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Zhang Q, Fan S, Xu X, Du S, Zhu G, Jiang C, Xia SA, Li Q, Wang Q, Qian D, Zhang M, Xiao H, Chen G, Zeng Z, He J. Efficacy and Toxicity of Moderately Hypofractionated Radiation Therapy with Helical TomoTherapy Versus Conventional Radiation Therapy in Patients with Unresectable Stage III Non-Small Cell Lung Cancer Receiving Concurrent Chemotherapy: A Multicenter, Randomized Phase 3 Trial. Int J Radiat Oncol Biol Phys 2024; 120:422-431. [PMID: 38631536 DOI: 10.1016/j.ijrobp.2024.03.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 03/08/2024] [Accepted: 03/20/2024] [Indexed: 04/19/2024]
Abstract
PURPOSE The standard treatment schedule for unresectable stage III non-small cell lung cancer (NSCLC) is chemotherapy with concurrent radiation therapy (60 Gy delivered in 30 fractions), although moderately hypofractionated radiation therapy (Hypo-RT) has also been considered as an alternative strategy. This study aimed to compare the efficacy and toxicity of moderately Hypo-RT with helical TomoTherapy versus conventionally fractionated radiation therapy (Con-RT) in patients with unresectable stage III NSCLC receiving concurrent chemotherapy. METHODS AND MATERIALS In this randomized, multicenter, nonblinded phase 3 clinical trial, eligible patients were randomised at a 1:1 ratio to either the Hypo-RT group (60 Gy in 20 fractions) or Con-RT group (60 Gy in 30 fractions). All patients received 2 cycles of concurrent platinum-based chemotherapy plus 2 cycles of consolidation therapy. The primary endpoint was 3-year overall survival (OS) in the intention-to-treat population. The secondary endpoints were progression-free survival and treatment-related adverse events. RESULTS A total of 146 patients were enrolled from July 27, 2018, to November 1, 2021. The median follow-up was 46 months. The 3-year OS rates in the Hypo-RT and Con-RT groups were 58.4% and 38.4%, respectively (P = .02). The median OS from randomisation was 41 months in the Hypo-RT group and 30 months in the Con-RT group (hazard ratio, 0.61; 95% confidence interval, 0.40-0.94; P = .02). There was no significant difference in the rates of grade ≥2 treatment-related adverse events between the 2 groups. CONCLUSIONS Moderately Hypo-RT using helical TomoTherapy may improve OS in patients with unresectable stage III NSCLC, while maintaining toxicity rates.
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Affiliation(s)
- Qi Zhang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shaonan Fan
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaohong Xu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shisuo Du
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guangying Zhu
- Department of Radiation Oncology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Chaoyang Jiang
- Department of Oncology, The General Hospital of Western Theater Command, Chengdu, Sichuan, China
| | - Shi-An Xia
- Department of Oncology, Xinhua Hospital Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Qiwen Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qifeng Wang
- Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China
| | - Dong Qian
- Department of Radiation Oncology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China
| | - Ming Zhang
- Department of Radiation Oncology, Yunnan Cancer Hospital & the Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
| | - Han Xiao
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Gang Chen
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhaochong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Jian He
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
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Bensenane R, Helfre S, Cao K, Carton M, Champion L, Girard N, Glorion M, Vieira T, Waissi W, Crehange G, Beddok A. Optimizing lung cancer radiation therapy: A systematic review of multifactorial risk assessment for radiation-induced lung toxicity. Cancer Treat Rev 2024; 124:102684. [PMID: 38278078 DOI: 10.1016/j.ctrv.2024.102684] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 12/27/2023] [Accepted: 01/11/2024] [Indexed: 01/28/2024]
Abstract
BACKGROUND Radiation therapy (RT) is essential in treating advanced lung cancer, but may lead to radiation pneumonitis (RP). This systematic review investigates the use of pulmonary function tests (PFT) and other parameters to predict and mitigate RP, thereby improving RT planning. METHODS A systematic review sifted through PubMed and on BioMed Central, targeting articles from September 2005 to December 2022 containing the keywords: Lung Cancer, Radiotherapy, and pulmonary function test. RESULTS From 1153 articles, 80 were included. RP was assessed using CTCAEv.4 in 30 % of these. Six studies evaluated post-RT quality of life in lung cancer patients, reporting no decline. Patients with RP and chronic obstructive pulmonary disease (COPD) generally exhibited poorer overall survival. Notably, forced expiratory volume in one second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) declined 24 months post-RT, while forced vital capacity (FVC) stayed stable. In the majority of studies, age over 60, tumors located in the lower part of the lung, and low FEV1 before RT were associated with a higher risk of RP. Dosimetric factors (V5, V20, MLD) and metabolic imaging emerged as significant predictors of RP risk. A clinical checklist blending patient and tumor characteristics, PFT results, and dosimetric criteria was proposed for assessing RP risk before RT. CONCLUSION The review reveals the multifactorial nature of RP development following RT in lung cancer. This approach should guide individualized management and calls for a prospective study to validate these findings and enhance RP prevention strategies.
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Affiliation(s)
- Rayan Bensenane
- Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France
| | - Sylvie Helfre
- Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France
| | - Kim Cao
- Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France
| | | | | | - Nicolas Girard
- Institut Curie, Department of Thoracic Oncology, Paris, France
| | | | - Thibaut Vieira
- Institut Mutualist Montsouris, Department of Pneumology, Paris, France
| | - Waisse Waissi
- Centre Léon Bérard, Department of Radiation Oncology, Lyon, France
| | - Gilles Crehange
- Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France
| | - Arnaud Beddok
- Institut Curie, PSL Research University, Radiation Oncology Department, Paris/Saint-Cloud/Orsay, France; Institut Curie, PSL Research University, University Paris Saclay, Inserm LITO, 91898 Orsay, France.
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Tambe NS, Pires IM, Moore CS, Wieczorek A, Upadhyay S, Beavis AW. Predicting personalised and progressive adaptive dose escalation to gross tumour volume using knowledge-based planning models for inoperable advanced-stage non-small cell lung cancer patients treated with volumetric modulated arc therapy. Biomed Phys Eng Express 2022; 8. [PMID: 35189613 DOI: 10.1088/2057-1976/ac56eb] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 02/21/2022] [Indexed: 11/12/2022]
Abstract
OBJECTIVES Increased radiation doses could improve local control and overall survival of lung cancer patients, however, this could be challenging without exceeding organs at risk (OAR) dose constraints especially for patients with advanced-stage disease. Increasing OAR doses could reduce the therapeutic ratio and quality of life. It is therefore important to investigate methods to increase the dose to target volume without exceeding OAR dose constraints. METHODS Gross tumour volume (GTV) was contoured on synthetic computerised tomography (sCT) datasets produced using the Velocity adaptive radiotherapy software for eleven patients. The fractions where GTV volume decreased compared to that prior to radiotherapy (reference plan) were considered for personalised progressive dose escalation. The dose to the adapted GTV (GTVAdaptive) was increased until OAR doses were affected (as compared to the original clinical plan). Planning target volume (PTV) coverage was maintained for all plans. Doses were also escalated to the reference plan (GTVClinical) using the same method. Adapted, dose-escalated, plans were combined to estimate accumulated dose, D99 (dose to 99%) of GTVAdapted, PTV D99 and OAR doses and compared with those in the original clinical plans. Knowledge-based planning (KBP) model was developed to predict D99 of the adapted GTV with OAR doses and PTV coverage kept similar to the original clinical plans; prediction accuracy and model verification were performed using further data sets. RESULTS Compared to the original clinical plan, dose to GTV was significantly increased without exceeding OAR doses. Adaptive dose-escalation increased the average D99 to GTVAdaptive by 15.1Gy and 8.7Gy compared to the clinical plans. The KBP models were verified and demonstrated prediction accuracy of 0.4% and 0.7% respectively. CONCLUSION Progressive adaptive dose escalation can significantly increase the dose to GTV without increasing OAR doses or compromising dose to microscopic disease. This may increase overall survival without increasing toxicities.
