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Radiotherapy for Thoracic Malignancies: New Advances and Challenges

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

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 12398

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Dr. Eric C. Ko

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Guest Editor

Department of Radiation Oncology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Interests: radiotherapy; stereotactic body radiation therapy; non-small cell lung cancer; immunotherapy
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Special Issue Information

Dear Colleagues,

As the Guest Editor for this Special Issue in the journal Cancers, I would like to reach out to request your contribution as an expert in the field of thoracic radiation oncology.

Recent advances in thoracic oncology have significantly improved our understanding of lung cancer and other thoracic malignancies, and offered critical insight to the selection of therapeutic approaches. The gains in the field have been multifaceted and complementary. Refinements in diagnostic imaging have improved our ability to detect cancers and accurately stage patients. Routine molecular characterization of lung cancers has led to the identification and validation of prognostic and predictive biomarkers. The widespread adoption of immunotherapy for advanced and metastatic lung cancer, as well as promising findings in small cohorts of earlier stage disease, have offered an additional therapeutic approach with impressive clinical outcomes in a subset of patients. In this setting and concomitant with all these advances, there has been broad adoption of advanced image guidance technologies and stereotactic body radiation therapy, which are central to the recent therapeutic gains by radiotherapy in lung cancer.

In this Special Issue, we will highlight key recent advances in radiotherapy for lung cancer and other thoracic malignancies. We will focus on current clinical evidence, summarize pertinent trials, and identify ongoing challenges. In line with the increasing appreciation of the heterogeneity of malignancies, we will discuss emerging concepts on personalized therapy for lung cancer.

Dr. Eric C. Ko
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

radiotherapy
stereotactic body radiation therapy
non-small cell lung cancer
immunotherapy
thoracic oncology

Published Papers (7 papers)

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Research

13 pages, 1500 KiB

Open AccessArticle

Effect of Segmental Abutting Esophagus-Sparing Technique to Reduce Severe Esophagitis in Limited-Stage Small-Cell Lung Cancer Patients Treated with Concurrent Hypofractionated Thoracic Radiation and Chemotherapy

by Jianyang Wang, Fei Han, Yuchao Ma, Yufan Yang, Yuqi Wu, Zimin Han, Xuejie Xie, Jianrong Dai, Nan Bi and Luhua Wang

Cancers 2023, 15(5), 1487; https://doi.org/10.3390/cancers15051487 - 27 Feb 2023

Viewed by 1318

Abstract

The aim of the current study is to evaluate the effect of segmental abutting esophagus-sparing (SAES) radiotherapy on reducing severe acute esophagitis in patients with limited-stage small-cell lung cancer treated with concurrent chemoradiotherapy. Thirty patients were enrolled from the experimental arm (45 Gy in 3 Gy daily fractions in 3 weeks) of an ongoing phase III trial (NCT 02688036). The whole esophagus was divided into the involved esophagus and the abutting esophagus (AE) according to the distance from the edge of the clinical target volume. All dosimetric parameters were significantly reduced for the whole esophagus and AE. The maximal and mean doses of the esophagus (47.4 ± 1.9 Gy and 13.5 ± 5.8 Gy, respectively) and AE (42.9 ± 2.3 Gy and 8.6 ± 3.6 Gy, respectively) in the SAES plan were significantly lower than those (esophagus 48.0 ± 1.9 Gy and 14.7± 6.1 Gy, AE 45.1 ± 2.4 Gy and 9.8 ± 4.2 Gy, respectively) in the non-SAES plan. With a median follow-up of 12.5 months, only one patient (3.3%) developed grade 3 acute esophagitis, and no grade 4–5 events happened. SAES radiotherapy has significant dosimetric advantages, which are successfully translated into clinical benefits and provide good feasibility for dose escalation to improve local control and prognosis in the future. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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12 pages, 2310 KiB

