32 (46.9 %), FOXP3+ TILs in 15/32 (46.9 %) and PD-1+ TILs in 1/32 (3.1 %) BM specimens. Patients with infiltration of CD45RO+ TILS had a significantly longer median survival time (11 months; 95 % CI 0.000-26.148) as compared to patients without the presence of CD45RO+ TILs (5 months; 95 % CI 0.966-9.034; p = 0.007; log rank test). Membranous PD-L1 on tumor cells was observed in 24/32 (75.0 %) BM specimens, with 11/32 (34.4 %) cases showing PD-L1 expression in over 5 % of viable BM tumor cells. PD-L1 expression on TILs was seen in 8/32 (25.0 %) and on tumor infiltrating macrophages in 9/32 (28.1 %) cases. Patients with PD-L1 expression on TILs presented with improved survival prognosis (6 versus 29 months; p = 0.002; log rank test). Among matched primary tumors, all (4/4; 100 %) specimens showed TIL infiltration, while PD-L1 expression found in only 1/4 (25.0 %) specimen. TIL infiltration and PD-L1 expression are commonly found in SCLC BM and presence of CD45RO+ memory T-cells and PD-L1+ TILs in SCLC BM seem to associate with favorable survival times. Our data suggest an active immune microenvironment in SCLC BM that may be targetable by immune-modulating drugs.

Purpose: Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring., Methods and Materials: We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression., Results: Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (≳20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model., Conclusions: Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Purpose: To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors., Materials and Methods: A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison., Results: After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort., Conclusions: Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Due to concerns about patients' wellbeing, open end-of-life communication is associated with reservation. Furthermore, sociocultural differences must be considered. The objective of this pilot study was therefore to investigate the information preferences of Austrian patients regarding cure rates and prognosis., Patients and Methods: The information preferences of 50 advanced lung cancer patients were assessed at their first visit to the Department of Radiation Oncology, Medical University of Vienna. Preferences in terms of content (cure rates and/or prognosis) and depth of the information (additional quantitative estimates) were addressed. After the individually adapted medical consultation, patients' satisfaction with the consultation and the emotional responses to the information were evaluated., Results: The majority of patients (76 %) requested information about cure rates and/or prognosis; nearly half of these (47 %) wanted additional quantitative estimates. Neither sociodemographic variables, disease characteristics, nor time since diagnosis had an impact on the information preferences. The individually adapted medical information showed no overall negative influence on the emotional responses; only patients receiving prognostic information had significantly higher distress scores after the consultation. High satisfaction with the individually adapted medical consultation was reported by 92 % of patients., Conclusion: Austrian physicians may offer end-of-life communication and directly ask patients about their information preferences, since patients seem able to decide whether or not prognostic information would overwhelm their emotional capacity and therefore to accept or reject the invitation. The disclosure of cure rates and/or prognosis with or without quantitative estimates-according to the patients' preferences-shows overall no negative impact on emotional reactions. The individually adapted consultation results in high patient satisfaction. Nevertheless, prognostic information may lead to higher distress.

Background: CMET represents an emerging therapy target for monoclonal antibodies and tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC)., Methods: We investigated CMET gene amplification status by fluorescence in-situ hybridization (FISH) and CMET protein expression by immunohistochemistry in a large series of 209 NSCLC brain metastases (BM; 165 adenocarcinoma, 20 squamous cell carcinoma, 11 adenosquamous carcinomas, 11 large cell carcinomas and two large cell neuroendocrine carcinomas) and correlated our results to clinic-pathological parameters and molecular data from previous studies., Results: We found CMET gene amplification in 36/167 (21.6%) and CMET protein expression in 87/196 (44.4%) of evaluable BM. There was a strong correlation between the presence of CMET gene amplification and CMET protein expression (P < 0.001, chi-square test). Furthermore, presence of CMET amplification correlated positively with presence of ALK amplifications (P = 0.039, chi-square test) and high HIF1 alpha index (P = 0.013, Mann-Whitney U-test). Neither CMET expression nor CMET gene amplification status correlated with patient outcome parameters or known prognostic factors., Conclusions: CMET overexpression and CMET amplification are commonly found in NSCLC BM and may represent a promising therapeutic target., (© 2014 John Wiley & Sons Ltd.)