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Affiliation(s)
- Nilesh S Tambe
- Radiation Physics Department, Hull University Teaching Hospitals NHS Trust, Queens Centre For Oncology And Haematology, Castle Hill Hospital, Castle Road, Cottingham, HU16 5JQ, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
| | - Isabel M Pires
- Biomedical Sciences, University of Hull, Cottingham Road,, Hardy Building,, Hull, Kingston upon Hull, HU6 7RX, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
| | - Craig Steven Moore
- Medical Physics, Hull University Teaching Hospitals NHS Trust, Queens Centre, Castle Hill Hospital, Cottingham, Hull, HU16 5LH, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
| | - Andrzej Wieczorek
- Hull University Teaching Hospitals NHS Trust, Department of Clinical Oncology, The Queen's Centre, Cottingham, Hull, Kingston upon Hull, HU3 2JZ, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
| | - Sunil Upadhyay
- Clinical Oncology Department, Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital,, Queen's Centre for Oncology and Hematology, Castle Road, Cottingham, Kingston upon Hull, HU16 5JQ, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
| | - Andrew W Beavis
- Department of Radiotherapy Physics, Hull University Teaching Hospitals NHS Trust, Castle Hill Hospital, Hull, Kingston upon Hull, HU3 2JZ, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
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Pallotta S, Marrazzo L, Calusi S, Castriconi R, Fiorino C, Loi G, Fiandra C. Implementation of automatic plan optimization in Italy: Status and perspectives. Phys Med 2021; 92:86-94. [PMID: 34875426 DOI: 10.1016/j.ejmp.2021.11.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/20/2021] [Accepted: 11/24/2021] [Indexed: 01/04/2023] Open
Abstract
PURPOSE To investigate and report on the diffusion and clinical use of automated radiotherapy planning systems in Italy and to assess the perspectives of the community of Italian medical physicists involved in radiotherapy on the use of these tools. MATERIALS AND METHODS A survey of medical physicists (one per Institute) of 175 radiotherapy centers in Italy was conducted between February 21st and April 1st, 2021. The information collected included the institute's characteristics, plan activity, availability/use of automatic tools and related issues regarding satisfaction, criticisms, expectations, and perceived professional modifications. Responses were analysed, including the impact of a few variables such as the institute type and experience. RESULTS 125 of the centers (71%) answered the survey, with regional variability (range: 47%-100%); among these, 49% have a TPS with some automatic option. Clinical use of automatic planning is present in 33% of the centers, with 13% applying it in >50% of their plans. Among the 125 responding centres the most used systems are Pinnacle (16%), Raystation (9%) and Eclipse (4%). The majority of participants consider the use of automated techniques to be beneficial, while only 1% do not see any advantage; 83% of respondents see the possibility of enriching their professional role as a potential benefit, while 3% see potential threats. CONCLUSIONS Our survey shows that 49% of the responding centres have an automatic planning solution although clinically used in only 33% of the cases. Most physicists consider the use of automated techniques to be beneficial and show a prevalently positive attitude.
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Affiliation(s)
- Stefania Pallotta
- University of Florence, Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Florence, Italy; Medical Physics Unit, AOU Careggi, Florence, Italy.
| | | | - Silvia Calusi
- University of Florence, Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Florence, Italy
| | | | - Claudio Fiorino
- Medical Physics, San Raffaele Scientific Institute, Milano, Italy
| | - Gianfranco Loi
- Medical Physics, AOU Maggiore della Carità, Novara, Italy
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Imano N, Kimura T, Kawahara D, Nishioka R, Fukumoto W, Kawano R, Kubo K, Katsuta T, Takeuchi Y, Nishibuchi I, Murakami Y, Horimasu Y, Masuda T, Fujitaka K, Hattori N, Nagata Y. Potential benefits of volumetric modulated arc therapy to reduce the incidence of ≥ grade 2 radiation pneumonitis in radiotherapy for locally advanced non-small cell lung cancer patients. Jpn J Clin Oncol 2021; 51:1729-1735. [PMID: 34625805 DOI: 10.1093/jjco/hyab163] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/29/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND The use of volumetric modulated arc therapy is gradually widespread for locally advanced non-small cell lung cancer. The purpose of this study was to identify the factors that caused ≥ grade 2 radiation pneumonitis and evaluate the impact of using volumetric modulated arc therapy on the incidence of ≥ grade 2 radiation pneumonitis by comparing three-dimensional conformal radiation therapy. METHODS We retrospectively evaluated 124 patients who underwent radical radiotherapy for locally advanced non-small cell lung cancer in our institution between 2008 and 2019. The following variables were analysed to detect the factors that affected ≥ grade 2 radiation pneumonitis; age, sex, the presence of interstitial lung disease, pulmonary emphysema, tumour location, stage, PTV/lung volume, lung V20Gy, total dose, concurrent chemoradiotherapy, adjuvant immune checkpoint inhibitor, radiotherapy method. Radiation pneumonitis was evaluated using the common terminology criteria for adverse events (version 5.0). RESULTS A total of 84 patients underwent three-dimensional conformal radiation therapy (3D-CRT group) and 40 patients underwent volumetric modulated arc therapy (VMAT group). The cumulative incidence of ≥ grade 2 radiation pneumonitis at 12 months was significantly lower in the VMAT group than in the 3D-CRT group (25% vs. 49.1%). The use of volumetric modulated arc therapy was a significant factor for ≥ grade 2 radiation pneumonitis (HR:0.32, 95% CI: 0.15-0.65, P = 0.0017) in addition to lung V20Gy (≥ 24%, HR:5.72 (95% CI: 2.87-11.4), P < 0.0001) and total dose (≥ 70 Gy, HR:2.64 (95% CI: 1.39-5.03), P = 0.0031) even after adjustment by multivariate analysis. CONCLUSIONS We identified factors associated with ≥ grade 2 radiation pneumonitis in radiotherapy for patients with locally advanced non-small cell lung cancer. Volumetric modulated arc therapy has potential benefits to reduce the risk of ≥ grade 2 radiation pneumonitis.
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Affiliation(s)
- Nobuki Imano
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tomoki Kimura
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
- Department of Radiation Oncology, Kochi Medical School, Kochi University, Nankoku-shi, Kochi, Japan
| | - Daisuke Kawahara
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Riku Nishioka
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Wataru Fukumoto
- Department of Diagnostic Radiology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Reo Kawano
- Clinical Research Center in Hiroshima, Hiroshima University Hospital, Hiroshima, Japan
| | - Katsumaro Kubo
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Katsuta
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuki Takeuchi
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ikuno Nishibuchi
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuji Murakami
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasushi Horimasu
- Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takeshi Masuda
- Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazunori Fujitaka
- Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Noboru Hattori
- Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yasushi Nagata
- Department of Radiation Oncology, Graduate School of Biomedical Health Sciences, Hiroshima University, Hiroshima, Japan
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Sequential chemo-hypofractionated RT versus concurrent standard CRT for locally advanced NSCLC: GRADE recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Radiol Med 2021; 126:1117-1128. [PMID: 33954898 DOI: 10.1007/s11547-021-01362-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 04/19/2021] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach. AIMS A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC MATERIALS AND METHODS: The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3-G4 toxicity, late pulmonary toxicity G3-G4, and acute esophageal toxicity G3-G4. RESULTS The probability of OS and G3-G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms. CONCLUSIONS The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.
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Kepka L, Socha J. Dose and fractionation schedules in radiotherapy for non-small cell lung cancer. Transl Lung Cancer Res 2021; 10:1969-1982. [PMID: 34012807 PMCID: PMC8107746 DOI: 10.21037/tlcr-20-253] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
In the field of radiotherapy (RT), the issues of total dose, fractionation, and overall treatment time for non-small cell lung cancer (NSCLC) have been extensively investigated. There is some evidence to suggest that higher treatment intensity of RT, when given alone or sequentially with chemotherapy (CHT), is associated with improved survival. However, there is no evidence that the outcome is improved by RT at a higher dose and/or higher intensity when it is used concurrently with CHT. Moreover, some reports on the combination of full dose CHT with a higher biological dose of RT warn of the significant risk posed by such intensification. Stereotactic body radiotherapy (SBRT) provides a high rate of local control in the management of early-stage NSCLC through the use of high ablative doses. However, in centrally located tumors the use of SBRT may carry a risk of serious damage to the great vessels, bronchi, and esophagus, owing to the high ablative doses needed for optimal tumor control. There is a similar problem with moderate hypofractionation in radical RT for locally advanced NSCLC, and more evidence needs to be gathered regarding the safety of such schedules, especially when used in combination with CHT. In this article, we review the current evidence and questions related to RT dose/fractionation in NSCLC.
