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Additional file 1: Figure S1. Correlation of mRNA expression level of IDO1 with protein expression of PD-L1 in TCGA LUAD tumors (A) and NSCLC cell lines (B).

These results suggest that both systemic Inflammatory status and treatment-related immunomodulation may affect the outcome of these patients a finding that highlight a possible involvement of immunesystem in ultimate antitumor effect of this regimen, and offer a solid rationale to test our metronomic regimen in a module of sequential combination with anti-PD-1/PDL-1 inhibitors.

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.

This study aimed to determine if diffusion-weighted imaging (DWI) can differentiate between benign and malignant lymph nodes in patients with head and neck cancer. A total of 55 patients with confirmed head and neck cancer and enlarged neck nodes were enrolled and evaluated by two radiologists using a workstation. Lymph nodes were analyzed using 3D regions of interest (ROIs) placed on T2-weighted images and compared to the corresponding DWI images. This study found that DWI and ADC values can be used to assess metastatic lymph nodes in the neck and that the sensitivity, specificity, and AUC of a narrower ROI for recognizing metastases were greater compared to the ADC value of the whole node. The study also found that the size of the ROI affects ADC values. The results suggest that DWI can accurately predict the status of cervical lymph nodes in patients with head and neck cancer and that it may be useful in diagnosing, determining the stage, developing a treatment plan, and monitoring these patients.

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

Background: Non-small-cell lung cancer (NSCLC) is a common, steady growing lung tumour that is often discovered when a surgical approach is forbidden. For locally advanced inoperable NSCLC, the clinical approach consists of a combination of chemotherapy and radiotherapy, eventually followed by adjuvant immunotherapy, a treatment that is useful but may cause several mild and severe adverse effect. Chest radiotherapy, specifically, may affect the heart and coronary artery, impairing heart function and causing pathologic changes in myocardial tissues. The aim of this study is to evaluate the damage coming from these therapies with the aid of cardiac imaging. Methods: This is a single-centre, prospective clinical trial. Patients with NSCLC who are enrolled will undergo computed tomography (CT) and magnetic resonance imaging (MRI) before chemotherapy 3 months, 6 months, and 9–12 months after the treatment. We expect to enrol 30 patients in 2 years. Conclusions: Our clinical trial will be an opportunity not only to highlight the timing and the radiation dose needed for pathological cardiac tissue changes to happen but will also provide useful data to set new follow-up schedules and strategies, keeping in mind that, more often than not, patients affected by NSCLC may present other heart- and lung-related pathological conditions.

Peripheral immune-checkpoint blockade with mAbs to programmed cell death receptor-1 (PD-1) (either nivolumab or pembrolizumab) or PD-Ligand-1 (PD-L1) (atezolizumab, durvalumab, or avelumab) alone or in combination with doublet chemotherapy represents an expanding treatment strategy for metastatic non-small cell lung cancer (mNSCLC) patients. This strategy lays on the capability of these mAbs to rescue tumor-specific cytotoxic T lymphocytes (CTLs) inactivated throughout PD-1 binding to PD-L1/2 in the tumor sites. This inhibitory interactive pathway is a physiological mechanism of prevention against dangerous overreactions and autoimmunity in case of prolonged and/or repeated CTL response to the same antigen peptides. Therefore, we have carried out a retrospective bioinformatics analysis by single-cell flow cytometry to evaluate if PD-1/PD-L1-blocking mAbs modulate the expression of specific peripheral immune cell subsets, potentially correlated with autoimmunity triggering in 28 mNSCLC patients. We recorded a treatment-related decline in CD4+ T-cell and B-cell subsets and in the neutrophil-to-lymphocyte ratio coupled with an increase in natural killer T (NKT), CD8+PD1+ T cells, and eosinophils. Treatment-related increase in autoantibodies [mainly antinuclear antibodies (ANAs) and extractable nuclear antigen (ENA) antibodies] as well as the frequency of immune-related adverse events were associated with the deregulation of specific immune subpopulations (e.g., NKT cells). Correlative biological/clinical studies with deep immune monitoring are badly needed for a better characterization of the effects produced by PD-1/PD-L1 immune-checkpoint blockade.

