Prostate cancer represents the third leading cause of cancer-related mortality in the male population. Androgen deprivation therapy efficacy has been significantly enhanced by the addition of docetaxel chemotherapy and androgen receptor pathway inhibitors (ARPI), such as abiraterone, enzalutamide, apalutamide, and darolutamide. These agents have demonstrated improvements in both overall survival (OS) and progression-free survival (PFS). Nevertheless, a subset of patients eventually progresses to metastatic castration-resistant prostate cancer (mCRPC). The prostate-specific antigen (PSA) nadir, defined as the lowest PSA level achieved during therapy, has emerged as an early surrogate marker of treatment response and favorable prognosis. We conducted a meta-analysis to elucidate the prognostic value of the depth of PSA response in patients with metastatic metastatic hormone-sensitive prostate cancer (mHSPC) treated with ARPI or docetaxel. This is a reconstructed individual patient data (IPD) meta-analysis, in which prospective and retrospective clinical trials concerning patients with mHSPC who received first-line therapy with an ARPI or docetaxel were included. Prospective or retrospective studies on mHSPC patients with available data on the lowest value of PSA reached were included. IPD from the Kaplan–Meier curves of enrolled studies were obtained with the software IPDfromKM. Primary endpoints of the analysis were overall survival (OS) and progression-free survival (PFS) in patients who reached a PSA nadir ≤ 0.2 versus PSA nadir > 0.2. A total of 8 reports from 8 studies were included, collecting data from 1638 patients for the OS analysis and 1104 for the PFS analysis. In terms of median PFS (mPFS), the PSA nadir ≤ 0.2 arm had an advantage: mPFS not reached (NR) versus 12.1 months HR 0.19 (95

Systemic inflammatory indices have been proposed as prognostic biomarkers in several malignancies; however, their role in patients receiving avelumab maintenance for advanced urothelial carcinoma (aUC) remains poorly defined. This study aimed to evaluate the prognostic impact of inflammatory markers in this context and to develop a composite score for outcome stratification. We retrospectively analyzed patients with aUC who were treated with avelumab maintenance therapy. Systemic inflammatory markers - including the neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) - were collected at baseline and after treatment initiation (cycle 3), and changes from baseline to cycle three were analyzed (increase versus stability/decrease). Overall survival (OS), the primary endpoint, was evaluated using Kaplan-Meier and Cox models. A prognostic score was created from the multivariable analysis. Time-dependent Receiver operating characteristics (ROC) analysis was employed to evaluate model discrimination at 6, 12, and 24 months. The prognostic impact on disease control rate (DCR - secondary endpoint) was assessed using logistic regression and ROC curves. A total of 358 patients were included in the study. In the multivariable analysis, high NLR, high NER, low LMR, increasing NLR trend, bone and liver metastases were independently associated with worse OS. These variables were incorporated into a 0-6 point prognostic score, which demonstrated good discrimination (C-index 0.76; AUC at 6, 12, and 24 months: 0.87, 0.75, and 0.73, respectively). The score remained prognostic across subgroups and following sensitivity analyses. High LMR, low NER, the absence of liver metastases, and the absence of bone metastases were independently associated with higher DCR. A response-associated score combining these variables showed a decreasing DCR from 69% (score 0) to 25% (score 4). Baseline and dynamic inflammatory markers may serve as prognostic factors for OS in patients with aUC undergoing avelumab maintenance therapy. A composite score that integrates laboratory and clinical features could allow for clinically meaningful stratification of survival and response outcomes, with potential applications in clinical practice. However, a prospective evaluation is necessary.

Immuno-checkpoint inhibitors (ICIs) represent the backbone for the first line combination therapies of metastatic renal cell carcinoma (mRCC) but their advantage in the IMDC favourable risk compared to sunitinib is debated. To estimate their efficacy we present an individual patient data (IPD) meta-analysis A systematic literature search from 2015 to 2024 was conducted on the MEDLINE. Five phase III studies, 1088 patients overall, were analyzed aaccording to PRISMA statement. (JAVELIN RENAL 101, CHECKMATE 214, KEYNOTE 426, CHECKMATE 9ER, CLEAR). An IPD meta-analysis was performed by reconstructing IPD from Kaplan-Meier curves. Primary endpoints were Progression Free Survival (PFS) and overall Survival (OS) in favorable risk patients comparing ICI-based therapies versus sunitinib as well as versus each other. For OS, there was a statistically significant superiority of Pembrolizumab-Lenvatinib rather than Nivolumab-Cabozantinib (HR 0.56 CI 95