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Affiliation(s)
- Lucyna Kepka
- Department of Radiotherapy, Military Institute of Medicine, Warsaw, Poland
| | - Joanna Socha
- Department of Radiotherapy, Military Institute of Medicine, Warsaw, Poland
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Impact of Low-Dose Irradiation of the Lung and Heart on Toxicity and Pulmonary Function Parameters after Thoracic Radiotherapy. Cancers (Basel) 2020; 13:cancers13010022. [PMID: 33374564 PMCID: PMC7793060 DOI: 10.3390/cancers13010022] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/14/2020] [Accepted: 12/19/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary To assess the impact of thoracic (low) dose irradiation on pulmonary function changes after thoracic radiotherapy (RT) data of 62 patients were analyzed. There were several significant correlations between pulmonary function and dose parameters of the lung and heart, most of which remained significant in the multivariate analysis. 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 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 (DLCO)). 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 DLCO and low-dose parameters of the lungs (V5Gy–V30Gy (%)) and irradiation of the heart during the follow-up up to 6 months after RT, as well as a temporary correlation of the V60Gy (%) on the blood gas parameters at 12 weeks after RT. On multivariate analysis, both heart and lung parameters had a significant impact on DLCO. 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 DLCO after thoracic radiotherapy. No influence on RP was found in this analysis.
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Marrazzo L, Arilli C, Pellegrini R, Bonomo P, Calusi S, Talamonti C, Casati M, Compagnucci A, Livi L, Pallotta S. Automated planning through robust templates and multicriterial optimization for lung VMAT SBRT of lung lesions. J Appl Clin Med Phys 2020; 21:114-120. [PMID: 32275353 PMCID: PMC7324702 DOI: 10.1002/acm2.12872] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 03/05/2020] [Accepted: 03/10/2020] [Indexed: 12/24/2022] Open
Abstract
Purpose To develop and validate a robust template for VMAT SBRT of lung lesions, using the multicriterial optimization (MCO) of a commercial treatment planning system. Methods The template was established and refined on 10 lung SBRT patients planned for 55 Gy/5 fr. To improve gradient and conformity a ring structure around the planning target volume (PTV) was set in the list of objectives. Ideal fluence optimization was conducted giving priority to organs at risk (OARs) and using the MCO, which further pushes OARs doses. Segmentation was conducted giving priority to PTV coverage. Two different templates were produced with different degrees of modulation, by setting the Fluence Smoothing parameter to Medium (MFS) and High (HFS). Each template was applied on 20 further patients. Automatic and manual plans were compared in terms of dosimetric parameters, delivery time, and complexity. Statistical significance of differences was evaluated using paired two‐sided Wilcoxon signed‐rank test. Results No statistically significant differences in PTV coverage and maximum dose were observed, while an improvement was observed in gradient and conformity. A general improvement in dose to OARs was seen, which resulted to be significant for chest wall V30 Gy, total lung V20 Gy, and spinal cord D0.1 cc. MFS plans are characterized by a higher modulation and longer delivery time than manual plans. HFS plans have a modulation and a delivery time comparable to manual plans, but still present an advantage in terms of gradient. Conclusion The automation of the planning process for lung SBRT using robust templates and MCO was demonstrated to be feasible and more efficient.
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Affiliation(s)
- Livia Marrazzo
- Careggi University Hospital, Medical Physic Unit, Florence, Italy
| | - Chiara Arilli
- Careggi University Hospital, Medical Physic Unit, Florence, Italy
| | | | | | - Silvia Calusi
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Cinzia Talamonti
- Careggi University Hospital, Medical Physic Unit, Florence, Italy.,Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Marta Casati
- Careggi University Hospital, Medical Physic Unit, Florence, Italy
| | | | - Lorenzo Livi
- Careggi University Hospital, Radiotherapy Unit, Florence, Italy.,Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Stefania Pallotta
- Careggi University Hospital, Medical Physic Unit, Florence, Italy.,Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
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Vekens K, Verbanck S, Collen C, Storme G, Barbé K, De Ridder M, Vanderhelst E. Pulmonary function changes following helical tomotherapy in patients with inoperable, locally advanced non-small cell lung cancer. Strahlenther Onkol 2019; 196:142-150. [PMID: 31300831 DOI: 10.1007/s00066-019-01489-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 06/22/2019] [Indexed: 12/25/2022]
Abstract
PURPOSE To evaluate alterations in pulmonary function indices after helical tomotherapy and explore potential associations with biologically corrected dosimetric parameters. PATIENTS AND METHODS In 64 patients with inoperable locally advanced non-small cell lung cancer, pulmonary function tests before and within 6 months after radiotherapy were evaluated retrospectively. In the case of concurrent chemotherapy a total dose of 67.2 Gy was delivered, otherwise 70.5 Gy was provided. In 44 patients, late pulmonary function changes (≥6 months after radiotherapy) could also be assessed. RESULTS In the entire patient group, there were significant declines in forced expiratory volume in 1s (FEV1) (average change -4.1% predicted; P = 0.007), in forced vital capacity (FVC) (-4.9% predicted; P = 0.002), total lung capacity (TLC) (-5.8% predicted; P = 0.0016) and DLCO (diffusing capacity of the lung for carbon monoxide corrected for hemoglobin level) (-8.6% predicted; P < 0.001) during the first 6 months. Corresponding FEV1, FVC, TLC and DLCO declines in the subgroup with late measurements (after 11.3 months on average) were -5.7, -7.4, -7.0, -9.8% predicted. A multivariate analysis including V5 Gy, V10 Gy, V20 Gy, V40 Gy, V60 Gy, mean lung dose (MLD), gross tumor volume (GTV) and planning target volume (PTV) as potential covariates showed that GTV was the most consistent contributor, being significant for ∆FEV1 (P = 0.003), ∆FVC (P = 0.003), ∆TLC (P = 0.001) and ∆DLCO (P = 0.01). V5 Gy or V10 Gy did not contribute to any of the lung function changes. CONCLUSIONS The decline in pulmonary function indices after helical tomotherapy was of similar magnitude to that observed in studies reporting the effect of conformal radiotherapy on lung function. Diffusion capacity was the parameter showing the largest decrease following radiation therapy as compared to baseline and correlated with gross tumor volume. None of the alterations in pulmonary function tests were associated with the lung volume receiving low-dose radiation.
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Affiliation(s)
- K Vekens
- Respiratory Division, University Hospital UZ Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium.
| | - S Verbanck
- Respiratory Division, University Hospital UZ Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - C Collen
- Department of Radiotherapy, University Hospital UZ Brussel, Brussels, Belgium
| | - G Storme
- Department of Radiotherapy, University Hospital UZ Brussel, Brussels, Belgium
| | - K Barbé
- Department of Biostatistics and Medical Informatics, Vrije Universiteit Brussel, Brussels, Belgium
| | - M De Ridder
- Department of Radiotherapy, University Hospital UZ Brussel, Brussels, Belgium
| | - E Vanderhelst
- Respiratory Division, University Hospital UZ Brussel, Laarbeeklaan 101, 1090, Brussels, Belgium
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Liu Y, Yue C, Zhu J, Yu H, Cheng Y, Yin Y, Li B, Dong J. A Megavoltage CT Image Enhancement Method for Image-Guided and Adaptive Helical TomoTherapy. Front Oncol 2019; 9:362. [PMID: 31134157 PMCID: PMC6524307 DOI: 10.3389/fonc.2019.00362] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 04/18/2019] [Indexed: 01/08/2023] Open
Abstract
Purpose: To propose a novel method to improve the mega-voltage CT (MVCT) image quality for helical TomoTherapy while maintaining the stability on dose calculation. Materials and Methods: The Block-Matching 3D-transform (BM3D) and Discriminative Feature Representation (DFR) methods were combined into a novel BM3D + DFR method for their respective advantages. A phantom (Catphan504) and three serials of clinical (head & neck, chest, and pelvis) MVCT images from 30 patients were acquired using the helical TomoTherapy system. The contrast-to-noise ratio (CNR) and edge detection algorithm (canny) was employed for image quality comparisons between the original and BM3D + DFR enhanced MVCT. A simulated rectangular field of 6 MV X-ray beams were vertically delivered on the original and post-processed MVCT serials of the same CT density phantom, and the dose curves on both serials were compared to test the effects of image enhancement on dose calculation accuracy. Results: In total, 466 transversal MVCT slices were acquired and processed by both BM3D and the proposed BM3D + DFR methods. Compared to the original MVCT image, the BM3D + DFR method presented a remarkable improvement in terms of the soft tissue contrast and noise reduction. For the phantom image, the CNR of the region of interest (ROI) was improved from 1.70 to 4.03. The average CNR of ROIs for 10 patients from each anatomical group, were increased significantly from 1.45 ± 1.51 to 2.09 ± 1.68 for the head & neck (p < 0.001), from 0.92 ± 0.78 to 1.36 ± 0.85 for the chest (p < 0.001), and from 1.12 ± 1.22 to 1.76 ± 1.31 for the pelvis (p < 0.001), respectively. The canny edge detection operator showed that BM3D + DFR provided clearer organ boundaries with less chaos. The root-mean-square of the dosimetry difference on the iso-center passed horizontal dose profile curves and vertical percentage depth dose curves were only 0.09% and 0.06%, respectively. Conclusions: The proposed BM3D + DFR method is feasible to improve the soft tissue contrast for the original MVCT images with coincidence in dose calculation and without compromising resolution. After integration in clinical workflow, the post-processed MVCT may be better applied on image-guided and adaptive helical TomoTherapy.
