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Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 18081

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Special Issue Editors

Dr. Percy Lee

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Guest Editor

Department of Radiation Oncology, City of Hope Orange County Lennar Foundation Cancer Center, Irvine, CA 92618, USA
Interests: thoracic cancers; gastrointestinal cancers; genitourinary cancers; 3D conformal radiation therapy; 4D radiotherapy; image-guided radiation therapy; intensity modulated radiation therapy; intracranial stereotactic radiosurgery; MRI-guided radiation therapy; proton radiotherapy; stereotactic body radiation therapy

Dr. Jyoti Malhotra

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Guest Editor

Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1000 FivePoint, Irvine, CA 92618, USA
Interests: thoracic medical oncology; immunotherapy

Dr. Arya Amini

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Guest Editor

Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA
Interests: head and neck cancers; skin cancers; lung cancers; breast cancer; gastrointestinal cancers; stereotactic body radiation therapy; stereotactic radiosurgery
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Special Issue Information

Dear Colleagues,

The landscape and treatment options for lung cancer for both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) is rapidly evolving. Patients are living longer due to advances in thoracic radiation therapy, immunotherapy, targeted therapy, and thoracic surgery. This Special Issue on the advances in thoracic oncology will provide a current update and overview, encompassing the role of these advances for both SCLC and NSCLC. We are pleased to include leading researchers that will provide a comprehensive summary as well as new evidence for the following topics: role of local therapy for brain metastases and prophylactic cranial irradiation in NSCLC and SCLC, thoracic re-irradiation for isolated thoracic recurrences, cardiac toxicities from thoracic radiotherapy and mitigation strategies, neoadjuvant therapy and peri-operative therapy for operable stage III NSCLC, oligometastatic and oligoprogressive lung cancer and the role of local therapy, personalized treatment approaches for frail or older patients with lung cancer, emerging systemic options (targeted therapy and immunotherapy) in lung cancer, and finally advances in the treatment paradigm for unresectable stage III NSCLC. Indeed, these are exciting times as treatment continues to improve for our patients with lung cancer.

Dr. Percy Lee
Dr. Jyoti Malhotra
Dr. Arya Amini
Guest Editors

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 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

small cell lung cancer (SCLC)
non-small cell lung cancer (NSCLC)
thoracic radiotherapy
neoadjuvant therapies
oligometastatic disease
targeted therapy
immunotherapy
unresectable stage III NSCLC
brain-directed radiation therapy small cell lung cancer (SCLC)
non-small cell lung cancer (NSCLC)
thoracic radiotherapy
neoadjuvant therapies
oligometastatic disease
targeted therapy
immunotherapy
unresectable stage III NSCLC
brain-directed radiation therapy

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Published Papers (9 papers)

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Research

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16 pages, 1061 KiB

Open AccessArticle

Harnessing Baseline Radiomic Features in Early-Stage NSCLC: What Role in Clinical Outcome Modeling for SBRT Candidates?

by Stefania Volpe, Maria Giulia Vincini, Mattia Zaffaroni, Aurora Gaeta, Sara Raimondi, Gaia Piperno, Jessica Franzetti, Francesca Colombo, Anna Maria Camarda, Federico Mastroleo, Francesca Botta, Lorenzo Spaggiari, Sara Gandini, Matthias Guckenberger, Roberto Orecchia, Monica Casiraghi and Barbara Alicja Jereczek-Fossa

Cancers 2025, 17(5), 908; https://doi.org/10.3390/cancers17050908 - 6 Mar 2025

Viewed by 721

Abstract

Aim: An Early-Stage Non-Small Cell Lung Cancer (ES-NSCLC) patient candidate for stereotactic body radiotherapy (SBRT) may start their treatment without a histopathological assessment, due to relevant comorbidities. The aim of this study is twofold: (i) build prognostic models to test the association between CT-derived radiomic features (RFs) and the outcomes of interest (overall survival (OS), progression-free survival (PFS) and loco-regional progression-free survival (LRPFS)); (ii) quantify whether the combination of clinical and radiomic descriptors yields better prediction than clinical descriptors alone in prognostic modeling for ES-NSCLC patients treated with SBRT. Methods: Simulation CT scans of ES-NSCLC patients treated with curative-intent SBRT at the European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy between 2013 and 2023 were retrospectively retrieved. PyRadiomics v3.0.1 was used for image preprocessing and subsequent RFs extraction and selection. A radiomic score was calculated for each patient, and three prognostic models (clinical model, radiomic model, clinical-radiomic model) for each survival endpoint were built. Relative performances were compared using the C-index. All analyses were considered statistically significant if p < 0.05. The statistical analyses were performed using R Software version 4.1. Results: A total of 100 patients met the inclusion criteria. Median age at diagnosis was 76 (IQR: 70–82) years, with a median Charlson Comorbidity Index (CCI) of 7 (IQR: 6–8). At the last available follow-up, 76 patients were free of disease, 17 were alive with disease, and 7 were deceased. Considering relapses, progression of any kind was diagnosed in 31 cases. Regarding model performances, the radiomic score allowed for excellent prognostic discrimination for all the considered endpoints. Of note, the use of RFs alone proved to be more informative than clinical characteristics alone for the prediction of both OS and LRPFS, but not for PFS, for which the individual predictive performances slightly favored the clinical model. Conclusion: The use of RFs for outcome prediction in this clinical setting is promising, and results seem to be rather consistent across studies, despite some methodological differences that should be acknowledged. Further studies are being planned in our group to externally validate these findings, and to better determine the potential of RFs as non-invasive and reproducible biomarkers in ES-NSCLC. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

