ANGELA DALIA RICCI

@sanita.puglia.it

Medical Oncology Unit
IRCCS Saverio De Bellis



           

https://researchid.co/dalia.ricci

RESEARCH, TEACHING, or OTHER INTERESTS

Oncology

103

Scopus Publications

Scopus Publications

  • Impact of time-of-day administration of immunotherapy on survival in metastatic renal cell carcinoma: the MOUSEION-09 meta-analysis
    Alessandro Rizzo, Fernando Sabino Marques Monteiro, Veronica Mollica, Andrey Soares, Oronzo Brunetti, Angela Dalia Ricci, Francesco Massari, and Matteo Santoni
    Springer Science and Business Media LLC

  • Circulating miR-23b-3p, miR-30e-3p, and miR-205-5p as Novel Predictive Biomarkers for Ramucirumab–Paclitaxel Therapy Outcomes in Advanced Gastric Cancer
    Emanuele Piccinno, Annalisa Schirizzi, Viviana Scalavino, Giampiero De Leonardis, Rossella Donghia, Alessia Fantasia, Angela Dalia Ricci, Claudio Lotesoriere, Gianluigi Giannelli, Grazia Serino,et al.
    MDPI AG
    Angiogenesis inhibition treatments are limited and are often too late for advanced gastric cancer (GC) patients, in whom its efficacy is reduced. New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity, could be useful biomarkers of GC. The present longitudinal study was focused on analyzing the expression levels of a blood miRNA signature in a cohort of 40 patients receiving second-line therapy combining Ramucirumab and Paclitaxel, stratified based on their Progression-Free Survival (PFS). Using differential and bioinformatic analysis, miR-205-5p, miR-30e-3p, and miR-23b-3p were selected as possible predictive biomarkers, with the results showing that they were more highly expressed in patients exhibiting longer PFS and that they were involved in modulating angiogenesis. Furthermore, patients with longer PFS showed a progressive and significant decrease in the selected miRNA to minimal levels. The loss of the protective effect and the increased expression of the hypothetical targets, including angiopoietin-2, were then observed. The hypothesis was supported by the inverse correlation found for miR-205-5p and angiopoietin-2. Circulating levels of miR-205-5p were protective (HR = 0.37, p = 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes.

  • Treatment Sequencing and Independent Outcomes of First- and Second-Line Chemotherapy in a Retrospective Series of Patients with Biliary Tract Cancer
    Giorgio Frega, Andrea Palloni, Chiara Deiana, Alessandro Rizzo, Angela Dalia Ricci, and Giovanni Brandi
    MDPI AG
    Background/Objectives: Biliary tract cancers (BTCs) are aggressive neoplasms with limited therapeutic options. The amount of prospective evidence is poor, and limited data are available on the impact of treatment sequencing on survival. Here we report a real-world experience of patients with advanced BTC treated with at least three lines of therapy. We evaluated the impact of sequential treatments, and we further compared the efficacy of Gemcitabine/Cisplatin (GemCis) and mFOLFOX to other first- and second-line chemotherapy regimens, respectively. Methods: Data on 60 patients with locally advanced or metastatic BTC under the care of a single Italian referral hospital and treated with at least three lines of chemotherapy were retrospectively collected. Data from 56 patients were included in the analysis. Survival analyses were performed using R software (v1.2.5042). Results: We compared the outcomes of patients treated according to the “standard” pre-immunotherapy sequence (GemCis and mFOLFOX in the first and second lines, respectively) versus those treated with all other combinations (“control” group). Our analysis did not show significant survival differences between the two groups. However, it should be noted that we selected long-survival patients by including only those who received at least three or more lines of chemotherapy. Focusing on the first-line setting, no significant differences in both mPFS and mOS emerged by comparing GemCis versus other doublets (mainly Gemcitabine/Oxaliplatin). Similarly, mPFS and mOS from second-line treatment did not statistically differ between patients treated with mFOLFOX versus those treated with other regimens (71% chemotherapy doublets). Conclusions: Our series provides real-world outcomes of patients with advanced BTC before the approval of immunotherapy. Even considering the monocentric and retrospective design, our study represents one of the first analyses on the impact of sequential treatment strategies in patients with BTC.

