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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. 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 18F-fluorodeoxyglucose (18F-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 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-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 18F-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. 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 18F-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 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9–54), the risk of locoregional progression in the 18F-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 18F-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 18F-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). 18F-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. German Cancer Aid (Deutsche Krebshilfe).

Background Current studies indicate that fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography ([ 18 F]FDG PET/CT) is the most accurate imaging modality for the detection of relapsed locally advanced non-small cell lung cancer (NSCLC) after curatively intended chemoradiotherapy. To this day, there is no objective and reproducible definition for the diagnosis of disease recurrence in PET/CT, the reading of which is relevantly influenced by post radiation inflammatory processes. The aim of this study was to evaluate and compare visual and threshold-based semi-automated evaluation criteria for the assessment of suspected tumor recurrence in a well-defined study population investigated during the randomized clinical PET-Plan trial. Methods This retrospective analysis comprises 114 PET/CT data sets of 82 patients from the PET-Plan multi-center study cohort who underwent [ 18 F]FDG PET/CT imaging at different timepoints for relapse, as suspected by CT. Scans were first analyzed visually by four blinded readers using a binary scoring system for each possible localization and the associated reader certainty of the evaluation. Visual evaluations were conducted repeatedly without and with additional knowledge of the initial staging PET and radiotherapy delineation volumes. In a second step, uptake was measured quantitatively using maximum standardized uptake value (SUVmax), peak standardized uptake value corrected for lean body mass (SULpeak), and a liver threshold-based quantitative assessment model. Resulting sensitivity and specificity for relapse detection were compared to the findings in the visual assessment. The gold standard of recurrence was independently defined by prospective study routine including external reviewers using CT, PET, biopsies and clinical course of the disease. Results Overall interobserver agreement (IOA) of the visual assessment was moderate with a high difference between secure (ĸ = 0.66) and insecure (ĸ = 0.24) evaluations. Additional knowledge of the initial staging PET and radiotherapy delineation volumes improved the sensitivity (0.85 vs 0.92) but did not show significant impact on the specificity (0.86 vs 0.89). PET parameters SUVmax and SULpeak showed lower accuracy compared to the visual assessment, whereas threshold-based reading showed similar sensitivity (0.86) and higher specificity (0.97). Conclusion Visual assessment especially if associated with high reader certainty shows very high interobserver agreement and high accuracy that can be further increased by baseline PET/CT information. The implementation of a patient individual liver threshold value definition, similar to the threshold definition in PERCIST, offers a more standardized method matching the accuracy of experienced readers albeit not providing further improvement of accuracy.

Prostate cancer is the most frequent cancer in men. For localized prostate cancer, surgery and radiotherapy are the standard treatment, with active surveillance also used in low-risk cases. For advanced/metastatic disease, androgen deprivation treatment is carried out. Further options include inhibitors of the androgen receptor axis and taxane-based chemotherapy. The avoidance of side effects should be considered, e.g., by dose adjustment. New options include poly(ADP-ribose) polymerase (PARP) inhibitors, and radioligand treatment. The existing guidelines only provide a few treatment recommendations for older patients; however, the treatment of older patients should primarily consider not only chronological age but also the patient's psychological and physical condition and preferences. In this context, the geriatric assessment represents an important instrument for determining the treatment strategy.

Lymph node metastases are common in pelvic urological tumors, and the age-related remodeling process of the pelvic lymph nodes influences metastatic behavior. The aim of this work is to characterize age-related degenerative changes in the pelvic lymph nodes with respect to their occurrence and extent. A total of 5173 pelvic lymph nodes of 390 patients aged 44 to 79 years (median 68 years, IQR 62–71 years) were histologically examined for degenerative structural changes. Lymph node size, lipomatous atrophy, capsular fibrosis, framework fibrosis, and calcifications were recorded semi-quantitatively and evaluated by age group. Significantly more lymph nodes <10 mm were found in older patients (p = 0.001). The incidence of framework fibrosis, capsular fibrosis, and calcifications increased significantly with increasing patient age (p < 0.001). In lipomatous atrophy, an increase in mild to moderate lipomatous atrophy was observed with increasing age (p < 0.001). In this, the largest study to date on this topic, age-related degenerative changes in pelvic lymph nodes were proven. Due to the consecutive decrease in hte filtration function of pelvic lymph nodes with increasing age, staging and therapy of metastatic pelvic urologic carcinomas should be reconsidered.

Das Prostatakarzinom ist das häufigste Karzinom beim Mann. Bei lokalisiertem Tumor stellen die Operation und die Strahlentherapie die Standardtherapie dar, bei niedrigem Risiko auch die aktive Überwachung. Im Fall der fortgeschrittenen/metastasierten Erkrankung erfolgt eine Androgendeprivationstherapie. Weitere Optionen sind Inhibitoren der Androgenrezeptorachse und taxanbasierte Chemotherapien. Die Vermeidung von Nebenwirkungen sollte z. B. durch Dosisanpassungen berücksichtigt werden. Neue Optionen ergeben sich durch Poly(ADP-ribose)-Polymerase(PARP)-Inhibitoren und Radioligandentherapie. Bestehende Leitlinien zum Prostatakarzinom enthalten nur wenige Empfehlungen für ältere Patienten. Jedoch sollte/sollten bei der Behandlung älterer Patienten nicht primär das chronologische Alter, sondern die psychische und physische Verfassung und die Präferenzen des Patienten berücksichtigt werden. Das geriatrische Assessment stellt ein wichtiges Instrument zur Festlegung der Behandlungsstrategie dar.