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12 pages, 415 KiB

Open AccessArticle

Salvage Reirradiation with Proton Beam Therapy for Locoregionally Recurrent Non-Small Cell Lung Cancer

by Matthew S. Ning, Abigael Odwuor, Joe Y. Chang, Saumil Gandhi, Zhongxing Liao, Steven H. Lin, Aileen Chen, James W. Welsh, Quynh-Nhu Nguyen, Michael S. O’Reilly, Stephen G. Chun, Julianna Bronk, David Qian and Percy Lee

Cancers 2024, 16(21), 3587; https://doi.org/10.3390/cancers16213587 - 24 Oct 2024

Cited by 1 | Viewed by 1325

Abstract

Background/Objectives: This retrospective study evaluates outcomes of 66 patients who underwent reirradiation (re-RT) with proton beam therapy (PBT) for recurrent non-small cell lung cancer. Methods: Toxicity was scored via the CTCAE v5.0, and outcomes estimated using the Kaplan–Meier method, with associations evaluated via Cox proportional hazards and logistic regression analyses. Results: Patients were treated to a median re-RT prescription of 66 Gy/33 fxs (BED10 = 79 Gy; IQR: 71–84 Gy) at an interval of 1.4 years from prior RT. Half (50%) received concurrent chemotherapy. At 14 months follow-up, the median OS and PFS were 5 months (95%CI: 13–17) and 12.5 months (95%CI: 10–15), respectively. On multivariable analysis, a higher RT dose (BED10 > 70 Gy) [HR0.37; 95%CI: 0.20–0.68, p = 0.001] and concurrent chemotherapy (HR0.48; 95%CI: 0.28–0.81, p = 0.007) were associated with improved PFS, while treatment site overlap was adversely associated (HR1.78; 95%CI: 1.05–3.02, p = 0.031). The median PFS for definitive RT with concurrent chemotherapy (n = 28), definitive RT alone (BED10 > 70 Gy) [n = 22], and lower prescription RT (BED10 < 70 Gy) [n = 16] was 15.5 months (95%CI: 7.3–23.7), 14.1 months (95%CI: 10.9–17.3), and 3.3 months (95%CI: 0–12.3), respectively (log-rank, p = 0.006), with corresponding 2-year estimates of 37% (±9), 18% (±8), and 12.5% (±8), respectively. The incidence of Grade 3+ toxicity was 10.5% (6% pulmonary; 3% esophageal; and 1.5% skin), including one Grade 4 bronchopulmonary hemorrhage but no Grade 5 events. Cases with central site overlap had higher composite Dmax to the esophagus (median 87 Gy [IQR:77–90]), great vessels (median 120 Gy [IQR:110–138]), and proximal bronchial tree (median 120 Gy [IQR:110–138]) as compared to other cases (p ≤ 0.001 for all). However, no significant associations were identified with Grade 3+ events. Conclusions: Thoracic re-RT with PBT is an option for recurrent NSCLC with acceptable outcomes and toxicity for select patients. When feasible, higher prescription doses (BED10 > 70 Gy) should be delivered for definitive intent, and concurrent chemotherapy may benefit individual cases. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

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Review

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13 pages, 217 KiB

Open AccessReview

Treatment Approaches for Oligoprogressive Non-Small Cell Lung Cancer: A Review of Ablative Radiotherapy

by William Gombrich, Nicholas Eustace, Yufei Liu, Ramya Muddasani, Adam Rock, Ravi Salgia, Terence Williams, Jyoti Malhotra, Percy Lee and Arya Amini

