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3 pages, 183 KiB

Open AccessEditorial

Advances in Lung Cancer Imaging and Therapy

by Egesta Lopci and Silvia Morbelli

Cancers 2022, 14(1), 58; https://doi.org/10.3390/cancers14010058 - 23 Dec 2021

Viewed by 2293

Abstract

This series of eight papers (five original articles, two reviews and one meta-analysis) is presented by international leaders covering various aspects of lung cancer management, starting with diagnostic imaging and analyzing the novel perspectives of therapy [...] Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

Research

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12 pages, 2523 KiB

Open AccessArticle

Blinded Independent Central Review (BICR) in New Therapeutic Lung Cancer Trials

by Hubert Beaumont, Antoine Iannessi, Yi Wang, Charles M. Voyton, Jennifer Cillario and Yan Liu

Cancers 2021, 13(18), 4533; https://doi.org/10.3390/cancers13184533 - 9 Sep 2021

Cited by 6 | Viewed by 2947

Abstract

Background: Double reads in blinded independent central reviews (BICRs) are recommended to control the quality of trials but they are prone to discordances. We analyzed inter-reader discordances in a pool of lung cancer trials using RECIST 1.1. Methods: We analyzed six lung cancer [...] Read more.

Background: Double reads in blinded independent central reviews (BICRs) are recommended to control the quality of trials but they are prone to discordances. We analyzed inter-reader discordances in a pool of lung cancer trials using RECIST 1.1. Methods: We analyzed six lung cancer BICR trials that included 1833 patients (10,684 time points) involving 17 radiologists. We analyzed the rate of discrepancy of each trial at the time-point and patient levels as well as testing inter-trial differences. The analysis of adjudication made it possible to compute the readers’ endorsement rates, the root causes of adjudications, and the proportions of “errors” versus “medically justifiable differences”. Results: The trials had significantly different discrepancy rates both at the time-point (average = 34.3%) and patient (average = 59.2%) levels. When considering only discrepancies for progressive disease, homogeneous discrepancy rates were found with an average of 32.9%, while readers’ endorsement rates ranged between 27.7% and 77.8%. Major causes of adjudication were different per trial, with medically justifiable differences being the most common, triggering 74.2% of total adjudications. Conclusions: We provide baseline performances for monitoring reader performance in trials with double reads. Intelligent reading system implementation along with appropriate reader training and monitoring are solutions that could mitigate a large portion of the commonly encountered reading errors. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

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15 pages, 934 KiB

Open AccessArticle

The Role of the Immune Metabolic Prognostic Index in Patients with Non-Small Cell Lung Cancer (NSCLC) in Radiological Progression during Treatment with Nivolumab

by Matteo Bauckneht, Carlo Genova, Giovanni Rossi, Erika Rijavec, Maria Giovanna Dal Bello, Giulia Ferrarazzo, Marco Tagliamento, Maria Isabella Donegani, Federica Biello, Silvia Chiola, Lodovica Zullo, Stefano Raffa, Francesco Lanfranchi, Giuseppe Cittadini, Cecilia Marini, Egesta Lopci, Gianmario Sambuceti, Francesco Grossi and Silvia Morbelli

Cancers 2021, 13(13), 3117; https://doi.org/10.3390/cancers13133117 - 22 Jun 2021

Cited by 17 | Viewed by 3896

Abstract

An emerging clinical need is represented by identifying reliable biomarkers able to discriminate between responders and non-responders among patients showing imaging progression during the administration of immune checkpoints inhibitors for advanced non-small cell lung cancer (NSCLC). In the present study, we analyzed the [...] Read more.