Integrins are transmembranous adhesion molecules postulated to be involved in the brain metastatic cascade. We investigated the correlation of alpha v beta 3 (αvβ3), alpha v beta 5 (αvβ5) and alpha v beta 6 (αvβ6) integrin isoform expression with clinical characteristics including survival times in lung cancer patients with brain metastases (BM). All BM from lung cancer operated at our institution between 1990 and 2011, were identified; where available, primary tumors were retrieved as well. Immunohistochemical analysis for αvβ3, αvβ5 and αvβ6 integrin subunits was performed and correlated with Ki67 and hypoxia-inducible factor (HIF)-1α indexes. Clinical data including survival data were obtained by chart review. 191 BM specimens of 191 patients with histologically confirmed lung cancer (172 non-small cell lung cancer and 19 small cell lung cancer) were included. In 18 patients matched primary tumor samples were available. αvβ6 expression was commonly found on BM tumor cells (103/191; 53.9 %) and showed a significant association with low Ki67 proliferation indices (46 vs. 36 %, p = 0.001, Mann-Whitney U test) and favorable survival times (p = 0.020; log rank test) in patients with non-squamous NSCLC BM. αvβ5 expression was highly expressed on vascular structures (167/191; 87.4 %) and tumor stroma in BM (151/191; 79.1 %) and associated with high HIF-1α indices (60 vs. 90, p = 0.007, Mann-Whitney U test). αvβ3 expression was more frequently found on vascular structures in BM than in primary tumors (68.1 vs. 5.6 %; p = 0.645; Chi square test) and its expression in BM tumor cells correlated with low Ki67 indices (41 vs. 28 %; p = 0.046, Mann-Whitney U test). Expression of αv integrin subunits seem to be of pathobiological and clinical relevance in patients with NSCLC BM. Further investigations of their involvement in the brain metastatic cascade and their role as biomarkers are warranted.

