Search Results (14)

The advent of immune checkpoint inhibitors (ICIs) has revolutionized the treatment paradigm of lung cancer, resulting in notable enhancements in patient survival. Nevertheless, evaluating treatment response in patients undergoing immunotherapy poses distinct challenges due to unconventional response patterns like pseudoprogressive disease (PPD), dissociated response (DR), and hyperprogressive disease (HPD). Conventional response criteria such as the RECIST 1.1 may not adequately address these complexities. To tackle this issue, novel response criteria such as the iRECIST and imRECIST have been proposed, enabling a more comprehensive assessment of treatment response by incorporating additional scans and considering the best overall response even after radiologic progressive disease evaluation. Additionally, [18F]FDG PET/CT imaging has emerged as a valuable modality for evaluating treatment response, with various metabolic response criteria such as the PERCIMT, imPERCIST, and iPERCIST developed to overcome the limitations of traditional criteria, particularly in detecting pseudoprogression. A multidisciplinary approach involving oncologists, radiologists, and nuclear medicine specialists is crucial for effectively navigating these complexities and enhancing patient outcomes in the era of immunotherapy for lung cancer. In this review, we delineate the key components of these guidelines, summarizing essential aspects for radiologists and nuclear medicine physicians. Furthermore, we provide insights into how imaging can guide the management of individual lung cancer patients in real-world multidisciplinary settings. Full article

Globally, the efforts to find the best cancer treatment are demanding and very intensive. Immunotherapy has gained an important role as a second or sometimes first line of treatment for various types of cancer. PD-1/PD-L1 checkpoint inhibitors are an impending category of immunotherapy, and their mechanism, as well as their interaction with T cells, are well studied. However, our knowledge about any possible effect(s) of immunotherapy on B cells is limited. In this prospective study, we asked the question of any possible alterations of circulating B cells (numbers and subsets) occurring during immunotherapy in patients with cancer and of the potential correlation of such changes with the outcomes and with development of immune-related adverse events (irAEs). We enrolled 20 cancer patients who received PD-1 checkpoint inhibitors and 8 healthy donors (HD). Patients underwent regular clinical assessment and imaging using the iRECIST criteria for 6 months following immunotherapy. Peripheral blood samples were collected before and during PD-1 checkpoint inhibitor therapy, and flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) was performed, evaluating various circulating B cell subset phenotypes, including mature naïve B cells, memory B cells, regulatory B cells (Bregs), antibody-secreting cells (ASCs), and age-related B cells (ABCs). Statistical analysis was employed to compare the differences of B cells between different groups and among sequential data within the same group. Total circulating CD19+ B cell counts remained stable across both groups (responders (R), nonresponders (NR)) and timepoints. However, there was a significant rise in mature naïve B cells and decline in memory B cells at the initiation of the treatment in the R group compared to healthy donors and to the NR group. Such changes were correlated with a good response to immunotherapy. On the contrary, higher numbers of ABCs at baseline were seen in the NR group and were correlated with resistance to treatment. As far as immune-related adverse events are concerned, no significant changes were recorded among the different B cell subpopulations evaluated in both groups. Our study provides preliminary data suggesting that B cell subset changes during immunotherapy may correlate with immune checkpoint inhibitor-induced clinical responses in patients with neoplasia. Further investigations to delineate the potential role(s) of B cells in patients undergoing immunotherapy are needed. Full article

In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported. Full article

Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)—complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease. Full article

Objectives: To compare the feasibility and reliability of manual versus software-assisted assessments of computed tomography scans according to iRECIST in patients undergoing immune-based cancer treatment. Methods: Computed tomography scans of 30 tumor patients undergoing cancer treatment were evaluated by four independent radiologists at baseline (BL) and two follow-ups (FU), resulting in a total of 360 tumor assessments (120 each at BL/FU1/FU2). After image interpretation, tumor burden and response status were either calculated manually or semi-automatically as defined by software, respectively. The reading time, calculated sum of longest diameter (SLD), and tumor response (e.g., “iStable Disease”) were determined for each assessment. After complete data collection, a consensus reading among the four readers was performed to establish a reference standard for the correct response assignments. The reading times, error rates, and inter-reader agreement on SLDs were statistically compared between the manual versus software-assisted approaches. Results: The reading time was significantly longer for the manual versus software-assisted assessments at both follow-ups (median [interquartile range] FU1: 4.00 min [2.17 min] vs. 2.50 min [1.00 min]; FU2: 3.75 min [1.88 min] vs. 2.00 min [1.50 min]; both p < 0.001). Regarding reliability, 2.5% of all the response assessments were incorrect at FU1 (3.3% manual; 0% software-assisted), which increased to 5.8% at FU2 (10% manual; 1.7% software-assisted), demonstrating higher error rates for manual readings. Quantitative SLD inter-reader agreement was inferior for the manual compared to the software-assisted assessments at both FUs (FU1: ICC = 0.91 vs. 0.93; FU2: ICC = 0.75 vs. 0.86). Conclusions: Software-assisted assessments may facilitate the iRECIST response evaluation of cancer patients in clinical routine by decreasing the reading time and reducing response misclassifications. Full article

