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Papers by Giovanni Brandi

Research paper thumbnail of Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

Angiogenesis, Mar 2, 2012

Research paper thumbnail of Critical diagnostic delay associated with unusual presentation of hepatocellular carcinoma (HCC) with orbital metastases: a case report

Annals of palliative medicine, Jul 1, 2021

Research paper thumbnail of The DNA damage repair (DDR) pathway in biliary tract cancer (BTC): a new Pandora’s box?

Research paper thumbnail of Rare histotypes of epithelial biliary tract tumors: A literature review

Critical Reviews in Oncology Hematology, 2023

Research paper thumbnail of IDH Inhibitors and Immunotherapy for Biliary Tract Cancer: A Marriage of Convenience?

International Journal of Molecular Sciences, Sep 17, 2022

Research paper thumbnail of Searching for novel multimodal treatments in oligometastatic pancreatic cancer

Research paper thumbnail of Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy

Frontiers in Oncology, Apr 5, 2023

Research paper thumbnail of Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?

Frontiers in Oncology, Dec 17, 2021

Research paper thumbnail of Stereotactic body radiation therapy in cholangiocarcinoma: a systematic review

British Journal of Radiology, May 1, 2019

Research paper thumbnail of Radiofrequency ablation, radiation therapy, transarterial chemoembolization, and yttrium 90: no differences for local treatment of liver cancer?

Research paper thumbnail of A Novel Prognostic Tool in Western and Eastern Biliary Tract Cancer Patients Treated in First-line Setting: the ECSIPOT Index

Journal of Gastrointestinal Cancer, 2021

The need to estimate prognosis of advanced BTC (aBTC) patients treated with first-line chemothera... more The need to estimate prognosis of advanced BTC (aBTC) patients treated with first-line chemotherapy is compelling. The aim of the study is to evaluate the ECSIPOT (psECogSIiPnigOT) index, influenced by PECS (PsECogSii) index, prognostic nutritional index (PNI), and GOT. This international study was conducted on a training cohort of 126 patients and in three validation cohorts, both European and Korean. ECSIPOT index formula: (PECS:0 = 1 point; PECS:1 = 1.4 points; PECS:2 = 3.2 points) + (PNI > 36.7 = 1 point; PNI < 36.7 = 2 points) + (GOT < 100 = 1 point; GOT > 100 = 2 points). Event-time distributions were estimated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. In the training cohort, mOS was 12.9, 6.3, and 2.8 months for patients with ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 2.11; ECSIPOT-2: HR 4.93; p < 0.0001). In the first validation cohort, mOS was 11.5, 7.3, and 3.3 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 1.74; ECSIPOT-2: HR 3.41; p < 0.0001). In the second validation cohort, mOS was 25.2, 12.5, and 3.0 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 2.33; ECSIPOT-2: HR 8.46; p < 0.0001). In the third validation cohort, mOS was 11.8, 8.1, and 4.6 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 1.47; ECSIPOT-2: HR 3.17; p < 0.0001). Multivariate analysis in all cohorts confirmed the ECSIPOT index as an independent prognostic factor for OS. The easy assessment and good risk-stratification performance make the ECSIPOT index a promising tool to comprehensively estimate the prognosis of aBTC patients.

Research paper thumbnail of Ivosidenib in IDH-mutant cholangiocarcinoma: where do we stand?

Expert Review of Precision Medicine and Drug Development, 2021

Introduction: Cholangiocarcinomas (CCAs) are rare and heterogeneous malignancies associated with ... more Introduction: Cholangiocarcinomas (CCAs) are rare and heterogeneous malignancies associated with poor prognosis, with most of the patients presenting with advanced disease at diagnosis. The recent advent of molecular profiling has led to the identification of several druggable genetic aberrations, and among these, there is an increasing interest in isocitrate dehydrogenase-1 (IDH-1) mutations, with the IDH-1 inhibitor ivosidenib that has reported interesting results in advanced CCA patients. Areas covered: Herein, we will critically discuss the current state of the art of ivosidenib in IDH-mutant CCA, especially focusing on efficacy and safety results of recent trials assessing this IDH-1 inhibitor. Expert opinion: According to the results of phase I studies and the recently published ClarIDHy phase III trial, the IDH-1 inhibitor ivosidenib seems to be associated with a manageable safety profile and interesting antitumor efficacy. In particular, the ClarIDHy showed that ivosidenib t...