(1) Background: The optimal chemotherapy (CHT) regimen for concurrent chemoradiation (cCRT) is not well defined. In this secondary analysis of the international randomized PET-Plan trial, we evaluate the efficacy of different CHT. (2) Methods: Patients with inoperable NSCLC were randomized at a 1:1 ratio regarding the target volume definition and received isotoxically dose-escalated cCRT using cisplatin 80 mg/m2 (day 1, 22) and vinorelbin 15 mg/m2 (day 1, 8, 22, 29) (P1) or cisplatin 20 mg/m2 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P2) or carboplatin AUC1 (day 1–5, 29–33) and vinorelbin 12.5 mg/m2 (day 1, 8, 15, 29, 36, 43) (P3) or other CHT at the treating physician’s discretion. (3) Results: Between 05/2009 and 11/2016, 205 patients were randomized and 172 included in the per-protocol analysis. Patients treated in P1 or P2 had a better overall survival (OS) compared to P3 (p = 0.015, p = 0.01, respectively). Patients treated with carboplatin had a worse OS compared to cisplatin (HR 1.78, p = 0.03), but the difference did not remain significant after adjusting for age, ECOG, cardiac function creatinine and completeness of CHT. (4) Conclusions: Carboplatin doublets show no significant difference compared to cisplatin, after adjusting for possibly relevant factors, probably due to existing selection bias.

Zusammenfassung Das Prostatakarzinom ist das häufigste Karzinom beim Mann. Bei lokalisiertem Tumor stellen die Operation und die Strahlentherapie die Standardtherapie dar, bei niedrigem Risiko auch die aktive Überwachung. Im Fall der fortgeschrittenen/metastasierten Erkrankung erfolgt eine Androgendeprivationstherapie. Weitere Optionen sind Inhibitoren der Androgenrezeptorachse und taxanbasierte Chemotherapien. Die Vermeidung von Nebenwirkungen sollte z. B. durch Dosisanpassungen berücksichtigt werden. Neue Optionen ergeben sich durch Poly(ADP-ribose)-Polymerase(PARP)-Inhibitoren und Radioligandentherapie. Bestehende Leitlinien zum Prostatakarzinom enthalten nur wenige Empfehlungen für ältere Patienten. Jedoch sollte/sollten bei der Behandlung älterer Patienten nicht primär das chronologische Alter, sondern die psychische und physische Verfassung und die Präferenzen des Patienten berücksichtigt werden. Das geriatrische Assessment stellt ein wichtiges Instrument zur Festlegung der Behandlungsstrategie dar.

Das Prostatakarzinom ist das häufigste Karzinom beim Mann. Bei lokalisiertem Tumor stellen die Operation und die Strahlentherapie die Standardtherapie dar, bei niedrigem Risiko auch die aktive Überwachung. Im Fall der fortgeschrittenen/metastasierten Erkrankung erfolgt eine Androgendeprivationstherapie. Weitere Optionen sind Inhibitoren der Androgenrezeptorachse und taxanbasierte Chemotherapien. Die Vermeidung von Nebenwirkungen sollte z. B. durch Dosisanpassungen berücksichtigt werden. Neue Optionen ergeben sich durch Poly(ADP-ribose)-Polymerase(PARP)-Inhibitoren und Radioligandentherapie. Bestehende Leitlinien zum Prostatakarzinom enthalten nur wenige Empfehlungen für ältere Patienten. Jedoch sollte/sollten bei der Behandlung älterer Patienten nicht primär das chronologische Alter, sondern die psychische und physische Verfassung und die Präferenzen des Patienten berücksichtigt werden. Das geriatrische Assessment stellt ein wichtiges Instrument zur Festlegung der Behandlungsstrategie dar.

Zusammenfassung Das Prostatakarzinom ist das häufigste Karzinom beim Mann. Bei lokalisiertem Tumor stellen die Operation und die Strahlentherapie die Standardtherapie dar, bei niedrigem Risiko auch die aktive Überwachung. Im Fall der fortgeschrittenen/metastasierten Erkrankung erfolgt eine Androgendeprivationstherapie. Weitere Optionen sind Inhibitoren der Androgenrezeptorachse und taxanbasierte Chemotherapien. Die Vermeidung von Nebenwirkungen sollte z. B. durch Dosisanpassungen berücksichtigt werden. Neue Optionen ergeben sich durch Poly(ADP-ribose)-Polymerase(PARP)-Inhibitoren und Radioligandentherapie. Bestehende Leitlinien zum Prostatakarzinom enthalten nur wenige Empfehlungen für ältere Patienten. Jedoch sollte/sollten bei der Behandlung älterer Patienten nicht primär das chronologische Alter, sondern die psychische und physische Verfassung und die Präferenzen des Patienten berücksichtigt werden. Das geriatrische Assessment stellt ein wichtiges Instrument zur Festlegung der Behandlungsstrategie dar.