Special Issue "Radiation Therapy in Thoracic Tumors: Recent Trends and Current Issues"

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

Deadline for manuscript submissions: 31 January 2022.

Special Issue Editors

Dr. Laura Cella
E-Mail Website
Guest Editor
Institute of Biostructures and Bioimaging, National Research Council (CNR), via Tommaso De Amicis, 95, Napoli, Italy
Interests: radiation oncology physics; radiation therapy optimization; radiation-induced side effects; clinical radiobiology; machine learning; voxel-based analysis
Dr. Giuseppe Palma
E-Mail Website
Guest Editor
Institute of Biostructures and Bioimaging, National Research Council (CNR), via Tommaso De Amicis, 95, Napoli, Italy
Interests: radiation therapy; magnetic resonance imaging; image analysis; algorithms; modeling
Dr. Andrew Hope
E-Mail Website
Guest Editor
1. Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada
2. Ontario and Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada
Interests: radiation-induced normal tissue toxicity; predictive modeling; machine learning

Special Issue Information

Dear Colleagues,

Over the past several years, radiation therapy for thoracic tumors and its treatment planning have significantly progressed. Thanks to recent advancements in technology, such as VMAT, particle therapy or SBRT, which have gone hand in hand with image guidance techniques and new fractionation paradigms, long-term disease control and improved quality of life have been attained. Despite the successes we have witnessed so far, however, further improved treatment strategies to tailor thoracic cancer care can be envisioned. Areas in particular need of novel insights include the personalization of treatment based on the molecular characteristics of individual tumors as well as on image-based data mining for treatment-related toxicity prediction.

This Special Issue will be focused on the discussion of recent studies and findings showing possible directions for moving the field of radiation therapy for thoracic tumors forward.

We invite the submission of original research papers as well as timely review articles related to these challenges and opportunities. Topics of interest include but are not limited to all recent trends and current issues related to radiation therapy of thoracic tumors.

Dr. Laura Cella
Dr. Giuseppe Palma
Dr. Andrew Hope
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 papers will be 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 2200 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

  • Lung cancer
  • Esophageal cancer
  • Thymoma and mesothelioma
  • Mediastinal Hodgkin's lymphoma
  • Molecular-imaging-based dose painting
  • Imaging for radiation therapy of thoracic tumors
  • Motion challenges in thoracic tumor RT
  • Advanced radiation techniques (MRI–Linac, proton therapy, carbon ion)
  • Treatment planning optimization
  • Tumor control and survival
  • Radiation induced toxicity in the thorax
  • Radiomics and machine learning

Published Papers (7 papers)