Background: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control., Methods and Materials: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection., Results: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED(ISO)) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED(ISO) and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED(ISO), age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively., Conclusions: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP modeling are expected through a nonlinear combination of multiple features, eventually helping in the task of personalized treatment planning., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: FGFR1 amplifications are common in squamous cell carcinoma and rare in adenocarcinoma of the lung, but have not been investigated in brain metastases of non-small cell lung cancer (NSCLC)., Materials and Methods: We performed fluorescent in situ hybridization (FISH) for FGFR1 and immunohistochemistry for pAKT, PI3K, HIF1a and Ki67 in 175 NSCLC brain metastases and 11 matched primary tumors. ALK gene rearrangement status was available from a previous study. We performed statistical correlations of clinical, histopathological and molecular data., Results: FGFR1 amplifications were found in a total of 30/175 (17%) brain metastases: 4/21 (19%) squamous cell carcinomas, 20/130 (15.3%) adenocarcinomas, 2/12 (16.6%) adenosquamous carcinomas, 4/9 (44.4%) large cell carcinomas and 0/3 neuroendocrine large cell carcinoma. FGFR1 gene status was identical between primary tumors and brain metastases in 9/11 evaluable cases. In 2/11 cases (1 adenosquamous and 1 large cell carcinoma), FGFR1 amplifications were present only in the brain metastasis and not in the primary tumor. Furthermore, we found a significant positive correlation of ALK and FGFR1 gene amplification status in brain metastases (p<0.001, Chi square test). Patients with high-level FGFR1 amplifications had significantly higher number of visceral metastases (p<0.001, Chi square test)., Conclusion: Our findings argue for an enrichment of FGFR1 amplifications in brain metastases of adenocarcinomas (where they were 5-fold more frequent than reported for primary tumors) and possibly also of other non-squamous carcinomas, but not in squamous cell carcinomas of the lung. These results may be relevant for targeted therapy and prophylaxis of NSCLC brain metastases., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose dT) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC)., Materials and Methods: This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1-8) and median single fraction dose was 12.5 Gy (2.9-33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60-100%). Assuming an α/β-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs)., Results: There was strong evidence for a dose-response relationship in the total patient cohort (BFs>20), which was lacking in single-fraction SBRT (BFs<3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (dT) at 11 Gy (68% CI 8-14 Gy) or 22 Gy (14-42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the dT parameter (p=0.07, BF=2.1 and p=0.86, BF=0.8, respectively). Generally, isocentric doses resulted in much better dose-response relationships than PTV encompassing doses (BFs>20)., Conclusion: Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Introduction: To evaluate safety and efficacy of stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) in a patterns-of-care and patterns-of-outcome analysis., Methods: The working group "Extracranial Stereotactic Radiotherapy" of the German Society for Radiation Oncology performed a retrospective multicenter analysis of practice and outcome after SBRT for stage I NSCLC. Sixteen German and Austrian centers with experience in pulmonary SBRT were asked to participate., Results: Data of 582 patients treated at 13 institutions between 1998 and 2011 were collected; all institutions, except one, were academic hospitals. A time trend to more advanced radiotherapy technologies and escalated irradiation doses was observed, but patient characteristics (age, performance status, pulmonary function) remained stable over time. Interinstitutional variability was substantial in all treatment characteristics but not in patient characteristics. After an average follow-up of 21 months, 3-year freedom from local progression (FFLP) and overall survival (OS) were 79.6% and 47.1%, respectively. The biological effective dose was the most significant factor influencing FFLP and OS: after more than 106 Gy biological effective dose as planning target volume encompassing dose (N = 164), 3-year FFLP and OS were 92.5% and 62.2%, respectively. No evidence of a learning curve or improvement of results with larger SBRT experience and implementation of new radiotherapy technologies was observed., Conclusion: SBRT for stage I NSCLC was safe and effective in this multi-institutional, academic environment, despite considerable interinstitutional variability and time trends in SBRT practice. Radiotherapy dose was identified as a major treatment factor influencing local tumor control and OS.

Background: This multicentric randomized phase II study investigated the feasibility and toxicity of temozolomide (TMZ) added to whole brain radiotherapy (WBRT) followed by adjuvant TMZ in patients with multiple brain metastases of non-small-cell lung cancer (NSCLC)., Methods: Patients with multiple brain metastases from NSCLC aged ≥ 18 years, classified according to recursive partitioning analysis class I or II and with adequate organ functions were eligible. Treatment consisted of WBRT + TMZ 75 mg/m² for 2 weeks followed at day 28 by TMZ 100 mg/m²/day 2 weeks on/2 weeks off for up to 6 months (radiochemotherapy, RCT) or WBRT alone (radiotherapy, RT)., Results: The study enrolled only 35 patients (22 patients in RCT and 13 in RT) and had to be closed prematurely due to poor accrual. The toxicity was mainly due to TMZ with WHO grade 3 and 4 thrombocytopenia in 3/22 versus 0/13, leucocytopenia in 1/22 versus 0/13 and lymphocytopenia in 7/22 versus 12/13 patients in RCT and RT respectively. Thirteen patients in RCT and six in RT progressed systemically and dropped out before first restaging of the response in brain. Median time to progression (TTP) was 2.4 months (95 % CI: 2-2.6 months) and 2.0 months (95 % CI: 0.5-3.5 months), median overall survival (OAS) was 3 months (95% CI: 1.7-3.1 months) and 6.3.months (95 % CI: 0.2-7.6 months) in RCT and RT, respectively., Conclusions: Like other studies before on patients with brain metastases, insufficient number of recruited patients does not allow conclusions on efficacy and toxicity as the study closed prematurely.