An emerging clinical need is represented by identifying reliable biomarkers able to discriminate between responders and non-responders among patients showing imaging progression during the administration of immune checkpoints inhibitors for advanced non-small cell lung cancer (NSCLC). In the present study, we analyzed the prognostic power of peripheral-blood systemic inflammation indexes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this clinical setting. In 45 patients showing radiological progression (defined as RECIST 1.1 progressive disease) during Nivolumab administration, the following lab and imaging parameters were collected: neutrophil-to-lymphocyte ratio (NLR), derived-NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), systemic inflammation index (SII), maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). MTV and SII independently predicted OS. Their combination in the immune metabolic prognostic index (IMPI) allowed the identification of patients who might benefit from immunotherapy continuation, despite radiological progression. The combination of FDG PET/CT volumetric data with SII also approximates the immune-metabolic response with respect to baseline, providing additional independent prognostic insights. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden, and their combination might disclose the radiological progression in NSCLC patients receiving Nivolumab. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

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11 pages, 1356 KiB

Open AccessArticle

Whole-Lesion Apparent Diffusion Coefficient Histogram Analysis: Significance for Discriminating Lung Cancer from Pulmonary Abscess and Mycobacterial Infection

by Katsuo Usuda, Shun Iwai, Aika Yamagata, Yoshihito Iijima, Nozomu Motono, Munetaka Matoba, Mariko Doai, Keiya Hirata and Hidetaka Uramoto

Cancers 2021, 13(11), 2720; https://doi.org/10.3390/cancers13112720 - 31 May 2021

Cited by 6 | Viewed by 2457

Abstract

Diffusion-weighted magnetic resonance imaging (DWI) can differentiate malignant from benign pulmonary nodules. However, it is difficult to differentiate pulmonary abscesses and mycobacterial infections (PAMIs) from lung cancers because PAMIs show restricted diffusion in DWI. The study purpose is to establish the role of [...] Read more.

Diffusion-weighted magnetic resonance imaging (DWI) can differentiate malignant from benign pulmonary nodules. However, it is difficult to differentiate pulmonary abscesses and mycobacterial infections (PAMIs) from lung cancers because PAMIs show restricted diffusion in DWI. The study purpose is to establish the role of ADC histogram for differentiating lung cancer from PAMI. There were 41 lung cancers (25 adenocarcinomas, 16 squamous cell carcinomas), and 19 PAMIs (9 pulmonary abscesses, 10 mycobacterial infections). Parameters more than 60% of the area under the ROC curve (AUC) were ADC, maximal ADC, mean ADC, median ADC, most frequency ADC, kurtosis of ADC, and volume of lesion. There were significant differences between lung cancer and PAMI in ADC, mean ADC, median ADC, and most frequency ADC. The ADC (1.19 ± 0.29 × 10⁻³ mm²/s) of lung cancer obtained from a single slice was significantly lower than that (1.44 ± 0.54) of PAMI (p = 0.0262). In contrast, mean, median, or most frequency ADC of lung cancer which was obtained in the ADC histogram was significantly higher than the value of each parameter of PAMI. ADC histogram could discriminate PAMIs from lung cancers by showing that AUCs of several parameters were more than 60%, and that several parameters of ADC of PAMI were significantly lower than those of lung cancer. ADC histogram has the potential to be a valuable tool to differentiate PAMI from lung cancer. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

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16 pages, 4005 KiB

Open AccessArticle

Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer

by Francesco Fiorica, Umberto Tebano, Milena Gabbani, Mariasole Perrone, Sonia Missiroli, Massimiliano Berretta, Jacopo Giuliani, Andrea Bonetti, Andrea Remo, Eva Pigozzi, Andrea Tontini, Giuseppe Napoli, Nicoletta Luca, Daniela Grigolato, Paolo Pinton and Carlotta Giorgi

Cancers 2021, 13(10), 2352; https://doi.org/10.3390/cancers13102352 - 13 May 2021

Cited by 16 | Viewed by 2779

Abstract

Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this [...] Read more.

Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88; p = 0.0003) and 0.85 (95% CI 0.78–0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87; p = 0.0005) and RR 0.82 (95% CI 0.67–0.99; p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

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11 pages, 1177 KiB

Open AccessArticle

Metabolic Parameters as Biomarkers of Response to Immunotherapy and Prognosis in Non-Small Cell Lung Cancer (NSCLC): A Real World Experience

by Lavinia Monaco, Maria Gemelli, Irene Gotuzzo, Matteo Bauckneht, Cinzia Crivellaro, Carlo Genova, Diego Cortinovis, Lodovica Zullo, Luca Carlofrancesco Ammoni, Davide Paolo Bernasconi, Giovanni Rossi, Silvia Morbelli and Luca Guerra

Cancers 2021, 13(7), 1634; https://doi.org/10.3390/cancers13071634 - 1 Apr 2021

Cited by 22 | Viewed by 2911

Abstract

Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do [...] Read more.

Immune-checkpoint inhibitors (ICIs) have been proven to have great efficacy in non-small cell lung cancer (NSCLC) as single agents or in combination therapy, being capable to induce deep and durable remission. However, severe adverse events may occur and about 40% of patients do not benefit from the treatment. Predictive factors of response to ICIs are needed in order to customize treatment. The aim of this study is to evaluate the correlation between quantitative positron emission tomography (PET) parameters defined before starting ICI therapy and responses to treatment and patient outcome. We retrospectively analyzed 92 NSCLC patients treated with nivolumab, pembrolizumab or atezolizumab. Basal PET/computed tomography (CT) scan parameters (whole-body metabolic tumor volume—wMTV, total lesion glycolysis—wTLG, higher standardized uptake volume maximum and mean—SUVmax and SUVmean) were calculated for each patient and correlated with outcomes. Patients who achieved disease control (complete response + partial response + stable disease) had significantly lower MTV median values than patients who had not (progressive disease) (77 vs. 160.2, p = 0.039). Furthermore, patients with MTV and TLG values lower than the median values had improved OS compared to patients with higher MTV and TLG (p = 0.03 and 0.05, respectively). No relation was found between the other parameters and outcome. In conclusion, baseline metabolic tumor burden, measured with MTV, might be an independent predictor of treatment response to ICI and a prognostic biomarker in NSCLC patients. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

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8 pages, 234 KiB

Open AccessArticle

Impact of Low-Dose Irradiation of the Lung and Heart on Toxicity and Pulmonary Function Parameters after Thoracic Radiotherapy

by Christina Schröder, André Buchali, Paul Windisch, Erwin Vu, Lucas Basler, Daniel R. Zwahlen and Robert Förster

Cancers 2021, 13(1), 22; https://doi.org/10.3390/cancers13010022 - 23 Dec 2020

Cited by 7 | Viewed by 1835

Abstract

Objective: To assess the impact of (low) dose irradiation to the lungs and heart on the incidence of pneumonitis and pulmonary function changes after thoracic radiotherapy (RT). Methods/Material: Data of 62 patients treated with curative thoracic radiotherapy were analyzed. Toxicity data and pulmonary [...] Read more.

Objective: To assess the impact of (low) dose irradiation to the lungs and heart on the incidence of pneumonitis and pulmonary function changes after thoracic radiotherapy (RT). Methods/Material: Data of 62 patients treated with curative thoracic radiotherapy were analyzed. Toxicity data and pulmonary function tests (PFTs) were obtained before RT and at 6 weeks, at 12 weeks, and at 6 months after RT. PFTs included ventilation (e.g., vital capacity) and diffusion parameters (e.g., diffusion capacity for carbon monoxide (DL_CO)). Dosimetric data of the lung and heart were extracted to assess the impact of dose on PFT changes and radiation pneumonitis (RP). Results: No statistically significant correlations between dose parameters and changes in ventilation parameters were found. There were statistically significant correlations between DL_CO and low-dose parameters of the lungs (V_5Gy–V_30Gy (%)) and irradiation of the heart during the follow-up up to 6 months after RT, as well as a temporary correlation of the V_60Gy (%) on the blood gas parameters at 12 weeks after RT. On multivariate analysis, both heart and lung parameters had a significant impact on DL_CO. There was no statistically significant influence of any patient or treatment-related (including dose parameters) factors on the incidence of ≥G2 pneumonitis. Conclusion: There seems to be a lasting impact of low dose irradiation to the lung as well as irradiation to the heart on the DL_CO after thoracic radiotherapy. No influence on RP was found in this analysis. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

14 pages, 1845 KiB

Open AccessArticle

Association of the Metabolic Score Using Baseline FDG-PET/CT and dNLR with Immunotherapy Outcomes in Advanced NSCLC Patients Treated with First-Line Pembrolizumab

by Romain-David Seban, Jean-Baptiste Assié, Etienne Giroux-Leprieur, Marie-Ange Massiani, Michael Soussan, Gérald Bonardel, Christos Chouaid, Margot Playe, Lucas Goldfarb, Boris Duchemann, Laura Mezquita, Nicolas Girard and Laurence Champion

Cancers 2020, 12(8), 2234; https://doi.org/10.3390/cancers12082234 - 10 Aug 2020

Cited by 31 | Viewed by 2757

Abstract

Background: We aimed to assess the clinical utility of a previously published score combining the total metabolic tumor volume (TMTV) on baseline FDG-PET/CT and pretreatment derived from the neutrophils to lymphocytes ratio (dNLR) for prognostication in NSCLC patients undergoing first-line immunotherapy (IT). [...] Read more.

Background: We aimed to assess the clinical utility of a previously published score combining the total metabolic tumor volume (TMTV) on baseline FDG-PET/CT and pretreatment derived from the neutrophils to lymphocytes ratio (dNLR) for prognostication in NSCLC patients undergoing first-line immunotherapy (IT). Methods: In this multicenter retrospective study, 63 advanced NSCLC patients with a PD-L1 tumor proportion score (TPS) ≥50%, who underwent FDG-PET/CT before first-line IT, treated from January 2017 to September 2019, were enrolled. Associations between this score and the progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and overall response rate (ORR) were evaluated. Results: The median (m) PFS and mOS were 7.7 (95% CI 4.9–10.6) and 12.1 (8.6–15.6) months, respectively, and DCR and ORR were 65% and 58%, respectively. mOS was 17.9 months (14.6 not reached) for the good group versus 13.8 (95%CI 8.4–18.9) and 6.6 (CI 2.0–11.2) months for the intermediate and poor groups, respectively. mPFS was 15.1 (95%CI 12.1–20.0) months for the good group versus 5.2 (1.9–8.5) and 1.9 (95%CI 1.3–2.5) months for the intermediate and poor groups, respectively. The poor prognosis group was associated with DCR and ORR (p < 0.05). Conclusions: The metabolic score combining TMTV on the baseline FDG-PET/CT scan and pretreatment dNLR was associated with the survival and response in a cohort of advanced NSCLC patients with ≥50% PD-L1 receiving frontline IT. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

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Review

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17 pages, 712 KiB

Open AccessEditor’s ChoiceReview

Non-Small-Cell Lung Cancer: New Rare Targets—New Targeted Therapies—State of The Art and Future Directions

by Katarzyna Stencel, Izabela Chmielewska, Janusz Milanowski and Rodryg Ramlau

Cancers 2021, 13(8), 1829; https://doi.org/10.3390/cancers13081829 - 12 Apr 2021

Cited by 16 | Viewed by 4234

Abstract

Lung cancer is the most common cause of cancer-related death worldwide, and the prognosis for stage IV remains poor. The presence of genetic alterations in tumor cells, such as EGFR and BRAF gene mutations, as well as ALK and ROS1 gene rearrangements, are [...] Read more.

Lung cancer is the most common cause of cancer-related death worldwide, and the prognosis for stage IV remains poor. The presence of genetic alterations in tumor cells, such as EGFR and BRAF gene mutations, as well as ALK and ROS1 gene rearrangements, are indications for targeted therapies. Many such treatments are already registered and used on a wide scale. In comparison to standard chemotherapy, they can prolong not only progression-free survival but also overall survival. Moreover, they are able to provide excellent quality of life and rapid improvement of cancer-related symptoms such as dyspnea, cough and pain. Recent years have witnessed great advances in both molecular diagnostics and new molecular therapies for non-small-cell lung cancer. This review presents new therapeutic targets in NSCLC, as well as drugs of which the activity against NTRK, RET, MET or HER2 gene alterations (including EGFR exon 20 insertions) has either been confirmed or is currently being evaluated. Although these particular genetic alterations in NSCLC are generally rare, each accounting for 1–2% of patients, in total about half of all patients have molecular alterations and may ultimately receive targeted therapies. Full article

(This article belongs to the Special Issue Advances in Lung Cancer Imaging and Therapy)

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