Lungenklinik Köln-Merheim

Background Nivolumab, an anti-PD-1 antibody, has shown efficacy and favorable safety in treating advanced/metastatic NSCLC.However, its mechanism of action poses risks for immune-related adverse events (irAEs).This study (category 3 EU-PASS) aims to evaluate the incidence and severity of irAEs, their management, outcomes, and overall survival (OS) in NSCLC patients treated with nivolumab.Methods This observational, multicenter, prospective study enrolled 759 NSCLC patients, with 718 evaluable.Patients receiving nivolumab for first time, alone or with ipilimumab in routine oncology practice, were included.Data were collected from 2016 to 2024 through electronic case report forms.Incidence of irAEs were reported, with severity graded using the Common Terminology Criteria for Adverse Events (CTCAE).OS was assessed using Kaplan-Meier analysis.Results Of the 718 patients, 701 (97.6%) received nivolumab monotherapy, and 17 (2.4%) received nivolumab in combination with ipilimumab.The histological types of NSCLC were 41.9% squamous and 58.1% non-squamous.At enrollment, in monotherapy group, the mean age was 67.7 years (SD 8.9), 65.8% were male, 84% had stage IV disease, and all (100%) had prior systemic cancer treatment.In combination group, the mean age was 65.9 (SD 8.7), 70.6% were male, all (100%) had stage IV disease, and 23.5% had prior systemic cancer treatment.Among monotherapy patients, 155 (22.1%) experienced irAEs, with skin reactions (12.3%) occurring in !10% of patients.In combination therapy, 6 (35.3%) experienced irAEs, with endocrinopathies and skin reactions (23.5% each) occurring in !10% of patients.IrAEs led to treatment discontinuation in 3.9% of monotherapy and 5.9% of combination therapy patients.Two fatal irAEs were reported (0.3%; both in the monotherapy therapy group).Grade 3 or 4 irAEs occurred only in monotherapy group (5.3%).To manage irAEs, systemic corticosteroids were common treatment for events such as colitis, hepatitis, nephritis and pneumonitis (for 50-71% of cases); topical corticosteroids for skin-related irAEs (for 53% of cases); and hormonal therapies for endocrinopathies (for 69% of cases).Most irAEs resolved without sequelae (68.5% monotherapy, 47.1% combination), with median time to resolution of 43 days for monotherapy and 261. 5 days for combination.The median OS (95% CI) was 10.28 months (9.56, 11.79) for monotherapy and 13.47 months (5.19, 20.50) for combination therapy.Conclusions The incidence and severity of irAEs in NSCLC patients treated with nivolumab was consistent with safety profile from clinical trials.No new safety signals were identified, and the benefit-risk profile of nivolumab for NSCLC remains favorable.

The increasing incidence of malignant lung diseases, neoadjuvant therapies, and the expected detection of operable stages through future lung cancer screening require differentiated preoperative decisions regarding functional operability against the background of an increase in respiratory diseases, especially COPD, but also interstitial lung diseases.Since the postoperative risk of cardiovascular and pulmonary complications after lung resection increases with the extent of lung parenchymal resection and the pre-existing impairment of organ function of the heart, lungs, kidneys, and metabolism, these also require special attention. Given the increasing number of elderly patients over 75 years of age, this also applies to frailty, which represents another key parameter in structured evaluation.

In most cases osteoarthritis of the ankle is of posttraumatic origin. Younger people are more frequently affected, which makes treatment aparticular challenge. In addition to conservative treatment numerous surgical procedures are available for the treatment of advanced arthrosis. The aim of this nationwide survey was to document the current status of the diagnostics and treatment of ankle arthritis in Germany. Members of the German Society for Orthopedics and Trauma Surgery (DGOU) were invited to participate in an anonymous online survey on the treatment of ankle joint osteoarthritis. The survey included 69questions on the person, on the diagnostic and treatment approaches as well as 3 clinical and radiological patient cases. The evaluation of the results of the survey included differences in the subgroups of participants based on the discipline, the location of activity, position and certification. From November 2019 to February2020 a total of 343members participated in the survey. For the diagnostics 96% requested conventional radiographs in a standing position and in 2 levels. Other native radiographs were considered necessary by less than half of respondents. Less than one third of participants sometimes (n = 87) or always (n = 18) use an outcome score. The therapeutic repertoire included supramalleolar osteotomy (n = 106), ankle arthroplasty (n = 100) and arthrodesis (n = 248). Open arthrodesis using screws through an anterior approach was the most frequently used surgical procedure. Diagnostic standards were regularly used in the treatment of ankle arthrosis. With respect to the surgical treatment there was a wide heterogeneity due to the pathological anatomy and preferences of the participants. Open arthrodesis was the most frequently selected procedure.