Purpose: It is generally agreed that the safe implementation of stereotactic body radiotherapy requires image guidance. The aim of this work was to assess interobserver variability in the delineation of lung lesions on cone-beam CT (CBCT) images compared with CT-based contouring for adaptive stereotactic body radiotherapy. The influence of target size was also evaluated., Methods and Materials: Eight radiation oncologists delineated gross tumor volumes in 12 patient cases (non-small cell lung cancer I-II or solitary metastasis) on planning CTs and on CBCTs. Cases were divided into two groups with tumor diameters of less than (Group A) or more than 2 cm (Group B). Comparison of mean volumes delineated by all observers and range and coefficient of variation were reported for each case and image modality. Interobserver variability was assessed by means of standard error of measurement, conformity index (CI), and its generalized observer-independent approach. The variance between single observers on CT and CBCT images was measured via interobserver reliability coefficient., Results: Interobserver variability on CT images was 17% with 0.79 reliability, compared with 21% variability on CBCT and 0.76 reliability. On both image modalities, values of the intraobserver reliability coefficient (0.99 for CT and 0.97 for CBCT) indicated high reproducibility of results. In general, lower interobserver agreement was observed for small lesions (CI(genA) = 0.62 ± 0.06 vs. CI(genB) = 0.70 ± 0.03, p < 0.05). The analysis of single patient cases revealed that presence of spicules, diffuse infiltrations, proximity of the tumors to the vessels and thoracic wall, and respiration motion artifacts presented the main sources of the variability., Conclusion: Interobserver variability for Stage I-II non-small cell lung cancer and lung metastasis was slightly higher on CBCT compared with CT. Absence of significant differences in interobserver variability suggests that CBCT imaging provides an effective tool for tumor localization, and image data could be also used for target volume delineation purposes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Dyspnea is common in advanced cancer patients with opioids as first line treatment., Objectives: To evaluate the level of knowledge about diagnosis and treatment of dyspnea in palliative care patients among 4th year students., Methods: A case report was distributed to the students describing acute dyspnea in a lung cancer patient. Students were asked to rank their diagnosis and treatment options by importance., Results: 633 medical students in their 4th year attended a seminar about palliative care. Of these, 423 (77%) completed the case report. The most frequent diagnostic option was measuring patient's oxygen saturation (n = 388), followed by auscultation (n = 339). As treatment options, students chose the delivery of oxygen (n = 393) as most important. The application of opioids was suggested by a total of 138 students., Conclusion: Although students did not have practical skills in treating advanced cancer patients with acute dyspnea, 32.6% would suggest an opioid as treatment option.

Background and Purpose: The aim of the present study was to investigate potential dosimetric benefits of proton therapy for hypofractionated stereotactic body radiotherapy (SBRT)., Materials and Method: Twelve patients undergoing hypofractionated SBRT at the Medical University Vienna were selected. Passively scattered protons (PT) and intensity modulated proton therapy (IMPT) were evaluated against a conformal photon technique (3D-CRT), assuming a fractionation of 3x15Gy, prescribed to the 65% isodose. For all treatment techniques shallow breathing with abdominal compression (SB+AC) was compared with a deep inspiration breath hold technique (DIBH). Treatment planning was done with XiO (CMS, USA). Target conformity, dose-volume histograms (DVH) and various associated dosimetric parameters were considered for the planning target volume (PTV), lung, heart and esophagus., Results: For both breathing conditions conformity indices were very similar. They were between 0.75 and 0.78 for IMPT and 3D-CRT and around 0.55 for PT using 2-3 beams. Irrespective of treatment modality, DVHs for the ipsilateral lung were improved with the DIBH technique. For the PT technique, the 2Gy isodose (V2Gy) covered on average 7-9% less lung volume compared to 3D-CRT, for IMPT this reduction was more than 10%. Volumes covered the 4 and 6Gy isodoses were 2-4% smaller for IMPT, but very similar for PT and 3D-CRT. Both proton techniques achieved full sparing of the contralateral lung and superior sparing of the heart. Maximum doses to the heart and esophagus were on average around 3Gy for 3D-CRT and almost 0Gy for both proton techniques. For 3D-CRT average V2Gy values for the heart could be reduced from 64% in shallow breathing to 34% in DIBH. V2Gy for protons was negligible., Conclusions: Only small dosimetric differences were found between photons and protons for SBRT of lung lesions. Whether these small dosimetric benefits translate in reduced side effects or have the potential to improve local control rates remains to be demonstrated in clinical studies.

