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Cancer Management in the Era of Immunotherapy

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 29584

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Dr. Egesta Lopci

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Guest Editor

Nuclear Medicine Unit, Humanitas Clinical and Research Hospital-IRCCS, Via Manzoni 56, 20089 Rozzano, 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,

A new era of cancer treatment has seen the light in the last decade, following the introduction of checkpoint inhibitors in clinical practice. Along the unprecedented results obtained in various cancer types, immunotherapy has unveiled new challenges and opportunities for all medical disciplines impicated in the process of patient management. From tumor microenvironment to mutational status, crossing by microbiota and host immune susceptibility, up to imaging response criteria, any predictive or prognostic factor to immunotherapy benefit has been investigated, and new parameters for positive outcome have been assessed. Beyond checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy has in parallel experienced a leap into FDA and EMA approval for B-cell lymphoma, bringing into evidence other immune-related adverse events related to immunotherapy. The next frontier relies on combination therapies, implementing “old” tools with “new” tricks in order to boost the best of anticancer mechanisms available, although sometimes at the expense of heavier side effects. Will the scientific community be able to overcome challenges and optimize cancer treatment? The future remains a mystery for anyone in this world, although proper acknowledgment of current standards of cancer management in the era of immunotherapy and an insight into perspectives of clinical research can be of help. The latter represent the aims of this Special Issue in the Journal of Clinical Medicine, focusing on “Cancer Management in the Era of Immunotherapy”.

Dr. Egesta Lopci
Guest Editor

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Keywords

immunotherapy
checkpoint inhibitors
CAR-T
combination therapy
radiotherapy
molecular imaging
response assessment

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Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 199 KiB

Open AccessEditorial

Meditating on Cancer Management at the Time of Immunotherapy

by Egesta Lopci

J. Clin. Med. 2022, 11(11), 3025; https://doi.org/10.3390/jcm11113025 - 27 May 2022

Viewed by 1263

Abstract

The introduction of checkpoint inhibitors in the last decade has prompted a new era in medical oncology and has opened the door to novel frontiers in cancer treatment [...] Full article

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

Research

Jump to: Editorial, Review

10 pages, 868 KiB

Open AccessArticle

Utility of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immune Inflammation Index as Prognostic, Predictive Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Nivolumab and Ipilimumab

by Koji Iinuma, Torai Enomoto, Kei Kawada, Shota Fujimoto, Takashi Ishida, Kimiaki Takagi, Shingo Nagai, Hiroki Ito, Makoto Kawase, Chie Nakai, Kota Kawase, Daiki Kato, Manabu Takai, Keita Nakane, Koji Kameyama and Takuya Koie

J. Clin. Med. 2021, 10(22), 5325; https://doi.org/10.3390/jcm10225325 - 16 Nov 2021

Cited by 30 | Viewed by 2382

Abstract

The aim of this study was to assess the utility of neutrophil-to-lymphocyte ratio (NLR), plate-let-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) as predictive biomarkers with oncological outcomes for metastatic renal cell carcinoma (mRCC) patients treated with nivolumab and ipilimumab (NIVO + IPI). We conducted a retrospective multicenter cohort study assessing patients with mRCC treated with NIVO + IPI at eight institutions in Japan. In this study, the follow-up period was median 14 months. The 1-year overall- and progression-free survival (PFS) rates were 89.1% and 63.1, respectively. The objective response rate (ORR) and disease control rate (DCR) were 41.9% and 81.4%, respectively. The 1-year PFS rates were 85.7% and 49.1% for NLR ≤ 2.8 and >2.8, respectively (p = 0.005), and 75.5% and 49.7% for PLR ≤ 215.6 and >215.6, respectively (p = 0.034). Regarding SII, the 1-year PFS rates were 90.0% and 54.8% when SII was ≤561.7 and >561.7, respectively (p = 0.023). Therefore, NLR, PLR, and SII levels in mRCC patients treated with NIVO + IPI may be useful in predicting oncological outcomes. Full article

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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15 pages, 1553 KiB

Open AccessArticle

Predictive Value of Baseline [18F]FDG PET/CT for Response to Systemic Therapy in Patients with Advanced Melanoma

by Virginia Liberini, Marco Rubatto, Riccardo Mimmo, Roberto Passera, Francesco Ceci, Paolo Fava, Luca Tonella, Giulia Polverari, Adriana Lesca, Marilena Bellò, Vincenzo Arena, Simone Ribero, Pietro Quaglino and Désirée Deandreis