Immunotherapy denotes an exemplar change in an oncological setting. Despite the effective application of these treatments across a broad range of tumors, only a minority of patients have beneficial effects. The efficacy of immunotherapy is affected by several factors, including human immunity, which is strongly correlated to genetic features, such as intra-tumor heterogeneity. Classic imaging assessment, based on computed tomography (CT) or magnetic resonance imaging (MRI), which is useful for conventional treatments, has a limited role in immunotherapy. The reason is due to different patterns of response and/or progression during this kind of treatment which differs from those seen during other treatments, such as the possibility to assess the wide spectrum of immunotherapy-correlated toxic effects (ir-AEs) as soon as possible. In addition, considering the unusual response patterns, the limits of conventional response criteria and the necessity of using related immune-response criteria are clear. Radiomics analysis is a recent field of great interest in a radiological setting and recently it has grown the idea that we could identify patients who will be fit for this treatment or who will develop ir-AEs. Full article

Objective: To evaluate the incidence of the abscopal response (AR) in patients with metastatic melanoma requiring palliative radiotherapy (RT). Patients and methods: Patients treated for metastatic melanoma between January 1998 and February 2020 in four oncology departments were screened. Patients with progression under immune checkpoint inhibitors or without ongoing systemic treatment, and requiring palliative RT were considered. The AR was defined as an objective response according to RECIST and/or iRECIST for at least one non-irradiated metastasis at distance (≥10 cm) from the irradiated lesion. Primary endpoint was the rate of AR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), local control (LC) of the irradiated lesion, and toxicity as assessed by CTCAE v5. Results: Over the period considered, 118 patients were included and analyzed. Fifteen patients (12.7%) had an AR. With a median follow-up of 7.7 months (range, 0.2–242.2), median OS and PFS after RT were significantly longer in patients with an AR compared to those without: 28 vs. 6.6 months (p < 0.01) and not reached vs. 3.2 months, respectively. No grade ≥2 toxicity was reported. Patients who developed an AR were more likely to be treated with immunotherapy (93.3% vs. 55.9%, p = 0.02). In multivariate analysis, they had a higher number of irradiated metastases treated concomitantly (HR = 16.9, p < 0.01) and a higher rate of mild infections during RT (HR = 403.5, p < 0.01). Conclusions: AR in metastatic melanoma seems to be highly prognostic of overall survival, although it is a rare phenomenon. It may be promoted by multiple concomitant treatments with RT and immunotherapy and by acute inflammatory events such as infection. Full article

Background: The purpose was to determine whether tumor response to CPI varies by organ and to characterize response patterns in a group of surgically treated metastatic RCC patients treated with Nivolumab. Methods: A retrospective analysis was undertaken between January 2016 and March 2020 on patients receiving Nivolumab for metastatic RCC, following first-line therapy and having at least one baseline and two follow-up scans. A Fisher’s exact test was used to compare categorical variables, and a Kruskal–Wallis test was used to compare continuous variables. Results: Twenty-one out of thirty patients evaluated were eligible, and they were divided into two groups: responders (n = 11) and non-responders (n = 10). According to all iRECIST standards, 18 (85.7 percent) of the 21 patients had PD (10 patients), PR (3 patients), or SD (8 patients). At baseline, 7, 15, 4, 13, 7, and 7 patients, respectively, had detectable hepatic metastasis and lung, brain, lymph node, soft tissue, and other intra-abdominal metastases; these patients were evaluated for organ-specific response. The ORRs for hepatic metastasis and lung, brain, lymph node, soft tissue, adrenals, and other intraperitoneal metastases were correspondingly 10%, 20%, 35%, 0%, and 25%. In total, 13 (61.9%) of them demonstrated varied responses to CPI therapy, with 6 (28.5%) demonstrating intra-organ differential responses. The lymph nodes (35%) had the best objective response (BOR), followed by the adrenals and peritoneum (both 25%), the brain (20%), and the lung (20%). The response rate was highest in adrenal gland lesions (2/4; 50%), followed by lymph nodes (13/19; 68.4 percent) and liver (5/10; 50%), whereas rates were lowest for lesions in the lung (9/25; 36%), intraperitoneal metastases (1/4; 25%), and brain (1/5; 20%). Conclusions: In renal cell carcinoma, checkpoint inhibitors have a variable response at different metastatic sites, with the best response occurring in lymph nodes and the least occurring in soft tissue. Full article