Purpose: To evaluate the dosimetric consequences for irradiated lung tissue for different respiration conditions for hypofractionated stereotactic body radiotherapy (SBRT)., Methods and Materials: Thirteen patients with lung lesion undergoing SBRT treatment in shallow breathing with abdominal compression (SB+AP) underwent additional multislice CT studies in free breathing (FB), deep inspiration and expiration breath hold (DIBH, DEBH). For each patient 6 different treatment plans were designed for the various respiration conditions applying standard (7/7/10 mm), reduced (5/5/5 mm) and individual margins. The FB plan with standard margins was used as a reference. The percentage of volume of the ipsilateral lung receiving total doses > or=12, 15> or= and > or=18 Gy, mean lung dose (D(mean)), NTCP corrected for fractionation effects and the total monitor units (MU) were evaluated., Results: With DIBH it was possible to reduce all lung dose parameters by about 20%. Applying reduced margins in DIBH, this reduction was even increased to about 40%. The standard technique (SB+AP) with individual margins showed similar results as DIBH with standard margins. DEBH showed some improvement over FB only when reduced margins were applied. Only for 5/13 patients NTCP values >1% were obtained. For these patients a significant NTCP reduction was achieved with DIBH techniques., Conclusions: In SBRT shallow breathing with abdominal compression produces acceptable results concerning lung DVHs. DIBH, especially with reduced margins, showed the best lung sparing. For the clinical implementation of such a technique some form of gating is advisable. However, there are some practical limitations due to high fractional doses.

Respiration can cause tumor movements in thoracic regions of up to 3 cm. To minimize motion effects several approaches, such as gating and deep inspiration breath hold (DIBH), are still under development. The goal of our study was to develop and evaluate a noninvasive system for gated DIBH (GDIBH) based on external markers. DIBH monitoring was based on an infrared tracking system and an in-house-developed software. The in-house software provided the breathing curve in real time and was used as on-line information for a prototype of a feedback device. Reproducibility and stability of the breath holds were evaluated without and with feedback. Thirty-five patients undergoing stereotactic body radiotherapy (SBRT) performed DIBH maneuvers after each treatment. For 16 patients dynamic imaging sequences on a multislice CT were used to determine the correlation between tumor and external markers. The relative reproducibility of DIBH maneuvers was improved with the feedback device (74.5% +/- 17.1% without versus 93.0% +/- 4.4% with feedback). The correlation between tumor and marker was good (Pearson correlation coefficient 0.83 +/- 0.17). The regression slopes showed great intersubject variability but on average the internal margin in a DIBH treatment situation could be theoretically reduced by 3 mm with the feedback device. DIBH monitoring could be realized in a noninvasive manner through external marker tracking. We conclude that reduction of internal margins can be achieved with a feedback system but should be performed with great care due to the individual behavior of target motion.