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Affiliation(s)
- Yaru Liu
- Network-Based Intelligent Computing, University of Jinan, Jinan, China
| | - Chenxi Yue
- Network-Based Intelligent Computing, University of Jinan, Jinan, China
| | - Jian Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, China.,Shandong Key Laboratory of Digital Medicine and Computer Assisted Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Haining Yu
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, China
| | - Yang Cheng
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, China
| | - Yong Yin
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, China
| | - Baosheng Li
- Department of Radiation Oncology, Shandong Cancer Hospital, Shandong University, Jinan, China
| | - Jiwen Dong
- Network-Based Intelligent Computing, University of Jinan, Jinan, China
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12
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Li S, Yang J, Liu J, Gao S, Liu B, Yan J. Dosimetric comparison of helical tomotherapy and conventional Linac-based X-knife stereotactic body radiation therapy for primary lung cancer or pulmonary metastases. J Thorac Dis 2018; 10:999-1006. [PMID: 29607173 DOI: 10.21037/jtd.2018.01.64] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background To compare helical tomotherapy (HT) with X-knife stereotactic body radiation therapy (HT-SBRT/X-SBRT) for primary or metastatic lung cancer regarding planning target volume (PTV) coverage, such as homogeneity index (HI), conformity index (CI) and dose-volume histogram (DVH) of organs at risk (OARs). Methods We retrospectively analyzed 21 patients receiving definitive radiation treatment for non-small cell lung cancer (NSCLC) or pulmonary metastases at our institution between March 2015 and October 2016. Tumors were irradiated with 4-10 Gy per fraction in 5-15 fractions. Plans were compared according to PTV coverage and OARs sparing. Results Significant differences between HT and X-knife were observed for both HI (P=0.003) and CI (P<0.001). The V5 (P=0.001), V10 (P=0.009), V20 (P=0.001), the mean lung dose (P=0.005) of total lung and maximum dose of the spinal cord (P=0.010) were significantly lower in the X-SBRT group than the HT-SBRT group. There were no significant differences for the V30 (P=0.075) and the mean heart dose (P=0.584) between the two groups. Conclusions X-SBRT was dosimetrically superior to HT-SBRT, when applied in these tumors' maximum diameters <5 cm. As HT resulted in increased low-dose volume, it is essential to optimize the patient selection in order to avoid severe radiation pneumonitis in HT-SBRT.
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Affiliation(s)
- Shuangshuang Li
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
| | - Ju Yang
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
| | - Juan Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
| | - Shanbao Gao
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
| | - Baorui Liu
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
| | - Jing Yan
- The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, China
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13
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Mukai Y, Omura M, Hashimoto H, Matsui K, Hongo H, Yamakabe W, Yoshida M, Hata M, Inoue T. Treatment outcome for locally advanced non-small-cell lung cancer using TomoDirect plan and its characteristics compared to the TomoHelical plan. J Med Radiat Sci 2018; 65:55-62. [PMID: 29393591 PMCID: PMC5846024 DOI: 10.1002/jmrs.265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 10/31/2017] [Accepted: 01/06/2018] [Indexed: 12/25/2022] Open
Abstract
Introduction TomoDirect (TD) is an intensity‐modulated radiotherapy system that uses a fixed gantry angle instead of the rotational beam delivery used in the TomoHelical (TH) system. This study was performed (1) to evaluate the treatment outcome of the TD plan for locally advanced non‐small‐cell lung cancer (NSCLC) and (2) to compare the characteristics of TD plans with those of TH plans. Methods Twenty‐one patients with NSCLC were treated using the TD system. The prescribed dose was 40 Gy/20 Fx for the initial planning target volume (PTV), which included the gross tumour volume (GTV) and lymph node regions. A boost plan of 20 Gy/10 Fx was then applied, focusing on the GTV. For the planning study, matched TH plans of 40 Gy for the initial PTV were created for each patient, to meet the same dosimetric constraints specified in the TD plans. Results The 2‐year overall survival, progression‐free survival and local control rates were 47%, 45% and 74% respectively. Grade 2 treatment‐related pneumonitis occurred in three (14%) patients. The planning study comparing TD and TH showed that dose distribution to GTV and PTV were not significantly different. The lung V5 Gy was lower in the TD plans than TH plans (46.4 ± 5.4 vs. 52.3 ± 8.5), while the V20 Gy was higher (26.2 ± 4 vs. 24 ± 4.3). The TD plans had a significantly shorter treatment time than TH plans (4.5 ± 1.3 min vs. 9.8 ± 1.5 min). Conclusions TD is a clinically acceptable treatment option for NSCSL. The quality of the TD and TH plans are comparable.
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Affiliation(s)
- Yuki Mukai
- Department of Radiology, Yokohama City University, Graduate School of Medicine, Yokohama, Kanagawa, Japan
| | - Motoko Omura
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Harumitu Hashimoto
- Department of Radiation Oncology, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Kanagawa, Japan
| | - Kengo Matsui
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Hideyuki Hongo
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Wataru Yamakabe
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Miwa Yoshida
- Department of Radiation Oncology, Shonan Kamakura General Hospital, Kamakura, Kanagawa, Japan
| | - Masaharu Hata
- Department of Radiology, Yokohama City University, Graduate School of Medicine, Yokohama, Kanagawa, Japan
| | - Tomio Inoue
- Department of Radiology, Yokohama City University, Graduate School of Medicine, Yokohama, Kanagawa, Japan
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The potential for increased tumor control probability in non-small cell lung cancer with a hypofractionated integrated boost to the gross tumor volume. Med Dosim 2018; 43:352-357. [PMID: 29289456 DOI: 10.1016/j.meddos.2017.11.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 11/08/2017] [Accepted: 11/21/2017] [Indexed: 12/25/2022]
Abstract
Treatment outcomes in locally advanced non-small cell lung cancer (NSCLC) to date have been poor, with normal tissue toxicity often limiting the dose that can be delivered to the tumor. Treatment intensification in NSCLC via targeted dose escalation with modern delivery techniques may offer the potential for a significant increase in tumor control probability (TCP) without a clinically significant increase in organ-at-risk (OAR) toxicity. In this planning study, 20 patients were re-planned with a volumetric modulated arc therapy (VMAT) and an inhomogeneous dose distribution with iteratively escalated doses to the gross tumor volume (iGTV) (composite GTV across multiple 4-dimensional computed tomography [4DCT] phases) in a series of 20 fraction regimes. For each plan OAR doses, target coverage and predicted TCPs were collected and compared with homogenous 3-dimensional (3D) and VMAT plans, as well as with each other. In 70% of patients, it was possible to escalate to 75 Gy in 20 fractions within OAR tolerances, opening the possibility of treating these patients to a biological effective dose (BED) of 103.1 Gy10. This planning study forms the basis of a clinical trial INTENSE (Inhomogeneous Targeted Dose Escalation in Non-Small CEll Lung Cancer), CTRIAL 15-47.
