• Immunotherapy
• PET/CT
• bladder cancer
• pembrolizumab
• pseudoprogression

• Humans
• Female
• Fluorodeoxyglucose F18
• Lymphoma, Large B-Cell, Diffuse/diagnostic imaging
• Positron Emission Tomography Computed Tomography
• Adult
• Disease Progression
• Tomography, X-Ray Computed
• Spleen/diagnostic imaging
• Spleen/pathology
• Multimodal Imaging

• Immune cells
• Immune microenvironment
• Immunotherapy
• Malignant pleural effusion

• 82205226 National Natural Science Foundation of China
• 82074410 National Natural Science Foundation of China

• immune checkpoint inhibitors
• immuno-oncology
• kidney cancer
• metastatic clear cell renal cell carcinoma
• treatment
• tyrosine kinase inhibitors

• Bladder urothelial carcinoma
• Case report
• Hyperprogression
• Immunotherapy
• Toripalimab

• Antibody
• Anticuerpo
• Carcinoma urotelial
• Immunohistochemistry
• Immunotherapy
• Inmunohistoquímica
• Inmunoterapia
• PD-L1
• Urothelial carcinoma

• Humans
• Urinary Bladder Neoplasms/therapy
• Carcinoma, Transitional Cell/therapy
• B7-H1 Antigen
• Consensus
• Immunotherapy/methods

• CD-47
• NLRP3 inflammasome inhibitor
• RRx-001
• bromonitrozidine
• cold tumors
• nivolumab
• tumor associated macrophage
• vascular normalization

• avelumab
• bladder cancer
• maintenance
• metastasis
• pseudoprogression

• Cabozantinib
• First line
• Primary refractory
• Renal cell carcinoma
• Second line

• Humans
• Carcinoma, Renal Cell/drug therapy
• Tyrosine Kinase Inhibitors
• Retrospective Studies
• Kidney Neoplasms/drug therapy

• cancer immunotherapy
• castration-resistant metastatic prostate cancer
• immunotherapy radiological findings
• pet-ct fluciclovine
• pseudo-progression

• PD-1
• PD-L1
• immune checkpoint inhibitors
• lymph nodes
• metastatic urothelial carcinoma
• response

With the introduction of immune checkpoint inhibitors (ICI) in recent years, the treatment landscape of metastatic urothelial cancer has undergone a substantial transformation. Nevertheless, disease progression after prior platinum-based chemotherapy and ICI pretreatment remains a challenging clinical situation with little evidence for following therapeutic options. The aim of this multicenter analysis was to examine the efficacy of the vinca alkaloid vinflunine after previous ICI therapy. In our cohort, post-ICI patients showed an overall response rate (ORR) of 22.4% compared to 15.6% within ICI-naïve patients (p = 0.451), and the clinical benefit rate (CBR) was 51.0% vs. 25.0% (p = 0.020), respectively. Post-ICI patients showed longer OS (8.78 vs. 5.72 months; p = 0.467) and longer PFS (3.09 vs. 2.14 months; p = 0.105). Our analysis demonstrates the clinical activity of vinflunine in a third- or later-line post-ICI setting, and the therapeutic benefit may be considerably higher than demonstrated in previous studies.

Background: Immune checkpoint inhibitors (ICI) are standard of care in patients with metastatic urothelial carcinoma (mUC) ineligible for cisplatin, and as second-line therapy after platinum-based chemotherapy. To date, few data exist about the efficacy of the former second-line chemotherapeutic agent vinflunine after the failure of sequential platinum-based chemotherapy and ICI treatment. The aim of this analysis was to examine the efficacy of vinflunine in a post-ICI third- or later-line setting. Methods: In this retrospective German multicenter study, data of mUC patients treated with vinflunine were reviewed in six centers between February 2010 and December 2021. All of the 105 included patients had radiologic progression after first-line platinum-based chemotherapy. The objective was to describe the efficacy of vinflunine in terms of overall response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and progression-free survival (PFS) for post-ICI and ICI-naïve patients, respectively. Results: In our cohort, 61 patients (58.1%) had preceding immunotherapy before vinflunine administration, and 44 patients (41.9%) were ICI-naïve. Patients with ICI pretreatment showed an ORR of 22.4% compared to 15.6% within ICI-naïve patients (p = 0.451), and CBR was 51.0% vs. 25.0% (p = 0.020), respectively. Post-ICI patients showed longer OS (8.78 vs. 5.72 months; p = 0.467) and longer PFS (3.09 vs. 2.14 months; p = 0.105). Conclusion: This analysis supports the sequential use of vinflunine in post-ICI patients since the vinca-alkaloid retains a measurable clinical activity in these heavily pretreated patients. The therapeutic benefit may be higher than demonstrated in previous studies.

