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Introduction: Penile metastases (PMs) are a rare clinical presentation mainly related to advanced stages of disease. Considering the low incidence, an optimal treatment approach has not yet been defined; surgery, chemotherapy, and radiotherapy (RT) are different options used in the vast majority with palliative intent. The advances in modern RT can represent an innovative tool in PM management and a curative option. This paper aimed to report the case of a PM patient treated with stereotactic body radiotherapy (SBRT) and perform a systematic literature review of current evidence on the RT approach to PM. Case Presentation: We reported the case of an 80-year-old patient with PM from primary bladder cancer. Following the surgical approach for the primary tumor, evidence of PM was shown, and the patient was admitted to SBRT treatment on PM after an adjuvant RT course on the pelvis. A 25 Gy in 5-fraction SBRT treatment was performed, and a complete clinical response was shown at the first follow-up. A PubMed/MEDLINE and Embase systematic review was carried out. The search strategy terms were [("penile metastasis"/exp OR "penile metastasis" OR (penile AND ("metastasis"/exp OR metastasis))) AND ("radiotherapy"/exp OR radiotherapy)] and only original articles up to October 24, 2023 were considered. Conclusion: A total of 174 studies were obtained using the previously mentioned search strategy, and the analysis was performed on 15 papers obtained following the complete selection process. All reported evidence was focused on the palliative approach of PM, showing good results in terms of symptom control. The potential role of modern RT in the management of PM has yet to be defined. The reported case showed the feasibility and the clinical impact of SBRT in PM treatment. [ABSTRACT FROM AUTHOR]

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. There is a critical lack of predictive biomarkers for patients with metastatic renal cell carcinoma receiving immunotherapy, therefore the identification of patients likely to benefit from this treatment represents a pressing clinical challenge. The Meet-URO 18 study is a multicentric, retrospective, translational study that delves into the immune tumor microenvironment (I-TME) of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line or beyond. Patients were categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Digital multitarget immunohistochemical analyses were performed on the I-TME of tumor samples of primary tumors or metastases. Primary analyses revealed that responders exhibited lower CD4 expression and higher levels of phosphorylated mTOR and CD56. Further extensive analysis of the I-TME focused on T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression assessed on tumor cells, and PD-L1 expression (SP263) assessed on both tumor and immune cells. Responders tumor tissue showed significantly lower CD4 expression, higher CD56 expression and a higher CD8/CD4 ratio compared with non-responders. Other parameters, including PD-L1 expression, did not reach statistical significance. This secondary analysis highlights the emerging significance of CD56 as a putative biomarker for immunotherapy, suggesting a critical role for regulatory CD4+ cells over cytotoxic CD8+ cells. [ABSTRACT FROM AUTHOR]

Background and aims: Gallbladder carcinoma is a rare but aggressive malignant neoplasm. The incidence of intra- or post-operative incidental gallbladder carcinoma diagnosis following laparoscopic cholecystectomy is estimated to be 1-2%. Aggressive re-resection is warranted as the majority of patients have residual disease either in the liver or the lymph nodes. However the use of a minimally invasive surgical approach (MISA) to perform a radicalization in these patients has not been investigated yet. We retrospectively analyzed surgical and oncologic outcome of a small selected cohort of patients with incidental gallbladder carcinoma whom underwent redo radicalization surgery by MISA. Material and methods: From April 2012 to June 2014 at our department six patients (three females and three males) with incidental findings of gallbladder carcinoma pT1b (stage I) following laparoscopic cholecystectomy, and referred to our center from other secondary-level referral hospitals, underwent a redo surgery for radicalization by means of laparoscopic (n. 3) or robotic approach (n. 3). A retrospective analysis of prospective collected data was performed. Results: The redo procedure consisted of a liver resection (segments IVb + V) and lymph nodes clearance of hepatoduodenal hilum and common hepatic artery. Conversion rate was zero. Median operative time was 290 (250-310) min. Estimate blood loss was 175 (100-350) ml. Total hospital stay was 6 (5-10) days. All liver resections were performed without inflow vascular clamping. One patient was re-operated for hemoperitoneum while peri-operative mortality was zero. Oncologically, an R0 resection was always achieved with a mean number of lymph nodes retrieved of 17,5 (14-22). The stage of the neoplasm was confirmed in all cases but one, who was found to have a pN1 status (stage IIIb). At 21 (6-32) months follow-up all patients are alive and no recurrence has been observed. Conclusions: Our data suggest that radicalization of patients with stage I incidental postoperative gallbladder carcinoma can be done by a MISA without compromising the oncologic outcome. Larger studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

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.)