Immunotherapy with checkpoint inhibitors has prompted a major change not only in cancer treatment but also in medical imaging. In parallel with the implementation of new drugs modulating the immune system, new response criteria have been developed, aiming to overcome clinical drawbacks related to the new, unusual, patterns of response characterizing both solid tumors and lymphoma during the course of immunotherapy. The acknowledgement of pseudo-progression, hyper-progression, immune-dissociated response and so forth, has become mandatory for all imagers dealing with this clinical scenario. A long list of acronyms, i.e., irRC, iRECIST, irRECIST, imRECIST, PECRIT, PERCIMT, imPERCIST, iPERCIST, depicts the enormous effort made by radiology and nuclear medicine physicians in the last decade to optimize imaging parameters for better prediction of clinical benefit in immunotherapy regimens. Quite frequently, a combination of clinical-laboratory data with imaging findings has been tested, proving the ability to stratify patients into various risk groups. The next steps necessarily require a large scale validation of the most robust criteria, as well as the clinical implementation of immune-targeting tracers for immuno-PET or the exploitation of radiomics and artificial intelligence as complementary tools during the course of immunotherapy administration. For the present review article, a summary of PET/CT role for immunotherapy monitoring will be provided. By scrolling into various cancer types and applied response criteria, the reader will obtain necessary information for better understanding the potentials and limitations of the modality in the clinical setting. Full article

The present review is focused on the role of diagnostic tomographic imaging such as computed tomography and magnetic resonance imaging to assess and predict tumor response to advanced medical treatments in metastatic renal cell carcinoma (RCC) patients. In this regard, antiangiogenic agents and immune checkpoint inhibitors (ICIs) have developed as advanced treatment options replacing the conventional therapy based on interferon-alpha and interleuchin-2 which had unfavorable toxicity profile and low response rates. In clinical practice, the imaging evaluation of treatment response in cancer patients is based on dimensional changes of tumor lesions in sequential scans; in particular, Response Evaluation Criteria in Solid Tumors (RECIST) have been defined for this purpose and also applied in patients with metastatic RCC. However, these new drugs with predominant cytostatic effect make RECIST insufficient to realize an adequate response imaging evaluation. Therefore, new imaging criteria (mCHOI and iRECIST) have been proposed to assess tumor response to advanced medical treatments of metastatic RCC, they correlate better than RECIST with the progression-free survival and overall survival. Finally, a potential role of radiomics and machine learning models has been suggested to predict tumor response. Full article

Dostarlimab is an immune checkpoint inhibitor (ICI) targeting the Programmed-Death-1 (PD-1) co-receptor, recently approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) as a novel therapy for recurrent or advanced endometrial cancer. We report the case of a 64-year-old woman, experiencing vaginal recurrence with microsatellite instability high/hypermutated of a FIGO stage IA grade 2 endometrial endometrioid adenocarcinoma. She received preoperative chemotherapy with four cycles of carboplatin plus paclitaxel, with stable disease on pelvic magnetic resonance imaging (MRI) and fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET/CT). Dostarlimab (500 mg intravenously every 3 weeks) was then introduced. The subsequent evaluation after three perfusions demonstrated a complete metabolic response on ¹⁸F-FDG PET/CT according to immunotherapy-modified PET response criteria in solid tumors (imPERCIST) criteria, then confirmed by MRI according to immune response evaluation criteria in solid tumors (iRECIST). This clinical description suggests that ¹⁸F-FDG PET/CT might take place among available tools for guiding the preoperative management for recurrent endometrial cancer patients receiving dostarlimab immunotherapy that should be further explored through clinical trials. Full article