Purpose: The present study explored the impact of intensity-modulated radiotherapy (IMRT) on stereotactic body RT (SBRT) of liver and lung lesions. Additionally, because target dose conformity can be affected by the leaf width of a multileaf collimator (MLC), especially for small targets and stereotactic applications, the use of a micro-MLC on "uniform intensity" conformal and intensity-modulated SBRT was evaluated., Methods and Materials: The present study included 10 patients treated previously with SBRT in our institution (seven lung and three liver lesions). All patients were treated with 3 x 12 Gy prescribed to the 65% isodose level. The actual MLC-based conformal treatment plan served as the standard for additional comparison. In total, seven alternative treatment plans were made for each patient: a standard (actual) plan and an IMRT plan, both calculated with Helax TMS (Nucletron) using a pencil beam model; and a recalculated standard and a recalculated IMRT plan on Helax TMS using a point dose kernel approach. These four treatment plans were based on a standard MLC with 1-cm leaf width. Additionally, the following micro-MLC (central leaf width 3 mm)-based treatment plans were calculated with the BrainSCAN (BrainLAB) system: standard, IMRT, and dynamic arc treatments. For each treatment plan, various target parameters (conformity, coverage, mean, maximal, and minimal target dose, equivalent uniform doses, and dose-volume histogram), as well as organs at risk parameters (3 Gy and 6 Gy volume, mean dose, dose-volume histogram) were evaluated. Finally, treatment efficiency was estimated from monitor units and the number of segments for IMRT solutions., Results: For both treatment planning systems, no significant difference could be observed in terms of target conformity between the standard and IMRT dose distributions. All dose distributions obtained with the micro-MLC showed significantly better conformity values compared with the standard and IMRT plans using a regular MLC. Dynamic arc plans were characterized by the steepest dose gradient and thus the smallest V(6 Gy) values, which were on average 7% smaller than the standard plans and 20% lower than the IMRT plans. Although the Helax TMS IMRT plans show about 18% more monitor units than the standard plan, BrainSCAN IMRT plans require approximately twice the number of monitor units relative to the standard plan. All treatment plans optimized with a pencil beam model but recalculated with a superposition method showed significant qualitative, as well as quantitative, differences, especially with respect to conformity and the dose to organs at risk., Conclusion: Standard conformal treatment techniques for SBRT could not be improved with inversely planned IMRT approaches. Dose calculation algorithms applied in optimization modules for IMRT applications in the thoracic region need to be based on the most accurate dose calculation algorithms, especially when using higher energy photon beams.

Thirty-two patients with metastatic renal cell carcinoma were treated as outpatients with individually dosed interferon alpha (IFN alpha). The individual maximum dose was based on the side effects. In 7 patients the course of the disease was influenced: 1 attained complete remission, 3 patients, partial remission and 3, stable disease. The outcome of therapy was not dose-dependent. Patients with lung metastases were more sensitive to IFN alpha than the others. Up to 20% of patients responded to the therapy.

A 34-year-old man underwent left hemicastration for malignant unclassified sex cord gonadal stromal tumor. At 6 months pulmonary metastases developed and the patient received 3 courses of chemotherapy consisting of cisplatin, bleomycin and etoposide. A residual focus in the right lung was excised and proved to be viable tumor. He then received 2 adjuvant courses of cisplatin, etoposide and ifosfamide. Six months later he was without evidence of disease. A review of the literature revealed 21 previous cases of malignant unclassified sex cord gonadal stromal tumor. Although chemotherapy usually fails in treating Leydig cell tumors our case corroborates 6 previous reports of favorable response to cisplatin-based chemotherapy. This finding suggests that different subtypes of sex cord gonadal stromal tumor respond differently to chemotherapy.

A rare case of metastatic nephroblastoma on the right side in a 28-year-old female patient is presented. Complete remission was achieved by inductive chemotherapy with vincristine, Adriamycin, actinomycin D and cyclophosphamide and subsequent radical nephrectomy. There was no evidence of disease 24 months after the initial diagnosis had been made. The problems specific to the diagnosis and treatment of adult Wilms tumor are discussed. A chemotherapy regimen known to be successful in childhood Wilms tumor was shown to be equally effective in our adult patient.