Valerio Nardone - Academia.edu (original) (raw)

Papers by Valerio Nardone

Cancers

Head and neck squamous cell carcinoma (HNSCC) is a highly challenging cancer [...]

Dermatology Practical & Conceptual

Exploration of targeted anti-tumor therapy, Dec 13, 2022

Aim: Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck ly... more Aim: Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck lymph node (LN) status is the major indicator of prognosis in all head and neck cancers, and the early detection of LN involvement is crucial in terms of therapy and prognosis. Diffusion-weighted imaging (DWI) is a non-invasive imaging technique used in magnetic resonance imaging (MRI) to characterize tissues based on the displacement motion of water molecules. This review aims to provide an overview of the current literature concerning quantitative diffusion imaging for LN staging in patients with HNSCC. Methods: This systematic review performed a literature search on the PubMed database (https://pubmed. ncbi.nlm.nih.gov/) for all relevant, peer-reviewed literature on the subject following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria, using the keywords: DWI, MRI, head and neck, staging, lymph node. Results: After excluding reviews, meta-analyses, case reports, and bibliometric studies, 18 relevant papers out of the 567 retrieved were selected for analysis. Conclusions: DWI improves the diagnosis, treatment planning, treatment response evaluation, and overall management of patients affected by HNSCC. More robust data to clarify the role of apparent diffusion coefficient (ADC) and DWI parameters are needed to develop models for prognosis and prediction in HNSCC cancer using MRI.

Diagnostics

Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma are the three main types... more Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma are the three main types of nonmelanoma skin cancers and their rates of occurrence and mortality have been steadily rising over the past few decades. For radiologists, it is still difficult to treat patients with advanced nonmelanoma skin cancer. Nonmelanoma skin cancer patients would benefit greatly from an improved diagnostic imaging-based risk stratification and staging method that takes into account patient characteristics. The risk is especially elevated among those who previously received systemic treatment or phototherapy. Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors. Risk stratification and staging tools are crucial in treatment planning and prognostic evaluation. PET/CT appears more sensitive and superior to CT and MRI for nodal and...

La radiologia medica

Non-small cell lung cancer (NSCLC) is frequently complicated by central nervous system (CNS) meta... more Non-small cell lung cancer (NSCLC) is frequently complicated by central nervous system (CNS) metastases affecting patients’ life expectancy and quality. At the present clinical trials including neurosurgery, radiotherapy (RT) and systemic treatments alone or in combination have provided controversial results. CNS involvement is even more frequent in NSCLC patients with EGFR activating mutations or ALK rearrangement suggesting a role of target therapy in the upfront treatment in place of loco-regionals treatments (i.e. RT and/or surgery). So far clinical research has not explored the potential role of accurate brain imaging (i.e. MRI instead of the routine total-body contrast CT and/or PET/CT staging) to identify patients that could benefit of local therapies. Moreover, for patients who require concomitant RT there are no clear guidelines on the timing of intervention with respect to innovative precision medicine approaches with Tyrosine Kinase Inhibitors, ALK-inhibitors and/or immun...

Radiotherapy and Oncology

Diagnostics

Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (N... more Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (NSCLC) patients, and no biomarkers are currently available in clinical practice. A novel and easy-to-calculate marker is the quantitative analysis of calcium plaque in the coronary, calculated on CT. It is called the Agatston score (or CAD score). At the same time, other potential predictors include cardiac ultrasonography and anamnesis of the patients. Our work aimed to correlate cardiac biomarkers with overall survival (OS) in NSCLC patients. We retrospectively analyzed patients with NSCLC discussed in the Multidisciplinary Tumor Board of our Institute for the present analysis between January 2018 and July 2022. Inclusion criteria were the availability of basal CT imaging of the thorax, cardiac ultrasonography with the calculation of ejection fraction (EF), and complete anamnesis, including assessment of co-pathologies and pharmacological drugs. The clinical data of the patients were re...

Journal of Personalized Medicine

Despite being usually delivered in oncological patients, radiotherapy can be used as a successful... more Despite being usually delivered in oncological patients, radiotherapy can be used as a successful treatment for several non-malignant disorders. Even though this use of radiotherapy has been scarcely investigated since the 1950s, more recent interest has actually shed the light on this approach. Thus, the aim of this narrative review is to analyze the applications of non-oncological radiotherapy in different disorders. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This review contains a narrative report and a critical discussion of non-oncological radiotherapy approaches. In conclusion, non-oncological radiotherapy is a safe and efficacious approach to treat several disorders that needs to be further investigated and used in clinical practice.