J. Clin. Med. 2021, 10(21), 4994; https://doi.org/10.3390/jcm10214994 - 27 Oct 2021

Cited by 5 | Viewed by 1996

Abstract

Background/Aim: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. Materials and Methods: Forty four melanoma patients, who underwent [18F]FDG-PET/CT before first-line target therapy (28/44) or immunotherapy (16/44), were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared using the Mann–Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan–Meier analysis. Results: Median (IQR) MTVwb and TLGwb were 13.1 mL and 72.4, respectively. Non-responder patients were 38/44, 26/28 and 12/16 at early evaluation, and 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target, and immunotherapy subgroup, respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p < 0.037) in the whole-cohort and target subgroup and MTVwb and TLGwb (all p < 0.022) in target subgroup. No significant differences were found for the immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversially, MTVlfn, TLGlfn, MTVsoft + lfn, TLGsoft + lfn, MTVwb and TLGwb were significantly associated (all p < 0.05) with OS in both the whole-cohort and target therapy subgroup. Conclusions: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS. Full article

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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12 pages, 2123 KiB

Open AccessArticle

Impact of Antibiotic Therapy and Metabolic Parameters in Non-Small Cell Lung Cancer Patients Receiving Checkpoint Inhibitors

by Angelo Castello, Sabrina Rossi, Luca Toschi and Egesta Lopci

J. Clin. Med. 2021, 10(6), 1251; https://doi.org/10.3390/jcm10061251 - 17 Mar 2021

Cited by 26 | Viewed by 2882

Abstract

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

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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13 pages, 8765 KiB

Open AccessArticle

The Clinical and Histopathological Features of Cutaneous Immune-Related Adverse Events and Their Outcomes

by Hiroki Hashimoto, Takamichi Ito, Toshio Ichiki, Yuichi Yamada, Yoshinao Oda and Masutaka Furue

J. Clin. Med. 2021, 10(4), 728; https://doi.org/10.3390/jcm10040728 - 12 Feb 2021

Cited by 9 | Viewed by 2964

Abstract

Immune checkpoint inhibitors (ICIs) cause a variety of inflammatory eruptions. The understanding of ICI-induced inflammatory eruptions with detailed histopathological findings is not adequate, particularly in Asian populations. In this study, we retrospectively reviewed 51 patients who were histopathologically diagnosed with cutaneous immune-related adverse events (irAEs) following ICI therapy between 2014 and 2020 at the Department of Dermatology of Kyushu University Hospital. Of the 51 patients (30 men, 21 women), maculopapular rash (38/51, 74.5%), erythema multiforme (2/51, 3.9%), lichenoid reaction (3/51, 5.9%), psoriasiform reaction (3/51, 5.9%), bullous pemphigoid (3/51, 5.9%), scleroderma-like reaction (1/51, 2.0%), and Stevens–Johnson syndrome (1/51, 2.0%) were observed. The clinical and histopathological findings of these eruptions were equivalent to typical cases of common drug eruptions. The onset of maculopapular rash was relatively early (more than half of events occurred within 1 month), whereas lichenoid reactions and autoimmune diseases occurred relatively late (4–8 months). With appropriate treatment and/or interruption of ICIs, most rashes improved (50/51, 98.0%). The ICI-induced inflammatory eruptions shared similar clinical and histopathological features with classical inflammatory eruptions, but a variety of inflammatory eruptions may occur with different degrees of severity. Dermatologists play an important role in providing specialized care for cutaneous irAEs. Full article

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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Review

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14 pages, 978 KiB

Open AccessReview

Neoadjuvant Chemo-Immunotherapy for Locally Advanced Non-Small-Cell Lung Cancer: A Review of the Literature

by Sara Franzi, Giovanni Mattioni, Erika Rijavec, Giorgio Alberto Croci and Davide Tosi

J. Clin. Med. 2022, 11(9), 2629; https://doi.org/10.3390/jcm11092629 - 7 May 2022

Cited by 12 | Viewed by 3513

Abstract

Non-small cell lung cancer accounts for approximately 80–85% of all lung cancers and at present represents the main cause of cancer death among both men and women. To date, surgery represents the cornerstone; nevertheless, around 40% of completely resected patients develop disease recurrence. Therefore, combining neoadjuvant chemo-immunotherapy and surgery might lead to improved survival. Immunotherapy is normally well tolerated, although significant adverse reactions have been reported in certain patients treated with inhibitors of immune checkpoints. In this review, we explore the current literature on the use of neoadjuvant chemo-immunotherapy followed by surgery for treatment of locally advanced non-small-cell lung cancer, with particular attention to the histological aspects, ongoing trials, and the most common surgical approaches. In conclusion, neoadjuvant immunotherapy whether combined or not with chemotherapy reveals a promising survival benefit for patients with advanced non-small-cell lung cancer; nevertheless, more data remain necessary to identify the best candidates for neoadjuvant regimens. Full article