• bladder cancer
• chemotherapy
• immune checkpoint inhibition
• immunotherapy
• metastatic urothelial carcinoma
• vinflunine

Background: Pembrolizumab is approved for patients with metastatic urothelial carcinoma (UC) who progressed under platinum therapy. The aim of this study was to assess the efficacy and safety of pembrolizumab in a cohort of real-life UC patients. Methods: This retrospective, observational study included advanced UC patients treated with pembrolizumab in a single institution in France. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS) at 6 months. Secondary endpoints were objective response rate (ORR), duration of response (DOR), disease control rate (DCR) and safety. Results: 78 patients were included in the study. The median OS was 7.3 months (3.8–12.2). The estimated OS rate at 6 months was 61.5% (50.5–72.6). The median PFS was 3.1 months (1.4–7.2). The estimated PFS rate at 6 months was 42.3% (31.1–53.5). The best ORR was 35.9%. The mean DOR was 95.5 days. The DCR was 30.8%. The most common treatment-related adverse events (AEs) of any grade were fatigue (46.2%), diarrhea (11.5%), pruritus (10.3%) and nausea (9.0%). There were no grade 3 AEs that occurred with an incidence of 5% or more. Conclusion: Our results confirmed those of randomized clinical trials concerning the treatment with pembrolizumab in patients with advanced UC that progressed after platinum-based chemotherapy.

• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Carcinoma, Transitional Cell/drug therapy
• Carcinoma, Transitional Cell/pathology
• Humans
• Retrospective Studies
• Urinary Bladder Neoplasms/drug therapy

Classical mathematical models of tumor growth have shaped our understanding of cancer and have broad practical implications for treatment scheduling and dosage. However, even the simplest textbook models have been barely validated in real world-data of human patients. In this study, we fitted a range of differential equation models to tumor volume measurements of patients undergoing chemotherapy or cancer immunotherapy for solid tumors. We used a large dataset of 1472 patients with three or more measurements per target lesion, of which 652 patients had six or more data points. We show that the early treatment response shows only moderate correlation with the final treatment response, demonstrating the need for nuanced models. We then perform a head-to-head comparison of six classical models which are widely used in the field: the Exponential, Logistic, Classic Bertalanffy, General Bertalanffy, Classic Gompertz and General Gompertz model. Several models provide a good fit to tumor volume measurements, with the Gompertz model providing the best balance between goodness of fit and number of parameters. Similarly, when fitting to early treatment data, the general Bertalanffy and Gompertz models yield the lowest mean absolute error to forecasted data, indicating that these models could potentially be effective at predicting treatment outcome. In summary, we provide a quantitative benchmark for classical textbook models and state-of-the art models of human tumor growth. We publicly release an anonymized version of our original data, providing the first benchmark set of human tumor growth data for evaluation of mathematical models.

Mathematical oncology uses quantitative models for prediction of tumor growth and treatment response. The theoretical foundation of mathematical oncology is provided by six classical mathematical models: the Exponential, Logistic, Classic Bertalanffy, General Bertalanffy, Classic Gompertz and General Gompertz model. These models have been introduced decades ago, have been used in thousands of scientific articles and are part of textbooks and curricula in mathematical oncology. However, these models have not been systematically tested in clinical data from actual patients. In this study, we have collected quantitative tumor volume measurements from thousands of patients in five large clinical trials of cancer immunotherapy. We use this dataset to systematically investigate how accurately mathematical models can describe tumor growth, showing that there are pronounced differences between models. In addition, we show that two of these models can predict tumor response to immunotherapy and chemotherapy at later time points when trained on early tumor growth dynamics. Thus, our article closes a conceptual gap in the literature and at the same time provides a simple tool to predict response to chemotherapy and immunotherapy on the level of individual patients.

