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Abstract Background Metastatic involvement of the ovary from malignant melanoma is uncommon and presents a diagnostic challenge. Most cases are associated with disseminated disease and carry a dismal prognosis. Delayed ovarian recurrences from melanoma may mimic primary ovarian cancer and lead to aggressive cytoreductive procedures. Case presentation A case of malignant melanoma in a premenopausal patient is presented with late abdominal and ovarian metastatic spread, where ascitic fluid cytology led to an accurate preoperative diagnosis and the avoidance of unnecessary surgical procedures. Conclusion Secondary ovarian involvement is associated with a poor prognosis and efforts should be made for adequate palliation. Pathologic diagnosis with non-invasive procedures is crucial in order to avoid unnecessary surgery. Surgical interventions may be undertaken only in selected cases of limited metastatic disease, where complete resection is expected

Testicular cancer is a disease with elusive pathogenesis. Recent studies demonstrated a relationship between insulin- like growth factor (IGF) signaling pathway and the pathogenesis of various types of cancer. On the other hand inconclusive data correlate increasing height, a trait depending on IGF signaling pathway, with increasing incidence of testicular cancer. Thus, it is possible that IGF system may be implicated in the pathogenesis of germ cell tumors. The purpose of the study was to identify the role of IGF signaling pathway in the pathogenesis of testicular germ cell tumors (GCTs). 50 patients with GCTs prior to the onset of chemotherapy and 16 male age matched controls were enrolled. Three blood samples were drawn from the patients, the first at baseline, the second 20-30 days after completion of the second cycle of chemotherapy and the third 9-14 months after the completion of chemotherapy; and one blood sample was drawn from the controls. We measured serum IGF-1 and IGFBP-3 and calculated their molar ratio using quantitative sandwich enzyme immunoassay technique. Patients and controls had similar demographic characteristics. Mean IGF-1/IGFBP-3 molar ratio was higher in patients than controls (0.27±0.07 vs. 0.11±0.03; p=0.02'7). IGF-1 decreased significantly between the baseline and 1 year after chemotherapy was completed (261.2±483 vs. 96.4±23.1 ng/mL, respectively; p<0.001) and between the second sample and the third sample (205.7±41.7 vs. 96.4±23.1 ng/mL; p<0.001 IGFBP-3 was increased after chemotherapy (mean values of first and second samples were 3545±687.3 vs. 4714±827.1 ng/mL; p=0.045, and mean values between first and third samples were 3591±697.6 vs. 5145±1073.2 ng/mL; p=0.005 IGF1/IGFBP3 molar ratio was found to decrease after initiation and completion of chemotherapy (mean values were: 0.269±0.05 vs. 0.211±0.04; between the first and third samples, p=0.035; 0.308±0.07 vs. 0.083±0.02 between the second and third samples, p<0.001and 0.211±0.04 vs. 0.084±0.02 between the first and second samples, p<0.00). The concept that IGF signaling system has a role in germ cell cancer pathogenesis is an appealing idea and our study seems to provide further evidence in favor of our initial hypothesis, although larger prospective studies are needed to further elucidate it. [ABSTRACT FROM AUTHOR]