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15
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Niezink AGH, de Jong RA, Muijs CT, Langendijk JA, Widder J. Pulmonary Function Changes After Radiotherapy for Lung or Esophageal Cancer: A Systematic Review Focusing on Dose-Volume Parameters. Oncologist 2017; 22:1257-1264. [PMID: 28550029 DOI: 10.1634/theoncologist.2016-0324] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Accepted: 03/28/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Despite technical developments in treatment delivery, radiation-induced lung toxicity (RILT) remains a crucial problem in thoracic radiotherapy. Clinically based RILT scores have their limitations, and more objective measures such as pulmonary functions tests (PFTs) might help to improve treatment strategies. PURPOSE To summarize the available evidence about the effect of dose to the lung in thoracic radiotherapy on forced expiratory volume in one second (FEV1) and diffusion capacity (DLCO) in patients with lung and esophageal cancer treated with curative intent. MATERIAL AND METHODS A systematic review following the PRISMA guidelines was performed, using MEDLINE and including clinical studies using (chemo)radiotherapy (CRT) or stereotactic ablative radiotherapy (SABR) for lung or CRT for esophageal cancer that reported both lung dose-volume histogram (DVH) parameters and changes in PFT results. Search terms included lung and esophageal neoplasms, respiratory function tests, and radiotherapy. RESULTS Fifteen studies met the inclusion criteria. Seven out of 13 studies on lung cancer reported significant declines (defined as a p value < .05) in PFT results. Both esophageal studies reported significant DLCO declines. One SABR study found a correlation between low lung-dose parameters and FEV1 decline. Relations between decline of FEV1 (three studies) or decline of DLCO (five studies), respectively, and DVH parameters were found in eight studies analyzing CRT. Furthermore, a heterogeneous range of clinical risk factors for pulmonary function changes were reported in the selected studies. CONCLUSIONS There is evidence that pulmonary function declines after RT in a dose-dependent manner, but solid data about lung DVH parameters predicting changes in PFT results are scarce. A major disadvantage was the wide variety of methods used, frequently lacking multivariable analyses. Studies using prospective high-quality data, analyzed with appropriate statistical methods, are needed. The Oncologist 2017;22:1257-1264 IMPLICATIONS FOR PRACTICE: Radiation-induced lung toxicity remains crucial in thoracic radiotherapy. To prevent this toxicity in the future and individualize patient treatment, objective measures of pulmonary toxicity are needed. Pulmonary function tests may provide such objective measures. This systematic review, included all available clinical studies using external beam radiotherapy for lung or esophageal cancer reporting pulmonary function combined with dose-volume histogram parameters. There is preliminary evidence that pulmonary function declines post radiotherapy in a dose-dependent manner. Data quality and analyses were generally limited. Analyses of high-quality data are therefore urgently needed to improve individualization of advanced radiation therapy.
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Affiliation(s)
- Anne G H Niezink
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Renske A de Jong
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Christina T Muijs
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Johannes A Langendijk
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Joachim Widder
- Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria
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16
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Lin G, Xiao H, Zeng Z, Xu Z, He J, Sun T, Liu J, Guo G, Ji W, Hu Y. Constraints for symptomatic radiation pneumonitis of helical tomotherapy hypofractionated simultaneous multitarget radiotherapy for pulmonary metastasis from hepatocellular carcinoma. Radiother Oncol 2017; 123:246-250. [PMID: 28314468 DOI: 10.1016/j.radonc.2017.02.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 01/24/2017] [Accepted: 02/01/2017] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND PURPOSE This study was aimed to identify the clinical and dosimetric parameters that predict symptomatic radiation pneumonitis (SRP, radiation pneumonitis≥2 grade) in patients with pulmonary metastasis from hepatocellular carcinoma (HCC) after helical tomotherapy (HT) hypofractionated simultaneous multitarget radiotherapy. MATERIALS AND METHODS 62 patients with 407 pulmonary metastases from HCC were consecutively treated with HT. The median radiation dose was a 49.7Gy in 4.0Gy/fraction to 95% of the planning target volume (PTV). The associations between the clinical and dosimetric data and incidences of SRP were analyzed. The dose-pneumonitis relationship was analyzed based on Biologically Effective Dose (BED). RESULTS Univariate analysis showed that the gross tumor volume (GTV), PTV, median lung dose (MLD), the number of pulmonary metastatic lesions (NPML), and the percentage of non-target normal lung (NTNL) volume receiving more than a BED of 3-50Gy (VBED3-50) were associated with SRP. Multivariate logistic regression analysis showed that VBED20 and NPML were significant parameters (both P<0.001) CONCLUSIONS: Our findings indicated that SRP can be predicted with NPML>5 and VBED20≥30.4% with the α/β ratio of 3Gy.
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Affiliation(s)
- Genlai Lin
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Han Xiao
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhaochong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
| | - Zhiyong Xu
- Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, China
| | - Jian He
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Taiwei Sun
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jin Liu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Genwu Guo
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weixing Ji
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Hu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
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Storme G, Dhaese S, Corens D, De Ridder M. The cost of cancer care is not related to its outcomes. Ecancermedicalscience 2016; 10:687. [PMID: 27994643 PMCID: PMC5130330 DOI: 10.3332/ecancer.2016.687] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Indexed: 12/02/2022] Open
Abstract
Solid tumours make up 90% of all proliferative diseases and the main action for cure remains surgery, removing the visible tumour as well as the surrounding tissue. Radiotherapy is an added value for eliminating local microscopic as well as regional disease. Systemic treatment has a small impact on the outcome but has a cost, which is as much as all the other actions such as diagnostic tools and treatments.
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Affiliation(s)
- Guy Storme
- Department of Radiation Oncology, UZ Brussel, Belgium
| | - S Dhaese
- Department of Radiation Oncology, UZ Brussel, Belgium
| | - D Corens
- Financial Department, UZ Brussel, Belgium
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Definitive Upfront Stereotactic Ablative Radiotherapy Combined with Image-Guided, Intensity Modulated Radiotherapy (IG-IMRT) or IG-IMRT Alone for Locally Advanced Non-Small Cell Lung Cancer. PLoS One 2016; 11:e0162453. [PMID: 27611833 PMCID: PMC5017732 DOI: 10.1371/journal.pone.0162453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Accepted: 08/23/2016] [Indexed: 11/19/2022] Open
Abstract
Background Image-guided (IG) intensity-modulated radiotherapy (IMRT) enables maximal tumor margin reduction for the sparing of organs at risk (OARs) when used to treat locally advanced non-small cell lung cancer (NSCLC) with definitive chemo-radiation. It also allows for the incorporation of stereotactic ablative radiotherapy (SABR) into the treatment regimen. Here, we describe our initial experience in combining definitive upfront SABR to the primary lesion with chemo-radiation delivered with conventionally fractionated IG-IMRT to the remaining regional disease; along with clinical outcome following chemo-radiation with conventionally fractionated IG-IMRT alone in the treatment of locally advanced NSCLC. Methods The clinical outcome of 29 patients with locally advanced NSCLC who underwent conventionally fractionated IG-IMRT, or definitive upfront SABR followed by IG-IMRT combined with chemotherapy (induction, concurrent, or both) was retrospectively reviewed. Results After a median follow up of 23.7 months, the median overall survival (OS) and progression-free survival (PFS) were 19.8 and 11.3 months, respectively. The 2 year local, regional, and distant control was 60%, 62%, and 38%, respectively. No local failure was observed in 3 patients following SABR + IG-IMRT while 6/26 patients failed locally following IG-IMRT alone. SABR + IG-IMRT was well tolerated. No ≥ grade 3 radiation-related toxicity was observed. Conclusion Definitive upfront SABR followed by IG-IMRT in selected patients with locally advanced NSCLC warrants further investigation in future clinical trials, while chemo-radiation with IG-IMRT alone was well tolerated.