• Immune checkpoint inhibitor
• Immunotherapy
• Prostate cancer
• Renal cell carcinoma
• Retreatment
• Urothelial carcinoma

• ICI
• PD-1
• PD-L1
• adjuvant therapy
• chemotherapy
• urothelial carcinoma

• Gallium-67
• Immune checkpoint inhibitor
• Immuno-oncology
• Pseudoprogression
• SPECT/CT
• ‘Hot’ & ‘cold’ tumor

• immunotherapy
• melanoma
• pseudotumor

The treatment scenario of metastatic renal cell carcinoma has drastically changed in recent years, with the advent of immunotherapy. Since 2015 immune-checkpoint inhibitors, either alone or in combination with other compounds, are constantly enriching the treatment scenario, with a drastic change of patients’ outcomes. The benefit from immunotherapy is difficult to capture with the currently available assessment radiological criteria. Often, with rhe use of immunotherapy, we can observe atypical patterns of response, such as hyperprogression or pseudoprogression. Pseudoprogression consists of an initial increase in tumor burden followed by a response to therapy, while hyperprogression is defined as a tumor growth rate that was at least 2-fold greater in patients with disease progression during immunotherapy. We performed a retrospective monocentric study to explore the impact of tumor growth rate change after immunotherapy administration as second or later line of treatment in patients with metastatic renal cell carcinoma.

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.

• RCC
• RECIST
• TGR
• immunotherapy
• nivolumab
• renal cell carcinoma
• tumor growth rate

Immunotherapy, which takes advantage of the immune system to eliminate cancer cells, has been widely studied and applied in oncology. Immune checkpoint inhibitors (ICIs) prevent the immune system from being turned off before cancer cells are eliminated. They have proven to be among the most promising and effective immunotherapies, with significant survival benefits and durable responses in diverse tumor types. However, an increasing number of retrospective studies have found that some patients treated with ICIs experience unusual responses, including accelerated proliferation of tumor cells and rapid progression of the disease, with poor outcomes. Such unexpected adverse events are termed hyperprogressive disease (HPD), and their occurrence suggests that ICIs are detrimental to a subset of cancer patients. HPD is common, with an incidence ranging between 4 and 29% in several cancer types. However, the mechanisms of HPD remain poorly understood, and no clinical predictive factors of HPD have been identified. In this review, we summarize current findings, including retrospective studies and case reports, and focus on several key issues including the defining characteristics, predictive biomarkers, potential mechanisms of HPD, and strategies for avoiding HPD after ICI treatment.

• hyperprogressive disease
• immune checkpoint inhibitors
• immunotherapy
• predictive biomarker
• pseudoprogression

• brain metastases
• combination
• immune checkpoint inhibitors
• radiotherapy
• renal cell carcinoma
• treatment resistance
• tumor immune microenvironment
• tyrosine kinase inhibitor

• Brain Neoplasms/immunology
• Brain Neoplasms/therapy
• Carcinoma, Renal Cell/pathology
• Humans
• Immunosuppression Therapy
• Immunotherapy
• Kidney Neoplasms/pathology
• Tumor Microenvironment

• anti-angiogenesis
• case report
• immune checkpoint inhibitor
• immune-related pneumonitis
• pseudoprogression
• urothelial carcinoma

• ATTRACTION-2
• Gastric or gastroesophageal junction cancer
• Long-term efficacy
• Nivolumab
• Treatment beyond progression

To evaluate the radiological tumor response patterns and compare the response assessments based on immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST 1.1 in metastatic clear-cell renal cell carcinoma (mccRCC) patients treated with programmed cell death-1 (PD-1) inhibitors.