Treatment response is usually assessed by the response evaluation criteria in solid tumors (RECIST). These criteria may not be adequate to evaluate the response to immunotherapy, considering the peculiar patterns of response reported with this therapy. With the advent of immunotherapy these criteria have been modified to include the evaluation of the peculiar responses seen with this type of therapy (iRECIST criteria), including pseudoprogressions and hyperprogressions. Tumor growth rate (TGR) is a dynamic evaluation that takes into account the kinetics of response to treatment and may help catch the real efficacy of an immunotherapy approach. We performed a retrospective monocentric study to explore the impact of TGR change after nivolumab administration as the second or later line of treatment in patients with metastatic renal cell carcinoma (RCC). We evaluated 27 patients, divided into three categories: Disease control (DC) if there was no PD; lower velocity PD (LvPD) if disease progressed but the TGR at second assessment (TGR2) was lower than the TGR at first assessment (TGR1); higher velocity PD (HvPD) if TGR2 was higher than TGR1. The median OS for the DC group was 11.0 months (95% CI 5.0–17.0) (reference) vs. (not reached) NR (95% CI NR-NR) for LvPD (HR 0.27; 95% CI 0.06–1.30; p 0.102) vs. NR (95% CI NR–NR) for HvPD (HR 0.23; 95% CI 0.06–0.88; p 0.032). There was no difference between LvPD and DC (HR 1.21; 95% CI 0.20–7.28; p 0.838). In patients with metastatic RCC, the second or later line of nivolumab treatment may lead to a deceleration in TGR resulting in an improved survival outcome similar to that observed in patients experiencing tumor regression. In this subgroup, especially in the presence of a clinical benefit, continuing the treatment beyond progression can be recommended. Full article

Introduction: In the current study, we aimed to assess the impact of antibiotics (ATB) and metabolic parameters on clinical outcome of non-small cell lung carcinoma (NSCLC) patients treated with immune checkpoint inhibitors (ICI). Methods: Data from fifty NSCLC patients referred for ICI between December 2015 and May 2019 were analyzed. All patients underwent 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) and contrast-enhanced CT at baseline and for response assessment after 6–8 weeks. Patients who received ATB within 1 month before or after the first dose of ICI were compared with those who did not. Response assessment according to iRECIST and EORTC was evaluated, as well as progression-free survival (PFS) and overall survival (OS). For semi-quantitative parameters, we computed metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their variations (∆). Results: Twenty NSCLC cases of 50 (40%) had received ATB. Patients receiving ATB had a higher number of metastases (p = 0.046), and were associated with an elevated tumor burden, expressed by TLG (687 vs. 235.3, p = 0.007) and MTV (125.6 vs. 40.6, p = 0.002), compared to no-ATB patients. According to iRECIST, progressive disease rate was significantly higher for ATB group (64.7% vs. 27.6%, p = 0.029). Likewise, PFS was shorter for ATB compared to no-ATB (median 4.1 vs. 12.4 months, p = 0.004), while no difference for OS was detected. On multivariate analysis, the effect of ATB remained significant for poor PFS along with performance status (ECOG ≥ 1), and ∆SUVmax. Conclusions: ATB therapy seems to be associated with a worse treatment response, PFS, and higher metabolic tumor burden in NSCLC patients treated with ICI. Full article

Despite wide recognition of iRECIST, evidence regarding the impact of iRECIST over RECIST 1.1 is lacking. We aimed to evaluate the impact of iRECIST on assessing treatment efficacy of immune checkpoint inhibitors (ICIs) over RECIST 1.1. Articles that evaluated the treatment response and outcome based on both RECIST 1.1 and iRECIST were eligible. Data regarding overall response rates (ORR) and disease control rate (DCR) based on RECIST 1.1 and iRECIST, and data required to estimate individual patient data of progression-free survival (PFS) were extracted. Estimates were compared using meta-regression and pooled incidence rate ratios. The pooled difference of restricted mean survival time (RMST) of PFS between two criteria were calculated. Eleven studies with 6210 patients were analyzed. The application of iRECIST had no impact on the response-related endpoint by showing no significantly different ORR and DCR from RECIST 1.1 (pooled ORR, 23.6% and 24.7% [p = 0.72]; pooled DCR, 45.3% and 48.7% [p = 0.56] for iRECIST and RECIST 1.1, respectively) and had a minor impact on a survival endpoint by showing longer RMST of PFS than RECIST 1.1 (pooled difference, 0.46 months; 95% CI, 0.10–0.82 months; p = 0.01). Such a modest benefit of iRECIST should be considered when we design a clinical trial for immune checkpoint inhibitors. Full article