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He J, Huang Y, Chen Y, Shi S, Ye L, Hu Y, Zhang J, Zeng Z. Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT. J Thorac Dis 2016; 8:862-71. [PMID: 27162660 DOI: 10.21037/jtd.2016.03.46] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND The standard treatment for stage III non-small-cell lung cancer (NSCLC) is still 60 Gy in conventional fractions combined with concurrent chemotherapy; however, the resulting local controls are disappointing. The aim of this study was to compare and assess the feasibility and efficacy of hypofractionated chemoradiotherapy using helical tomotherapy (HT) with conventional fractionation as opposed to using three-dimensional conformal radiotherapy (3D-CRT) for stage III NSCLC. METHODS Sixty-nine patients with stage III (AJCC 7th edition) NSCLC who underwent definitive radiation treatment at our institution between July 2011 and November 2013 were reviewed and analyzed retrospectively. A dose of 60 Gy in 20 fractions was delivered in the HT group (n=34), whereas 60 Gy in 30 fractions in the 3D-CRT group (n=35). Primary endpoints were toxicity, overall response rate, overall survival (OS) and progression-free survival (PFS). RESULTS The median follow-up period was 26.4 months. V20 (P=0.005), V30 (P=0.001), V40 (P=0.004), mean lung dose (P=0.000) and max dose of spinal cord (P=0.005) were significantly lower in the HT group than in the 3D-CRT group. There was no significant difference in the incidences of acute radiation pneumonitis (RP) ≥ grade 2 between the two groups, whereas the incidences of acute radiation esophagitis ≥ grade 2 were significantly lower in the HT group than in the 3D-CRT group (P=0.027). Two-year overall response rate was significantly higher in the HT group than in the 3D-CRT group (P=0.015). One- and 2-year OS rates were significantly higher in the HT group (95.0% and 68.7%, respectively) than in the 3D-CRT group (85.5% and 47.6%, respectively; P=0.0236). One- and 2-year PFS rates were significantly higher in the HT group (57.8% and 26.3%, respectively) than in the 3D-CRT group (32.7% and 11.4%, respectively; P=0.0351). Univariate analysis indicated that performance status (PS), T stage and radiotherapy technique were significant prognostic factors for both OS and PFS. Multivariate analysis indicated that PS and radiotherapy technique were independent prognostic factors of OS and PS was independent prognostic factor of PFS. CONCLUSIONS Hypofractionated chemoradiotherapy via HT can shorten the radiotherapy time without increasing treatment-related toxicity. The preliminary findings are that OS and PFS can be improved by hypofractionated chemoradiotherapy via HT for patients with stage III NSCLC.
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Affiliation(s)
- Jian He
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yan Huang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yixing Chen
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Shiming Shi
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Luxi Ye
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yong Hu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jianying Zhang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhaochong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Ren XC, Wang QY, Zhang R, Chen XJ, Wang N, Liu YE, Zong J, Guo ZJ, Wang DY, Lin Q. Accelerated hypofractionated three-dimensional conformal radiation therapy (3 Gy/fraction) combined with concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer: preliminary results of an early terminated phase II trial. BMC Cancer 2016; 16:288. [PMID: 27108080 PMCID: PMC4842268 DOI: 10.1186/s12885-016-2314-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 04/13/2016] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Increasing the biological effective dose (BED) of radiotherapy for non-small cell lung cancer (NSCLC) can increase local control rates and improve overall survival. Compared with conventional fractionated radiotherapy, accelerated hypofractionated radiotherapy can yield higher BED, shorten the total treatment time, and theoretically obtain better efficacy. However, currently, there is no optimal hypofractionated radiotherapy regimen. Based on phase I trial results, we performed this phase II trial to further evaluate the safety and preliminary efficacy of accelerated hypofractionated three-dimensional conformal radiation therapy(3-DCRT) combined with concurrent chemotherapy for patients with unresectable stage III NSCLC. METHODS Patients with previously untreated unresectable stage III NSCLC received 3-DCRT with a total dose of 69 Gy, delivered at 3 Gy per fraction, once daily, five fractions per week, completed within 4.6 weeks. At the same time, platinum doublet chemotherapy was applied. RESULTS After 12 patients were enrolled in the group, the trial was terminated early. There were five cases of grade III radiation esophagitis, of which four cases completed the radiation doses of 51 Gy, 51 Gy, 54 Gy, and 66 Gy, and one case had 16 days of radiation interruption. The incidence of grade III acute esophagitis in patients receiving an irradiation dose per fraction ≥2.7 Gy on the esophagus was 83.3% (5/6). The incidence of symptomatic grade III radiation pneumonitis among the seven patients who completed 69 Gy according to the plan was 28.6% (2/7). The median local control (LC) and overall survival (OS) were not achieved; the 1-year LC rate was 59.3%, and the 1-year OS rate was 78.6%. CONCLUSION For unresectable stage III NSCLC, the accelerated hypofractionated radiotherapy with a total dose of 69 Gy (3 Gy/f) combined with concurrent chemotherapy might result in severe radiation esophagitis and pneumonitis to severely affect the completion of the radiotherapy. Therefore, we considered that this regimen was infeasible. During the hypofractionated radiotherapy with concurrent chemotherapy, the irradiation dose per fraction to esophagus should be lower than 2.7 Gy. Further studies should be performed using esophageal tolerance as a metric in dose escalation protocols. TRIAL REGISTRATION NCT02720614, the date of registration: March 23, 2016.
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Affiliation(s)
- Xiao-Cang Ren
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
| | - Quan-Yu Wang
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
| | - Rui Zhang
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
| | - Xue-Ji Chen
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
| | - Na Wang
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
| | - Yue-E Liu
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
| | - Jie Zong
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
| | - Zhi-Jun Guo
- />Department of Radiology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu, Hebei Province 062552 P.R. China
| | - Dong-Ying Wang
- />Department of Cardiovascular Medicine, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu, Hebei Province 062552 P.R. China
| | - Qiang Lin
- />Department of Oncology, North China Petroleum Bureau General Hospital of Hebei Medical University, 8 Huizhan Avenue, Renqiu City, Hebei Province 062552 P.R. China
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Normal tissue considerations and dose-volume constraints in the moderately hypofractionated treatment of non-small cell lung cancer. Radiother Oncol 2016; 119:423-31. [PMID: 27084120 DOI: 10.1016/j.radonc.2016.03.013] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2015] [Revised: 02/15/2016] [Accepted: 03/11/2016] [Indexed: 12/25/2022]
Abstract
Hypofractionated radiation therapy (RT) regimes in non-small cell lung cancer (NSCLC) have become increasingly popular with a number of international trials currently underway. The majority of the dose-volume-constraints (DVCs) published in the literature refer to conventional 2Gy per fraction deliveries. Here relevant organs-at-risk (OARs) are identified and available dose-volume constraint data discussed and summarised for moderately hypofractionated NSCLC regimes. The OARs examined include lung, brachial plexus, heart, oesophagus, airway and spinal cord. Where available the toxicity rates are also reported with all data summarised tabulated to aid its use in the clinic.
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De Tollenaere C, Lievens Y, Vandecasteele K, Vermaelen K, Surmont V. Unresectable stage III non-small-cell lung cancer: Have we made any progress? World J Respirol 2015; 5:140-151. [DOI: 10.5320/wjr.v5.i2.140] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 03/27/2015] [Accepted: 06/08/2015] [Indexed: 02/06/2023] Open
Abstract
Lung cancer is responsible for the most cancer deaths worldwide with an incidence that is still rising. One third of patients have unresectable stage IIIA or stage IIIB disease. The standard of care for locally advanced disease in patients with good performance status consists of combined modality therapy in particular concurrent chemoradiotherapy. But despite a lot of efforts done in the past, local control and survival of patients with unresectable stage III non-small-cell lung cancer (NSCLC) remains poor. Improving outcomes for patients with unresectable stage III NSCLC has therefore been an area of ongoing research. Research has focused on improving systemic therapy, improving radiation therapy or adding a maintenance therapy to consolidate the initial therapy. Also implementation of newer targeted therapies and immunotherapy has been investigated as well as the option of prophylactic cranial irradiation. This article reviews the latest literature on improving local control and preventing distant metastases. It seems that we have reached a plateau with conventional chemotherapy. Radiotherapy dose escalation did not improve outcome although increasing radiation dose-intensity with new radiotherapy techniques and the use of newer agents, e.g., immunotherapy might be promising. In the future well-designed clinical trials are necessary to prove those promising results.
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Zhu Z, Fu X. The radiation techniques of tomotherapy & intensity-modulated radiation therapy applied to lung cancer. Transl Lung Cancer Res 2015. [PMID: 26207214 DOI: 10.3978/j.issn.2218-6751.2015.01.07] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Radiotherapy (RT) plays an important role in the management of lung cancer. Development of radiation techniques is a possible way to improve the effect of RT by reducing toxicities through better sparing the surrounding normal tissues. This article will review the application of two forms of intensity-modulated radiation therapy (IMRT), fixed-field IMRT and helical tomotherapy (HT) in lung cancer, including dosimetric and clinical studies. The advantages and potential disadvantages of these two techniques are also discussed.