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Research

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Article
Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer
Cancers 2021, 13(23), 5923; https://doi.org/10.3390/cancers13235923 - 25 Nov 2021
Viewed by 177
Abstract
Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and [...] Read more.
Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process. Full article
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Article
Enhancing Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer Patients with iCE, a Novel System for Automated Multi-Criterial Treatment Planning Including Beam Angle Optimization
Cancers 2021, 13(22), 5683; https://doi.org/10.3390/cancers13225683 - 13 Nov 2021
Viewed by 430
Abstract
In this study, the novel iCE radiotherapy treatment planning system (TPS) for automated multi-criterial planning with integrated beam angle optimization (BAO) was developed, and applied to optimize organ at risk (OAR) sparing and systematically investigate the impact of beam angles on radiotherapy dose [...] Read more.
In this study, the novel iCE radiotherapy treatment planning system (TPS) for automated multi-criterial planning with integrated beam angle optimization (BAO) was developed, and applied to optimize organ at risk (OAR) sparing and systematically investigate the impact of beam angles on radiotherapy dose in locally advanced non-small cell lung cancer (LA-NSCLC). iCE consists of an in-house, sophisticated multi-criterial optimizer with integrated BAO, coupled to a broadly used commercial TPS. The in-house optimizer performs fluence map optimization to automatically generate an intensity-modulated radiotherapy (IMRT) plan with optimal beam angles for each patient. The obtained angles and dose-volume histograms are then used to automatically generate the final deliverable plan with the commercial TPS. For the majority of 26 LA-NSCLC patients, iCE achieved improved heart and esophagus sparing compared to the manually created clinical plans, with significant reductions in the median heart Dmean (8.1 vs. 9.0 Gy, p = 0.02) and esophagus Dmean (18.5 vs. 20.3 Gy, p = 0.02), and reductions of up to 6.7 Gy and 5.8 Gy for individual patients. iCE was superior to automated planning using manually selected beam angles. Differences in the OAR doses of iCE plans with 6 beams compared to 4 and 8 beams were statistically significant overall, but highly patient-specific. In conclusion, automated planning with integrated BAO can further enhance and individualize radiotherapy for LA-NSCLC. Full article
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Article
Potential Morbidity Reduction for Lung Stereotactic Body Radiation Therapy Using Respiratory Gating
Cancers 2021, 13(20), 5092; https://doi.org/10.3390/cancers13205092 - 12 Oct 2021
Viewed by 306
Abstract
We investigated the potential of respiratory gating to mitigate the motion-caused misdosage in lung stereotactic body radiotherapy (SBRT). For fourteen patients with lung tumors, we investigated treatment plans for a gating window (GW) including three breathing phases around the maximum exhalation phase, GW40–60. [...] Read more.
We investigated the potential of respiratory gating to mitigate the motion-caused misdosage in lung stereotactic body radiotherapy (SBRT). For fourteen patients with lung tumors, we investigated treatment plans for a gating window (GW) including three breathing phases around the maximum exhalation phase, GW40–60. For a subset of six patients, we also assessed a preceding three-phase GW20–40 and six-phase GW20–70. We analyzed the target volume, lung, esophagus, and heart doses. Using normal tissue complication probability (NTCP) models, we estimated radiation pneumonitis and esophagitis risks. Compared to plans without gating, GW40–60 significantly reduced doses to organs at risk without impairing the tumor doses. On average, the mean lung dose decreased by 0.6 Gy (p < 0.001), treated lung V20Gy by 2.4% (p = 0.003), esophageal dose to 5cc by 2.0 Gy (p = 0.003), and maximum heart dose by 3.2 Gy (p = 0.009). The model-estimated mean risks of 11% for pneumonitis and 12% for esophagitis without gating decreased upon GW40–60 to 7% and 9%, respectively. For the highest-risk patient, gating reduced the pneumonitis risk from 43% to 32%. Gating is most beneficial for patients with high-toxicity risks. Pre-treatment toxicity risk assessment may help optimize patient selection for gating, as well as GW selection for individual patients. Full article
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Article
Radiation Pneumonitis in Thoracic Cancer Patients: Multi-Center Voxel-Based Analysis
Cancers 2021, 13(14), 3553; https://doi.org/10.3390/cancers13143553 - 15 Jul 2021
Cited by 2 | Viewed by 637
Abstract
This study investigates the dose–response patterns associated with radiation pneumonitis (RP) in patients treated for thoracic malignancies with different radiation modalities. To this end, voxel-based analysis (VBA) empowered by a novel strategy for the characterization of spatial properties of dose maps was applied. [...] Read more.
This study investigates the dose–response patterns associated with radiation pneumonitis (RP) in patients treated for thoracic malignancies with different radiation modalities. To this end, voxel-based analysis (VBA) empowered by a novel strategy for the characterization of spatial properties of dose maps was applied. Data from 382 lung cancer and mediastinal lymphoma patients from three institutions treated with different radiation therapy (RT) techniques were analyzed. Each planning CT and biologically effective dose map (α/β = 3 Gy) was spatially normalized on a common anatomical reference. The VBA of local dose differences between patients with and without RP was performed and the clusters of voxels with dose differences that significantly correlated with RP at a p-level of 0.05 were generated accordingly. The robustness of VBA inference was evaluated by a novel characterization for spatial properties of dose maps based on probabilistic independent component analysis (PICA) and connectograms. This lays robust foundations to the obtained findings that the lower parts of the lungs and the heart play a prominent role in the development of RP. Connectograms showed that the dataset can support a radiobiological differentiation between the main heart and lung substructures. Full article
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Review