  • High levels of autotaxin and lysophosphatidic acid predict poor outcome in treatment of resectable gastric carcinoma
    Annalisa Schirizzi, Rossella Donghia, Valentina De Nunzio, Natasha Renna, Matteo Centonze, Giampiero De Leonardis, Vincenza Lorusso, Alessia Fantasia, Sergio Coletta, Dolores Stabile,et al.
    Elsevier BV

  • Tumor Immune Microenvironment in Intrahepatic Cholangiocarcinoma: Regulatory Mechanisms, Functions, and Therapeutic Implications
    Angela Dalia Ricci, Alessandro Rizzo, Annalisa Schirizzi, Rosalba D’Alessandro, Giorgio Frega, Giovanni Brandi, Endrit Shahini, Raffaele Cozzolongo, Claudio Lotesoriere, and Gianluigi Giannelli
    MDPI AG
    Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations. Tumor immune microenvironment (TIME) of these hepatobiliary tumors has been evaluated and is under assessment in this setting in order to boost the efficacy of ICIs and to convert these immunologically “cold” tumors to “hot” tumors. Herein, the review TIME of ICCA and its critical function in immunotherapy. Moreover, this paper also discusses potential avenues for future research, including novel targets for immunotherapy and emerging treatment plans aimed to increase the effectiveness of immunotherapy and survival rates for iCCA patients.


  • Immunotherapy in biliary tract cancer: are we finally on the right path?
    Angela Dalia Ricci, Alessandro Rizzo, and Claudio Lotesoriere
    Elsevier BV

  • Autotaxin–Lysophosphatidate Axis: Promoter of Cancer Development and Possible Therapeutic Implications
    Carmelo Laface, Angela Dalia Ricci, Simona Vallarelli, Carmela Ostuni, Alessandro Rizzo, Francesca Ambrogio, Matteo Centonze, Annalisa Schirizzi, Giampiero De Leonardis, Rosalba D’Alessandro,et al.
    MDPI AG
    Autotaxin (ATX) is a member of the ectonucleotide pyrophosphate/phosphodiesterase (ENPP) family; it is encoded by the ENPP2 gene. ATX is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA). LPA is responsible for the transduction of various signal pathways through the interaction with at least six G protein-coupled receptors, LPA Receptors 1 to 6 (LPAR1–6). The ATX–LPA axis is involved in various physiological and pathological processes, such as angiogenesis, embryonic development, inflammation, fibrosis, and obesity. However, significant research also reported its connection to carcinogenesis, immune escape, metastasis, tumor microenvironment, cancer stem cells, and therapeutic resistance. Moreover, several studies suggested ATX and LPA as relevant biomarkers and/or therapeutic targets. In this review of the literature, we aimed to deepen knowledge about the role of the ATX–LPA axis as a promoter of cancer development, progression and invasion, and therapeutic resistance. Finally, we explored its potential application as a prognostic/predictive biomarker and therapeutic target for tumor treatment.

  • Immunobiology of biliary tract cancer and recent clinical findings in approved and upcoming immune checkpoint inhibitors
    Carmelo Laface, Emanuela Fina, Angela Dalia Ricci, Deniz Can Guven, Francesca Ambrogio, Simona De Summa, Elsa Vitale, Raffaella Massafra, Oronzo Brunetti, and Alessandro Rizzo
    Informa UK Limited
    INTRODUCTION Recently, immunotherapy has offered new hope for treating biliary tract cancer (BTC). However, several issues are to be considered, including the lack of validated predictive biomarkers that could help to identify patient groups which are most likely to benefit from such therapeutic approaches. AREAS COVERED In the current article, we will provide an overview of recent results and ongoing and future research directions of immunotherapy in BTC, with a special focus on recently published, practice-changing data, and ongoing active and recruiting clinical trials. EXPERT OPINION At this moment, dozens of clinical trials in phases I to III are evaluating the role of cancer immunotherapy in this setting, with the hope of adding more therapeutic options for BTC patients. Future research must focus on the development of novel agents and combinations, but the validation of biomarkers remains an urgent need. As more research results emerge, novel combinatorial strategies are destined to further transform the treatment paradigm for this heterogeneous and aggressive tumor type.