In the context of precision oncology, understanding the molecular drivers of colorectal cancer (CRC) is critical for improving prognosis and guiding targeted therapy. FBXW7 is a tumor suppressor that plays a pivotal role in CRC by regulating the degradation of key oncogenic proteins, influencing tumor initiation, growth, therapeutic response, and metastatic behavior. Mutations in FBXW7 occur in 6-10% of CRC. Despite its biological relevance, the prognostic and predictive role of FBXW7 in CRC remains unclear, with inconsistent findings across studies. This systematic review collects and analyzes current evidence on FBXW7 mutations and expression in CRC, emphasizing its potential role in risk stratification, therapeutic response, and personalized treatment approaches. A total of 113 records were selected on PubMed, SCOPUS, Web of Science and Cochrane Central Register of Controlled Trials from 2015 and January 2025, of which 48 examined the preclinical landscape of FBXW7 in CRC and 65 focused on its clinical role. FBXW7 mutations are associated with different clinicopathological patterns, including early-onset disease, microsatellite instability, and co-occurring driver alterations, all of which shape prognosis and treatment outcomes. While some variants correlate with immune infiltration and better survival, others, especially when co-mutated, predict aggressive disease and poor outcomes. Furthermore, FBXW7 alterations contribute to chemoresistance and anti-EGFR therapy resistance but also reveal potential therapeutic vulnerabilities. These findings underscore FBXW7's promise as a prognostic biomarker and a potential target for precision oncology strategies in colorectal cancer.

AbstractBackgroundWe present a systematic review and meta‐analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor‐targeted agent (ARTA) in first‐ and second‐line settings.MethodsPrimary endpoints are radiographic progression free survival (rPFS) and overall survival (OS) in patients with mCRPC and either unselected, homologous recombination repair wild‐type (HRR−), homologous recombination repair mutated (HRR+) or with BRCA1, BRCA2, or ATM mutation. The effect of PARPi + ARTA in the second‐line setting is also explored. Safety is a secondary end‐point.ResultsA total of five phase III (first line: MAGNITUDE, PROpel, TALAPRO‐2; second line: PROfound, TRITON3) and two phase II RCTs (second line: NCT01972217, NCT01576172) were selected. In the first‐line setting, rPFS was significantly improved in PARPi + ARTA arm in all comers (HR 0.70, p < 0.00001), HRR− (HR 0.76, p = 0.005), HRR+ (HR 0.57, p = 0.0003), and BRCA1/2‐mutated patients (HR: 0.33, p < 0.00001). OS was improved in the population with HRR+ status (HR 0.76, p = 0.02) but not statistically significant in BRCA1/2‐mutated patients (HR 0.57, 95% CI 0.30–1.08, p = 0.08). In the second line, PARPi improves rPFS (HR for BRCA2 0.31, p = 0.002) and OS (HR for BRCA1/2 0.71, p = 0.01) only in such patients. In this setting, no advantage was reported by adding a PARPi to an ARTA. The arm with PARPi either as monotherapy or in combination with ARTA showed a significantly higher toxicity profile.ConclusionsPARPi‐based therapy represents a compelling treatment option for HRR+ mCRPC, mainly BRCA1/2‐mutated patients. However, further biomarker analysis are needed in order to identify other responsive patients across the different disease settings.