Open AccessArticle

Malignant Pleural Mesothelioma: Preliminary Toxicity Results of Adjuvant Radiotherapy Hypofractionation in a Prospective Trial (MESO-RT)

by Elisabetta Parisi, Donatella Arpa, Giulia Ghigi, Lucia Fabbri, Flavia Foca, Luca Tontini, Elisa Neri, Martina Pieri, Simona Cima, Marco Angelo Burgio, Maria Luisa Belli, Luca Luzzi and Antonino Romeo

Cancers 2023, 15(4), 1057; https://doi.org/10.3390/cancers15041057 - 07 Feb 2023

Viewed by 1287

Abstract

Malignant Pleural Mesothelioma (MPM) is a rare malignancy with an overall poor prognosis. The standard therapeutic strategy in early-stage disease is trimodality therapy. In this publication, we report the preliminary toxicity results of the first 20 patients treated with accelerated hypofractionated radiotherapy. Between July 2017 to June 2019, 20 MPM patients were enrolled and treated with accelerated hypofractionated radiotherapy using helical tomotherapy and intensity-modulated arc therapy. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. Only one case of G3 toxicity was reported, which was a bilateral pneumonitis that occurred two years after treatment probably due to superinfection. Median Time to Progression reached 18.2 months while one- and three-year Overall Survival rates were 85% (95% CI:60.4–94.9) and 49.5% (95% CI:26.5–68.9), respectively. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. Survival rates and Time to Progression are encouraging. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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12 pages, 683 KiB

Open AccessArticle

Early Identification of Pneumonitis in Patients Irradiated for Lung Cancer—Final Results of the PARALUC Trial

by Dirk Rades, Elisa M. Werner, Esther Glatzel, Sabine Bohnet, Steven E. Schild, Søren S. Tvilsted and Stefan Janssen

Cancers 2023, 15(2), 326; https://doi.org/10.3390/cancers15020326 - 04 Jan 2023

Cited by 2 | Viewed by 1269

Abstract

Radiotherapy of lung cancer may cause pneumonitis that generally occurs weeks or months following therapy and can be missed. This prospective trial aimed to pave the way for a mobile application (app) allowing early diagnosis of pneumonitis. The primary goal was the identification of the optimal cut-off of a score to detect pneumonitis of grade ≥2 after radiotherapy for lung cancer. Based on the severity of symptoms (cough, dyspnea, fever), scoring points were 0–9. Receiver operating characteristic (ROC)-curves were used to describe the sensitivity and specificity. The area under the ROC-curve (AUC) was calculated to judge the accuracy of the score, Youden-index was employed to define the optimal cut-off. Until trial termination, 57 of 98 patients were included. Eight of 42 patients evaluable for the primary endpoint (presence or absence of radiation pneumonitis) experienced pneumonitis. AUC was 0.987 (0.961–1.000). The highest sensitivity was achieved with 0–4 points (100%), followed by 5 points (87.5%), highest specificity with 5–6 points (100%). The highest Youden-index was found for 5 points (87.5%). The rate of patient satisfaction with the symptom-based scoring system was 93.5%. A cut-off of 5 points was identified as optimal to differentiate between pneumonitis and no pneumonitis. Moreover, pneumonitis was significantly associated with an increase of ≥3 points from baseline (p < 0.0001). The scoring system provided excellent accuracy and high patient satisfaction. Important foundations for the development of a mobile application were laid. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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10 pages, 1782 KiB

Open AccessArticle

A “Seed-and-Soil” Radiomics Model Predicts Brain Metastasis Development in Lung Cancer: Implications for Risk-Stratified Prophylactic Cranial Irradiation