Zusammenfassung Ziel der Studie Ziel dieser prospektiven Pilotstudie war es, im ambulanten Krankengut einer phlebologischen Schwerpunktpraxis zu ermitteln, ob im Intervall 2–4 Monate post-COVID mit einer erhöhten Inzidenz thromboembolischer Ereignisse zu rechnen ist. Methodik Im Rahmen einer systematischen Nachuntersuchung von COVID-Folgeerkrankungen wurden 103 konsekutive Patienten zur Teilnahme an einer phlebologischen Untersuchung eingeschlossen. Diese umfasste nach einem standardisierten Untersuchungsprotokoll neben der Anamnese die Bestimmung der klinischen Wahrscheinlichkeit nach Wells, die komplette Kompressions- und Farbduplexsonografie und die laborchemische Bestimmung der D-Dimere. Ergebnisse Insgesamt ließen sich 4 thrombotische Ereignisse nachweisen (3,9%). Davon betrafen 2 das tiefe (1,9%) und 2 das oberflächliche (1,9%) Beinvenensystem. In Bezug auf das durchschnittliche Patientengut der phlebologischen Schwerpunktpraxis (TVT-Häufigkeit von 1,48%) ergab sich jedoch keine signifikante TVT-Häufung in dem hier untersuchten Kollektiv (p=0,69). Schlussfolgerung Die auffällige, aber insgesamt relativ niedrige Inzidenz von Thrombosen als Folge einer SARS-CoV-2-Infektion stützt die Annahme, dass Patienten mit erhöhtem Thromboserisikoprofil nicht nur in der Akutphase der COVID-Infektion, sondern auch noch nach 2–4 Monaten post-COVID einer vermehrten Aufmerksamkeit bedürfen.

Access to the jugular fossa pathologies (JFPs) via the transmastoid infralabyrinthine approach (TI-A) using the nonrerouting technique (removing the bone anterior and posterior to the facial nerve while leaving the nerve protected within the fallopian canal) or with the short-rerouting technique (rerouting the mastoid segment of the facial nerve anteriorly) has been described in previous studies. The objective of this study is to compare the access to Fisch class C lesions (JFPs extending or destroying the infralabyrinthine and apical compartment of the temporal bone with or without involving the carotid canal) between the nonrerouting and the short-rerouting techniques. Also, some tailored steps to the nonrerouting technique (NR-T) were outlined to enhance access to the jugular fossa (JF) as an alternative to the short-rerouting technique. Neuronavigated TI-A was performed using the nonrerouting, tailored nonrerouting, and short-rerouting techniques on both sides of 10 human head specimens. Exposed area, horizontal distance, surgical freedom, and horizontal angle were calculated using vector coordinates for nonrerouting and short-rerouting techniques. The short-rerouting technique had significantly higher values than the NR-T ( P < .01) for the exposed area (169.1 ± SD 11.5 mm 2 vs 151.0 ± SD 12.4 mm 2 ), horizontal distance (15.9 ± SD 0.6 mm vs 10.6 ± SD 0.5 mm 2 ), surgical freedom (19 650.2 ± SD 722.5 mm 2 vs 17 233.8 ± SD 631.7 mm 2 ), and horizontal angle (75.2 ± SD 5.1° vs 61.7 ± SD 4.6°). However, adding some tailored steps to the NR-T permitted comparable access to the JF. Neuronavigated TI-A with the short-rerouting technique permits wider access to the JF compared with the NR-T. However, the tailored NR-T provides comparable access to the JF and may be a better option for class C1 and selected class C2 and C3 JFPs.

Since patients with unresectable stage III NSCLC who are unfit for chemotherapy (CHT) due to age or frailty receive radiotherapy (RT) only, they do not have the opportunity to benefit from durvalumab consolidation after radiochemotherapy, raising the concern of undertreatment. Synergistic effects are expected when combining restored anti-tumor immune response elicited by immune checkpoint inhibition with an RT-induced increase in immunogenicity. The latter could be further boosted by hypofractionated RT, which might also be more practicable for the patient. TRADE-hypo (NCT04351256) is an open-label, allocated phase II trial addressing safety and efficacy of durvalumab (1.500 mg Q4W, max. 12 months) combined with either hypo- (55 Gy = 20 x 2.75 Gy, “HYPO”) or conventionally fractionated thoracic RT (60 Gy = 30 x 2 Gy, “CON”) in previously untreated NSCLC stage III patients unfit for CHT (planned n=88). A safety stop-and-go phase (6+6 design) in the HYPO-arm addressed the potential higher pneumonitis risk. An interim futility analysis was planned with 18 response-evaluable patients in each arm (after RT start, ≥1 dose durvalumab, ≥1 response assessment (RECIST1.1), futility rule ≤ 8 responses). By 11/2022, a total of 38 patients were enrolled (n=13 in HYPO, n=25 in CON). In the HYPO-arm, 2 pneumonitis grade ≥3 events occurred, resulting in permanent recruitment stop in this arm as per protocol. In the CON-arm, benefit-risk evaluation remained favorable, and the trial continued with recruitment into this arm only. Interim futility analysis was conducted in the CON-arm only and was positive with 11/18 patients achieving tumor response (5 stable, 2 progressive disease). An increased risk for pneumonitis was found in the HYPO-arm during the safety phase, leading to recruitment stop in this arm and continuation of TRADE-hypo with only the CON-arm. Interim futility analysis for the CON-arm was positive suggesting a benefit for the novel combination of durvalumab and thoracic RT for patients not suitable for CHT. Additional safety, efficacy, and biomarker data are expected for 05/25.