e16572 Background: Avelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients’ benefits while minimizing toxicity. Systemic inflammatory indexes have been studied as prognostic biomarkers for immune checkpoint inhibitors in many tumor types, but their role in mUC is still debatable. We hypothesized that systemic inflammatory indexes could be correlated with survival in mUC patients treated with maintenance avelumab. Methods: Meet-URO25 is a multicenter Italian prospective/retrospective registry of mUC patients treated with first-line avelumab maintenance from 01/2021 to 12/2024. In the SAILOR/Meet-URO25a sub-analysis, we investigated the correlation with overall survival (OS) of five inflammatory indexes (neutrophil-to-lymphocyte ratio [NLR], lymphocyte-to-monocyte ratio [LMR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-eosinophil ratio [NLR], and systemic-inflammation-index [SII]) at baseline and after 3 cycles of avelumab. ROC curves with Youden’s test, the Kaplan-Meier method with log-rank test, and Cox regression analyses were used. Results: 258 patients (106 female; median age: 63yrs) were included in the analysis. Low baseline NLR (Hazard ratio [HR] 0.37; 95% confidence interval [CI] 0.19-0.73; p: 0.016) and SII (HR 0.75; 95%CI 0.52-0.98; p: 0.033) were associated with better OS. After 3 cycles of therapy, decreasing NLR (HR 0.64; 95%CI 0.43-0.94; p: 0.02), NER (HR 0.67; 95%CI 0.46-0.99; p: 0.006) and SII (HR 0.55; 95%CI 0.37-0.81; p: 0.002) were significantly associated with longer OS. In the multivariate analysis, the presence of liver metastases, response both to first-line chemotherapy and avelumab, baseline NLR, early NLR and NER reduction were independent predictors of OS. Conclusions: Our results suggest that baseline levels of NLR and systemic inflammatory indexes and their kinetics after avelumab initiation may be prognostic in pts with mUC. The combined evaluation of systemic inflammatory indexes and their early changes should be further investigated to obtain additional prognostic or predictive value.

Introduction:In the last two decades, tyrosine-kinase inhibitors (TKIs) have dramatically changed the prognosis of lung and breast cancers, with significant benefits in the metastatic setting and, more recently, in the adjuvant setting for selected groups of patients. Despite their favorable oncological effects, TKIs carry a high risk for drug-drug interactions (DDIs) due to their pharmacokinetics (PK), which depend on both pH-dependent absorption and liver metabolism. However, DDIs are frequently related to "potential DDIs" (pDDIs), and their clinical relevance is often underestimated; there is also a lack of practical guidance for clinicians. Methods and materials:We conducted a narrative review restricted to the last 20 years, involving adult individuals (aged 18 years or older) with lung or breast cancers treated with TKIs and clinical data on potential DDIs, along with reported toxicities or outcomes. Results:We summarized the pharmacokinetic profiles and the clinical evidence of 11 TKIs used for lung or breast cancers. Moreover, we provided an easy-to-use guide to help physicians in clinical practice with recommended dose adjustments or cautions necessary to prevent severe adverse events or possible changes in TKI availability in the presence of other interfering drugs. Conclusion:The level of evidence for DDIs during TKI treatment is low because most available data are from phase I studies in healthy volunteers and few phase II studies in cancer patients. However, since the occurrence of DDIs can be clinically significant and a prompt drug reconciliation process can be useful to prevent them, further prospective, large-sample-size clinical trials should be carried out.

(1) Background: We estimated the prevalence and clinical outcomes of sarcopenia among breast cancer patients. (2) Methods: A systematic literature search was carried out for the period between July 2023 and October 2023. Studies with breast cancer patients evaluated for sarcopenia in relation to overall survival (OS), progression-free survival (PFS), relapse of disease (DFS), pathological complete response (pCR), or toxicity to chemotherapy were included. (3) Results: Out of 359 screened studies, 16 were eligible for meta-analysis, including 6130 patients, of whom 5284 with non-MBC. Sarcopenia was evaluated with the computed tomography (CT) scan skeletal muscle index and, in two studies, with the dual-energy x-ray absorptiometry (DEXA) appendicular lean mass index. Using different classifications and cut-off points, overall, there were 2007 sarcopenic patients (33%), of whom 1901 (95%) presented with non-MBC. Sarcopenia was associated with a 33% and 29% higher risk of mortality and progression/relapse of disease, respectively. Sarcopenic patients were more likely to develop grade 3–4 toxicity (OR 3.58, 95% CI 2.11–6.06, p < 0.0001). In the neoadjuvant setting, a higher rate of pCR was observed among sarcopenic patients (49%) (OR 2.74, 95% CI 0.92–8.22). (4) Conclusions: Our meta-analysis confirms the correlation between sarcopenia and negative outcomes, especially in terms of higher toxicity.