Cancers 2025, 17(7), 1233; https://doi.org/10.3390/cancers17071233 - 5 Apr 2025

Viewed by 679

Abstract

Oligoprogressive disease refers to the setting of a prior or ongoing receipt of systemic therapy, with typically up to three metastatic areas having increased in size and/or avidity compared to the start of the systemic therapy. The role of local ablative therapy (LAT) including radiation has mostly been evaluated in the oligometastatic setting with limited data in oligoprogression. A similar principle of using ablative radiation in the oligometastatic setting may be applied to consolidative therapy for oligoprogressive disease. If systemic therapy can control the majority of the disease, and a few areas of therapy-resistant clones continue to proliferate, then potentially controlling those few resistant clones while maintaining systemic control may be beneficial. Doing so may also extend the duration of benefit of the systemic therapy and reserve next systemic line options at a later point, and potentially improve progression free survival (PFS). Here, we review the current data evaluating the role of radiation in oligoprogressive non-small cell lung cancer (NSCLC) and ongoing trials. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

31 pages, 1578 KiB

Open AccessReview

Emerging Targeted Therapies in Non-Small-Cell Lung Cancer (NSCLC)

by Syeda A. Mina, Mohamed Shanshal, Konstantinos Leventakos and Kaushal Parikh

Cancers 2025, 17(3), 353; https://doi.org/10.3390/cancers17030353 - 22 Jan 2025

Cited by 2 | Viewed by 3769

Abstract

Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages of lung cancer. Newer advances in common and novel oncogenic drivers continue to occur at vigorous speed, making it challenging to stay up to date with the rapidly evolving field. In this article, we review the emerging perspectives in the treatment of actionable targets in lung cancer. We focus on the development of newer KRAS-directed therapies, particularly on non-G12C mutations, pan-RAS inhibitors, and RAS-GTP inhibitors. We also describe the current standard of care for EGFR- and ALK-altered NSCLC and dive into the novel treatments expected to be in the clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, and FGFR alterations as emerging targets in non-small-cell lung cancer. Finally, we conclude this review with the current body of evidence for targeting TROP-2 as a novel target, potentially of importance in post-targeted therapy scenarios. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

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21 pages, 316 KiB

Open AccessReview

Updates in Management of Unresectable Stage III Non Small Cell Lung Cancer: A Radiation Oncology Perspective

by Lakshmi Rekha Narra, Ritesh Kumar, Matthew P. Deek and Salma K. Jabbour

Cancers 2024, 16(24), 4233; https://doi.org/10.3390/cancers16244233 - 19 Dec 2024

Viewed by 1739

Abstract

Unresectable stage III non-small-cell lung cancer (NSCLC) remains a clinical challenge, due to the need for optimal local and systemic control. The management of unresectable Stage III NSCLC has evolved with advancements in radiation therapy (RT), systemic therapies, and immunotherapy. For patients with locally advanced NSCLC who are not surgical candidates, concurrent chemoradiotherapy (CRT) has modest survival outcomes, due to both local progression and distant metastasis. Efforts to enhance outcomes have led to dose-escalation trials, advances in modern RT techniques such as intensity-modulated RT (IMRT) and proton beam therapy (PBT), and the integration of adaptive RT to optimize target coverage while sparing organs at risk. Concurrent and consolidative immunotherapy, particularly with PD-L1 inhibitors, has shown promise, as evidenced by the PACIFIC trial, which demonstrated improved progression-free survival (PFS) and overall survival (OS) with durvalumab following CRT. Ongoing trials are now investigating novel immunotherapy combinations and targeted therapies in this setting, including dual checkpoint inhibition, DNA repair inhibitors, and molecularly targeted agents like osimertinib for EGFR-mutated NSCLC. Emerging biomarkers, such as circulating tumor DNA and radiomics, offer potential for personalizing treatment and predicting outcomes. Additionally, PBT and MR-guided adaptive RT have shown the potential to reduce toxicities while maintaining efficacy. Integrating these novel approaches may offer opportunities for optimizing treatment responses and minimizing adverse effects in this challenging patient population. Further investigation into patient stratification, biomarker-driven therapy, and refined therapeutic combinations is essential to improve long-term outcomes in unresectable Stage III NSCLC. This narrative review explores the current management strategies for unresectable Stage III NSCLC, from a radiation oncology perspective. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

20 pages, 563 KiB

Open AccessReview

Optimizing Care Across the Continuum for Older Adults with Lung Cancer: A Review

by Leah Thompson, Caterina Florissi, Jaewon Yoon, Anupama Singh and Anurag Saraf

Cancers 2024, 16(22), 3800; https://doi.org/10.3390/cancers16223800 - 12 Nov 2024