Background/aim: At present, multidisciplinary tumor boards (MDTB) are considered best practice in oncology. However, web-based virtualization of MDTB may increase participation in meetings, the number of cases discussed, and adherence to guidelines, deliver better treatment, and eventually improve outcomes for patients with prostate cancer., Patients and Methods: This is an observational study focused on exploring the structuring process and implementing a multi-institutional virtual MDTB in Sicily, Italy. Other endpoints included the analysis of cooperation between participants, adherence to guidelines, patient outcomes, and patient satisfaction., Results: Overall, 126 patients were referred to the virtual MDTB for a total of 302 cases discussed in an 18-month period. Nearly 45% of cases were referred from general hospitals or tertiary centers, 38% from comprehensive cancer centers, and only 17% from academic ones. Most health professional participants (95%) reported eliminating geographical barriers and consequently reducing costs and saving time as key advantages of virtual meetings over face-to-face ones. Using a specifically designed platform for virtual MDTBs was another excellent point, especially to geolocate clinical trials and time-lapse data storage. The majority of referred patients had stage T 3-4 prostate cancer (79%). Overall, 71% of proposals discussed were approved unchanged, while 19% changed after the virtual MDTB discussion. Debated points were mostly radiologic, surgical, medical, or radiation treatment-related issues. In particular, the prescriptive appropriateness of positron emission tomography with 68Ga-prostatic specific membrane antigen, newer drugs, radiation versus surgical approach, stage T3-4 cases, and adjuvant therapy represented the most debated issues. The proposed diagnostic and/or therapeutic options were controlled for adherence to the guidelines and/or updated scientific evidence. Overall, 98% of approved proposals and changes were in line with the guidelines. Overall, most participants felt virtual MDTB was very useful and case discussions led to a major change of strategy in 19% of cases., Conclusion: Virtual MDTBs are a very useful way to achieve best management of prostate cancer while saving time and fostering cooperation., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Several studies on 18F-FDG-PET/CT have investigated the prognostic role of this imaging modality in different tumors after treatment. Nevertheless, its role in restaging patients with recurrent CM still needs to be defined., Objective: The aim of this retrospective multicenter study was to evaluate the clinical and prognostic impact of 18F-FDG-PET/CT on the restaging process of cutaneous melanoma (CM) after surgery in patients with suspected distant recurrent disease or suspected metastatic progression disease., Materials and Methods: 74 patients surgically treated for CM underwent 18F-FDG-PET/CT for suspected distant recurrent disease or suspected metastatic progression disease. The diagnostic accuracy of visually interpreted 18F-FDG-PET/CT was obtained by considering histology (n=21 patients), other diagnostic imaging modalities performed within 2 months of PET/CT (CT in 52/74 patients and Whole-Body MRI in 18/74 patients) and clinical follow-up (n=74 patients) for at least 24 months containing all the clinical and diagnostic information useful for the PET performance assessment and outcome. Progression-free survival (PFS) and overall survival (OS) were assessed by using the Kaplan- Meier method. The risk of progression (Hazard Ratio-HR) was computed by the Cox regression analysis., Results: Suspicion of recurrent CM was confirmed in 24/27 patients with a positive 18F-FDG-PET/CT scan. Overall, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG-PET/CT were 82%, 93%, 88%, 89%, and 89%, respectively, with area under the curve being 0.87 (95%IC 0.78-0.97; p<0.05). 18F-FDG-PET/CT findings significantly influenced the therapeutic management in 18 patients (modifying therapy in 10 patients; guiding surgery in 8 patients). After 2 years of follow-up, PFS was significantly longer in patients with a negative vs. a positive 18F-FDG-PET/CT scan (90% vs 46%, p<0.05; Fig. 1). Moreover, a negative scan was associated with a significantly longer OS than a positive one (76% vs 39% after 2 years, p<0.05; Fig. 2). In addition, a positive 18F-FDG-PET/CT scan was associated with an increased risk of disease progression (HR=8.2; p<0,05)., Conclusion: 18F-FDG-PET/CT showed a valuable diagnostic performance in patients with suspicion of recurrent CM. This imaging modality might have an important prognostic value in predicting the survival outcomes, assessing the risk of disease progression, and guiding treatment decision making., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.)