All mccRCC patients treated with PD-1 inhibitors at Henan Cancer Hospital, China, between January 2018 and April 2019, were retrospectively studied. A total of 30 mccRCC patients (20 males and 10 females; mean age, 55.6 years; age range, 37–79 years) were analyzed. The target lesions were quantified on consecutive CT scans during therapy using iRECIST and RECIST 1.1. The tumor growth rate was calculated before and after therapy initiation. The response patterns were analyzed, and the differences in tumor response assessments of the two criteria were compared. The intra- and inter-observer variabilities of iRECIST and RECIST 1.1 were also analyzed.

The objective response rate throughout therapy was 50% (95% confidence interval [CI]: 32.1–67.9) based on iRECIST and 30% (95% CI: 13.6–46.4) based on RECIST 1.1. The time-to-progression (TTP) based on iRECIST was longer than that based on RECIST 1.1 (median TTP: not reached vs. 170 days, p = 0.04). iRECIST and RECIST 1.1 were discordant in 8 cases, which were evaluated as immune-unconfirmed PD based on iRECIST and PD based on RECIST 1.1. Six patients (20%, 6/30) had pseudoprogression based on iRECIST, of which four demonstrated early pseudoprogression and two had delayed pseudoprogression. Significant differences in the tumor response assessments based on the two criteria were observed (p < 0.001). No patients demonstrated hyperprogression during the study period.

Our study confirmed that the iRECIST criteria are more capable of capturing immune-related atypical responses during immunotherapy, whereas conventional RECIST 1.1 may underestimate the benefit of PD-1 inhibitors. Pseudoprogression is not rare in mccRCC patients during PD-1 inhibitor therapy, and it may last for more than the recommended maximum of 8 weeks, indicating a limitation of the current strategy for immune response monitoring.

• Clear cell renal cell carcinoma
• Immune-checkpoint inhibitor
• PD-1
• Tumor response
• iRECIST criteria

• adjuvant
• immunotherapy
• muscle-infiltrating bladder cancer (MIBC)
• neoadjuvant
• predictive biomarkers

Bladder cancer (BC) is the 10th most common cancer worldwide. Approximately one quarter of patients with BC have muscle-invasive disease (MIBC). Muscle-invasive disease carries a poor prognosis and choosing the optimal treatment option is critical to improve patients’ outcomes. Ongoing research supports the role of 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18F-FDG PET) in guiding patient-specific management decisions throughout the course of MIBC. As an imaging modality, 18F-FDG PET is acquired simultaneously with either computed tomography (CT) or MRI to offer a hybrid approach combining anatomical and metabolic information that complement each other. At initial staging, 18F-FDG PET/CT enhances the detection of extravesical disease, particularly in patients classified as oligometastatic by conventional imaging. 18F-FDG PET/CT has value in monitoring response to neoadjuvant and systemic chemotherapy, as well as in localizing relapse after treatment. In the new era of immunotherapy, 18F-FDG PET/CT may also be useful to monitor treatment efficacy as well as to detect immune-related adverse events. With the advent of artificial intelligence techniques such as radiomics and deep learning, these hybrid medical images can be mined for quantitative data, providing incremental value over current standard-of-care clinical and biological data. This approach has the potential to produce a major paradigm shift toward data-driven precision medicine with the ultimate goal of personalized medicine. In this review, we highlight current literature reporting the role of 18F-FDG PET in supporting personalized management decisions for patients with MIBC. Specific topics reviewed include the incremental value of 18F-FDG PET in prognostication, pre-operative planning, response assessment, prediction of recurrence, and diagnosing drug toxicity.

• PET – Positron Emission Tomography
• bladder cancer
• immunotherapy
• muscle invasive bladder cancer
• staging

Brain metastasis (BM) is generally one of poor prognostic factors in patients with advanced renal cell carcinoma. However, because of longer control of extra-cranial disease by the recent introduction of molecular target therapy and immune checkpoint inhibitor, the incidence of BM has been recently increasing and to progress the treatment of BM is one of urgent medical unmet needs. Although the pivotal clinical trials usually excluded patients with BM, BM subgroup data from the prospective and retrospective series have been gradually accumulated. To select the appropriate strategy, individual patient and tumor characteristics (e.g., Karnofsky Performance Status (KPS), systemic cancer burden, the number/size/location of BM) are important information. Among the local treatments, the technology of stereotactic radiosurgery (SRT) has been especially advanced and its adaptation has been expanded. The combination of SRT with molecular target therapy and/or immune checkpoint inhibitor would be promising to further enhance the efficacy without increased toxicity.