Clinical and Translational Imaging

Introduction The aim of the narrative review was to analyse the applications of nuclear medicine ... more Introduction The aim of the narrative review was to analyse the applications of nuclear medicine (NM) techniques such as PET/CT with different tracers in combination with radiotherapy for the clinical management of glioblastoma patients. Materials and methods Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. Results This paper contains a narrative report and a critical discussion of NM approaches in combination with radiotherapy in glioma patients. Conclusions NM can provide the Radiation Oncologist several aids that can be useful in the clinical management of glioblastoma patients. At the same, these results need to be validated in prospective and multicenter trials.

Tomography

Introduction. Coronavirus SARS-CoV-2, the causative agent of COVID-19, primarily causes a respira... more Introduction. Coronavirus SARS-CoV-2, the causative agent of COVID-19, primarily causes a respiratory tract infection that is not limited to respiratory distress syndrome, but it is also implicated in other body systems. Systemic complications were reported due to an exaggerated inflammatory response, which involves severe alveolar damage in the lungs and exacerbates the hypercoagulation that leads to venous thrombosis, ischemic attack, vascular dysfunction and infarction of visceral abdominal organs. Some complications are related to anticoagulant drugs that are administrated to stabilize hypercoagulability, but increase the risk of bleeding, hematoma and hemorrhage. The aim of this study is to report the diagnostic role of CT in the early diagnosis and management of patients with severe COVID-19 complications through the most interesting cases in our experience. Material and Methods. The retrospective analysis of patients studied for COVID-19 in our institution and hospitals, whic...

Frontiers in Oncology

BackgroundRadiomics can provide quantitative features from medical imaging that can be correlated... more BackgroundRadiomics can provide quantitative features from medical imaging that can be correlated to clinical endpoints. The challenges relevant to robustness of radiomics features have been analyzed by many researchers, as it seems to be influenced by acquisition and reconstruction protocols, as well as by the segmentation of the region of interest (ROI). Prostate cancer (PCa) represents a difficult playground for this technique, due to discrepancies in the identification of the cancer lesion and the heterogeneity of the acquisition protocols. The aim of this study was to investigate the reliability of radiomics in PCa magnetic resonance imaging (MRI).MethodsA homogeneous cohort of patients with a PSA rise that underwent multiparametric MRI imaging of the prostate before biopsy was tested in this study. All the patients were acquired with the same MRI scanner, with a standardized protocol. The identification and the contouring of the region of interest (ROI) of an MRI suspicious ca...

Current Oncology

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients... more Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called “cold tumors” still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination wi...

Cancers

We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodol... more We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefor...

Annals of Nuclear Medicine

American Journal of Clinical Oncology, 2022

Introduction: In the current study, we have investigated the effects of the different modalities ... more Introduction: In the current study, we have investigated the effects of the different modalities of treatment (volume of radiotherapy [RT], previous surgery) as well as the Gleason score of prostate cancer (PC) on the lymphocyte composition of PC patients undergoing RT. Methods: This is a monoinstitutional study that prospectively included PC patients that underwent RT from January 2016 until December 2017. To compare the different evaluations, the Wilcoxon signed-rank test was used among 2 times (Timepoint 0 to Timepoint 1). Percentage variation was calculated for all the lymphocyte subpopulation and was correlated with clinical parameters (previous surgery, Gleason score, and pelvic irradiation) with the χ2 test. The statistical analysis was repeated also on the stratified dataset according to the above parameters (previous surgery, Gleason score, and whole pelvic radiotherapy [WPRT]). Results: One hundred and eleven patients were included in the present analysis. All the lymphocyte subpopulations resulted significantly lower after RT. The modifications of several lymphocyte subpopulations correlated with previous surgery, Gleason score, and WPRT, although stratified analysis demonstrated that WPRT showed the greatest correlation. Conclusion: Our results could be used to design a prospective trial in order to study the use of WPRT on the lymphocyte subpopulations.