In the last two-decades, innovative drugs have revolutionized cancer treatments, demonstrating a significant improvement in overall survival. These drugs may present several pharmacokinetics interactions with non-oncological drugs, and vice versa, and, non-oncological drugs can modify oncological treatment outcome both with pharmacokinetic interaction and with an “off-target impact” on the tumor microenvironment or on the peripheral immune response. It’s supposed that the presence of a drug-drug interaction (DDI) is associated with an increased risk of reduced anti-tumor effects or severe toxicities. However, clinical evidence that correlate the DDI presence with outcome are few, and results are difficult to compare because of difference in data collection and heterogeneous population. This review reports all the clinical evidence about DDI to provide an easy-to-use guide for DDI management and dose adjustment in solid tumors treated with inhibitors of the cyclin-dependent kinases CDK4-6, Antibody-drug conjugates, Poly ADPribose polymerase inhibitors, androgen-receptor targeted agents, or immunecheckpoints inhibitors.

Introduction. Platinum-based chemotherapy represents the standard of care (SoC) for the first-line treatment of advanced urothelial carcinoma (mUC). The benefit of adding immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy was recently investigated. We performed an individual patient data (IPD) meta-analysis of phase 3 clinical trials comparing ICI-based treatments. Methods. A systematic literature search was conducted on the MEDLINE and CENTRAL databases. The results were filtered by including only reports on clinical trials or randomized clinical trials from 2018 to 2023, including 3047 patients from four clinical trials (EV302, CHECKMATE-901, IMVIGOR130, KEYNOTE-361). An IPD meta-analysis was performed by reconstructing IPD from Kaplan-Meier curves. The primary endpoints were overall survival (OS) and progression-free survival (PFS) of Pembrolizumab + EV compared to experimental arms of the other trials of immunotherapy + chemotherapy. Results. The OS analysis showed an advantage of IPD from EV302 vs. all the other trials. For EV302 vs. KEYNOTE-361, the HR was 0.51; for EV302 vs. IMVIGOR130, the HR was 0.47; and for EV302 vs. CHECKMATE-901, the HR was 0.66 (CI 95% 0.51-0.85). In the PFS analysis, the EV302 arm showed a statistically significant advantage compared to CHECKMATE-901 (HR 0.66) and versus IMVIGOR130 (HR 0.51). Limitations: By using reconstructed IPD curves, it was not possible to adjust patient-level covariates, and the heterogeneity of the included population may have affected the pooled results. Conclusions: The EV302 experimental arm showed better OS and PFS when compared to the other immunochemotherapy combinations. An immunochemotherapy combination strategy at the beginning of treatment in mUC seems to be superior in terms of OS and PFS compared to platinum-based chemotherapy alone. EV-Pembrolizumab resulted to have better outcomes compared to avelumab, rather than other immunochemotherapy combinations. However, given the heterogeneity of these studies, a longer follow up and prospective trials are needed to confirm these data.

IntroductionThe classic paradigm for the management of locally advanced rectal cancer (LARC) consists of (chemo)radiotherapy (C)RT), total mesorectal excision, and adjuvant chemotherapy (CHT). At present, due to the high rate of distant metastasis (up to 30%), the total neoadjuvant therapy (TNT) with the administration of systemic CHT in the neoadjuvant setting has gained acceptance as standard of care.Our aim is to critically review the current literature on LARC management and summarize the different approaches recently proposed to improve clinical outcomes. It represents a starting step to develop an effective strategy that ultimately could harmonize the standard of care in daily clinical practice.IntroductionThe classic paradigm for the management of locally advanced rectal cancer (LARC) consists of (chemo)radiotherapy (C)RT), total mesorectal excision, and adjuvant chemotherapy (CHT). At present, due to the high rate of distant metastasis (up to 30%), the total neoadjuvant therapy (TNT) with the administration of systemic CHT in the neoadjuvant setting has gained acceptance as standard of care.Our aim is to critically review the current literature on LARC management and summarize the different approaches recently proposed to improve clinical outcomes. It represents a starting step to develop an effective strategy that ultimately could harmonize the standard of care in daily clinical practice.Areas coveredStudies reporting the impact of TNT approaches were deemed eligible. De-escalation strategies, including non-operative management (NOM) after TNT, as well as RT omission or systemic therapy alone, were also investigated.Expert opinionThe year 2020 has seen promising new data from randomized phase III trials in the field of LARC management. Nowadays, TNT strategy has been accepted as the primary treatment for LARC. The role of de-escalation strategies is still unknown. The goal is to achieve better survival outcomes with improving quality of life. Only selected patients are likely to benefit from NOM or immunotherapy alone.

