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Background: Immunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy., Methods: The Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS., Results: Overall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 - 10.1), while mPFS was 7.0 months (95% CI: 5.7 - 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59)., Conclusion: We found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS., Competing Interests: Dr. SB received honoraria as speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, Roche, Eli Lilly, AstraZeneca, Pierre-Fabre, Novartis, Merck, Gentili, Astellas. Dr. SR received honoraria as speaker at scientific events and travel accommodation from BMS, Amgen, GSK, Ipsen, Astellas, Janssen, MSD. Dr. DB received honoraria as advisory role by Ipsen, Astellas, Janssen, Novartis, BMS, MSD, Pfizer, Merck and travel accommodation from Ipsen, Janssen, MSD, Merck. Dr. UD services as advisory/board member of Astellas, Bayer, BMS, IPSEN, Janssen, Merck, Pfizer, Sanofi, received research grant/funding to the institution from AstraZeneca, Roche, Sanofi and travel/accommodations/expenses from BMS BMS, IPSEN, Janssen, Pfizer. Dr. SC received honoraria as speaker at scientific events/advisory boards and travel accommodation from BMS, Ipsen, MSD, Pierre-Fabre, Bayer, Gentili. Dr. PZ reports outside the submitted work personal fees for advisory role, speaker engagements and travel and accommodation expenses from Merck Sharp & Dohme MSD, Astellas, Janssen, Sanofi, Ipsen, Pfizer, Novartis, Bristol Meyer Squibb, Amgen, Astrazeneca, Roche and Bayer. Dr. GPro services advisory boards/consulting for Astellas, AstraZeneca, BMS, Janssen, IPSEN, Merk, MSD, Novartis, Pfizer. Dr. CB received honoraria from advisory board/clinical trials/conference speaking/travel grant with Astellas, AstraZeneca, Bayer, BMS, Clovis, Exelixis, GSK, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer, Roche, Sanofi. Dr. MSo services advisory boards/consulting for Janssen, received research funding from Janssen, Roche and Merck and received travel accomodation from Ipsen, BMS, Janssen, Pfizer, Novartis, Astellas, Sanofi, Roche. Dr. FM services advisory boards for Pfizer and MSD. Dr. PR services advisory boards for MSD, AstraZeneca and Janssen. Dr. GF services advisory boards for Astellas, Janssen, Pfizer, Bayer, MSD, Merck and received travel accomodation from Astellas, Janssen, Bayer. Dr. GB reports personal fees from AstraZeneca and Astellas for speaker bureau. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Murianni, Signori, Buti, Rebuzzi, Bimbatti, De Giorgi, Chiellino, Galli, Zucali, Masini, Naglieri, Procopio, Milella, Fratino, Baldessari, Ricotta, Mollica, Sorarù, Tudini, Prati, Malgeri, Atzori, Di Napoli, Caffo, Spada, Morelli, Prati, Nolè, Vignani, Cavo, Lipari, Roviello, Catalano, Damassi, Cremante, Rescigno, Fornarini and Banna.)

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders ' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression ( p = 0.014), higher CD56 expression ( p = 0.046) and higher CD8/CD4 ratio ( p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.

Background/aim: Radiation therapy (RT) represents a therapeutic option in breast cancer (BC). Even if a great number of BC patients receive RT, not all of them report benefits, due to radioresistance that gets activated through several factors, such as the hormone receptor status. Herein, we analyzed the gene expression profiles (GEP) induced by RT in triple-negative BC (TNBC) MDA-MB-231, to study signalling networks involved in radioresistance., Materials and Methods: GEP of MDA-MB-231 BC cells treated with a high dose of radiation, went through cDNA microarray analysis. In addition, to examine the cellular effects induced by RT, analyses of morphology and clonogenic evaluation were also conducted., Results: A descriptive report of GEP and pathways induced by IR is reported from our microarray data. Moreover, the MDA-MB-231 Radioresistent Cell Fraction (RCF) selected, included specific molecules able to drive radioresistance., Conclusion: In summary, our data highlight, the RT response of TNBC MDA-MB-231 cell line at a transcriptional level, in terms of activating radioresistance in these cells, as a model of late-stage BC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: An association has been reported between lung cancer and John Cunningham (JC) virus infection. The aim of this study was to evaluate the prevalence of JC virus in a small cohort of patients with lung adenocarcinoma and assess its presence in nodal metastasis., Materials and Methods: Consecutive samples of 13 surgically-removed lung tumors and 13 surrounding normal cancer-free tissues were selected. Five cases included metastatic lymph nodes. JC virus infection was assessed through nested PCR., Results: Seven out of thirteen patients with lung adenocarcinoma had a positive PCR test for JC virus. One of the five patients with nodal metastasis had a positive PCR test for JC virus. None of the thirteen specimens from the control group presented with JC virus infection. The difference between the two groups regarding JC virus infection was statistically significant (p=0.008)., Conclusion: Our study suggests that JC virus might be involved in lung carcinogenesis., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)