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Cancers
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PET/CT in Tumor Immunotherapy Assessment
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PET/CT in Tumor Immunotherapy Assessment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (27 October 2023) | Viewed by 17397

Special Issue Editor

Dr. Egesta Lopci

E-Mail Website
Guest Editor
Department of Nuclear Medicine, IRCCS Humanitas Research Hospital, 20089 Milan, Italy
Interests: molecular imaging; positron emission tomography; cancer imaging; immunotherapy; treatment response assessment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The role of diagnostic imaging in the management of patients with cancer is regarded as essential at all disease stages. The implementation of advanced imaging modalities, thanks to the technological progress that has been achieved, has facilitated the assessment of malignant lesions and their monitoring during the course of therapy. Positron emission tomography represents one of the pillars of molecular imaging in oncology, and has become a fundamental modality for response evaluation in several tumor types. Although more intensively debated than for other indications, PET/CT has also gained a role in tumor immunotherapy assessment. Of particular interest is the metabolic information obtained with [18F]FDG PET/CT at baseline (before the administration of immunomodulatory drugs) and during the course of treatment. At both time points, either solid tumors or malignant lymphomas must be investigated to obtain predictive imaging biomarkers and help optimize patient management. In this Issue we are also interested in immune-PET for immunotherapy assessment. The ability to non-invasively visualize the immune system or the expression of checkpoints with radiolabeled ligands opens the door to unprecedented applications for immune-PET.

Therefore, this Special Issue is dedicated to the role of PET/CT in the context of malignant tumors treated with immunotherapy.

Dr. Egesta Lopci
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • positron emission tomography
  • PET/CT
  • immune PET
  • immunotherapy
  • checkpoint inhibitors
  • CAR-T
  • immunomodulatory
  • combination therapy
  • molecular imaging
  • response assessment
  • tumor
  • lymphoma

Published Papers (9 papers)

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Research

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12 pages, 3185 KiB  
Article
Prognostic Value of Baseline 18F-FDG PET/CT to Predict Brain Metastasis Development in Melanoma Patients
by Forough Kalantari, Seyed Ali Mirshahvalad, Magdalena Hoellwerth, Gregor Schweighofer-Zwink, Ursula Huber-Schönauer, Wolfgang Hitzl, Gundula Rendl, Peter Koelblinger, Christian Pirich and Mohsen Beheshti
Cancers 2024, 16(1), 127; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16010127 - 26 Dec 2023
Viewed by 1655
Abstract
To investigate the value of 18F-FDG-PET/CT in predicting the occurrence of brain metastases in melanoma patients, in this retrospective study 201 consecutive patients with pathology-proven melanoma, between 2008 and 2021, were reviewed. Those who underwent 18F-FDG-PET/CT for initial staging were considered [...] Read more.
To investigate the value of 18F-FDG-PET/CT in predicting the occurrence of brain metastases in melanoma patients, in this retrospective study 201 consecutive patients with pathology-proven melanoma, between 2008 and 2021, were reviewed. Those who underwent 18F-FDG-PET/CT for initial staging were considered eligible. Baseline assessment included histopathology, 18F-FDG-PET/CT, and brain MRI. Also, all patients had serial follow-ups for diagnosing brain metastasis development. Baseline 18F-FDG-PET/CT parameters were analysed using competing risk regression models to analyze their correlation with the occurrence of brain metastases. Overall, 159 patients entered the study. The median follow-up was six years. Among clinical variables, the initial M-stage and TNM-stage were significantly correlated with brain metastasis. Regarding 18F-FDG-PET/CT parameters, regional metastatic lymph node uptake values, as well as prominent SULmax (pSULmax) and prominent SUVmean (pSUVmean), were significantly correlated with the outcome. Cumulative incidences were 10% (6.3–16%), 31% (24.4–38.9%), and 35.2% (28.5–43.5%) after 1, 5, and 10 years. There were significant correlations between pSULmax (p-value < 0.001) and pSULpeak (p-value < 0.001) and the occurrence of brain metastases. The higher these values, the sooner the patient developed brain metastases. Thus, baseline 18F-FDG-PET/CT may have the potential to predict brain metastasis in melanoma patients. Those with high total metabolic activity should undergo follow-up/complementary evaluations, such as brain MRI. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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15 pages, 4102 KiB  
Article
Increased Thyroidal Activity on Routine FDG-PET/CT after Combination Immune Checkpoint Inhibition: Temporal Associations with Clinical and Biochemical Thyroiditis
by Anna Galligan, Roslyn Wallace, Balasubramanian Krishnamurthy, Thomas W. H. Kay, Nirupa Sachithanandan, Cherie Chiang, Shahneen Sandhu, Rodney J. Hicks and Amir Iravani
Cancers 2023, 15(24), 5803; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15245803 - 11 Dec 2023
Cited by 1 | Viewed by 964
Abstract
Background: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. Methods: A retrospective [...] Read more.
Background: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. Methods: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. Results: At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3–32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%, p < 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4–98.0), kappa 0.83. Conclusion: Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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14 pages, 2600 KiB  
Article
Total Metabolic Tumor Volume on 18F-FDG PET/CT Is a Useful Prognostic Biomarker for Patients with Extensive Small-Cell Lung Cancer Undergoing First-Line Chemo-Immunotherapy
by Julia Grambow-Velilla, Romain-David Seban, Kader Chouahnia, Jean-Baptiste Assié, Laurence Champion, Nicolas Girard, Gerald Bonardel, Lise Matton, Michael Soussan, Christos Chouaïd and Boris Duchemann
Cancers 2023, 15(8), 2223; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15082223 - 10 Apr 2023
Viewed by 1516
Abstract
Background: We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy. Methods: In this multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: [...] Read more.
Background: We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy. Methods: In this multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: chemo-immunotherapy (CIT) versus chemotherapy alone (CT). All patients underwent baseline 18-FDG PET/CT before therapy between June 2016 and September 2021. We evaluated clinical, biological, and PET parameters, and used cutoffs from previously published studies or predictiveness curves to assess the association with progression-free survival (PFS) or overall survival (OS) with Cox prediction models. Results: Sixty-eight patients were included (CIT: CT) (36: 32 patients). The median PFS was 5.9:6.5 months, while the median OS was 12.1:9.8 months. dNLR (the derived neutrophils/(leucocytes-neutrophils) ratio) was an independent predictor of short PFS and OS in the two cohorts (p < 0.05). High total metabolic tumor volume (TMTVhigh if > 241 cm3) correlated with outcomes, but only in the CIT cohort (PFS for TMTVhigh in multivariable analysis: HR 2.5; 95%CI 1.1–5.9). Conclusion: Baseline 18F-FDG PET/CT using TMTV could help to predict worse outcomes for ES-SCLC patients undergoing first-line CIT. This suggests that baseline TMTV may be used to identify patients that are unlikely to benefit from CIT. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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Review

