Neoadjuvant immune checkpoint inhibitors in resectable non-small-cell lung cancer: a systematic review.

BACKGROUND: The neoadjuvant use of immune checkpoint inhibitors (ICIs) in resectable non-small-cell lung cancer (NSCLC) is currently an area of active ongoing research. The place of neoadjuvant ICIs in the treatment guidelines needs to be determined. We carried out a systematic review of published data on neoadjuvant ICIs in resectable NSCLC to study its efficacy and safety. PATIENTS AND METHODS: A literature search was carried out using the MEDLINE (PubMed) and Embase databases to retrieve articles and conference abstracts of clinical trials measuring the efficacy [major pathological response (MPR) and pathological complete response (pCR)] and safety (failure to undergo resection, surgical delay, treatment-related adverse events (trAEs) grade ≥3) of neoadjuvant immunotherapy in resectable NSCLC until July 2021. RESULTS: Nineteen studies with a total of 1066 patients were included in this systematic review. Neoadjuvant immunotherapy was associated with improved pathological response rates, especially in combination with chemotherapy. Using mono ICI, dual therapy-ICI, chemoradiation-ICI, radiotherapy-ICI, and chemo-ICI, the MPR rates were 0%-45%, 50%, 73%, 53%, and 27%-86%, respectively. Regarding pCR, the rates were 7%-16%, 33%-38%, 27%, 27%, and 9%-63%, respectively. Safety endpoints using monotherapy-ICI, dual therapy-ICI, chemoradiation-ICI, radiotherapy-ICI, and chemo-ICI showed a failure to undergo resection in 0%-17%, 19%-33%, 8%, 13%, and 0%-46%, respectively. The trAEs grade ≥3 rates were 0%-20%, 10%-33%, 7%, 23%, and 0%-67%, respectively. CONCLUSION: In patients with resectable NSCLC stage, neoadjuvant immunotherapy can improve pathological response rates with acceptable toxicity. Further research is needed to identify patients who may benefit most from this approach, and adequately powered trials to establish clinically meaningful benefits are awaited.

A Bayesian approach for estimating detection times in horses: exploring the pharmacokinetics of a urinary acepromazine metabolite.

We describe the population pharmacokinetics of an acepromazine (ACP) metabolite (2-(1-hydroxyethyl)promazine) (HEPS) in horses for the estimation of likely detection times in plasma and urine. ACP (30 mg) was administered to 12 horses, and blood and urine samples were taken at frequent intervals for chemical analysis. A bayesian hierarchical model was fitted to describe concentration-time data and cumulative urine amounts for HEPS. The metabolite HEPS was modelled separately from the parent ACP as the half-life of the parent was considerably less than that of the metabolite. The clearance (Cl/F(PM)) and volume of distribution (V/F(PM)), scaled by the fraction of parent converted to metabolite, were estimated as 769 L/h and 6874 L, respectively. For a typical horse in the study, after receiving 30 mg of ACP, the upper limit of the detection time was 35 h in plasma and 100 h in urine, assuming an arbitrary limit of detection of 1 lg/L and a small (≈0.01) probability of detection. The model derived allowed the probability of detection to be estimated at the population level. This analysis was conducted on data collected from only 12 horses, but we assume that this is representative of the wider population.

[Sarcomas in syrian hamster, induced by an oncorna virus and cellfree transmissible (author's transl)]. / Durch ein Oncornavirus induzierte, zellfrei übertragbare Sarkome des Goldhamsters

1. Application of hamster papova virus to newborns of Syrian hamster has produced some s.c. sarcomas after a 5 to 6 month latency period, by virtue of the strong inducer effect of this papova virus to endogenous (latent) oncorna viruses. 2. Cellfree filtrates from a polymorphorus-cell sarcoma produced in this way, when applied to newborn hamsters of the spontaneously tumour-free hamster line HaP, again lead to sarcoma formation after a latency period of 3--8 months in about 20% of the animals; the same holds for cellfree filtrates of these cellfree induced sarcomas and their transplantation generations. 3. In these tumours C-type oncorna viruses, but no papova virus, could be demonstrated regularly. 4. The hamster specificity of this sarcoma virus is suggested by the complete absence of a tumorigenic effect of the cellfree filtrates from these hamster sarcomas in mice and rats. The preferential induction of hamster sarcomas by sarcoma filtrates, in conjunction with the fact that filtrates from hamster leukoses, indicates a certain difference between hamster leukemia and hamster sarcoma viruses.

[Study on transplantable, melanin containing hamster papova virusinduced skin tumours in Syrian hamster (author's transl)]. / Befunde an transplantablen, melaninhaltigen, durch Hamster-Papova-Virus induzierten Hauttumoren beim Goldhamster

A melanin containing skin tumour of trichoepitheliomatic character, induced by a virus some 40 nm large, is described showing neither infiltrative nor metastasizing growth. The multiple, flat, mostly confluent tumour nodes appear in all parts of the skin, especially in dorsal skin, at the chin, eyes, and ears. The tumours are mostly blue black as a result of hemosiderin and melanin deposits; these pigmentations occur in connective-tissue cells, the tumour cells and the abounding keratinizing cysts. The blastomic character of these tumours, which in part are reminiscent of tricho-epitheliomas, can be demonstrated by transplantation experiments, in which with increasing number of passages are observed a decrease of latent period, disappearance of pigment formation, and increase in histologic de-differentiation.

Induction of transmissible lymphomas in Syrian hamsters by application of DNA from viral hamster papovavirus-induced tumors and by cell-free filtrates from human tumors.

DNA isolated from skin epitheliomas containing papovavirus induced lymphomas within four to eight weeks in 40 to 50 per cent of newborn Syrian hamsters injected. This DNA effect was eliminated by DNase but not by RNase and was not induced by DNA preparations of transplanted epitheliomas or the induced lymphomas. Lymphomas were similarly induced by cellfree filtrates from certain human tumors such as gastric carcinomas and ovarian tumors. Little or no lymphoma effects were observed following injections with filtrates derived from normal human or animal tissues or human blood. The lymphomas induced by DNA and human tumors were transmissible by cell-free filtrates to newborn Syrian hamsters; however, successful serial passage, like the primary lymphomas induced by the DNA preparations, depended upon the use of a newborn hamster from a special breeding colony of hamsters.