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Affiliation(s)
- Zhengfei Zhu
- 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200433, China ; 3 Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Xiaolong Fu
- 1 Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China ; 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200433, China ; 3 Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
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Kaster TS, Yaremko B, Palma DA, Rodrigues GB. Radical-intent hypofractionated radiotherapy for locally advanced non-small-cell lung cancer: a systematic review of the literature. Clin Lung Cancer 2014; 16:71-9. [PMID: 25450876 DOI: 10.1016/j.cllc.2014.08.002] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 08/14/2014] [Accepted: 08/26/2014] [Indexed: 02/08/2023]
Abstract
PURPOSE To identify survival and toxicity characteristics associated with radical-intent hypofractionated radiotherapy for the treatment of stage III non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS Relevant studies were identified from a systematic PubMed search of articles published between January 1990 and January 2014. All studies were peer reviewed and included both retrospective and prospective studies of NSCLC patients being treated with radical hypofractionated radiotherapy. Data on overall survival (OS) and toxicity were extracted from each of the studies where available. RESULTS Of 685 studies initially identified by the search, a total of 33 studies were found to be relevant and were included in this systematic review. The number of fractions ranged from 15 to 35, the dose per fraction ranged from 2.3 to 3.5 Gy, and the delivered dose ranged from 45.0 to 85.5 Gy. Fifteen of the studies included concurrent chemotherapy, while 18 did not. OS was found to be associated with tumor biological effective dose, with the Pearson correlation coefficient ranging from 0.34 to 0.48. For both concurrent and nonconcurrent chemoradiotherapy acute pulmonary, late esophageal and late pulmonary incidences of toxicity ranged from 1.2% to 12.2%, but had 95% confidence intervals that included zero. The greatest incidence of toxicity was acute esophageal toxicity at 14.9% (95% confidence interval, 0.7%, 29.1%). CONCLUSIONS There is a moderate linear relationship between biological effective dose and OS, and greater acute esophageal toxicity with concurrent chemotherapy. Improving outcomes in stage III NSCLC may involve some form of hypofractionation in the context of systemic concurrent therapy.
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Affiliation(s)
- Tyler S Kaster
- Department of Radiation Oncology, Western University, London, Ontario; Faculty of Medicine, University of Ottawa, Ottawa, Ontario
| | - Brian Yaremko
- Department of Radiation Oncology, Western University, London, Ontario
| | - David A Palma
- Department of Radiation Oncology, Western University, London, Ontario
| | - George B Rodrigues
- Department of Radiation Oncology, Western University, London, Ontario; Department of Epidemiology and Biostatistics, Western University, London, Ontario.
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Yang ZX, Shen JT, Li YP, Zhao K, Shi CH, Xiao Y, Yu JJ, Guo WD, Li CC, Wang YQ, Li XL. Helical tomotherapy for cancer treatment: a rapid health technology assessment. J Evid Based Med 2014; 7:192-218. [PMID: 25156336 DOI: 10.1111/jebm.12109] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Accepted: 06/09/2014] [Indexed: 02/05/2023]
Abstract
OBJECTIVES Helical tomotherapy (HT) can be applied to treat complex malignant cancer with high-precise radiotherapy, and it can reduce the damage to normal tissues and improve treatment effects. But the procurement of HT must be approved by relevant departments of administration affairs. This study, appointed by the National Health and Family Planning Commission of China and undertook by the National Health Development Research Center and the Chinese Evidence-Based Medicine Centre, was aimed to rapidly assess the effectiveness, safety, costs, and applicability of HT, so as to provide currently available best evidence for decision-makers of health policies. METHODS We electronically searched databases including PubMed, EMbase, The Cochrane Library, CNKI, WanFang Data, VIP, CBM, and other professional websites. Two reviewer independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed quality, and then performed descriptive analysis. RESULTS (i) We finally included 150 studies, encompassing 5 HTAs, 18 CCTs, and 127 observational studies. (ii) The included HTAs were published during 2006-2009, providing fairly less evidence of low quality and the results of 145 primary studies showed that: HT had been used mainly in the treatments of 14 kinds of cancer, with low total toxicity and high survival rates. Although the quality of the included studies was poor, there was much evidence about prostate cancer, head and neck cancer, nasopharynx cancer, cervical cancer, lung cancer and liver cancer, with enough sample and fairly reliable results in HT efficacy and safety. And (iii) a total of 56 clinical trials were registered in Clinicaltrials.gov, most of which were registered by the occident. Among them, 9 were completed but the results had not been published yet. CONCLUSIONS The evidence of this study showed that, HT is safe and effective in clinic. But the abovementioned conclusion needs to be verified by conducting more high-quality studies with long-term follow-up. The costs of HT in procurement, maintenance, and application are high; and the skills, training, and qualification of operators are required. We suggest that the procurement of HT should be reduced; it should be allocated rationally and effectively used after comprehensive assessment in China's cancer epidemiology characteristics, health resource allocation, disease burden, medical service level, etc.; and also high-quality studies with long-term follow-up should be financially supported on the basis of establishing projects, so as to provide local evidence and consistently guide and improve scientific decision-making.
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Affiliation(s)
- Zong Xia Yang
- Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, Chengdu, China
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Chi A, Nguyen NP, Welsh JS, Tse W, Monga M, Oduntan O, Almubarak M, Rogers J, Remick SC, Gius D. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond. Front Oncol 2014; 4:156. [PMID: 24999451 PMCID: PMC4064255 DOI: 10.3389/fonc.2014.00156] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2014] [Accepted: 06/04/2014] [Indexed: 12/25/2022] Open
Abstract
Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion.
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Affiliation(s)
- Alexander Chi
- Department of Radiation Oncology, Mary Babb Randolph Cancer Center of West Virginia University , Morgantown, WV , USA
| | - Nam Phong Nguyen
- The International Geriatric Radiotherapy Group , Tucson, AZ , USA
| | - James S Welsh
- Northern Illinois University Institute for Neutron Therapy at Fermilab , Batavia, IL , USA
| | - William Tse
- Division of Hematology and Oncology, Mary Babb Randolph Cancer Center of West Virginia University , Morgantown, WV , USA
| | - Manish Monga
- Division of Hematology and Oncology, Mary Babb Randolph Cancer Center of West Virginia University , Morgantown, WV , USA
| | - Olusola Oduntan
- Thoracic Surgery, Mary Babb Randolph Cancer Center of West Virginia University , Morgantown, WV , USA
| | - Mohammed Almubarak
- Division of Hematology and Oncology, Mary Babb Randolph Cancer Center of West Virginia University , Morgantown, WV , USA
| | - John Rogers
- Division of Hematology and Oncology, Mary Babb Randolph Cancer Center of West Virginia University , Morgantown, WV , USA
| | - Scot C Remick
- Division of Hematology and Oncology, Mary Babb Randolph Cancer Center of West Virginia University , Morgantown, WV , USA
| | - David Gius
- Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University , Chicago, IL , USA
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Donato V, Arcangeli S, Monaco A, Caruso C, Cianciulli M, Boboc G, Chiostrini C, Rauco R, Pressello MC. Moderately Escalated Hypofractionated (Chemo) Radiotherapy Delivered with Helical Intensity-Modulated Technique in Stage III Unresectable Non-Small Cell Lung Cancer. Front Oncol 2013; 3:286. [PMID: 24303369 PMCID: PMC3831267 DOI: 10.3389/fonc.2013.00286] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Accepted: 11/04/2013] [Indexed: 12/25/2022] Open
Abstract
Purpose: To assess clinical outcomes and toxicities in patients with stage III unresectable non-small cell lung cancer (NSCLC) treated with a moderately escalated hypofractionated radiotherapy delivered with Helical Intensity-Modulated Technique in combination with sequential or concurrent chemotherapy. Materials and Methods: Sixty-one consecutive patients considered non-progressive after two cycles of induction chemotherapy were treated with a moderately escalated hypofractionated radiation course of 30 daily fractions of 2.25–2.28 Gy each administered in 6 weeks up to a total dose of 67.5–68.4 Gy (range, 64.5–71.3 Gy). Thirty-two received sequential RT after two more cycles (total = 4 cycles) of chemotherapy, while 29 were treated with concurrent chemo-radiation. The target was considered the gross tumor volume and the clinically proven nodal regions, without elective nodal irradiation. Results: With a median follow up of 27 months (range 6–40), 1-year and 2-year OS rate for all patients was 77 and 53%, respectively, with a median survival duration of 18.6 months in the sequential group and 24.1 months in the concomitant group. No Grade ≥4 acute and late toxicity was reported. Acute Grade 3 treatment-related pneumonitis was detected in 10% of patients. Two patients, both receiving the concurrent schedule, developed a Grade 3 acute esophagitis. The overall incidence of late Grade 3 lung toxicity was 5%. No patients experienced a Grade 3 late esophageal toxicity. Conclusion: A moderately hypofractionated radiation course delivered with a Helical Intensity-Modulated Technique is a feasible treatment option for patients with unresectable locally advanced NSCLC receiving chemotherapy (sequentially or concurrently). Hypofractionated radiotherapy with a dedicated technique allows safely dose escalation, minimizing the effect of tumor repopulation that may occur with prolonged treatment time.