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16 pages, 322 KiB  
Review
The Era of Immunotherapy in Small-Cell Lung Cancer: More Shadows Than Light?
by Sabrina Rossi, Arianna Pagliaro, Angelica Michelini, Pierina Navarria, Elena Clerici, Davide Franceschini, Luca Toschi, Giovanna Finocchiaro, Marta Scorsetti and Armando Santoro
Cancers 2023, 15(24), 5761; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15245761 - 08 Dec 2023
Cited by 1 | Viewed by 1070
Abstract
Small-cell lung cancer is an extremely chemo-sensitive disease; the addition of immunotherapy to chemotherapy has demonstrated a slight clinical benefit in pivotal trials, even with a statistically significant difference in terms of survival outcomes when compared to chemotherapy alone. In this scenario, the [...] Read more.
Small-cell lung cancer is an extremely chemo-sensitive disease; the addition of immunotherapy to chemotherapy has demonstrated a slight clinical benefit in pivotal trials, even with a statistically significant difference in terms of survival outcomes when compared to chemotherapy alone. In this scenario, the role of radiotherapy as a consolidation treatment in thoracic disease or as a prophylactic therapy in the brain should be clarified. In addition, due to the frailty and the poor prognostic characteristics of these patients, the need for predictive biomarkers that could support the use of immunotherapy is crucial. PD-L1 and TMB are not actually considered definitive biomarkers due to the heterogeneity of results in the literature. A new molecular classification of small-cell lung cancer based on the expression of key transcription factors seems to clarify the disease behavior, but the knowledge of this molecular subtype is still insufficient and the application in clinical practice far from reality; this classification could lead to a better understanding of SCLC disease and could provide the right direction for more personalized treatment. The aim of this review is to investigate the current knowledge in this field, evaluating whether there are predictive biomarkers and clinical patient characteristics that could help us to identify those patients who are more likely to respond to immunotherapy. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
15 pages, 4209 KiB  
Review
Clinical Application of ImmunoPET Targeting Checkpoint Inhibitors
by Elisabetta Maria Abenavoli, Flavia Linguanti, Raffaella Calabretta, Roberto C. Delgado Bolton, Valentina Berti and Egesta Lopci
Cancers 2023, 15(23), 5675; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15235675 - 30 Nov 2023
Cited by 2 | Viewed by 876
Abstract
In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. However, not all patients benefit from ICI therapy and some are at risk of developing [...] Read more.
In the last decade, monoclonal antibodies (mAbs) targeting CTLA-4, PD-1, or PD-L1 have been developed and immune checkpoint inhibitors (ICIs) have become the main approach in cancer immunotherapy. However, not all patients benefit from ICI therapy and some are at risk of developing treatment-induced side-effects. These aspects, in parallel with the imaging challenges related to response assessments during immunotherapy, have driven scientific research to the discovery of new predictive biomarkers to individualize patients who could benefit from ICIs. In this context, molecular imaging using PET (positron emission tomography), which allows for whole-body tumor visualization, may be a promising non-invasive method for the determination of patients’ sensitivity to antibody drugs. Several PET tracers, diverse from 2-[18F]FDG (or 2-Deoxy-2-[18F]fluoroglucose), have been developed to image immune checkpoints (ICs) or key elements of the immune system, although most of them are still in preclinical phases. Herein, we present the current state of the ImmunoPET-targeting of IC proteins with mAbs and antibody fragments, with a main focus on the latest developments in clinical molecular imaging studies of solid tumors. Moreover, given the relevance of the immune system and of tumor-infiltrating lymphocytes in particular in the prediction of the benefit of ICIs, we dedicate a portion of this review to ImmunoPET-targeting T cells. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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19 pages, 1342 KiB  
Review
PET/CT in Patients with Breast Cancer Treated with Immunotherapy
by Sofia C. Vaz, Stephanie L. Graff, Arlindo R. Ferreira, Márcio Debiasi and Lioe-Fee de Geus-Oei
Cancers 2023, 15(9), 2620; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15092620 - 05 May 2023
Viewed by 2410
Abstract
Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes [...] Read more.
Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes the studies supporting the use of immunotherapy in BC. Furthermore, the usefulness of 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) positron emission/computerized tomography (PET/CT) to image the tumor heterogeneity and to assess treatment response is explored, including the different criteria to interpret 2-[18F]FDG PET/CT imaging. The concept of immuno-PET is also described, by explaining the advantages of mapping treatment targets with a non-invasive and whole-body tool. Several radiopharmaceuticals in the preclinical phase are referred too, and, considering their promising results, translation to human studies is needed to support their use in clinical practice. Overall, this is an evolving field in BC treatment, despite PET imaging developments, the future trends also include expanding immunotherapy to early-stage BC and using other biomarkers. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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29 pages, 11357 KiB  
Review
FDG-PET/CT in the Monitoring of Lymphoma Immunotherapy Response: Current Status and Future Prospects
by Akram Al-Ibraheem, Ahmed Saad Abdlkadir, Malik E. Juweid, Kamal Al-Rabi, Mohammad Ma’koseh, Hikmat Abdel-Razeq and Asem Mansour
Cancers 2023, 15(4), 1063; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15041063 - 07 Feb 2023
Cited by 5 | Viewed by 3833
Abstract
Cancer immunotherapy has been extensively investigated in lymphoma over the last three decades. This new treatment modality is now established as a way to manage and maintain several stages and subtypes of lymphoma. The establishment of this novel therapy has necessitated the development [...] Read more.
Cancer immunotherapy has been extensively investigated in lymphoma over the last three decades. This new treatment modality is now established as a way to manage and maintain several stages and subtypes of lymphoma. The establishment of this novel therapy has necessitated the development of new imaging response criteria to evaluate and follow up with cancer patients. Several FDG PET/CT-based response criteria have emerged to address and encompass the various most commonly observed response patterns. Many of the proposed response criteria are currently being used to evaluate and predict responses. The purpose of this review is to address the efficacy and side effects of cancer immunotherapy and to correlate this with the proposed criteria and relevant patterns of FDG PET/CT in lymphoma immunotherapy as applicable. The latest updates and future prospects in lymphoma immunotherapy, as well as PET/CT potentials, will be discussed. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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14 pages, 783 KiB  
Review
Metabolic Imaging in B-Cell Lymphomas during CAR-T Cell Therapy
by Flavia Linguanti, Elisabetta Maria Abenavoli, Valentina Berti and Egesta Lopci
Cancers 2022, 14(19), 4700; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194700 - 27 Sep 2022
Cited by 6 | Viewed by 2375
Abstract
Chimeric antigen receptor–engineered (CAR) T cells are emerging powerful therapies for patients with refractory/relapsed B-cell lymphomas. [18F]FDG PET/CT plays a key role during staging and response assessment in patients with lymphoma; however, the evidence about its utility in CAR-T therapies for [...] Read more.
Chimeric antigen receptor–engineered (CAR) T cells are emerging powerful therapies for patients with refractory/relapsed B-cell lymphomas. [18F]FDG PET/CT plays a key role during staging and response assessment in patients with lymphoma; however, the evidence about its utility in CAR-T therapies for lymphomas is limited. This review article aims to provide an overview of the role of PET/CT during CAR-T cell therapy in B-cell lymphomas, focusing on the prognostic value of metabolic parameters, as well as on response assessment. Data from the literature report on the use of [18F]FDG PET/CT at the baseline with two scans performed before treatment started focused on the time of decision (TD) PET/CT and time of transfusion (TT) PET/CT. Metabolic tumor burden is the most studied parameter associated with disease progression and overall survival, making us able to predict the occurrence of adverse effects. Instead, for post-therapy evaluation, 1 month (M1) PET/CT seems the preferable time slot for response assessment and in this setting, the Deauville 5-point scale (DS), volumetric analyses, SUVmax, and its variation between different time points (∆SUVmax) have been evaluated, confirming the usefulness of M1 PET/CT, especially in the case of pseudoprogression. Additionally, an emerging role of PET/CT brain scans is reported for the evaluation of neurotoxicity related to CAR-T therapies. Overall, PET/CT results to be an accurate method in all phases of CAR-T treatment, with particular interest in assessing treatment response. Moreover, PET parameters have been reported to be reliable predictors of outcome and severe toxicity. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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Other