  • VEGFA Status as a Predictive Marker of Therapy Outcome in Metastatic Gastric Cancer Patients Following Ramucirumab-Based Treatment
    Annalisa Schirizzi, Aram Arshadi, Doron Tolomeo, Laura Schirosi, Anna Maria Valentini, Giampiero De Leonardis, Maria Grazia Refolo, Rossella Donghia, Clelia Tiziana Storlazzi, Alfredo Zito,et al.
    MDPI AG
    Metastatic gastric cancer (mGC) often has a poor prognosis and may benefit from a few targeted therapies. Ramucirumab-based anti-angiogenic therapy targeting the VEGFR2 represents a milestone in the second-line treatment of mGC. Several studies on different cancers are focusing on the major VEGFR2 ligand status, meaning VEGFA gene copy number and protein overexpression, as a prognostic marker and predictor of response to anti-angiogenic therapy. Following this insight, our study aims to examine the role of VEGFA status as a predictive biomarker for the outcome of second-line therapy with Ramucirumab and paclitaxel in mGC patients. To this purpose, the copy number of the VEGFA gene, by fluorescence in situ hybridization experiments, and its expression in tumor tissue as well as the density of micro-vessels, by immunohistochemistry experiments, were assessed in samples derived from mGC patients. This analysis found that amplification of VEGFA concomitantly with VEGFA overexpression and overexpression of VEGFA with micro-vessels density are more represented in patients showing disease control during treatment with Ramucirumab. In addition, in the analyzed series, it was found that amplification was not always associated with overexpression of VEGFA, but overexpression of VEGFA correlates with high micro-vessel density. In conclusion, overexpression of VEGFA could emerge as a potential biomarker to predict the response to anti-angiogenic therapy.

  • The Potential Role of Adjuvant Chemoradiotherapy in Patients with Microscopically Positive (R1) Surgical Margins after Resection of Cholangiocarcinoma
    Andrea Palloni, Silvia Bisello, Ilaria Maggio, Maria Massucci, Andrea Galuppi, Alessandro Di Federico, Alessandro Rizzo, Angela Dalia Ricci, Giambattista Siepe, Alessio Giuseppe Morganti,et al.
    MDPI AG
    (1) Background: Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms with dismal prognosis and the role of adjuvant chemoradiotherapy in high-risk resected patients is unclear. (2) Methods: We retrospectively analyzed the outcomes of BTC patients who received curative intent surgery with microscopically positive resection margins (R1) and adjuvant chemoradioradiotherapy (CCRT) or chemotherapy (CHT) from January 2001 to December 201. (3) Results: Out of 65 patients who underwent R1 resection, 26 received adjuvant CHT and 39 adjuvant CCRT. The median recurrence-free survival (RFS) in the CHT and CHRT groups was 13.2 and 26.8 months, respectively (p = 0.41). Median overall survival (OS) was higher in the CHRT group (41.9 months) as compared to the CHT group (32.2 months), but the difference was not statistically significant (HR 0.88; p = 0.7). A promising trend in favor of CHRT was observed in N0 patients. Finally, no statistically significant differences were observed between patients undergoing adjuvant CHRT after R1 resection and patients treated with chemotherapy alone after R0 surgery. (4) Conclusions: Our study did not show a significant survival benefit with adjuvant CHRT over CHT alone in BTC patients with positive resection margins, while a promising trend was observed.