Cancers, 2021

Background: Multimodality treatment is considered the best treatment strategy for malignant pleur... more Background: Multimodality treatment is considered the best treatment strategy for malignant pleural mesothelioma (MPM). However, the ideal combination of them is still a matter of controversy. Here, we report a case series of MPM treated with a trimodality approach: induction chemotherapy (CT), pleurectomy/decortication (P/D), postoperative radiotherapy (RT) and post-operative CT. Methods: A retrospective case series of 17 MPM patients treated between 2013 and 2020 is presented. Patients had epithelial or mixed MPM diagnosed by video-assisted thoracoscopy and pathologic IMIG stage I or II disease. Treatment details and radiological data were collected. Induction therapy consisted of combination of cisplatin and pemetrexed, every 21 days for two cycles. P/D was performed 4–6 weeks after induction CT, post-operative RT 3–6 weeks after surgery, while post-operative CT was given 4–6 weeks after RT, with the same schedule of induction. Results: All patients showed objective response or s...

Radiotherapy and Oncology, 2021

Oncotarget, 2015

Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic... more Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growthfactor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs >1:

Cancers

Head and neck squamous cell carcinoma (HNSCC) is a highly challenging cancer [...]

Dermatology Practical & Conceptual

Exploration of targeted anti-tumor therapy, Dec 13, 2022

Aim: Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck ly... more Aim: Head and neck squamous cell cancer (HNSCC) is the ninth most common tumor worldwide. Neck lymph node (LN) status is the major indicator of prognosis in all head and neck cancers, and the early detection of LN involvement is crucial in terms of therapy and prognosis. Diffusion-weighted imaging (DWI) is a non-invasive imaging technique used in magnetic resonance imaging (MRI) to characterize tissues based on the displacement motion of water molecules. This review aims to provide an overview of the current literature concerning quantitative diffusion imaging for LN staging in patients with HNSCC. Methods: This systematic review performed a literature search on the PubMed database (https://pubmed. ncbi.nlm.nih.gov/) for all relevant, peer-reviewed literature on the subject following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) criteria, using the keywords: DWI, MRI, head and neck, staging, lymph node. Results: After excluding reviews, meta-analyses, case reports, and bibliometric studies, 18 relevant papers out of the 567 retrieved were selected for analysis. Conclusions: DWI improves the diagnosis, treatment planning, treatment response evaluation, and overall management of patients affected by HNSCC. More robust data to clarify the role of apparent diffusion coefficient (ADC) and DWI parameters are needed to develop models for prognosis and prediction in HNSCC cancer using MRI.

Diagnostics

Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma are the three main types... more Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma are the three main types of nonmelanoma skin cancers and their rates of occurrence and mortality have been steadily rising over the past few decades. For radiologists, it is still difficult to treat patients with advanced nonmelanoma skin cancer. Nonmelanoma skin cancer patients would benefit greatly from an improved diagnostic imaging-based risk stratification and staging method that takes into account patient characteristics. The risk is especially elevated among those who previously received systemic treatment or phototherapy. Systemic treatments, including biologic therapies and methotrexate (MTX), are effective in managing immune-mediated diseases; however, they may increase susceptibility to NMSC due to immunosuppression or other factors. Risk stratification and staging tools are crucial in treatment planning and prognostic evaluation. PET/CT appears more sensitive and superior to CT and MRI for nodal and...

La radiologia medica

Non-small cell lung cancer (NSCLC) is frequently complicated by central nervous system (CNS) meta... more Non-small cell lung cancer (NSCLC) is frequently complicated by central nervous system (CNS) metastases affecting patients’ life expectancy and quality. At the present clinical trials including neurosurgery, radiotherapy (RT) and systemic treatments alone or in combination have provided controversial results. CNS involvement is even more frequent in NSCLC patients with EGFR activating mutations or ALK rearrangement suggesting a role of target therapy in the upfront treatment in place of loco-regionals treatments (i.e. RT and/or surgery). So far clinical research has not explored the potential role of accurate brain imaging (i.e. MRI instead of the routine total-body contrast CT and/or PET/CT staging) to identify patients that could benefit of local therapies. Moreover, for patients who require concomitant RT there are no clear guidelines on the timing of intervention with respect to innovative precision medicine approaches with Tyrosine Kinase Inhibitors, ALK-inhibitors and/or immun...