by Xiao Chu, Jing Gong, Xi Yang, Jianjiao Ni, Yajia Gu and Zhengfei Zhu

Cancers 2023, 15(1), 307; https://doi.org/10.3390/cancers15010307 - 02 Jan 2023

Cited by 5 | Viewed by 2534

Abstract

Introduction: Brain is a major site of metastasis for lung cancer, and effective therapy for developed brain metastasis (BM) is limited. Prophylactic cranial irradiation (PCI) has been shown to reduce BM rate and improve survival in small cell lung cancer, but this result was not replicated in unselected non-small cell lung cancer (NSCLC) and had the risk of inducing neurocognitive dysfunctions. We aimed to develop a radiomics BM prediction model for BM risk stratification in NSCLC patients. Methods: 256 NSCLC patients with no BM at baseline brain magnetic resonance imaging (MRI) were selected; 128 patients developed BM within three years after diagnosis and 128 remained BM-free. For radiomics analysis, both the BM and non-BM groups were randomly distributed into training and testing datasets at an 70%:30% ratio. Both brain MRI (representing the soil) and chest computed tomography (CT, representing the seed) radiomic features were extracted to develop the BM prediction models. We first developed the radiomic models using the training dataset (89 non-BM and 90 BM cases) and subsequently validated the models in the testing dataset (39 non-BM and 38 BM cases). A radiomics BM score (RadBM score) was generated, and BM-free survival were compared between RadBM score-high and RadBM score-low groups. Results: The radiomics model developed from baseline brain MRI features alone can predict BM development in NSCLC patients. A fusion model integrating brain MRI features with primary tumor CT features (seed-and-soil model) provided synergetic effect and was more efficient in predicting BM (areas under the receiver operating characteristic curve 0.84 (95% confidence interval: 0.80–0.89) and 0.80 (95% confidence interval: 0.71–0.88) in the training and testing datasets, respectively). BM-free survival was significantly shorter in the RadBM score-high group versus the RadBM score-low group (Log-rank, p < 0.001). Hazard ratios for BM were 1.056 (95% confidence interval: 1.044–1.068) per 0.01 increment in RadBM score. Cumulative BM rates at three years were 75.8% and 24.2% for the RadBM score-high and RadBM score-low groups, respectively. Only 1.2% (7/565) of the BM lesions were located within the hippocampal avoidance region. Conclusion: The results demonstrated that intrinsic features of a non-metastatic brain exert a significant impact on BM development, which is first-in-class in metastasis prediction studies. A radiomics BM prediction model utilizing both primary tumor and pre-metastatic brain features might provide a useful tool for individualized PCI administration in NSCLC patients more prone to develop BM. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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11 pages, 1343 KiB

Open AccessArticle

Atypical Response in Metastatic Non-Small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitors: Radiographic Patterns and Clinical Value of Local Therapy

by Shanshan Jiang, Jinmeng Zhang, Li Chu, Xiao Chu, Xi Yang, Yida Li, Tiantian Guo, Yue Zhou, Dayu Xu, Jiuang Mao, Zhiqin Zheng, Yulin An, Hua Sun, Huiling Dong, Silai Yu, Ruiting Ye, Jie Hu, Qian Chu, Jianjiao Ni and Zhengfei Zhu

Cancers 2023, 15(1), 180; https://doi.org/10.3390/cancers15010180 - 28 Dec 2022

Cited by 2 | Viewed by 1597

Abstract

Purpose: To explore the clinical characteristics, management, and survival outcomes of advanced NSCLC patients treated with PD-1/PD-L1 inhibitors who presented with an atypical response (AR). Methods: A total of 926 PD-1/PD-L1-inhibitor-treated patients with metastatic NSCLC from three academic centers were retrospectively reviewed. All measurable lesions were evaluated by RECIST version 1.1. Results: Fifty-six (6.1%) patients developed AR. The median time to the occurrence of AR was 2.0 months. Patients with no fewer than 3 metastatic organs at baseline were more prone to develop AR in advanced NSCLC (p = 0.038). The common sites of progressive lesions were lymph nodes (33.8%) and lungs (29.7%). The majority (78.2%) of patients with AR had only 1–2 progressive tumor lesions, and most (89.1%) of the progressive lesions developed from originally existing tumor sites. There was no significance in terms of survival between patients with AR and those with typical response (TR). Local therapy was an independent predictor for PFS of patients with AR (p = 0.025). Conclusions: AR was not an uncommon event in patients with metastatic NSCLC treated with PD-1/PD-L1 inhibitors, and it had a comparable prognosis to those with TR. Proper local therapy targeting progressive lesions without discontinuing original PD-1/PD-L1 inhibitors may improve patient survival. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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12 pages, 2417 KiB