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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15 pages, 843 KiB

Open AccessReview

The Role of Radiomics in the Era of Immune Checkpoint Inhibitors: A New Protagonist in the Jungle of Response Criteria

by Angelo Castello, Massimo Castellani, Luigia Florimonte, Luca Urso, Luigi Mansi and Egesta Lopci

J. Clin. Med. 2022, 11(6), 1740; https://doi.org/10.3390/jcm11061740 - 21 Mar 2022

Cited by 18 | Viewed by 3401

Abstract

Immune checkpoint inhibitors (ICI) have demonstrated encouraging results in terms of durable clinical benefit and survival in several malignancies. Nevertheless, the search to identify an “ideal” biomarker for predicting response to ICI is still far from over. Radiomics is a new translational field of study aiming to extract, by dedicated software, several features from a given medical image, ranging from intensity distribution and spatial heterogeneity to higher-order statistical parameters. Based on these premises, our review aims to summarize the current status of radiomics as a potential predictor of clinical response following immunotherapy treatment. A comprehensive search of PubMed results was conducted. All studies published in English up to and including December 2021 were selected, comprising those that explored computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) for radiomic analyses in the setting of ICI. Several studies have demonstrated the potential applicability of radiomic features in the monitoring of the therapeutic response beyond the traditional morphologic and metabolic criteria, as well as in the prediction of survival or non-invasive assessment of the tumor microenvironment. Nevertheless, important limitations emerge from our review in terms of standardization in feature selection, data sharing, and methods, as well as in external validation. Additionally, there is still need for prospective clinical trials to confirm the potential significant role of radiomics during immunotherapy. Full article

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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10 pages, 1599 KiB

Open AccessReview

Non-Small-Cell Lung Cancer Patients with Coexistence of High PD-L1 Expression and RET Fusion—Which Path Should We Follow? Case Reports and Literature Review

by Magdalena Knetki-Wróblewska, Kamila Wojas-Krawczyk, Dariusz M. Kowalski and Maciej Krzakowski

J. Clin. Med. 2022, 11(6), 1630; https://doi.org/10.3390/jcm11061630 - 15 Mar 2022

Cited by 5 | Viewed by 2445

Abstract

Pembrolizumab is widely used in first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC) with high PD-L1 expression. The activity of pembrolizumab in NSCLC patients with rare molecular alterations is poorly characterised. RET gene rearrangements are identified in 1–2% of lung cancer patients. Here, we present two cases of RET-rearranged NSCLC patients with high PD-L1 expression (>50%), treated with pembrolizumab within routine clinical practice. Pembrolizumab was ineffective in both cases—single-agent immunotherapy seems to be of limited value in this group of patients. Selective RET-inhibitors, if available, are the optimal treatment for patients with RET fusion nowadays. The best sequence of the therapy is still not defined. Full article

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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13 pages, 691 KiB

Open AccessReview

Checkpoint Inhibitors and the Gut

by Tuan Tran, Nguyen Giang Tien Tran and Vincent Ho

J. Clin. Med. 2022, 11(3), 824; https://doi.org/10.3390/jcm11030824 - 4 Feb 2022

Cited by 7 | Viewed by 2490

Abstract

Checkpoint inhibitors have revolutionized treatments in modern oncology, including many conditions previously relegated to palliative therapies only. However, emerging recognition of checkpoint inhibitor-related adverse events has complicated the status of checkpoint inhibitor-related therapies. This review article discusses gastrointestinal adverse events as a result [...] Read more.

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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22 pages, 13502 KiB

Open AccessReview

Immunotherapy Monitoring with Immune Checkpoint Inhibitors Based on [¹⁸F]FDG PET/CT in Metastatic Melanomas and Lung Cancer

by Egesta Lopci

J. Clin. Med. 2021, 10(21), 5160; https://doi.org/10.3390/jcm10215160 - 3 Nov 2021

Cited by 21 | Viewed by 4941

Abstract

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

(This article belongs to the Special Issue Cancer Management in the Era of Immunotherapy)

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