Radiotherapy and Oncology

Diagnostics

Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (N... more Treatment-induced cardiac toxicity represents an important issue in non-small cell lung cancer (NSCLC) patients, and no biomarkers are currently available in clinical practice. A novel and easy-to-calculate marker is the quantitative analysis of calcium plaque in the coronary, calculated on CT. It is called the Agatston score (or CAD score). At the same time, other potential predictors include cardiac ultrasonography and anamnesis of the patients. Our work aimed to correlate cardiac biomarkers with overall survival (OS) in NSCLC patients. We retrospectively analyzed patients with NSCLC discussed in the Multidisciplinary Tumor Board of our Institute for the present analysis between January 2018 and July 2022. Inclusion criteria were the availability of basal CT imaging of the thorax, cardiac ultrasonography with the calculation of ejection fraction (EF), and complete anamnesis, including assessment of co-pathologies and pharmacological drugs. The clinical data of the patients were re...

Journal of Personalized Medicine

Despite being usually delivered in oncological patients, radiotherapy can be used as a successful... more Despite being usually delivered in oncological patients, radiotherapy can be used as a successful treatment for several non-malignant disorders. Even though this use of radiotherapy has been scarcely investigated since the 1950s, more recent interest has actually shed the light on this approach. Thus, the aim of this narrative review is to analyze the applications of non-oncological radiotherapy in different disorders. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This review contains a narrative report and a critical discussion of non-oncological radiotherapy approaches. In conclusion, non-oncological radiotherapy is a safe and efficacious approach to treat several disorders that needs to be further investigated and used in clinical practice.

Clinical and Translational Imaging

Introduction The aim of the narrative review was to analyse the applications of nuclear medicine ... more Introduction The aim of the narrative review was to analyse the applications of nuclear medicine (NM) techniques such as PET/CT with different tracers in combination with radiotherapy for the clinical management of glioblastoma patients. Materials and methods Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. Results This paper contains a narrative report and a critical discussion of NM approaches in combination with radiotherapy in glioma patients. Conclusions NM can provide the Radiation Oncologist several aids that can be useful in the clinical management of glioblastoma patients. At the same, these results need to be validated in prospective and multicenter trials.

Tomography

Introduction. Coronavirus SARS-CoV-2, the causative agent of COVID-19, primarily causes a respira... more Introduction. Coronavirus SARS-CoV-2, the causative agent of COVID-19, primarily causes a respiratory tract infection that is not limited to respiratory distress syndrome, but it is also implicated in other body systems. Systemic complications were reported due to an exaggerated inflammatory response, which involves severe alveolar damage in the lungs and exacerbates the hypercoagulation that leads to venous thrombosis, ischemic attack, vascular dysfunction and infarction of visceral abdominal organs. Some complications are related to anticoagulant drugs that are administrated to stabilize hypercoagulability, but increase the risk of bleeding, hematoma and hemorrhage. The aim of this study is to report the diagnostic role of CT in the early diagnosis and management of patients with severe COVID-19 complications through the most interesting cases in our experience. Material and Methods. The retrospective analysis of patients studied for COVID-19 in our institution and hospitals, whic...

Frontiers in Oncology

BackgroundRadiomics can provide quantitative features from medical imaging that can be correlated... more BackgroundRadiomics can provide quantitative features from medical imaging that can be correlated to clinical endpoints. The challenges relevant to robustness of radiomics features have been analyzed by many researchers, as it seems to be influenced by acquisition and reconstruction protocols, as well as by the segmentation of the region of interest (ROI). Prostate cancer (PCa) represents a difficult playground for this technique, due to discrepancies in the identification of the cancer lesion and the heterogeneity of the acquisition protocols. The aim of this study was to investigate the reliability of radiomics in PCa magnetic resonance imaging (MRI).MethodsA homogeneous cohort of patients with a PSA rise that underwent multiparametric MRI imaging of the prostate before biopsy was tested in this study. All the patients were acquired with the same MRI scanner, with a standardized protocol. The identification and the contouring of the region of interest (ROI) of an MRI suspicious ca...

Current Oncology

Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients... more Despite the rising evidence in favor of immunotherapy (IT), the treatment of oncological patients affected by so-called “cold tumors” still represents an open issue. Cold tumors are characterized by an immunosuppressive (so-called cold) tumor microenvironment (TME), which favors host immune system suppression, cancer immune-escape, and a worse response to IT. However, the TME is not a static element, but dynamically mutates and can be changed. Radiotherapy (RT) can modulate a cold microenvironment, rendering it better at tumor killing by priming the quiescent host immune system, with a consequent increase in immunotherapy response. The combination of TME radiomodulation and IT could therefore be a strategy for those patients affected by cold tumors, with limited or no response to IT. Thus, this review aims to provide an easy, rapid, and practical overview of how RT could convert the cold TME and why cold tumor radiomodulation could represent an interesting strategy in combination wi...