Open AccessArticle

Interobserver Variability Prediction of Primary Gross Tumor in a Patient with Non-Small Cell Lung Cancer

by Wonjoong Cheon, Seonghoon Jeong, Jong Hwi Jeong, Young Kyung Lim, Dongho Shin, Se Byeong Lee, Doo Yeul Lee, Sung Uk Lee, Yang Gun Suh, Sung Ho Moon, Tae Hyun Kim and Haksoo Kim

Cancers 2022, 14(23), 5893; https://doi.org/10.3390/cancers14235893 - 29 Nov 2022

Viewed by 1257

Abstract

This research addresses the problem of interobserver variability (IOV), in which different oncologists manually delineate varying primary gross tumor volume (pGTV) contours, adding risk to targeted radiation treatments. Thus, a method of IOV reduction is urgently needed. Hypothesizing that the radiation oncologist’s IOV may shrink with the aid of IOV maps, we propose IOV prediction network (IOV-Net), a deep-learning model that uses the fuzzy membership function to produce high-quality maps based on computed tomography (CT) images. To test the prediction accuracy, a ground-truth pGTV IOV map was created using the manual contour delineations of radiation therapy structures provided by five expert oncologists. Then, we tasked IOV-Net with producing a map of its own. The mean squared error (prediction vs. ground truth) and its standard deviation were 0.0038 and 0.0005, respectively. To test the clinical feasibility of our method, CT images were divided into two groups, and oncologists from our institution created manual contours with and without IOV map guidance. The Dice similarity coefficient and Jaccard index increased by ~6 and 7%, respectively, and the Hausdorff distance decreased by 2.5 mm, indicating a statistically significant IOV reduction (p < 0.05). Hence, IOV-net and its resultant IOV maps have the potential to improve radiation therapy efficacy worldwide. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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11 pages, 974 KiB

Open AccessArticle

Clinical Outcomes Following Proton and Photon Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer

by Bong Kyung Bae, Kyungmi Yang, Jae Myung Noh, Hongryull Pyo and Yong Chan Ahn

Cancers 2022, 14(17), 4152; https://doi.org/10.3390/cancers14174152 - 27 Aug 2022

Cited by 4 | Viewed by 2134

Abstract

We aimed to report the clinical outcomes following stereotactic body radiation therapy (SBRT) using photon or proton equipment in early-stage lung cancer. We retrospectively reviewed 202 cT1-2N0M0 lung cancer patients who underwent SBRT with 60 Gy in four consecutive fractions between 2010 and 2019 at our institution: 168 photon SBRT and 34 proton SBRT. Patients who underwent proton SBRT had relatively poor baseline lung condition compared to those who underwent photon SBRT. Clinical outcomes were comparable between treatment modalities: 5-year local control (90.8% vs. 83.6%, p = 0.602); progression-free survival (61.6% vs. 57.8%, p = 0.370); overall survival (51.7% vs. 51.9%, p = 0.475); and cause-specific survival (70.3% vs. 62.6%, p = 0.618). There was no statistically significant difference in grade ≥ 2 toxicities: radiation pneumonitis (19.6% vs. 26.4%, p = 0.371); musculoskeletal (13.7% vs. 5.9%, p = 0.264); and skin (3.6% vs. 0.0%, p = 0.604). In the binary logistic regression analysis of grade ≥3 radiation pneumonitis, poor performance status and poor baseline diffusion capacity of lung for carbon monoxide were significant. To summarize, though patients with high risk of developing lung toxicity underwent proton SBRT more frequently, the SBRT techniques resulted in comparable oncologic outcomes with similar toxicity profiles. Proton SBRT could be considered for patients at high risk of radiation pneumonitis. Full article

(This article belongs to the Special Issue Radiotherapy for Thoracic Malignancies: New Advances and Challenges)

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