Research paper thumbnail of Immune-based combinations for metastatic triple negative breast cancer in clinical trials: current knowledge and therapeutic prospects

Expert Opinion on Investigational Drugs, 2021

INTRODUCTION Immune checkpoint inhibitor (ICI) monotherapy appears to be effective in a small coh... more INTRODUCTION Immune checkpoint inhibitor (ICI) monotherapy appears to be effective in a small cohort of patients with metastatic triple negative breast cancer (mTNBC). This supports the exploration of strategies for increasing the efficacy of immunotherapy. To enhance overall response and clinical outcomes, several immune-based combinations are being investigated. AREAS COVERED The authors present a synopsis of current, state of art immune-based combinations in this setting and reflect on future possibilities. They shed light on recently presented and published clinical trials and ongoing studies. A literature search was conducted in October 2021; in addition, abstracts of international cancer meetings were reviewed. EXPERT OPINION Clinical trials suggest that ICI monotherapy could be beneficial in a minority of mTNBC patients; conversely, several immune-based combinations have reported notable results in recently presented or published studies. Some of these combination strategies have been approved for mTNBC - as in the case of chemoimmunotherapy in PD-L1 positive patients. Numerous trials are investigating novel ICI-based combinations and their results are eagerly awaited.

Research paper thumbnail of Microbiota and prostate cancer

Seminars in Cancer Biology, 2021

Prostate cancer remains the most frequently diagnosed non-skin malignancy in male patients, still... more Prostate cancer remains the most frequently diagnosed non-skin malignancy in male patients, still representing one of the main causes of cancer-related death worldwide. Evidence is mounting that suggests the putative role of microbiota in the carcinogenesis as well as in modulating the efficacy and activity of anticancer treatments (e.g., chemotherapy, immune checkpoint inhibitors, targeted therapies) in a large number of hematological and solid tumors. However, few data are available regarding the interactions between prostate cancer and microbiome so far, in particular in terms of the impact of microbiota on disease development, pathogenesis, and response to medical treatments in this genitourinary malignancy. Herein, we provide an overview of current knowledge, novel insights and emerging therapeutic approaches related to gastrointestinal and genitourinary microbiome in prostate cancer patients, especially focusing on available evidence and published trials on this topic.

Research paper thumbnail of The power of kindness: curative treatment with metronomic combination in advanced hepatocellular carcinoma

Anti-Cancer Drugs, 2021

The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is... more The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patien...

Research paper thumbnail of Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Research paper thumbnail of Recent advances of immunotherapy for biliary tract cancer

Expert Review of Gastroenterology & Hepatology, 2021

Research paper thumbnail of Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database

British Journal of Clinical Pharmacology, 2020

AimsTo provide an overview of immune checkpoint inhibitors (ICIs) safety profile using the Italia... more AimsTo provide an overview of immune checkpoint inhibitors (ICIs) safety profile using the Italian spontaneous adverse drug reaction (ADR) reporting system.MethodsWe selected all ADR reports attributed to ipilimumab (CTLA‐4 inhibitor), nivolumab, pembrolizumab, atezolizumab (PD‐1/PD‐L1 inhibitors) from the Italian spontaneous reporting system (2011–2018). Descriptive analyses of reports for ICIs have been conducted. Time to onset of adverse effects was stratified by system organ class. Reporting odds ratio was used as measure of ADR reporting disproportionality. ICI‐related ADR reports were compared with 2 reference groups, i.e. all other suspected drugs or all other antineoplastic agents.ResultsOverall, 2217 (0.7%) reports were related to ICIs (nivolumab: 72.2% of those reports; ipilimumab: 14.3%; pembrolizumab: 10.3%; and atezolizumab: 3.5%). ICI‐related ADR reports mostly involved males (65%) and median age was 67 (interquartile range 59–73) years. Serious reports accounted for 4...

Research paper thumbnail of Focus on metastatic right-sided colon cancer: the best overall response to the first-line non-EGFR treatment correlates with better overall survival

Research paper thumbnail of Prediction of overall survival with 2nd-line (L2OS) chemotherapy (CT) in patients (Pts) with advanced biliary tract cancer (aBTC): AGEO CT2BIL cohort update and international multicenter external validations

Journal of Clinical Oncology, 2018

e16119Background: Benefit of CT beyond standard 1st-line (L1) gemcitabine plus cisplatin (GEMCIS)... more e16119Background: Benefit of CT beyond standard 1st-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) in aBTC is unclear. Our aim was to identify and validate prognostic factors ...