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21 pages, 4316 KiB  
Systematic Review
Diagnostic Performance of [18F]F-FDG Positron Emission Tomography (PET) in Non-Ophthalmic Malignant Melanoma: A Systematic Review and Meta-Analysis of More Than 10,000 Melanoma Patients
by Nazanin Zamani-Siahkali, Seyed Ali Mirshahvalad, Christian Pirich and Mohsen Beheshti
Cancers 2024, 16(1), 215; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16010215 - 02 Jan 2024
Viewed by 982
Abstract
We described the diagnostic performance of [18F]F-FDG-PET in malignant melanoma by conducting a comprehensive systematic review and meta-analysis of the existing literature. The study was designed following PRISMA-DTA. Original articles with adequate crude data for meta-analytic calculations that evaluated [18 [...] Read more.
We described the diagnostic performance of [18F]F-FDG-PET in malignant melanoma by conducting a comprehensive systematic review and meta-analysis of the existing literature. The study was designed following PRISMA-DTA. Original articles with adequate crude data for meta-analytic calculations that evaluated [18F]F-FDG-PET and compared it with a valid reference standard were considered eligible. The pooled measurements were calculated based on the data level (patient/lesion-based). Regarding sub-groups, diagnostic performances were calculated for local, regional and distant involvement. The bivariate model was employed to calculate sensitivity and specificity. The initial search resulted in 6678 studies. Finally, 100 entered the meta-analysis, containing 82 patient-based (10,403 patients) and 32 lesion-based (6188 lesions) datasets. At patient level, overall, [18F]F-FDG-PET had pooled sensitivity and specificity of 81% (95%CI: 73–87%) and 92% (95%CI: 90–94%), respectively. To detect regional lymph node metastasis, the pooled sensitivity and specificity were 56% (95%CI: 40–72%) and 97% (95%CI: 94–99%), respectively. To detect distant metastasis, they were 88% (95%CI: 81–93%) and 94% (95%CI: 91–96%), respectively. At lesion level, [18F]F-FDG-PET had a pooled sensitivity and specificity of 70% (95%CI: 57–80%) and 94% (95%CI: 88–97%), respectively. Thus, [18F]F-FDG-PET is a valuable diagnostic modality for melanoma assessment. It was accurate in various clinical scenarios. However, despite its high specificity, it showed low sensitivity in detecting regional lymph node metastasis and could not replace lymph node biopsy. Full article
(This article belongs to the Special Issue PET/CT in Tumor Immunotherapy Assessment)
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