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 retrospectively collected, and the CAD scores was calculated on a CT scan. All of these parameters were correlated with overall survival (OS) with univariate analysis (Kaplan–Meier analysis) and multivariate analysis (Cox regression analysis). Following the above-mentioned inclusion criteria, 173 patients were included in the present analysis. Of those, 120 patients died in the follow-up period (69.6%), and the median overall survival (OS) was 28 months (mean 47.2 months, 95% CI, 36–57 months). In univariate analysis, several parameters that significantly correlated with lower OS were the stage (p < 0.001), the CAD grading (p < 0.001), history of ischemic heart disease (p: 0.034), use of beta blocker drugs (p: 0.036), and cardiac ejection fraction (p: 0.005). In multivariate analysis, the only parameters that remained significant were as follows: CAD score (p: 0.014, OR 1.56, 95% CI: 1.04–1.83), stage (p: 0.016, OR: 1.26, 95% CI: 1.05–1.53), and cardiac ejection fraction (p: 0.011, OR 0.46, 95% CI: 0.25–0.84). Both CAD score and ejection fraction are correlated with survival in NSCLC patients at all stages of the disease. Independently from the treatment choice, a cardiological evaluation is mandatory for patients with NSCLC.

The purpose of this pictorial essay is to review the imaging findings of adrenal lesions. Adrenal lesions could be divided into functioning or non-functioning masses, primary or metastatic, and benign or malignant. Imaging techniques have undergone significant advances in recent years. The most significant objective of adrenal imaging is represented by the detection and, when possible, characterization of adrenal lesions in order to direct patient management correctly. The detection and management of adrenal lesions is based on cross-sectional imaging obtained with non-contrast CT (tumour density), contrast-enhanced CT including delayed washout (either absolute percentage washout or relative percentage one) and finally with MR chemical shift analysis (loss of signal intensity between in-phase and out-of-phase images including both qualitative and quantitative estimates of signal loss). The small incidental adrenal nodules are benign, in most of cases; some tumors such as lipid-rich adenoma and myelolipoma have characteristic features that can be diagnosed accurately in CT. On contrary, if the presenting contrast-enhanced CT shows an adrenal mass with uncertain or malignant morphologic features, particularly in patients with a known history of malignancy, further evaluations should be considered. The most significative implications for radiologists are represented by how to assess risk of malignancy on imaging and what follow-up to indicate if an adrenal incidentaloma is not surgically removed.

Cholangiocarcinoma (CC) accounts for about 3% of the gastrointestinal and 10-25% of all hepatobiliary malignancies. It arises from the epithelium of the bile duct and it can be classified in intrahaepatic (ICC), perihilar (PCC) and distal (DCC) cholangiocarcinoma, depending on the anatomical location. About 50-60% of the cases are PCC. Early detection is very difficult for the lack of symptoms, and most of the patients are not resectable at the time of diagnosis. IRE is a non-thermal ablation technique that determines cellular apoptosis by electrical impulses without involving extracellular matrix like MW or RF ablation (MWA and RFA). The aim of our study is to demonstrate the safety, feasibility and efficacy of this procedure in the treatment of cholangiocarcinoma according to our experience. From 2015 to 2019, fifteen patients with unre-sectable perhilar and intrahepatic colangiocarcinoma (7 female and 8 male, mean age 69.2) were referred to our department to be enrolled in our prospective study that was approved by local Ethical Committee. Eight lesions were defined iCC and seven of them pCC. Six patients had biliary STENT and four external percutaneous transhepatic biliary drainage (PTBD). The IRE procedure was performed to expert radiologist (G.B.) under CT guidance using the Nanoknife IRE device (Angiodynamics, Queensbury, NY). The data before and after treatment were compared using Wilcoxon Rank Test and the survival outcome was evaluated using Kaplan Meyer Test. All procedures performed under CT guidance have been successfully completed. Treated lesions were located seven perhilar and eight intrahepatic sites and showed a mean volume 66.3 (SD 70.9; IC ranged from 5.57 to 267.20 cm(3)). No major complications were observed. From 30 to 90 days, the mortality rate was around 0%. Progression of the disease in all cases were not observed. Only one patient was reported increase of the Ca19-9 without sign of pancreatitis and bile obstruction. The imaging follow-up showed the local disease control with a decrease of the entire volume of the lesion and a further reduction of the densitometric values. From the comparison between the mean volumes for each group (before and after treatment), the Wilcoxon Rank test demonstrated the statistical significant difference with a p value < 0.01. On the contrary, it is believed that this results encouraging in considering the IRE procedure the safe, feasible and effective method in the treatment of the CC