AbstractBreast cancer represents the most common malignancy in women worldwide. In most cases, metastasis is the leading cause of mortality. Early diagnosis is still challenging despite standardised, government‐led screening programs, but is crucial in achieving improved survival rates. Additionally, a deeper understanding of the metastatic potential of breast cancer is critical for developing therapeutic interventions to combat widespread disease. Cutaneous metastasis from underlying breast carcinoma is uncommon as the first manifestation of visceral malignancies and is commonly observed in advanced‐stage malignancies, often associated with poor prognosis, and a prompt, precise tissue diagnosis is mandatory. A high index of suspicion in oncologic patients is required to diagnose these lesions, as they can mimic benign skin manifestations and clinical findings may be subtle and going unnoticed. We report on a case of a 76‐year‐old female patient presenting to our non‐invasive diagnostic outpatient clinic with an unusual cutaneous presentation, as an early sign of locally advanced invasive ductal carcinoma breast cancer recurrence. The aim of our article is to underline the importance of the dermatologist in the multi‐disciplinary oncologic diagnostic process, including non‐invasive imaging evaluation of cutaneous lesions, especially insidious breast carcinomas. Dynamic optical coherence tomography (D‐OCT) is not routinely used due to its cost, therefore lesion's aspect has not been completely described, consequently, the correct evaluation of skin architecture appearance can add important information, especially in cutaneous oncology where it can help in early diagnosis or cancer recurrency. OCT may contribute to the detection of subclinical cutaneous manifestations of cancer or recurrence, in particular, when they are difficult to differentiate clinically from benign lesion. In the case we described, OCT of suspected lesion showed the loss of the DEJ with solid nests and irregular vessels.

Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, “primary refractory” (Pref), face dismal outcomes. Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref patients. This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan–Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve. In our study, the Pref rate was 19

In mCRC patient with resectable metastases, the radical surgery represents the only curative treatment option, also locoregional treatments showed a survival advantage, but long-term outcomes remain disappointing. Although "pseudo-adjuvant" CT in resected mCRC is currently encouraged by the international guidelines, this treatment is still debated, and its efficacy remains controversial. We conducted a retrospective analysis of mCRC patients treated with surgery of primary tumor and surgical and/or locoregional treatment of metastases at Sant 'Andrea Hospital of Rome, from January 2002 to April 2022. The aim of the study was to evaluate a survival advantage from the addition of sequential systemic CT to surgical and/or locoregional treatment and investigate the correlation between clinical-pathological factors and treatments with survival outcomes. A total of 63 patients were evaluated, the 57% (N=36) was male and the median age was 63 years. The primary tumor site was right, transverse and left colon in 27% (N=17), 4.8% (N=3) and 36.5% (N=23) of the patients respectively, while in the 31.7% (N=20) was rectum. The sites of treated metastases were liver, lung, lymph nodes and other organs in 60.3% (N=38), 27% (N=17), 1.6% (N=1) and 6.3% (N=4) of cases, respectively. The 19% presented mucinous histology, the 86.5% mutation in RAS gene and 27.9% in BRAF. The 88.9% of patients underwent surgery on metastases, the 3.2% locoregional treatment and 7.9% both. The "pseudo-adjuvant" CT was poly-CT 5-Fluorouracil (5-FU) based in 39.6% (N=25), 5-FU single agent CT in 27% (N=17), poly-CT plus biological agent according to RAS status in 25,4% (N=16) and 5-FU plus biological agent in 8% (N=5) of cases. The univariate analysis for disease free survival (DFS) showed a statistically significant correlation with nodal disease involvement (N1) [HR=2.93 (1.28-6.68); p-value = 0.010] and with the wild-type status of KRAS [HR = 0.35 (0.16-0.79); p-value = 0.012] with a median (m) DFS in KRAS WT patients of 17 months versus 11 months for KRAS mt (p-value = 0.007). A correlation statistically significant was reported between "pseudo-adjuvant" 5-FU based poly-CT and DFS [HR = 1.35 (1.0-1.84); p-value = 0.05] with a mDFS of 16 months (CI 95% 11-20 months) in CT group versus 14 months (IC 95% 6-21 months) in CT plus biological agent group (p-value = 0.042) In terms of overall survival (OS) this correlation was confirmed [HR = 1.40 (1.01-1.96); p-value = 0.046], with a mOS of 67 months (IC 95% 56-77 months) versus 43 months (IC 95% 24-61 months) (p-value = 0.041). Our retrospective and monocentric study confirmed literature data, showing a better DFS and OS in patients treated with "pseudo-adjuvant" CT after surgical and/or locoregional treatment of mCRC, without no further benefit with the addition of biological agents. The management of patients with resected mCRC appear difficult and should always be discussed in a multidisciplinary expert team, to offer the best effective treatment and improve survival outcomes.

