[Operability and Pathological Response of Non-Small Cell Lung Cancer (NSCLC) after Neoadjuvant Therapy with Immune Checkpoint Inhibition]. / Operabilität und pathologisches Ansprechen des Lungenkarzinoms nach neoadjuvanter Therapie mit Immun-Checkpoint-Inhibitoren.

BACKGROUND: The blockade of immune escape mechanisms (e. g. PD1 /PD-L1) using immune checkpoint inhibition (ICI) can significantly prolong survival and induce remission in patients with advanced non-small cell lung cancer (NSCLC). Less is known about neoadjuvant ICI in patients with resectable (UICC stage III) or oligometastatic (UICC stage IVa) NSCLC. METHODS: Tissue biopsies from patients with advanced or oligometastatic NSCLC were screened for PD-L1 expression. In case of PD-L1-expression > 50 %, ECOG status of 0 or 1 and expected operability, patients received ICI. After about four weeks, patients underwent thoracic surgical resection. In all patients, a complete staging, including PET-CT, cMRI, and endobronchial ultrasound, was performed. The tolerability, the radiological and the histopathological tumor response as well as the surgical and oncological outcomes were analyzed. FINDINGS: Four patients (2 male, 2 female, age 56 - 78 years, n = 3 adenocarcinoma, n = 1 squamous cell carcinoma) with local advanced tumors received ICI before surgical resection. In three cases the mediastinal lymph nodes were positive. One patient had a single cerebral metastasis which was treated with radiotherapy. All four patients underwent therapy with two to six cycles of ICI (3â€Š× pembrolizumab, 1â€Š× atezolizumab) without any complication, and ICI did not delay the time of surgical resection. According to iRECIST, three patients showed partial response (PR), one patient had stable disease (SD). All tumors were completely resected. The thoracic surgical procedures proved to be technically unproblematic despite inflammatory changes. There were neither treatment-related deaths nor perioperative complications. In the resectates, complete pathological response (CPR, regression grade III ) and regression grade IIb were detected twice. The average time of follow-up was 12 (1 - 24) months. Patients with PPR developed distant metastasis after six months or a local recurrence after four months. The CPR patient is relapse free to date. CONCLUSION: In selected patients, neoadjuvant therapy with ICI is well tolerated and can induce a complete remission of the tumor. Treatment with ICI has no negative impact on the surgical procedure. Prognosis seems to be promising in CPR and limited in PPR.

New processing of lupin protein isolates and functional properties.

A growing demand for functional plant proteins could be identified, which properties are customized for specific applications and formulations as food ingredients. Native lupin proteins (alpha, beta, gamma) conglutin have a good solubility at appropriately chosen conditions. A novel procedure has been proposed to maintain the native protein properties. Lupin proteins are extracted from hexane deoiled lupin. The protein product type E comprises high molecular weight proteins (alpha, beta-conglutin), which are separated using alkaline extraction and acid precipitation procedures. The protein product type F is enriched in the gamma-conglutin fraction and is separated from the acid pre-extract applying cross flow filtration at pH 7-8. For the zirconium oxide membrane the filtration rate can be increased by appropriately chosen pH conditions up to 70 l/m2h. Lupin protein fraction (type E and F) are highly soluble protein isolates with outstanding emulsification, salt tolerance and foaming properties. These new lupin proteins (type E and F) offer extremely interesting properties for application in food systems and are available from pilot plant fractionation.