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Review
Current Situation of Proton Therapy for Hodgkin Lymphoma: From Expectations to Evidence
Cancers 2021, 13(15), 3746; https://doi.org/10.3390/cancers13153746 - 26 Jul 2021
Viewed by 608
Abstract
Consolidative radiation therapy (RT) is of prime importance for early-stage Hodgkin lymphoma (HL) management since it significantly increases progression-free survival (PFS). Nevertheless, first-generation techniques, relying on large irradiation fields, delivered significant radiation doses to critical organs-at-risk (OARs, such as the heart, to the [...] Read more.
Consolidative radiation therapy (RT) is of prime importance for early-stage Hodgkin lymphoma (HL) management since it significantly increases progression-free survival (PFS). Nevertheless, first-generation techniques, relying on large irradiation fields, delivered significant radiation doses to critical organs-at-risk (OARs, such as the heart, to the lung or the breasts) when treating mediastinal HL; consequently, secondary cancers, and cardiac and lung toxicity were substantially increased. Fortunately, HL RT has drastically evolved and, nowadays, state-of-the-art RT techniques efficiently spare critical organs-at-risks without altering local control or overall survival. Recently, proton therapy has been evaluated for mediastinal HL treatment, due to its possibility to significantly reduce integral dose to OARs, which is expected to limit second neoplasm risk and reduce late toxicity. Nevertheless, clinical experience for this recent technique is still limited worldwide. Based on current literature, this critical review aims to examine the current practice of proton therapy for mediastinal HL irradiation. Full article
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Review
Development and Implementation of Proton Therapy for Hodgkin Lymphoma: Challenges and Perspectives
Cancers 2021, 13(15), 3744; https://doi.org/10.3390/cancers13153744 - 26 Jul 2021
Viewed by 521
Abstract
Consolidative radiation therapy for early-stage Hodgkin lymphoma (HL) improves progression-free survival. Unfortunately, first-generation techniques, relying on large irradiation fields, were associated with an increased risk of secondary cancers, and of cardiac and lung toxicity. Fortunately, the use of smaller target volumes combined with [...] Read more.
Consolidative radiation therapy for early-stage Hodgkin lymphoma (HL) improves progression-free survival. Unfortunately, first-generation techniques, relying on large irradiation fields, were associated with an increased risk of secondary cancers, and of cardiac and lung toxicity. Fortunately, the use of smaller target volumes combined with technological advances in treatment techniques currently allows efficient organs-at-risk sparing without altering tumoral control. Recently, proton therapy has been evaluated for mediastinal HL treatment due to its potential to significantly reduce the dose to organs-at-risk, such as cardiac substructures. This is expected to limit late radiation-induced toxicity and possibly, second-neoplasm risk, compared with last-generation intensity-modulated radiation therapy. However, the democratization of this new technique faces multiple issues. Determination of which patient may benefit the most from proton therapy is subject to intense debate. The development of new effective systemic chemotherapy and organizational, societal, and political considerations might represent impediments to the larger-scale implementation of HL proton therapy. Based on the current literature, this critical review aims to discuss current challenges and controversies that may impede the larger-scale implementation of mediastinal HL proton therapy. Full article
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Other

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Brief Report
Radiation-Induced Dyspnea in Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy
Cancers 2021, 13(15), 3734; https://doi.org/10.3390/cancers13153734 - 25 Jul 2021
Viewed by 732
Abstract
In this study, we investigated the prognostic factors for radiation-induced dyspnea after hypo-fractionated radiation therapy (RT) in 106 patients treated with Stereotactic Body RT for Non-Small-Cell Lung Cancer (NSCLC). The median prescription dose was 50 Gy (range: 40–54 Gy), delivered in a median [...] Read more.
In this study, we investigated the prognostic factors for radiation-induced dyspnea after hypo-fractionated radiation therapy (RT) in 106 patients treated with Stereotactic Body RT for Non-Small-Cell Lung Cancer (NSCLC). The median prescription dose was 50 Gy (range: 40–54 Gy), delivered in a median of four fractions (range: 3–12). Dyspnea within six months after SBRT was scored according to CTCAE v.4.0. Biologically Effective Dose (α/β = 3 Gy) volume histograms for lungs and heart were extracted. Dosimetric parameters along with patient-specific and treatment-related factors were analyzed, multivariable logistic regression method with Leave-One-Out (LOO) internal validation applied. Model performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC) and calibration plot parameters. Fifty-seven patients (53.8%) out of 106 developed dyspnea of any grade after SBRT (25/57 grade ≥ 2 cases). A three-variable predictive model including patient comorbidity (COPD), heart volume and the relative lungs volume receiving more than 15 Gy was selected. The model displays an encouraging performance given by a training ROC-AUC = 0.71 [95%CI 0.61–0.80] and a LOO-ROC-AUC = 0.64 [95%CI 0.53–0.74]. Further modeling efforts are needed for dyspnea prediction in hypo-fractionated treatments in order to identify patients at high risk for developing lung toxicity more accurately. Full article
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