  • Anaplastic Classic Kaposi Sarcoma: PD-L1 Expression and Response to Immunotherapy: A Case Report and Review of the Literature
    Ivan Lolli, Anna Maria Valentini, Angela Dalia Ricci, and Raffaele Armentano
    Harborside Press, LLC
    Anaplastic classic Kaposi sarcoma (CKS) is an extremely rare pathologic variant of CKS characterized by high aggressiveness and poor prognosis. We report the clinical course of this malignant histologic form in an otherwise healthy 67-year-old male from Apulia in Southern Italy. The anaplastic progression arose during a long history of CKS and developed after multiple local and systemic treatments. The extremely aggressive and chemorefractory nature of the disease dictated amputation of a lower limb and, later, surgery for metastatic pulmonary involvement. At subsequent relapse, therapy with the anti–PD-1 inhibitor pembrolizumab was started. The immunotherapy was selected based on the PD-L1 expression in the tumor and tumor microenvironment. Remarkably, PD-1 blockade induced a complete and durable response in the patient, with a disease-free survival that has exceeded 18 months, and follow-up is still ongoing.

  • The evolution of biliary tract cancer: introducing a special focus issue from Immunotherapy
    Lauren Coyle, Alessandro Rizzo, and Dalia Ricci
    Informa UK Limited

  • Durvalumab in advanced cholangiocarcinoma: is someone knocking down the door?
    Angela Dalia Ricci, Rosalba D'Alessandro, Alessandro Rizzo, Annalisa Schirizzi, Simona Vallarelli, Carmela Ostuni, Laura Troiani, Ivan Roberto Lolli, Claudio Lotesoriere, and Gianluigi Giannelli
    Informa UK Limited
    Following the practice-changing results observed in several hematological and solid tumors, immunotherapy with immune checkpoint inhibitors (ICIs) has been tested in cholangiocarcinoma (CCA) patients. However, ICI monotherapy has had disappointing results in CCA, and phase I-III clinical trials have assessed whether combinatorial strategies including immunotherapy plus other anticancer agents may have a synergistic activity. The TOPAZ-1 trial has recently highlighted improved survival in CCA patients receiving first-line durvalumab plus gemcitabine-cisplatin compared with gemcitabine plus cisplatin alone, and several guidelines consider adding durvalumab to the reference doublet as standard of care. This article provides an overview of durvalumab pharmacology, safety and efficacy in CCA, highlighting current and future research directions in this setting.

  • Targeting Angiogenesis in the Era of Biliary Tract Cancer Immunotherapy: Biological Rationale, Clinical Implications, and Future Research Avenues
    Annalisa Schirizzi, Giampiero De Leonardis, Vincenza Lorusso, Rossella Donghia, Alessandro Rizzo, Simona Vallarelli, Carmela Ostuni, Laura Troiani, Ivan Roberto Lolli, Gianluigi Giannelli,et al.
    MDPI AG
    Although biliary tract cancers are traditionally considered rare in Western countries, their incidence and mortality rates are rising worldwide. A better knowledge of the genomic landscape of these tumor types has broadened the number of molecular targeted therapies, including angiogenesis inhibitors. The role of immune checkpoint inhibitors (ICIs) could potentially change the first-line therapeutic approach, but monotherapy with ICIs has shown disappointing results in CCA. Several clinical trials are evaluating combination strategies that include immunotherapy together with other anticancer agents with a synergistic activity. The tumor microenvironment (TME) composition plays a pivotal role in the prognosis of BTC patients. The accumulation of immunosuppressive cell types, such as tumor-associated macrophages (TAMs) and regulatory T-cells, together with the poor infiltration of cytotoxic CD8+ T-cells, is known to predispose to a poor prognosis owing to the establishment of resistance mechanisms. Likewise, angiogenesis is recognized as a major player in modulating the TME in an immunosuppressive manner. This is the mechanistic rationale for combination treatment schemes blocking both immunity and angiogenesis. In this scenario, this review aims to provide an overview of the most recent completed or ongoing clinical trials combining immunotherapy and angiogenesis inhibitors with/without a chemotherapy backbone.