The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade > = 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint.

Oligometastatic disease has been described as an intermediate clinical state between localized cancer and systemically metastasized disease. Recent clinical studies have shown prolonged survival when aggressive locoregional approaches are added to systemic therapies in patients with oligometastases. The aim of this review is to outline the newest options to treat oligometastatic colorectal cancer (CRC), also considering its molecular patterns. We present an overview of the available local treatment strategies, including surgical procedures, stereotactic body radiation therapy (SBRT), thermal ablation, as well as trans-arterial chemoembolization (TACE) and selective internal radiotherapy (SIRT). Moreover, since imaging methods provide crucial information for the early diagnosis and management of oligometastatic CRC, we discuss the role of modern radiologic techniques in selecting patients that are amenable to potentially curative locoregional treatments.

The new landscape of treatments for metastatic clear cell renal carcinoma (mRCC) is constantly expanding, but it is associated with the emergence of novel toxicities, adding to up to those observed in the tyrosine-kinase inhibitor (TKI) era. Indeed, the introduction of immune checkpoint inhibitors (ICIs) alone or in combination has been associated with the development of immune-related adverse events (irAEs) involving multiple-organ systems which, even if rarely, had led to fatal outcomes. Moreover, due to the relatively recent addition of ICIs to the previously available treatments, the potential additive adverse effects of these combinations are still unknown. A prompt recognition and management of these toxicities currently represents a fundamental issue in oncology, since it correlates with the outcome of cancer patients. Even if clinical guidelines provide indications for the management of irAEs, no specific protocol to evaluate the individual risk of developing an adverse event during therapy is currently available. A multidisciplinary approach addressing appropriate interventions aimed at reducing the risk of any insidious, severe, and/or dose-limiting toxicity might represent the most efficacious strategy to timely prevent and manage severe irAEs, allowing indirectly to improve both patients' cancer-specific survival and quality of life. In this review, we reported a five-case series of toxicity events that occurred at our center during treatment for mRCC followed by the remarks of physicians from different specialties, pinpointing the relevant role of an integrated and extended multidisciplinary team in a modern model of mRCC patient management.

IntroductionChemokines are small, secreted peptides involved in the mediation of the immune cell recruitment. Chemokines have been implicated in several diseases including autoimmune diseases, viral infections and also played a critical role in the genesis and development of several malignant tumors. CXCL12 is a homeostatic CXC chemokine involved in the process of proliferation, and tumor spread. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, that is still lacking effective therapies and with a dramatically poor prognosis.MethodWe conducted a scientific literature search on Pubmed and Google Scholar including retrospective, prospective studies and reviews focused on the current research elucidating the emerging role of CXCL12 and its receptors CXCR4 – CXCR7 in the pathogenesis of pancreatic cancer.ResultsConsidering the mechanism of immunomodulation of the CXCL12-CXCR4-CXCR7 axis, as well as the potential interaction with the microenvironment in the PDAC, several combined therapeutic approaches have been studied and developed, to overcome the “cold” immunological setting of PDAC, like combining CXCL12 axis inhibitors with anti PD-1/PDL1 drugs.ConclusionUnderstanding the role of this chemokine’s axis in disease initiation and progression may provide the basis for developing new potential biomarkers as well as therapeutic targets for related pancreatic cancers.