Research paper thumbnail of Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

Angiogenesis, Mar 2, 2012

Research paper thumbnail of Critical diagnostic delay associated with unusual presentation of hepatocellular carcinoma (HCC) with orbital metastases: a case report

Annals of palliative medicine, Jul 1, 2021

Research paper thumbnail of The DNA damage repair (DDR) pathway in biliary tract cancer (BTC): a new Pandora’s box?

Research paper thumbnail of Rare histotypes of epithelial biliary tract tumors: A literature review

Critical Reviews in Oncology Hematology, 2023

Research paper thumbnail of IDH Inhibitors and Immunotherapy for Biliary Tract Cancer: A Marriage of Convenience?

International Journal of Molecular Sciences, Sep 17, 2022

Research paper thumbnail of Searching for novel multimodal treatments in oligometastatic pancreatic cancer

Research paper thumbnail of Survival trends over 20 years in patients with advanced cholangiocarcinoma: Results from a national retrospective analysis of 922 cases in Italy

Frontiers in Oncology, Apr 5, 2023

Research paper thumbnail of Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?

Frontiers in Oncology, Dec 17, 2021

Research paper thumbnail of Stereotactic body radiation therapy in cholangiocarcinoma: a systematic review

British Journal of Radiology, May 1, 2019

Research paper thumbnail of Radiofrequency ablation, radiation therapy, transarterial chemoembolization, and yttrium 90: no differences for local treatment of liver cancer?

Research paper thumbnail of A Novel Prognostic Tool in Western and Eastern Biliary Tract Cancer Patients Treated in First-line Setting: the ECSIPOT Index

Journal of Gastrointestinal Cancer, 2021

The need to estimate prognosis of advanced BTC (aBTC) patients treated with first-line chemothera... more The need to estimate prognosis of advanced BTC (aBTC) patients treated with first-line chemotherapy is compelling. The aim of the study is to evaluate the ECSIPOT (psECogSIiPnigOT) index, influenced by PECS (PsECogSii) index, prognostic nutritional index (PNI), and GOT. This international study was conducted on a training cohort of 126 patients and in three validation cohorts, both European and Korean. ECSIPOT index formula: (PECS:0 = 1 point; PECS:1 = 1.4 points; PECS:2 = 3.2 points) + (PNI > 36.7 = 1 point; PNI < 36.7 = 2 points) + (GOT < 100 = 1 point; GOT > 100 = 2 points). Event-time distributions were estimated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. In the training cohort, mOS was 12.9, 6.3, and 2.8 months for patients with ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 2.11; ECSIPOT-2: HR 4.93; p < 0.0001). In the first validation cohort, mOS was 11.5, 7.3, and 3.3 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR 1; ECSIPOT-1: HR 1.74; ECSIPOT-2: HR 3.41; p < 0.0001). In the second validation cohort, mOS was 25.2, 12.5, and 3.0 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 2.33; ECSIPOT-2: HR 8.46; p < 0.0001). In the third validation cohort, mOS was 11.8, 8.1, and 4.6 months for ECSIPOT-0, ECSIPOT-1, and ECSIPOT-2, respectively (ECSIPOT-0: HR = 1; ECSIPOT-1: HR 1.47; ECSIPOT-2: HR 3.17; p < 0.0001). Multivariate analysis in all cohorts confirmed the ECSIPOT index as an independent prognostic factor for OS. The easy assessment and good risk-stratification performance make the ECSIPOT index a promising tool to comprehensively estimate the prognosis of aBTC patients.

Research paper thumbnail of Ivosidenib in IDH-mutant cholangiocarcinoma: where do we stand?

Expert Review of Precision Medicine and Drug Development, 2021

Introduction: Cholangiocarcinomas (CCAs) are rare and heterogeneous malignancies associated with ... more Introduction: Cholangiocarcinomas (CCAs) are rare and heterogeneous malignancies associated with poor prognosis, with most of the patients presenting with advanced disease at diagnosis. The recent advent of molecular profiling has led to the identification of several druggable genetic aberrations, and among these, there is an increasing interest in isocitrate dehydrogenase-1 (IDH-1) mutations, with the IDH-1 inhibitor ivosidenib that has reported interesting results in advanced CCA patients. Areas covered: Herein, we will critically discuss the current state of the art of ivosidenib in IDH-mutant CCA, especially focusing on efficacy and safety results of recent trials assessing this IDH-1 inhibitor. Expert opinion: According to the results of phase I studies and the recently published ClarIDHy phase III trial, the IDH-1 inhibitor ivosidenib seems to be associated with a manageable safety profile and interesting antitumor efficacy. In particular, the ClarIDHy showed that ivosidenib t...