In patients with renal cell carcinoma, brain metastasis is generally one of the poor prognostic factors. However, the recent introduction of molecular target therapy and immune checkpoint inhibitor has remarkably advanced the systemic treatment of metastatic renal cell carcinoma and prolonged the patients’ survival. The pivotal clinical trials of those agents usually excluded patients with brain metastasis. The incidence of brain metastasis has been increasing in the actual clinical setting because of longer control of extra-cranial disease. Brain metastasis subgroup data from the prospective and retrospective series have been gradually accumulated about the risk classification of brain metastasis and the efficacy and safety of those new agents for brain metastasis. While the local treatment against brain metastasis includes neurosurgery, stereotactic radiosurgery, and conventional whole brain radiation therapy, the technology of stereotactic radiosurgery has been especially advanced, and the combination with systemic therapy such as molecular target therapy and immune checkpoint inhibitor is considered promising. This review summarizes recent progression of multimodality treatment of brain metastasis of renal cell carcinoma from literature data and explores the future direction of the treatment.

• brain metastasis
• immune checkpoint inhibitor (ICI), whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), prognosis
• renal cell carcinoma
• review
• targeted therapy

The functions of, and interactions between, the innate and adaptive immune systems are vital for anticancer immunity. Cytotoxic T cells expressing cell-surface CD8 are the most powerful effectors in the anticancer immune response and form the backbone of current successful cancer immunotherapies. Immune-checkpoint inhibitors are designed to target immune-inhibitory receptors that function to regulate the immune response, whereas adoptive cell-transfer therapies use CD8⁺ T cells with genetically modified receptors—chimaeric antigen receptors—to specify and enhance CD8⁺ T-cell functionality. New generations of cytotoxic T cells with genetically modified or synthetic receptors are being developed and evaluated in clinical trials. Furthermore, combinatory regimens might optimise treatment effects and reduce adverse events. This review summarises advances in research on the most prominent immune effectors in cancer and cancer immunotherapy, cytotoxic T cells, and discusses possible implications for future cancer treatment.

• Cost-utility analyses
• atezolizumab
• health technology assessments
• immunotherapy
• metastatic bladder cancer

• Antibodies, Monoclonal, Humanized/economics
• Antibodies, Monoclonal, Humanized/pharmacology
• Antibodies, Monoclonal, Humanized/therapeutic use
• Cost-Benefit Analysis
• Disease Progression
• Female
• Humans
• Male
• Neoplasm Metastasis
• Progression-Free Survival
• Urinary Bladder Neoplasms/drug therapy
• Urinary Bladder Neoplasms/economics
• Urinary Bladder Neoplasms/mortality
• Urinary Bladder Neoplasms/secondary

• Carcinoma, transitional cell
• Drug therapy
• Immunotherapy
• Therapeutics

• Antineoplastic Agents, Immunological/adverse effects
• Carcinoma, Transitional Cell/drug therapy
• Cisplatin
• Humans
• Urinary Bladder Neoplasms/drug therapy

Following the administration of immune checkpoint inhibitors, an unexpected pattern of response designated as hyperprogression may be observed in certain patients. This paradoxical response corresponds to an acceleration in tumor growth and a dramatic decrease of patient survival. The reported incidence rates of hyperprogressive disease are highly variable, ranging between 4 and 29%. In this review, we have performed a literature search on hyperprogressive disease, including both retrospective studies and case reports, and discuss potential predictive biomarkers as well as potential mechanisms associated with immune-checkpoint inhibitor associated hyperprogression.

• hyperprogressive disease
• immune checkpoint inhibitors
• predictive factors
• solid tumor
• tumor growth

• bladder cancer
• predictive markers

• B7-H1 Antigen
• Genomics
• Humans
• Lymphocytes
• Neutrophils
• Precision Medicine
• Prognosis
• Programmed Cell Death 1 Receptor
• Retrospective Studies