Introduction: Lung cancer represents the leading cause of cancer mortality across the worlds. At present, less than 30% of the patients can undergo curative surgery, while the majority of them (65%) are diagnosed with metastatic disease and directed to systemic treatments. In this context there is a subset of patients (25%) with locally advanced stage disease whose outcome might be improved by using combined strategies of treatment including chemotherapy, radiotherapy and surgery. Areas covered: Here we reviewed possible combination strategies aimed to improve the outcome of lung cancer patients, focusing on the role of radiotherapy both in the adjuvant and oligo-metastatic setting and in synergy with immunotherapy, and finally, we afforded the new challenges concerning the advanced RT and precision oncology. We carried out a focused analysis concerning the key clinical management weaknesses as well as the potential that current research holds. Expert commentary: We believe that the most promising clinical trials in this specific patient subset will build their rationale on the results of well-designed translational models aimed to test the combination of cytotoxic drugs, radiobiology, and immune-pharmacology. In this context, remarkable investigational fields are focused on the attempt to combine radiotherapy with chemo-immunological strategies and precision medicine protocols.

Radiosurgery (SRS) is widely used in the treatment of brain oligo-metastases from NSCLC. The aim of present study is to evaluate the extent of perilesional edema in brain metastases as predictive factor of treatment response. This single center retrospective study included 42 consecutive patients (January 2011–December 2014) with 1–2 brain metastasis from NSCLC treated with Radiosurgery (SRS). Extent of perilesional edema was measured as maximal extension from the edge of lesion and classified as minor (

Context: Radiation-induced lumbosacral plexopathy is still under-recognized although its symptomatology can really lower the quality of life and impair self-sufficient functions of patients often cured of cancer. Objectives: This review aimed to depict radiation-induced lumbosacral plexopathy through a systematic review of the available literature and discuss various aspects of the clinical management of this pathology. Data Sources: We searched for all English medical papers registered in Web of Knowledge, PubMed, Google Scholar, and ScienceDirect from January 1990 to November 2018. Study Selection: From among all articles concerning radiotherapy and lumbosacral plexopathy, we included papers that dealt with human samples and excluded non-human samples and case reports. Results: Out of 1,312 articles, we selected 42 articles of which 21 met the eligibility criteria and were included in the present analysis. Five papers were general reviews, three focused on the diagnosis of disease, three analyzed the role of different therapies, and the remaining 10 articles concerned the methodology of radiation therapy. Conclusion: In the next future, we must analyze the dosimetry parameters and the clinical parameters, with appropriate follow-up times, thus providing sufficient data to use for developing organ sparing strategies tailored to individual patients. Therefore, we can reduce this type of side effects that have a huge impact on the quality of life of patients.

The focus of this review deals with the management of elderly patients with early stage breast cancer, discussing the role of systemic therapies [endocrine therapy (ET), chemotherapy, novel agents] and radiation therapy (RT). Several studies have evaluated in elderly low risk patients the possibility of omitting the RT but, at the same time, higher locoregional relapse (LR) rates without significant impact on overall survival (OS) were observed in all studies when RT was excluded. Technological improvements [intensity-modulated RT (IMRT), volumetric modulated arc therapy (VMAT), high dose brachy therapy (HDBT)] are very useful in order to reduce cosmetic outcome and improve quality of life of frail patients. The optimal sequence of ET, concomitant or sequential to RT, is currently under investigation, and specifically in the elderly it is questioned the possible choice of prolonged therapy after standard 5 years. Data regarding chemotherapy suggesting no benefit of OS in endocrine responsive diseases, whereas endocrine non-responsive breast cancer still showed a better outcome. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen is recognized as the standard protocol, although age-dependent increase in therapy related mortality was reported. Neoadjuvant chemotherapy in elderly showed a lower ratio of pathological complete response in comparison to younger patients, but triple negative breast cancer patients showed a good prognosis regarding OS, comparable to younger patients. The risk of cardiotoxicity seems to increase with age, so the use trastuzumab in this setting is much debated. Currently, other anti-HER2 agents (pertuzumab, lapatinib) are used in neoadjuvant setting, but the data on elderly are still premature. Novel molecules are rapidly changing the clinical management of breast cancer patients but are tested especially in locally advanced and metastatic setting. Among these, particularly interesting are inhibitors of CDK4 and 6, alpelisib (PI3K enzymes mutations), immune checkpoint (PD1, PDL1, CTLA4) inhibitors, atezolizumab. Elderly patients are under-represented in clinical trials, although ageing can be frequently correlated with a decrease in the effectiveness of the immune system. For elderly women, treatment decisions should be individually decided, taking into account the geriatric assessment and limited life expectancy and tumor characteristics.