Research paper thumbnail of Immune-based combinations for metastatic triple negative breast cancer in clinical trials: current knowledge and therapeutic prospects

Expert Opinion on Investigational Drugs, 2021

INTRODUCTION Immune checkpoint inhibitor (ICI) monotherapy appears to be effective in a small coh... more INTRODUCTION Immune checkpoint inhibitor (ICI) monotherapy appears to be effective in a small cohort of patients with metastatic triple negative breast cancer (mTNBC). This supports the exploration of strategies for increasing the efficacy of immunotherapy. To enhance overall response and clinical outcomes, several immune-based combinations are being investigated. AREAS COVERED The authors present a synopsis of current, state of art immune-based combinations in this setting and reflect on future possibilities. They shed light on recently presented and published clinical trials and ongoing studies. A literature search was conducted in October 2021; in addition, abstracts of international cancer meetings were reviewed. EXPERT OPINION Clinical trials suggest that ICI monotherapy could be beneficial in a minority of mTNBC patients; conversely, several immune-based combinations have reported notable results in recently presented or published studies. Some of these combination strategies have been approved for mTNBC - as in the case of chemoimmunotherapy in PD-L1 positive patients. Numerous trials are investigating novel ICI-based combinations and their results are eagerly awaited.

Research paper thumbnail of Microbiota and prostate cancer

Seminars in Cancer Biology, 2021

Prostate cancer remains the most frequently diagnosed non-skin malignancy in male patients, still... more Prostate cancer remains the most frequently diagnosed non-skin malignancy in male patients, still representing one of the main causes of cancer-related death worldwide. Evidence is mounting that suggests the putative role of microbiota in the carcinogenesis as well as in modulating the efficacy and activity of anticancer treatments (e.g., chemotherapy, immune checkpoint inhibitors, targeted therapies) in a large number of hematological and solid tumors. However, few data are available regarding the interactions between prostate cancer and microbiome so far, in particular in terms of the impact of microbiota on disease development, pathogenesis, and response to medical treatments in this genitourinary malignancy. Herein, we provide an overview of current knowledge, novel insights and emerging therapeutic approaches related to gastrointestinal and genitourinary microbiome in prostate cancer patients, especially focusing on available evidence and published trials on this topic.

Research paper thumbnail of The power of kindness: curative treatment with metronomic combination in advanced hepatocellular carcinoma

Anti-Cancer Drugs, 2021

The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is... more The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patien...

Research paper thumbnail of Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Research paper thumbnail of Recent advances of immunotherapy for biliary tract cancer

Expert Review of Gastroenterology & Hepatology, 2021

Research paper thumbnail of Safety profile of immune checkpoint inhibitors: An analysis of the Italian spontaneous reporting system database

British Journal of Clinical Pharmacology, 2020

AimsTo provide an overview of immune checkpoint inhibitors (ICIs) safety profile using the Italia... more AimsTo provide an overview of immune checkpoint inhibitors (ICIs) safety profile using the Italian spontaneous adverse drug reaction (ADR) reporting system.MethodsWe selected all ADR reports attributed to ipilimumab (CTLA‐4 inhibitor), nivolumab, pembrolizumab, atezolizumab (PD‐1/PD‐L1 inhibitors) from the Italian spontaneous reporting system (2011–2018). Descriptive analyses of reports for ICIs have been conducted. Time to onset of adverse effects was stratified by system organ class. Reporting odds ratio was used as measure of ADR reporting disproportionality. ICI‐related ADR reports were compared with 2 reference groups, i.e. all other suspected drugs or all other antineoplastic agents.ResultsOverall, 2217 (0.7%) reports were related to ICIs (nivolumab: 72.2% of those reports; ipilimumab: 14.3%; pembrolizumab: 10.3%; and atezolizumab: 3.5%). ICI‐related ADR reports mostly involved males (65%) and median age was 67 (interquartile range 59–73) years. Serious reports accounted for 4...

Research paper thumbnail of Focus on metastatic right-sided colon cancer: the best overall response to the first-line non-EGFR treatment correlates with better overall survival

Research paper thumbnail of Prediction of overall survival with 2nd-line (L2OS) chemotherapy (CT) in patients (Pts) with advanced biliary tract cancer (aBTC): AGEO CT2BIL cohort update and international multicenter external validations

Journal of Clinical Oncology, 2018

e16119Background: Benefit of CT beyond standard 1st-line (L1) gemcitabine plus cisplatin (GEMCIS)... more e16119Background: Benefit of CT beyond standard 1st-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) in aBTC is unclear. Our aim was to identify and validate prognostic factors ...