Cancers

We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodol... more We performed a pilot study to evaluate the use of MRI delta texture analysis (D-TA) as a methodological item able to predict the frequency of complete pathological responses and, consequently, the outcome of patients with locally advanced rectal cancer addressed to neoadjuvant chemoradiotherapy (C-RT) and subsequently, to radical surgery. In particular, we carried out a retrospective analysis including 100 patients with locally advanced rectal adenocarcinoma who received C-RT and then radical surgery in three different oncological institutions between January 2013 and December 2019. Our experimental design was focused on the evaluation of the gross tumor volume (GTV) at baseline and after C-RT by means of MRI, which was contoured on T2, DWI, and ADC sequences. Multiple texture parameters were extracted by using a LifeX Software, while D-TA was calculated as percentage of variations in the two time points. Both univariate and multivariate analysis (logistic regression) were, therefor...

Annals of Nuclear Medicine

American Journal of Clinical Oncology, 2022

Introduction: In the current study, we have investigated the effects of the different modalities ... more Introduction: In the current study, we have investigated the effects of the different modalities of treatment (volume of radiotherapy [RT], previous surgery) as well as the Gleason score of prostate cancer (PC) on the lymphocyte composition of PC patients undergoing RT. Methods: This is a monoinstitutional study that prospectively included PC patients that underwent RT from January 2016 until December 2017. To compare the different evaluations, the Wilcoxon signed-rank test was used among 2 times (Timepoint 0 to Timepoint 1). Percentage variation was calculated for all the lymphocyte subpopulation and was correlated with clinical parameters (previous surgery, Gleason score, and pelvic irradiation) with the χ2 test. The statistical analysis was repeated also on the stratified dataset according to the above parameters (previous surgery, Gleason score, and whole pelvic radiotherapy [WPRT]). Results: One hundred and eleven patients were included in the present analysis. All the lymphocyte subpopulations resulted significantly lower after RT. The modifications of several lymphocyte subpopulations correlated with previous surgery, Gleason score, and WPRT, although stratified analysis demonstrated that WPRT showed the greatest correlation. Conclusion: Our results could be used to design a prospective trial in order to study the use of WPRT on the lymphocyte subpopulations.

Cancers, 2021

Background: Multimodality treatment is considered the best treatment strategy for malignant pleur... more Background: Multimodality treatment is considered the best treatment strategy for malignant pleural mesothelioma (MPM). However, the ideal combination of them is still a matter of controversy. Here, we report a case series of MPM treated with a trimodality approach: induction chemotherapy (CT), pleurectomy/decortication (P/D), postoperative radiotherapy (RT) and post-operative CT. Methods: A retrospective case series of 17 MPM patients treated between 2013 and 2020 is presented. Patients had epithelial or mixed MPM diagnosed by video-assisted thoracoscopy and pathologic IMIG stage I or II disease. Treatment details and radiological data were collected. Induction therapy consisted of combination of cisplatin and pemetrexed, every 21 days for two cycles. P/D was performed 4–6 weeks after induction CT, post-operative RT 3–6 weeks after surgery, while post-operative CT was given 4–6 weeks after RT, with the same schedule of induction. Results: All patients showed objective response or s...

Radiotherapy and Oncology, 2021

Oncotarget, 2015

Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic... more Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growthfactor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation. In order to assess this, we carried out a retrospective analysis in a subset of 69 consecutive patients who received the mPEBev regimen within the BEVA2007 trial. Forty-five of these patients, also received palliative RT of one or more metastatic sites. Statistical analysis (a Log-rank test) revealed a much longer median survival in the group of patients who received RT [mCH vs mCH + RT: 12.1 +/-2.5 (95%CI 3.35-8.6) vs 22.12 +/-4.3 (95%CI 11.9-26.087) months; P=0.015] with no difference in progression-free survival. In particular, their survival correlated with the mPEBev regimen ability to induce the percentage of activated dendritic cells (DCs) (CD3-CD11b+CD15-CD83+CD80+) [Fold to baseline value (FBV) ≤1 vs >1: