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15 pages, 977 KiB

Open AccessArticle

Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs): Outcomes in a Multiethnic Urban Cohort

by Angelica D’Aiello, Juan Lin, Rasim Gucalp, Vafa Tabatabaie, Haiying Cheng, Noah A. Bloomgarden, Yaron Tomer and Balazs Halmos

Cancers 2021, 13(6), 1464; https://doi.org/10.3390/cancers13061464 - 23 Mar 2021

Cited by 12 | Viewed by 2456

Abstract

We sought to characterize thyroid dysfunction and its association with baseline clinical and demographic characteristics, as well as progression-free survival (PFS), in a multiethnic cohort of lung cancer patients treated with ICIs. A retrospective chart review of lung cancer patients receiving an anti-PD1 [...] Read more.

We sought to characterize thyroid dysfunction and its association with baseline clinical and demographic characteristics, as well as progression-free survival (PFS), in a multiethnic cohort of lung cancer patients treated with ICIs. A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent was performed. Multivariate Cox proportional hazards were fitted to compare time to thyroid dysfunction among race subgroups controlling for age, gender, treatment type, and duration. Thyroid dysfunction was based on laboratory testing; clinical symptoms were not required. PFS at a 24-week landmark analysis point among patients with and without thyroid dysfunction was compared using a log-rank test. We identified 205 subjects that received ICIs, including 76 (37.1%) who developed thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races (p = 0.92). Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction (p = 0.81 and p = 0.67, respectively). Thyrotoxicosis occurred at higher rates in Black (25, 31.6%) subjects than in White (7, 16.7%) and Hispanic (8, 12.7%) subjects when employing the log-rank test (p = 0.016) and multivariate Cox regression (HR 0.48, p = 0.09 for White and HR 0.36, p = 0.01 for Hispanic compared to Black subjects). PFS was similar among subjects with and without thyroid dysfunction when applying the log-rank test (p = 0.353). Gender, concurrent treatment with chemotherapy, and PFS were not associated with thyroid dysfunction in patients receiving ICIs; however, Black race was a risk factor for thyrotoxicosis. The mechanisms underlying the role of race in the development of irAEs warrant further study. Full article

(This article belongs to the Special Issue Thoracic Cancers)

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13 pages, 861 KiB

Open AccessArticle

A Matching-Adjusted Indirect Comparison of Pembrolizumab + Chemotherapy vs. Nivolumab + Ipilimumab as First-Line Therapies in Patients with PD-L1 TPS ≥1% Metastatic NSCLC

by Balazs Halmos, Thomas Burke, Chrysostomos Kalyvas, Ralph Insinga, Kristel Vandormael, Andrew Frederickson and Bilal Piperdi

Cancers 2020, 12(12), 3648; https://doi.org/10.3390/cancers12123648 - 04 Dec 2020

Cited by 15 | Viewed by 4667

Abstract

Background: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. Methods: An anchored matching-adjusted indirect [...] Read more.

Background: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. Methods: An anchored matching-adjusted indirect comparison (MAIC) was conducted using pooled individual patient data (IPD) from the ITT population in KEYNOTE-021G, KEYNOTE-189 and KEYNOTE-407 (n = 816) and published aggregate data of nivolumab + ipilimumab from CheckMate 227 Part 1A (n = 793). To adjust for cross-trial differences in baseline characteristics, data from KEYNOTE-021G/KEYNOTE-189/KEYNOTE-407 were re-weighted to match the baseline characteristics of CheckMate 227 Part 1A. Outcomes included OS, PFS and ORR. Base case analyses were restricted to patients with PD-L1 TPS ≥1%, with sub-group analyses in PD-L1 TPS ≥50% and 1–49%. Results: The estimated HR (95% CI) of pembrolizumab + chemotherapy vs nivolumab + ipilimumab was 0.80 (0.59,1.09) and 0.53 (0.41,0.68) for OS and PFS, respectively. For ORR, the estimated risk ratio was 1.8 (1.3,2.4) for pembrolizumab + chemotherapy vs nivolumab + ipilimumab and the risk difference was 25.5% (15.0,36.0). PD-L1 TPS ≥50% and 1–49% sub-groups showed an OS HR of 0.89 (0.58,1.36) and 0.68 (0.46,1.01), respectively. Conclusion: These MAIC results suggest that pembrolizumab + chemotherapy leads to a greater clinical benefit vs nivolumab + ipilimumab in patients with PD-L1 TPS ≥1% across multiple endpoints. Full article

(This article belongs to the Special Issue Thoracic Cancers)

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14 pages, 937 KiB

Open AccessFeature PaperArticle

Prognostic Factors and Long-Term Survival in Locally Advanced NSCLC with Pathological Complete Response after Surgical Resection Following Neoadjuvant Therapy

by Filippo Lococo, Carolina Sassorossi, Dania Nachira, Marco Chiappetta, Leonardo Petracca Ciavarella, Emanuele Vita, Luca Boldrini, Jessica Evangelista, Alfredo Cesario, Emilio Bria and Stefano Margaritora

Cancers 2020, 12(12), 3572; https://doi.org/10.3390/cancers12123572 - 30 Nov 2020

Cited by 8 | Viewed by 1725

Abstract

Background: Outcomes for locally advanced NSCLC with pathological complete response (pCR), i.e., pT0N0 after induction chemoradiotherapy (IT), have been seldom investigated. Herein, long-term results, in this highly selected group of patients, have been evaluated with the aim to identify prognostic predictive factors. Methods: [...] Read more.

Background: Outcomes for locally advanced NSCLC with pathological complete response (pCR), i.e., pT0N0 after induction chemoradiotherapy (IT), have been seldom investigated. Herein, long-term results, in this highly selected group of patients, have been evaluated with the aim to identify prognostic predictive factors. Methods: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent IT, possibly following surgery, from January 1992 to December 2019, were considered for this retrospective analysis. Survival rates and prognostic factors have been studied with Kaplan-Meier analysis, log-rank and Cox regression analysis. Results: Three-hundred and forty-three consecutive patients underwent IT in the considered period. Out of them, 279 were addressed to surgery; among them, pCR has been observed in 62 patients (18% of the total and 22% of the operated patients). In the pCR-group, clinical staging was IIb in 3 (5%) patients, IIIa in 28 (45%) patients and IIIb in 31 (50%). Surgery consisted of (bi)lobectomy in the majority of cases (80.7%), followed by pneumonectomy (19.3%). Adjuvant therapy was administered in 33 (53.2%) patients. Five-year overall survival and disease-free survival have been respectively 56.18% and 48.84%. The relative risk of death, observed with the Cox regression analysis, was 4.4 times higher (95% confidence interval (CI): 1.632–11.695, p = 0.03) for patients with N2 multi-station disease, 2.6 times higher (95% CI: 1.066–6.407, p = 0.036) for patients treated with pneumonectomy and 3 times higher (95% CI: 1.302–6.809, p = 0.01) for patients who did not receive adjuvant therapy. Conclusions: Rewarding long-term results could be expected in locally advanced NSCLC patients with pCR after IT followed by surgery. Baseline N2 single-station disease and adjuvant therapy after surgery seem to be associated with better prognosis, while pneumonectomy is associated with poorer outcomes. Full article

(This article belongs to the Special Issue Thoracic Cancers)

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9 pages, 1448 KiB

Open AccessArticle

Neurofilament Light Chain as A Biomarker for Brain Metastases

by Anne Winther-Larsen, Claus Vinter Bødker Hviid, Peter Meldgaard, Boe Sandahl Sorensen and Birgitte Sandfeld-Paulsen

Cancers 2020, 12(10), 2852; https://doi.org/10.3390/cancers12102852 - 02 Oct 2020

Cited by 18 | Viewed by 3577

Abstract

Background: Brain metastases are feared complications in cancer. Treatment by neurosurgical resection and stereotactic radiosurgery are only available when metastatic lesions are limited and early detection is warranted. The neurofilament light chain (NfL) is a sensitive neuron-specific biomarker released following neuronal decay. We [...] Read more.

Background: Brain metastases are feared complications in cancer. Treatment by neurosurgical resection and stereotactic radiosurgery are only available when metastatic lesions are limited and early detection is warranted. The neurofilament light chain (NfL) is a sensitive neuron-specific biomarker released following neuronal decay. We explored serum NfL as a biomarker of brain metastases. Methods: Serum was collected from 43 stage IV lung cancer patients with brain metastases and 25 stage I lung cancer patients. Serum was collected at time of cancer diagnosis and at time of brain metastasis diagnosis. In nine patients with brain metastases, additional samples were available between the two time points. NfL was quantified by Single Molecule Array (Simoa)™. Results: The median NfL level was significantly higher in patients with brain metastases than in patients without (35 versus 16 pg/mL, p = 0.001) and separated patients with an area under the curve of 0.77 (0.66–0.89). An increase in NfL could be measured median 3 months (range: 1–5) before the brain metastasis diagnosis. Further, a high level of NfL at time of brain metastasis diagnosis correlated with an inferior survival (hazard ratio: 2.10 (95% confidence interval: 1.11–3.98)). Conclusions: This study implies that NfL could be a potential biomarker of brain metastases. Full article

(This article belongs to the Special Issue Thoracic Cancers)

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12 pages, 680 KiB

Open AccessArticle

8th Edition Tumor, Node, and Metastasis T-Stage Prognosis Discrepancies: Solid Component Diameter Predicts Prognosis Better than Invasive Component Diameter

by Kazuhito Funai, Akikazu Kawase, Kiyomichi Mizuno, Shin Koyama and Norihiko Shiiya

Cancers 2020, 12(6), 1577; https://doi.org/10.3390/cancers12061577 - 15 Jun 2020

Cited by 2 | Viewed by 1769

Abstract

The biggest change in the 8th edition of the tumor, lymph node, and metastasis (TNM) classification is the recommendation of the solid component diameter and invasive size for determining the clinical and pathological T-factor, respectively. Here, we validated new proposals for the Lung [...] Read more.

The biggest change in the 8th edition of the tumor, lymph node, and metastasis (TNM) classification is the recommendation of the solid component diameter and invasive size for determining the clinical and pathological T-factor, respectively. Here, we validated new proposals for the Lung Cancer TNM classification’s revision and compared clinical and pathological T-stages. We retrospectively analyzed 177 cases of non-small cell lung cancers without lymph node metastasis, and involving complete resection, that occurred in our department between January 2017 and March 2019. We reviewed the overall tumor diameter, solid component diameter, and clinical T-factor on computed tomography (CT), and the pathological tumor diameter, pathological invasion diameter, pathological T-factor, and prognosis. The difference between the pathological invasive size and solid size on CT was within 5 mm in 99 cases (56%). At a two-year recurrence-free survival rate, the clinical T-stage demonstrated a better prognostic outcome than the pathological T-stage. Despite including the benign findings, the solid component diameter was better correlated with prognosis than the invasive size. Therefore, in cases of discrepancies of clinically and pathologically detected tumor size, the solid CT size should also be used for the pathological T classification. Full article

(This article belongs to the Special Issue Thoracic Cancers)

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Review

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21 pages, 318 KiB

Open AccessReview

Immunotherapy Moves to the Early-Stage Setting in Non-Small Cell Lung Cancer: Emerging Evidence and the Role of Biomarkers

by Xabier Mielgo-Rubio, Virginia Calvo, Javier Luna, Jordi Remon, Margarita Martín, Pedro Berraondo, José Ramón Jarabo, Oliver Higuera, Esther Conde, Javier De Castro, Mariano Provencio, Florentino Hernando Trancho, Fernando López-Ríos and Felipe Couñago

Cancers 2020, 12(11), 3459; https://doi.org/10.3390/cancers12113459 - 20 Nov 2020

Cited by 13 | Viewed by 3618

Abstract

Despite numerous advances in targeted therapy and immunotherapy in the last decade, lung cancer continues to present the highest mortality rate of all cancers. Targeted therapy based on specific genomic alterations, together with PD-1 and CTLA-4 axis blocking-based immunotherapy, have significantly improved survival [...] Read more.

Despite numerous advances in targeted therapy and immunotherapy in the last decade, lung cancer continues to present the highest mortality rate of all cancers. Targeted therapy based on specific genomic alterations, together with PD-1 and CTLA-4 axis blocking-based immunotherapy, have significantly improved survival in advanced non-small cell lung cancer (NSCLC) and both therapies are now well-established in this clinical setting. However, it is time for immunotherapy to be applied in patients with early-stage disease, which would be an important qualitative leap in the treatment of lung cancer patients with curative intent. Preliminary data from a multitude of studies are highly promising, but therapeutic decision-making should be guided by an understanding of the molecular features of the tumour and host. In the present review, we discuss the most recently published studies and ongoing clinical trials, controversies, future challenges and the role of biomarkers in the selection of best therapeutic options. Full article

(This article belongs to the Special Issue Thoracic Cancers)

18 pages, 254 KiB

Open AccessReview

Advances and Therapeutic Perspectives in Extended-Stage Small-Cell Lung Cancer

by Thomas Pierret, Anne-Claire Toffart, Matteo Giaj Levra, Denis Moro-Sibilot and Elisa Gobbini

Cancers 2020, 12(11), 3224; https://doi.org/10.3390/cancers12113224 - 01 Nov 2020

Cited by 2 | Viewed by 2044

Abstract

Extended small cell lung cancer (ED-SCLC) is a very aggressive disease, characterized by rapid growth and an early tendency to relapse. In contrast to non-small cell lung cancer, no therapeutic innovation has improved survival in patients with ED-SCLC over the past 20 years. [...] Read more.

Extended small cell lung cancer (ED-SCLC) is a very aggressive disease, characterized by rapid growth and an early tendency to relapse. In contrast to non-small cell lung cancer, no therapeutic innovation has improved survival in patients with ED-SCLC over the past 20 years. Recently, immunotherapy has shown an important role in the management of these patients, emerging as the treatment of first choice in combination with chemotherapy and completely changing the therapeutic paradigm. However, patients’ selection for this strategy is still challenging due to a lack of reliable predictive biomarkers. Conversely, the immunotherapy efficacy beyond the first line is pretty disappointing and innovative chemotherapies or target agents seem to be more promising in this setting. Some of them are also under evaluation as an upfront strategy and they will probably change the treatment algorithm in the next future. This proposal provides a comprehensive overview of available treatment strategies for ED-SCLC patients, highlighting their strengths and weaknesses. Full article

(This article belongs to the Special Issue Thoracic Cancers)

19 pages, 1257 KiB

Open AccessReview

Implementing ctDNA Analysis in the Clinic: Challenges and Opportunities in Non-Small Cell Lung Cancer

by Elisa Gobbini, Aurélie Swalduz, Matteo Giaj Levra, Sandra Ortiz-Cuaran, Anne-Claire Toffart, Maurice Pérol, Denis Moro-Sibilot and Pierre Saintigny

Cancers 2020, 12(11), 3112; https://doi.org/10.3390/cancers12113112 - 24 Oct 2020

Cited by 23 | Viewed by 4605

Abstract

Tumor genomic profiling has a dramatic impact on the selection of targeted treatment and for the identification of resistance mechanisms at the time of progression. Solid tissue biopsies are sometimes challenging, and liquid biopsies are used as a non-invasive alternative when tissue is [...] Read more.

Tumor genomic profiling has a dramatic impact on the selection of targeted treatment and for the identification of resistance mechanisms at the time of progression. Solid tissue biopsies are sometimes challenging, and liquid biopsies are used as a non-invasive alternative when tissue is limiting. The clinical relevance of tumor genotyping through analysis of ctDNA is now widely recognized at all steps of the clinical evaluation process in metastatic non-small cell lung cancer (NSCLC) patients. ctDNA analysis through liquid biopsy has recently gained increasing attention as well in the management of early and locally advanced, not oncogene-addicted, NSCLC. Its potential applications in early disease detection and the response evaluation to radical treatments are promising. The aim of this review is to summarize the landscape of liquid biopsies in clinical practice and also to provide an overview of the potential perspectives of development focusing on early detection and screening, the assessment of minimal residual disease, and its potential role in predicting response to immunotherapy. In addition to available studies demonstrating the clinical relevance of liquid biopsies, there is a need for standardization and well-designed clinical trials to demonstrate its clinical utility. Full article

(This article belongs to the Special Issue Thoracic Cancers)

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