The aim of this multi-center retrospective study was to evaluate the incidence of hyperprogressive disease (HPD) after second-line treatment with pembrolizumab in patients (n = 167) with metastatic non-small-cell lung cancer (NSCLC) whose tumors expressed programmed cell death ligand 1 (PD-L1) in ≥ 1% and to search for hematological and imaging biomarkers associated with its development. Prior to chemotherapy, neutrophil : lymphocyte ratio (NLR1) and platelet : lymphocyte ratio (PLR1), and prior to immunotherapy, NLR2 and PLR2 were retrospectively analyzed. The psoas major muscle area (PMMA) was calculated at the L3 position on computed tomography before chemotherapy (PMMA1) and before immunotherapy (PMMA2) (n = 112). Patients with ∆PMMA (1-PMMA2/ PMMA1) × 100 ≥ 10% were considered to have sarcopenia (low muscle mass). After treatment with pembrolizumab on the first computerized tomography (CT) scan evaluation, patients were subdivided as follows as: hyperprogressors (HPs), progressors (Ps), non-progressors (NPs) and pseudoprogressors (PPs). HPs had significantly higher ∆PMMA levels, NLR2 and PLR2 than the other patients. Moreover, in multinomial logistic regression analysis, higher levels of ∆PMMA were associated with a decreased likelihood of being a P [odds ratio (OR) = 0•81; 95% confidence interval (CI) = 0•65-0•99; P = 0•047] or an NP (OR = 0•76; 95% CI = 0•62-0•94; P = 0•012) versus an HP. Higher NLRs tended to decrease the likelihood of being a P versus an HP (OR = 0•66; 95% CI = 0•42-1•06; P = 0•09) and significantly decreased the likelihood of being an NP versus an HP (OR = 0•44; 95% CI = 0•28-0•69; P < 0•0001). Our data suggest that a high pre-immunotherapy NLR2 and the presence of sarcopenia are potential risk factors for the development of HPD.

Background: Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein with a large extracellular domain with overexpression of the prostatic tumour cells. Several small molecules of PSMA ligands of inhibitors binding to the active site of PSMA were developed. [ 99m Tc]Tc-PSMA-T4 is a new radiopharmaceutical (Polatom) for imaging loco-regional metastases and/or local relapse in patients with prostate cancer.The purpose of this work was to evaluate the clinical application of SPECT-CT imaging with [ 99m Tc]Tc-PSMA-T4 in patients with recurrent prostate cancer.Material and methods: Thirty-six patients with prostate cancer, aged 60-80 years with biochemical relapse of PSA (ranged from 0.1 to 73 ng/mL) were included. Three patients were studied after tru-cut biopsy, hormonal and cytoreductive radiotherapy and 33 patients out of 36 -after radical treatment (total prostatectomy or definitive radiotherapy of the tumour). All of them underwent whole-body imaging examinations with subsequent target SPECT-CT studies of the pelvis, abdomen and/or chest, 1-3 hrs post i.v. administration of [ 99m Tc]Tc-PSMA-T4. The average activity dose was 6.3 MBq/kg in a man of 70 kg. A Dual-head SPECT-CT gamma camera with a low dose CT scan (Symbia T2, Siemens) was used. The images were interpreted based on all other clinical and radiological data. Follow-up could be conducted in 11/36 patients during that period.Results: Normal biodistribution of the radiopharmaceutical with high activity background was observed in the liver, spleen, kidneys, lacrimal and salivary glands, bowels and urinary bladder. Positive imaging for local relapse in the prostate bad was imaged in 21 patients, lymph node metastases -in 16 cases, bone lesions -in 10 cases, pulmonary metastases -in 2 cases, hepatic lesions were visualised in one of them and in another -adrenal suprarenal metastasis with intensive tracer uptake significant for overexpression of PSMA. There was a suspicion for local recurrences in 4 patients with negative MRT studies who were followed up. In 3 cases, previously treated bone metastases were partially negative without tracer uptake, only some progressive bone lesions were positive. Five patients were with negative results. Sensitivity was 84.37% (27/32), specificity -100% (4/4) and accuracy -86.11% (31/36). Conclusions:In conclusion SPECT-CT imaging with [ 99m Tc]Tc-PSMA-T4 could be applied in patients with prostate cancer for the diagnosis of recurrent disease to determine personalized treatment for each patient. Specific uptake of this tracer, depicted by SPECT-CT images has clinical importance of identifying and assessing PSMA expression before consideration of Radio Ligand Therapy (RLT) with [ 177 Lu]Lu-PSMA. SPECT-CT imaging with [ 99m Tc]PSMA is promising and reliable nuclear medicine approach to monitoring therapeutic effect after treatment and for restaging of the disease.

Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with Tc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

Resveratrol is a naturally occurring polyphenol which has various beneficial effects, such as anti-inflammatory, anti-tumor, anti-aging, antioxidant, and neuroprotective effects, among others. The anti-cancer activity of resveratrol has been related to alterations in sphingolipid metabolism. We analyzed the effect of resveratrol on the enzymes responsible for accumulation of the two sphingolipids with highest functional activity—apoptosis promoting ceramide (CER) and proliferation-stimulating sphingosine-1-phosphate (S1P)—in human lung adenocarcinoma A549 cells. Resveratrol treatment induced an increase in CER and sphingosine (SPH) and a decrease in sphingomyelin (SM) and S1P. Our results showed that the most common mode of CER accumulation, through sphingomyelinase-induced hydrolysis of SM, was not responsible for a CER increase despite the reduction in SM in A549 plasma membranes. However, both the activity and the expression of CER synthase 6 were upregulated in resveratrol-treated cells, implying that CER was accumulated as a result of stimulated de novo synthesis. Furthermore, the enzyme responsible for CER hydrolysis, alkaline ceramidase, was not altered, suggesting that it was not related to changes in the CER level. The enzyme maintaining the balance between apoptosis and proliferation, sphingosine kinase 1 (SK1), was downregulated, and its expression was reduced, resulting in a decrease in S1P levels in resveratrol-treated lung adenocarcinoma cells. In addition, incubation of resveratrol-treated A549 cells with the SK1 inhibitors DMS and fingolimod additionally downregulated SK1 without affecting its expression. The present studies provide information concerning the biochemical processes underlying the influence of resveratrol on sphingolipid metabolism in A549 lung cancer cells and reveal possibilities for combined use of polyphenols with specific anti-proliferative agents that could serve as the basis for the development of complex therapeutic strategies.

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