  • Immune-Based Combination Therapies for Advanced Hepatocellular Carcinoma
    Riccardo Carloni, Simone Sabbioni, Alessandro Rizzo, Angela Dalia Ricci, Andrea Palloni, Cataldo Petrarota, Antonio Cusmai, Simona Tavolari, Gennaro Gadaleta-Caldarola, and Giovanni Brandi
    Informa UK Limited
    Abstract Hepatocellular carcinoma (HCC) is the fourth most frequent cause of cancer-related death worldwide. HCC frequently presents as advanced disease at diagnosis, and disease relapse following radical surgery is frequent. In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced HCC, particularly with the introduction of atezolizumab/bevacizumab as the new standard of care for first-line treatment. Recently, dual immune checkpoint blockade with durvalumab plus tremelimumab has also emerged as an effective first-line treatment for advanced HCC and most of the research is currently focused on developing combination treatments based mainly on ICIs. In this review, we will discuss the rationale and ongoing clinical trials of immune-based combination therapies for the treatment of advanced HCC, also focusing on new immunotherapy strategies such as chimeric antigen receptor T cells (CAR-T) and anti-cancer vaccines.

  • Are FGFR and IDH1-2 alterations a positive prognostic factor in intrahepatic cholangiocarcinoma? An unresolved issue
    Giovanni Brandi, Chiara Deiana, Linda Galvani, Andrea Palloni, Angela Dalia Ricci, Alessandro Rizzo, and Simona Tavolari
    Frontiers Media SA
    Despite representing some of the most common and investigated molecular changes in intrahepatic cholangiocarcinoma (iCCA), the prognostic role of FGFR and IDH1/2 alterations still remains an open question. In this review we provide a critical analysis of available literature data regarding this topic, underlining the strengths and pitfalls of each study reported. Despite the overall poor quality of current available studies, a general trend toward a better overall survival for FGFR2 rearrangements and, possibly, for FGFR2-3 alterations can be inferred. On the other hand, the positive prognostic role of IDH1/2 mutation seems much more uncertain. In this scenario, better designed clinical trials in these subsets of iCCA patients are needed in order to get definitive conclusions on this issue.

  • Immune-Based Combinations versus Sorafenib as First-Line Treatment for Advanced Hepatocellular Carcinoma: A Meta-Analysis
    Alessandro Rizzo, Angela Dalia Ricci, Annarita Fanizzi, Raffaella Massafra, Raffaele De Luca, and Giovanni Brandi
    MDPI AG
    Recent years have observed the emergence of novel therapeutic opportunities for advanced hepatocellular carcinoma (HCC), such as combination therapies including immune checkpoint inhibitors. We performed a meta-analysis with the aim to compare median overall survival (OS), median progression-free survival (PFS), complete response (CR) rate, and partial response (PR) rate in advanced HCC patients receiving immune-based combinations versus sorafenib. A total of 2176 HCC patients were available for the meta-analysis (immune-based combinations = 1334; sorafenib = 842) and four trials were included. Immune-based combinations decreased the risk of death by 27% (HR, 0.73; 95% CI, 0.65–0.83; p < 0.001); similarly, a PFS benefit was observed (HR, 0.64; 95% CI, 0.5–0.84; p < 0.001). In addition, immune-based combinations showed better CR rate and PR rate, with ORs of 12.4 (95% CI, 3.02–50.85; p < 0.001) and 3.48 (95% CI, 2.52–4.8; p < 0.03), respectively. The current study further confirms that first-line immune-based combinations have a place in the management of HCC. The CR rate observed in HCC patients receiving immune-based combinations appears more than twelve times higher compared with sorafenib monotherapy, supporting the long-term benefit of these combinatorial strategies, with even the possibility to cure advanced disease.