Tumor immunologic microenvironment is strongly involved in tumor progression and the presence of tumor infiltrating lymphocytes (TIL) with different phenotypes has been demonstrated to be of prognostic relevance in different malignancies. We investigated whether TIL infiltration of tumor tissues could also predict the outcome of prostate cancer patients. To this end, we carried out a retrospective analysis correlating the outcome of locally advanced prostate cancer patients undergone salvage radiotherapy upon relapse after radical surgery with the infiltration by different TIL populations. Twenty-two patients with resectable prostate cancer, with a mean age of 67 (+/−3.93) years, who received salvage radiotherapy with a mean of 69.66 (+/− 3.178) Gy in 8 weeks, between June 1999 and January 2009 and with a median follow up of 123 (+/− 55.82) months, were enrolled in this study. We evaluated, by immunohistochemistry, the intratumoral (t) and peripheral stroma (p) infiltration by CD45, CD3, CD4, CD8, CCR7, FoxP3 or PD-1-positive cells on tumor samples taken at the diagnosis (d) and relapse times (R). We correlated these variables with patients' biochemical progression free survival (bPFS), post-radiotherapy progression free survival (PFS), and overall survival (OS). Substantial changes in the rate of TIL subsets were found between the first and the second biopsy with progressive increase in CD4, CCR7, FoxP3, PD-1+ cells. Our analysis revealed that higher CD8p,R+ and lower PD-1R+ TIL scores correlated to a longer bPFS. Higher CD8p,R+ and CCR7t,R+ TIL scores and lower CD45p,R+ and FoxP3p,R+ TIL scores correlated to a prolonged PFS and OS. These results suggest that the immunological microenvironment of primary tumor is strictly correlated with patient outcome and provide the rationale for immunological treatment of prostate cancer.

BACKGROUND : Stereotactic irradiation is widely used in brain oligo-metastases treatment. The aim of this study is to evaluate the prognostic value of magnetic resonance imaging (MRI) texture analysis (TA) of brain metastases (BM) of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS : This study included thirty-eight consecutive patients undergoing stereotactic irradiation, that is, stereotactic fractionated radiotherapy (SRT) or radiosurgery (SRS), from January 2011 to December 2014 for 1-2 brain BM from NSCLC. Whole-brain radiotherapy (WBRT) was not delivered. The diagnostic MRI DICOM (Digital Imaging and Communications in Medicine) images were collected and analyzed with a homemade ImageJ macro, and typical TA parameters (mean, standard deviation, skewness, kurtosis, entropy, and uniformity) were evaluated for: brain progression-free survival; modality of brain metastatic progression (local progression or/and new metastases); and overall survival, after SRT/SRS. RESULTS: After SRT/SRS 14 patients (36.8%) experienced recurrence in the brain, with a recurrence in the irradiated site (five patients, 13.2%), new metastases (11 patients, 28.9%), local recurrence and new metastases (two patients, 5.25%). Nineteen patients (50%) died of tumor progression or other causes. Entropy and uniformity were significantly associated with local progression, whereas kurtosis was significantly associated with both local progression and new brain metastases. CONCLUSIONS : These results appear promising, since the knowledge of factors correlated with the modality of brain progression after stereotactic irradiation of brain oligo-metastatic foci of NSCLC might help in driving the best treatment in these patients (association of SRT/SRS with WBRT? Increase of SRT/SRS dose?). Our preliminary data needs confirmation in large patient series.