BackgroundThe inclusion of immune checkpoint inhibitors (ICIs) in therapeutic algorithms has led to significant survival benefits in patients with various metastatic cancers. Concurrently, an increasing number of neurological immune related adverse events (IRAE) has been observed. In this retrospective analysis, we examine the ICI-induced incidence of cerebral pseudoprogression and propose a classification system.MethodsWe screened our hospital information system to identify patients with any in-house ICI treatment for any tumor disease during the years 2007-2019. All patients with cerebral MR imaging (cMRI) of sufficient diagnostic quality were included. cMRIs were retrospectively analyzed according to immunotherapy response assessment for neuro-oncology (iRANO) criteria.ResultsWe identified 12 cases of cerebral pseudoprogression in 123 patients treated with ICIs and sufficient MRI. These patients were receiving ICI therapy for lung cancer (n=5), malignant melanoma (n=4), glioblastoma (n=1), hepatocellular carcinoma (n=1) or lymphoma (n=1) when cerebral pseudoprogression was detected. Median time from the start of ICI treatment to pseudoprogression was 5 months. All but one patient developed neurological symptoms. Three different patterns of cerebral pseudoprogression could be distinguished: new or increasing contrast-enhancing lesions, new or increasing T2 predominant lesions and cerebral vasculitis type pattern.ConclusionCerebral pseudoprogression followed three distinct patterns and was detectable in 3.2% of all patients during ICI treatment and in 9.75% of the patients with sufficient brain imaging follow up. The fact that all but one of the affected patients developed neurological symptoms, which would be classified as progressive disease according to iRANO criteria, mandates vigilance in the diagnosis and treatment of ICI-induced cerebral lesions.

Background Neoadjuvant immunochemotherapy is currently being tested in pivotal trials for stage I-III NSCLC. The impact of immunochemotherapy in patients with oligometastastic disease remains undefined. This study aimed to compare the outcomes of radical treatment after the neoadjuvant course of immunochemotherapy versus chemotherapy. Methods We retrospectively analyzed patients with oligometastastic disease who were treated with immunochemotherapy or chemotherapy combined with local ablation of metastases and radical primary tumor resection between 2017 and 2021. Group A included eight patients with immunochemotherapy; Group B included seven patients with chemotherapy. Descriptive statistical analysis included the characteristics of the patients, tumors, and outcomes. Results There was no difference in postoperative morbidity rates between the groups (p=0.626). The 30-day mortality in both groups was 0%. The median overall survival for Group A was not reached, with a median follow-up time of 25 (range:13-35) months; the median overall survival for Group B was 26 (range:5-53) months. In Group A, all patients remained alive; in contrast, in Group B, four patients died (p=0.026). There was no local thoracic recurrence in either group. In Group B, recurrent disease was identified significantly more often (12.5% vs. 85.75%;p=0.009). The rates of complete and major pathologic response were 37.5% and 0% in Group A and 42.85% and 14.25% in Group B, respectively. Conclusion Despite the small patient number and short-term results, the progression-free and overall survival in patients with oligometastastic disease after local therapy for metastases and primary tumor resection following neoadjuvant course of immunochemotherapy might be promising compared to chemotherapy.

Brain metastases are a common finding upon initial diagnosis of otherwise locally limited non-small cell lung cancer. We present a retrospective case series describing three cases of patients with symptomatic, synchronous brain metastases and resectable lung tumors. The patients received local ablative treatment of the brain metastases followed by neoadjuvant immunochemotherapy with pemetrexed, cisplatin, and pembrolizumab. Afterwards, resection of the pulmonary lesion with curative intent was performed. One patient showed progressive disease 12 months after initial diagnosis, and passed away 31 months after initial diagnosis. Two of the patients are still alive and maintain a good quality of life with a progression-free survival and overall survival of 28 and 35 months, respectively, illustrating the potential of novel combinatorial treatment approaches.