Background/aim: Real-world data on the EGFR mutational profile upon progression after first/second-generation EGFR-TKI treatment in patients with advanced non-small-cell lung cancer (NSCLC) and treatment strategies employed thereon are needed., Patients and Methods: This observational study was conducted in 23 hospital-based lung cancer Centers in Greece (protocol code: D133FR00126). Ninety-six eligible patients were consecutively enrolled between July-2017 and September-2019. Re-biopsy was performed in 18 of 79 patients who tested T790M-negative in liquid biopsy after progression in the first-line (1L) setting., Results: Of the study population, 21.9% tested T790M-positive, while 72.9% proceeded to 2L treatment, mainly comprising of a third-generation EGFR-TKI (48.6%), a switch to chemotherapy (30.0%), or chemo-immunotherapy (17.1%). The objective response rate (ORR) in 2L was 27.9% in T790M-negative and 50.0% in T790M-positive patients. Of evaluable patients, 67.2% experienced disease progression; median progression-free survival (PFS) was 5.7 and 10.0 months among T790M-negative and positive patients, respectively. Among T790M-negative patients, longer median PFS and post-progression survival were observed with third-generation EGFR-TKI treatment., Conclusion: Mutational status and treatment strategy were identified as critical determinants of clinical outcomes in the 2L-setting of EGFR-mutated NSCLC patients in real-world settings in Greece, with early diagnosis, appropriate molecular testing and high-efficacy treatments at first lines positively affecting ORR and PFS., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been extensively used in Greece in this setting; however, real-world data regarding molecular epidemiology and financial implications of afatinib use are lacking., Materials and Methods: This was an observational, non-interventional, multicenter, retrospective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reimbursed by the payer were considered., Results: A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37-91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9-51.4), the median PFS was 14.3 months (95% CI 12.2-16.4), and the median OS was 29 months (95% CI 25.6-33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5-18.5) and 28.1 months (95% CI 21.1-32.6), respectively. The mean expenditure for the treatment of each patient equals €25,333.68; with €21,865.06 being attributed to drug acquisition costs, €3325.35 to monitoring costs and €143.27 to adverse event treatment-related costs., Conclusion: Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC., Clinical Trial Registration: Clinicaltrials.gov NCT04640870., Competing Interests: Dr Giannis Mountzios report personal fees from Roche Hellas, personal fees from BMS Greece, personal fees from MSD Greece, personal fees from AstraZeneca Greece, personal fees from Pfizer Greece, personal fees from Takeda Greece, personal fees from Boehringer Greece, outside the submitted work; Professor Athanassios Vozikis report personal fees from BMS, personal fees from Roche, personal fees from TAKEDA, personal fees from ANGELINI, outside the submitted work; Dr Anastasios Grivas report personal fees, non-financial support from Bristol-Myers Squibb, personal fees, non-financial support from LEO Pharma, personal fees, non-financial support from Novartis Greece, personal fees, non-financial support from AstraZeneca, personal fees, non-financial support from Amgen, personal fees, non-financial support from Pierre Fabre, personal fees, non-financial support from Boehringer Ingelheim, personal fees, non-financial support from Roche, outside the submitted work; Dr Georgios Rigakos report grants from pfizer, grants from Merck, grants from roche, outside the submitted work; Professor George Fountzilas report personal fees from Pfizer, personal fees from Novartis, personal fees from Roche, personal fees from AstraZeneca, outside the submitted work; and Stock ownership: Genprex, Daiichi Sankyo, ARIAD, RFL Holdings, FORMYCON. Dr Helena Linardou report personal fees from Roche, personal fees from Astra Zeneca, personal fees from Novartis, personal fees from MSD, personal fees from BMS, personal fees from Merck, personal fees from Pfizer, personal fees from Amgen, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2021 Mountzios et al.)

Gamma-irradiation leads to apoptosis and cell cycle arrest in eukaryotic cells. Olomoucine is a novel purine analog acting as a cyclin-dependent kinase inhibitor. The effects of olomoucine in gamma-irradiation mediated cell growth inhibition and apoptosis were studied in the Raji cell line (Burkitt's lymphoma). Gamma-irradiation caused a G2 arrest, increasing the G2/M fragment of the cells. Apoptosis by gamma-irradiation was apparent both by DNA-electrophoresis and PARP-1 cleavage. The combination of olomoucine with irradiation caused an increased G2 arrest and decreased cell survival and DNA synthesis in the non-apoptotic fraction of the remaining cells. Irradiation, as well as olomoucine and the combination of both, induced apoptosis. It seems that olomoucine delays the apoptotic process and inhibits DNA fragmentation, but it decreased survival, cell cycle progression and proliferation of irradiated cells.

Background: NSC 290205 (A) is a hybrid synthetic antitumor ester, which combines a D-lactam derivative of androsterone and nitrogen mustard. In this study, the antitumor activity of A in combination with ADR (AHOP) was investigated in comparison with the standard CHOP regimen., Materials and Methods: PAN02 adenocarcinoma was used in this study. C57Bl mice were used for chemotherapy evaluation. The activity was assessed from the inhibition of tumor growth and the oncostatic parameter T/C%., Results: Treatment with A or cyclophosphamide produced almost equal borderline activity. Moreover, both the CHOP and AHOP regimens showed significant and comparable antitumor effects. AHOP caused the maximum effect, inhibiting tumor growth by 56.8%. CHOP was less effective, producing 47.7% tumor inhibition., Conclusion: It is very likely that the D-lactamic steroid (androstan) alkylator forA, containing the amide group -NH-CO-, combined with ADR which intercalates between DNA base-pairs, is the explanation for the higher activity of AHOP as compared to CHOP.