Viewed by 1358

Abstract

Older adults with lung cancer experience inferior clinical outcomes compared to their younger counterparts. This review provides the scaffolding to address these disparities by delineating (1) the distinct and varied care needs of older adults with lung malignancies, (2) evidence-based measures for identifying subgroups within this population meriting tailored approaches to care, (3) age-specific considerations for the selection of cancer-directed therapy, and (4) opportunities for future work to enhance clinical outcomes and care delivery. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

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41 pages, 992 KiB

Open AccessReview

Advances in the Management of Lung Cancer Brain Metastases

by Kathryn G. Hockemeyer, Chad G. Rusthoven and Luke R. G. Pike

Cancers 2024, 16(22), 3780; https://doi.org/10.3390/cancers16223780 - 9 Nov 2024

Cited by 2 | Viewed by 2631

Abstract

Lung cancer, both non-small cell and small cell, harbors a high propensity for spreading to the central nervous system. Radiation therapy remains the backbone of the management of brain metastases. Recent advances in stereotactic radiosurgery have expanded its indications and ongoing studies seek to elucidate optimal fractionation and coordination with systemic therapies, especially targeted inhibitors with intracranial efficacy. Efforts in whole-brain radiotherapy aim to preserve neurocognition and to investigate the need for prophylactic cranial irradiation. As novel combinatorial strategies are tested and prognostic/predictive biomarkers are identified and tested, the management of brain metastases in lung cancer will become increasingly personalized to optimally balance intracranial efficacy with preserving neurocognitive function and patient values. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

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12 pages, 608 KiB

Open AccessReview

Novel Immunotherapeutics for the Treatment of Non-Small Cell Lung Cancer (NSCLC) Resistant to PD-1/PD-L1 Inhibitors

by Jyoti Malhotra, Amy Huang, Arya Amini and Percy Lee

Cancers 2024, 16(21), 3603; https://doi.org/10.3390/cancers16213603 - 25 Oct 2024

Cited by 1 | Viewed by 2886

Abstract

Immunotherapy with PD-1/PD-L1 inhibitors is the standard method of care for the treatment of newly diagnosed advanced or metastatic NSCLC, with or without chemotherapy. Many tumors, however, develop resistance to these immunotherapy agents. There is a need to develop more effective therapies for patients with metastatic NSCLC in the second-line setting and beyond. In this review, we present an overview of novel immunotherapies being investigated regarding the treatment of these patients. We summarize completed, as well as ongoing, trials investigating these therapies as monotherapy or in combination with PD-1/PD-L1 inhibitors. These include immune co-stimulatory antibodies, T-cell agonists, oncolytic viruses, vaccines, TIL therapies, and CAR-T therapies. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

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22 pages, 1392 KiB

Open AccessReview

Harnessing the Power of Radiotherapy for Lung Cancer: A Narrative Review of the Evolving Role of Magnetic Resonance Imaging Guidance

by Sarah Hsin Cheng, Shao-Yun Lee and Hsin-Hua Lee

Cancers 2024, 16(15), 2710; https://doi.org/10.3390/cancers16152710 - 30 Jul 2024

Cited by 1 | Viewed by 2135

Abstract

Compared with computed tomography (CT), magnetic resonance imaging (MRI) traditionally plays a very limited role in lung cancer management, although there is plenty of room for improvement in the current CT-based workflow, for example, in structures such as the brachial plexus and chest wall invasion, which are difficult to visualize with CT alone. Furthermore, in the treatment of high-risk tumors such as ultracentral lung cancer, treatment-associated toxicity currently still outweighs its benefits. The advent of MR-Linac, an MRI-guided radiotherapy (RT) that combines MRI with a linear accelerator, could potentially address these limitations. Compared with CT-based technologies, MR-Linac could offer superior soft tissue visualization, daily adaptive capability, real-time target tracking, and an early assessment of treatment response. Clinically, it could be especially advantageous in the treatment of central/ultracentral lung cancer, early-stage lung cancer, and locally advanced lung cancer. Increasing demands for stereotactic body radiotherapy (SBRT) for lung cancer have led to MR-Linac adoption in some cancer centers. In this review, a broad overview of the latest research on imaging-guided radiotherapy (IGRT) with MR-Linac for lung cancer management is provided, and development pertaining to artificial intelligence is also highlighted. New avenues of research are also discussed. Full article

(This article belongs to the Special Issue Advances in Thoracic Oncology: A Multi-disciplinary Approach to Lung Cancer)

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