  • Treatment-related adverse events of first-line immunotherapy versus sorafenib for advanced hepatocellular carcinoma: a meta-analysis
    Alessandro Rizzo, Riccardo Carloni, Angela Dalia Ricci, Antonio Cusmai, Mariarita Laforgia, Concetta Calabrò, Valentina Ungaro, Donato Oreste, Mario Sollitto, Gennaro Palmiotti,et al.
    Informa UK Limited
    ABSTRACT Background Despite all the improvements achieved over the last decade, the use of immune checkpoint inhibitors (ICIs) has been associated to a wide range of adverse drug events, which are frequently markedly different from those observed with cytotoxic chemotherapy and targeted therapies, such as sorafenib. Research design and methods We performed a meta-analysis with the aim to compare grade 3/4 treatment-related adverse events (TRAEs), grade 5 TRAEs, serious TRAEs, and TRAEs leading to discontinuation in ICIs versus sorafenib across phase III clinical trials of first-line treatment for advanced hepatocellular carcinoma (HCC). Results Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Patients treated with ICIs showed higher risk of serious TRAEs (OR 1.48, 95% CI = 1.16–1.9) while sorafenib treatment was associated with higher risk of TRAEs leading to discontinuation (OR 0.65, 95% CI = 0.48–0.89). No differences in grade 3/4 TRAEs and grade 5 TRAEs. Conclusions Beyond activity and efficacy, careful consideration should be given to toxicity while choosing the appropriate first-line treatment in HCC.

  • The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis
    Deniz Can Guven, Taha Koray Sahin, Enes Erul, Alessandro Rizzo, Angela Dalia Ricci, Sercan Aksoy, and Suayib Yalcin
    Frontiers Media SA
    Background: The albumin levels may potentially be used as a prognostic biomarker in patients with cancertreated with immune checkpoint inhibitors (ICIs) due to its close relationship with nutritional and inflammatory status. However, the available data is limited with heterogeneous patient cohorts, sample sizes and variable cut-offs. Therefore, we conducted a systematic review and meta-analysis to evaluate the association between survival outcomes and albumin levels in patients treated with ICIs.Methods: We conducted a systematic review using the PubMed, Web of Science, and Embase databases to filter the published studies up to 1 June 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model due to the high degree of heterogeneity. The primary outcome measure was hazard ratio (HR) with 95% confidence intervals (CI). The study protocol was registered with the PROSPERO registry (Registration Number: CRD42022337746).Results: Thirty-six studies encompassing 8406 cancer patients with advanced disease were included in the meta-analyses. Almost half of the studies were conducted in NSCLC cohorts (n = 15), and 3.5 gr/dL was the most frequently used albumin cut-off in the included studies (n = 20). Patients with lower albumin levels had a significantly increased risk of death (HR: 1.65, 95% CI: 1.52–1.80, p < 0.0001) than patients with higher albumin levels. Subgroup analyses for study location, sample size, tumor type and albumin cut-off were demonstrated consistent results. Furthermore, in the subgroup analysis of eight studies using albumin levels as a continuous prognostic factor, every 1 gr/dL decrease in albumin levels was associated with significantly increased risk of death by a factor of 10% (HR: 1.10, 95% CI: 1.05–1.16, p = 0.0002). Similar to analyses with overall survival, the patients with lower albumin levels had an increased risk of progression or death compared to patients with higher albumin levels (HR: 1.76, 95% CI: 1.40–2.21, p < 0.001).Conclusion: The available evidence demonstrates that albumin levels may be a prognostic biomarker in advanced cancer patients treated with ICIs. Further research is needed to delineate the role of albumin levels in patients treated with ICIs in the adjuvant setting, as well as the possible benefit of therapeutic approaches to improve hypoalbuminemia.

