State of affairs regarding targeted pharmacological therapy of cancers metastasized to the brain.

In 1999 a visionary short article by The Wall Street Journal writers Robert Langreth and Michael Waldholz popularized the new term "personalized medicine," that is to say, the targeting of drugs to each unique genetic profile. From today's perspective, targeted approaches have clearly found the widest use in the antineoplastic domain. The current review was initiated to review the progress that has been made regarding the treatment of patients with advanced cancer and brain metastases. PubMed was searched for the terms brain metastasis, brain metastases, or metastatic brain in the Title/Abstract. Selection was limited to randomized controlled trial (RCT) and publication date January 2010 to February 2022. Following visual review, 51 papers on metastatic lung cancer, 12 on metastatic breast cancer, and 9 on malignant melanoma were retained and underwent full analysis. Information was extracted from the papers giving specific numbers for intracranial response rate and/or overall survival. Since most pharmacological trials on advanced cancers excluded patients with brain metastases and since hardly any information on adjuvant radiotherapy and radiosurgery is available from the pharmacological trials, precise assessment of the effect of targeted medication for the subgroups with brain metastases is difficult. Some quantitative information regarding the success of targeted pharmacological therapy is only available for patients with breast and lung cancer and melanoma. Overall, targeted approaches approximately doubled the lifespan in the subgroups of brain metastases from tumors with targetable surface receptors such as anaplastic lymphoma kinase (ALK) fusion receptor in non-small cell lung cancer or human epidermal growth factor receptor 2 (HER2)-positive breast cancer. For these types, overall survival in the situation of brain metastases is now more than a year. For receptor-negative lung cancer and melanoma, introduction of immune checkpoint blockers brought a substantial advance, although overall survival for melanoma metastasized to the brain appears to remain in the range of 6 to 9 months. The outlook for small cell lung cancer metastasized to the brain apparently remains poor. The introduction of targeted therapy roughly doubled survival times of advanced cancers including those metastasized to the brain, but so far, targeted therapy does not differ essentially from chemotherapy, therefore also facing tumors developing escape mechanisms. With the improved perspective of patients suffering from brain metastases, it becomes important to further optimize treatment of this specific patient group within the framework of randomized trials.

Successful salvage of recurrent leptomeningeal disease in large cell neuroendocrine lung cancer with stereotactic radiotherapy.

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer.

Non-thermal processing of pineapple (Ananas comosus [L.] Merr.) juice using continuous pressure change technology (PCT): HS-SPME-GC-MS profiling, descriptive sensory analysis, and consumer acceptance.

The effects of single and twofold continuous pressure change technology (PCT) applications on the volatiles and sensory characteristics of pineapple juice were studied. Fresh and thermally pasteurised juices were additionally characterised. 128 volatiles were tentatively assigned in the four juices. Thermal pasteurisation and a single PCT treatment caused substantial losses in total volatiles of 6 and 20%, respectively. A second PCT passage further reduced the volatiles (36%) and is thus not recommended. PCT-treated samples were clearly distinguished from the remaining juices by principal component analysis. The descriptive sensory profiles, assessed by trained panellists, were not substantially affected by thermal pasteurisation and non-thermal PCT. The fresh juice exhibited a significant fishy off-flavour. In the consumer acceptance test, the thermally pasteurised juice was highly rated compared to both PCT-treated and the fresh juice. This study highlights the potential of PCT to avoid the genesis of off-flavours in fresh-like pineapple juice.

HPLC-DAD-APCI-MSn analysis of the genuine carotenoid pattern of pineapple (Ananas comosus [L.] Merr.) infructescence.

The genuine carotenoid pattern of pineapple infructescence was assessed by HPLC-DAD-APCI-MSn analysis. Prevailing pigments in the shell of 'MD2' (syn. "Extra Sweet") fruit were (all-E)-lutein and (all-E)-ß-carotene, in addition to chlorophylls a and b. The edible flesh contained (all-E)-violaxanthin, (all-E)-ß-carotene, and diverse esters of (9Z)-violaxanthin with caprylic, capric, lauric, and myristic acid. The latter esters have been reported for the first time as pineapple constituents. Total carotenoid concentrations in the edible fractions of the four varieties 'Sugar Loaf', 'Smooth Cayenne', 'MD2', and 'Queen Victoria' cultivated in Ghana ranged between 29 and 565 µg/100 g of fresh weight (FW). Total carotenoids in the flesh of fully ripe 'MD2' fruit exported by air freight amounted to 302 µg/100 g of FW, those in green ripe samples dispatched by sea freight to 359-432 µg/100 g of FW. All yellow fleshed cultivars exhibited a highly similar qualitative carotenoid profile.

Spinal Metastases of Supratentorial Glioblastoma with Primitive Neuronal Component.

BACKGROUND: Glioblastoma multiforme with a primitive neuronal component is a rare entity, with few cases reported in the literature. CASE DESCRIPTION: A patient who had a supratentorial glioblastoma multiforme with a primitive neuronal component developed spinal metastasis during the disease course. With his history of leukemia during childhood, he was likely exposed to therapeutic ionizing brain radiation, which could have increased the risk of developing brain cancer in adulthood. CONCLUSIONS: The range of incidence rates of dissemination in the literature is 2%-4%, typically in cases of cerebellar glioblastoma multiforme, but as high as 25% in autopsy series. Our case highlights several other topics in the literature, such as immunohistochemical patterns that differ between the primary tumor and spinal metastases and dissemination locations, typically leptomeningeal or ventricular invasion.