  • Neoadjuvant Dovitinib in Early- and Intermediate-Stage Hepatocellular Carcinoma
    Alessandro Rizzo, Angela Dalia Ricci, and Giovanni Brandi
    Oxford University Press (OUP)
    This letter to the editor comments on recently reported results of a phase II study of dovitinib therapy for hepatocellular carcinoma

  • Trans-Arterial Chemoembolization Plus Systemic Treatments for Hepatocellular Carcinoma: An Update
    Alessandro Rizzo, Angela Dalia Ricci, and Giovanni Brandi
    MDPI AG
    Recent years have seen the advent of novel treatment options for hepatocellular carcinoma (HCC). Given a strong biological rationale supporting this strategy, multiple studies have explored the role of combination treatments including locoregional plus systemic therapies to produce a synergistic effect and enhance antitumor activity. Among locoregional therapies, several clinical trials assessing trans-arterial chemoembolization (TACE) have been recently presented and published. In the current paper, we discuss available evidence and current and future research on combined TACE and systemic treatments, including antiangiogenic agents, immune checkpoint inhibitors, and immune-based combinations for HCC patients.

  • Second-Line Chemotherapy in Elderly Patients with Advanced Biliary Tract Cancer: A Multicenter Real-World Study
    Alessandro Rizzo, Massimiliano Salati, Giorgio Frega, Valeria Merz, Francesco Caputo, Alessandro Di Federico, Andrea Palloni, Riccardo Carloni, Angela Dalia Ricci, Gennaro Gadaleta-Caldarola,et al.
    MDPI AG
    Objectives: The ABC-06 and the NIFTY trials recently established the role of second-line chemotherapy (2L) in patients with advanced biliary tract cancer (BTC). Our real-world study aimed to explore 2L in BTC patients aged ≥ 70 years old and to compare their outcomes with younger subjects. Methods: Institutional registries across three academic medical centers were retrospectively reviewed. The Kaplan–Meier methods were used to estimate survival, and the log-rank test was used to make comparisons. Results: A total of 190 BTC patients treated with 2L were identified and included in the analysis. Among them, 52 (27.3%) were aged ≥ 70 years (range 70–87 years). No statistically significant differences in both median overall survival (mOS) and median progression-free survival (mPFS) were recorded between the elderly and younger patients. Absolute lymphocyte count < 1000/mmc (p < 0.001) and albumin level < 3 g/dL (p < 0.001) were independently associated with worse prognoses. Conclusions: The results of this real-world study suggest that for patients aged ≥ 70 years, 2L could be equally effective for younger patients with survival outcomes aligned to those from the ABC-06 and NIFTY trials. The delivery of 2L should be carefully evaluated and monitored in this patient subset.

  • Targeting tumor microenvironment for cholangiocarcinoma: Opportunities for precision medicine
    Riccardo Carloni, Alessandro Rizzo, Angela Dalia Ricci, Alessandro Di Federico, Raffaele De Luca, Deniz Can Guven, Suayib Yalcin, and Giovanni Brandi
    Elsevier BV

  • The Use of Phytochemicals to Improve the Efficacy of Immune Checkpoint Inhibitors: Opportunities and Challenges
    Deniz Can Guven, Taha Koray Sahin, Alessandro Rizzo, Angela Dalia Ricci, Sercan Aksoy, and Kazim Sahin
    MDPI AG
    Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and reshaped medical oncology practice over the past decade. However, despite unprecedented and durable clinical responses, most patients eventually fail to respond to ICI therapy due to primary or acquired resistance. There is a great need for complementary alternative medicine, such as botanicals and nutritional supplements, because of their capability to modulate a myriad of molecular mechanisms to prevent immunotherapy resistance and reduce its adverse effects. Mounting evidence suggests that phytochemicals, biologically active compounds derived from plants, can favorably regulate key signaling pathways involved in tumor development and progression. In addition, phytochemicals have been found to exert anticancer effects by altering the expression of checkpoint inhibitors of the immune response. The immunomodulatory activity of phytochemicals in the tumor microenvironment has recently received immense interest. Based on these immunomodulatory activities, phytochemicals could be candidates for combination with ICIs in future clinical studies. The current review focuses on the available evidence for combining phytochemicals with a discussion on the promising opportunities to enhance the efficacy of immune checkpoint inhibitors and potential challenges resulting from these combinations.