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Affiliation(s)
- Vittorio Donato
- Department of Radiotherapy, Azienda Ospedaliera S.Camillo-Forlanini , Rome , Italy
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Osti MF, Agolli L, Valeriani M, Falco T, Bracci S, De Sanctis V, Enrici RM. Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2013; 85:e157-e163. [PMID: 23182393 DOI: 10.1016/j.ijrobp.2012.10.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 10/01/2012] [Accepted: 10/08/2012] [Indexed: 11/15/2022]
Abstract
PURPOSE Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. METHODS AND MATERIALS Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. RESULTS The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. CONCLUSIONS Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized studies are needed to compare HypoRT to conventional treatment.
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Affiliation(s)
- Mattia Falchetto Osti
- Institute of Radiation Oncology, La Sapienza University, Sant'Andrea Hospital, Rome, Italy
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Bree ID, van Hinsberg MG, van Veelen LR. High-dose radiotherapy in inoperable nonsmall cell lung cancer: Comparison of volumetric modulated arc therapy, dynamic IMRT and 3D conformal radiotherapy. Med Dosim 2012; 37:353-7. [DOI: 10.1016/j.meddos.2011.12.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2011] [Accepted: 12/31/2011] [Indexed: 12/25/2022]
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Superiority of conventional intensity-modulated radiotherapy over helical tomotherapy in locally advanced non-small cell lung cancer. A comparative plan analysis. Strahlenther Onkol 2012; 188:901-9. [PMID: 22895625 DOI: 10.1007/s00066-012-0159-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2012] [Accepted: 05/16/2012] [Indexed: 12/21/2022]
Abstract
PURPOSE To compare helical tomotherapy (HT) and conventional intensity-modulated radiotherapy (IMRT) using a variety of dosimetric and radiobiologic indexes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS A total of 20 patients with LA-NSCLC were enrolled. IMRT plans with 4-6 coplanar beams and HT plans were generated for each patient. Dose distributions and dosimetric indexes for the tumors and critical structures were computed for both plans and compared. RESULTS Both modalities created highly conformal plans. They did not differ in the volumes of lung exposed to > 20 Gy of radiation. The average mean lung dose, volume receiving ≥ 30 Gy, and volume receiving ≥ 10 Gy in HT planning were 18.3 Gy, 18.5%, and 57.1%, respectively, compared to 19.4 Gy, 25.4%, and 48.9%, respectively, with IMRT (p = 0.004, p < 0.001, and p < 0.001). The differences between HT and IMRT in lung volume receiving ≥ 10-20 Gy increased significantly as the planning target volume (PTV) increased. For 6 patients who had PTV greater than 700 cm(3), IMRT was superior to HT for 5 patients in terms of lung volume receiving ≥ 5-20 Gy. The integral dose to the entire thorax in HT plans was significantly higher than in IMRT plans. CONCLUSION HT gave significantly better control of mean lung dose and volume receiving ≥ 30-40 Gy, whereas IMRT provided better control of the lung volume receiving ≥ 5-15 Gy and the integral dose to entire thorax. In most patients with PTV greater than 700 cm(3), IMRT was superior to HT in terms of lung volume receiving ≥ 5-20 Gy. It is therefore advised that caution should be exercised when planning LA-NSCLC using HT.
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Rong Y, Welsh JS. Dosimetric and clinical review of helical tomotherapy. Expert Rev Anticancer Ther 2011; 11:309-20. [PMID: 21342048 DOI: 10.1586/era.10.175] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
As a modality for delivering rotational therapy, helical tomotherapy offers dosimetric advantages by combining a continuously rotating gantry with a binary multileaf collimator. Helical tomotherapy, embodied in the TomoTherapy(®) Hi-Art II(®) system, delivers intensity-modulated fan beams in a helical pattern using binary multileaf collimator leaves while the couch is translated through the gantry. Helical tomotherapy offers the possibility of treating a variety of cases--from simple to complex--with improved target conformality and sensitive structure sparing compared with 3D or conventional static field IMRT plans, thereby allowing biologically effective dose escalation. For precise irradiation and possible treatment adaptation, the fully integrated on-board image-guidance system provides online volumetric images of patient anatomy using 3.5-MV x-ray beams and the xenon computed tomography detector. Several review articles were published before the year 2007 but emphasized the technical aspects of helical tomotherapy. In this article, we review very recent papers and focus on the dosimetric and clinical aspects of helical tomotherapy.
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Affiliation(s)
- Yi Rong
- Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, 600 Highland Avenue, Madison, WI, USA.
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Chi A, Jang SY, Welsh JS, Nguyen NP, Ong E, Gobar L, Komaki R. Feasibility of helical tomotherapy in stereotactic body radiation therapy for centrally located early stage non‒small-cell lung cancer or lung metastases. Int J Radiat Oncol Biol Phys 2011; 81:856-62. [PMID: 21255942 DOI: 10.1016/j.ijrobp.2010.11.051] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2010] [Revised: 11/16/2010] [Accepted: 11/25/2010] [Indexed: 12/25/2022]
Abstract
PURPOSE To investigate the ability of helical tomotherapy (HT) to spare critical organs immediately adjacent to the tumor target in stereotactic body radiation therapy (SBRT) for centrally located lung lesions. METHODS AND MATERIALS HT SBRT plans for 10 patients with centrally located lesions or lesions immediately adjacent to a critical structure were generated. A total of 70 Gy in 10 fractions was prescribed to the planning target volume (PTV) to satisfy a target volume coverage of ≥95% PTV receiving 70 Gy and an established set of dose constraints for the organs at risk (OARs). Quality assurance (QA) of the HT plans was performed with both ion chamber and film measurements. RESULTS The PTV coverage criteria was met with 95% of the PTV receiving 70.68 ± 0.33 Gy for all cases even though the OARs immediately adjacent to the PTV ranged from 0.38 to 0.85 cm away. The mean lung dose (MLD), and V(20) were 7.15 ± 1.44 Gy, and 11.93 ± 3.24 % for the total lung, respectively. The dose parameters of MLD, V(5), V(10), and V(20) for the contralateral lung were significantly lower than those for the ipsilateral lung (p < 0.05). An average dose fall off from the PTV periphery to the edge of the immediately adjacent OAR was 47.6% over an average distance of 4.87 mm. Comparison of calculated and measured doses with the ion chamber showed an average of 1.85% point dose error, whereas an average mean gamma and the area with a gamma larger than 1 of 0.20 and 0.94% were observed, respectively. CONCLUSION HT allows the sparing of critical structures immediately adjacent to the tumor target, thus making SBRT for these centrally located lesions feasible.
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Affiliation(s)
- Alexander Chi
- Department of Radiation Oncology, the University of Arizona, Tucson, AZ 85724-5081, USA.
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Bral S, De Ridder M, Duchateau M, Gevaert T, Engels B, Schallier D, Storme G. Daily megavoltage computed tomography in lung cancer radiotherapy: correlation between volumetric changes and local outcome. Int J Radiat Oncol Biol Phys 2010; 80:1338-42. [PMID: 20638192 DOI: 10.1016/j.ijrobp.2010.04.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2009] [Revised: 04/08/2010] [Accepted: 04/08/2010] [Indexed: 11/16/2022]
Abstract
PURPOSE To assess the predictive or comparative value of volumetric changes, measured on daily megavoltage computed tomography during radiotherapy for lung cancer. PATIENTS AND METHODS We included 80 patients with locally advanced non-small-cell lung cancer treated with image-guided intensity-modulated radiotherapy. The radiotherapy was combined with concurrent chemotherapy, combined with induction chemotherapy, or given as primary treatment. Patients entered two parallel studies with moderately hypofractionated radiotherapy. Tumor volume contouring was done on the daily acquired images. A regression coefficient was derived from the volumetric changes on megavoltage computed tomography, and its predictive value was validated. Logarithmic or polynomial fits were applied to the intratreatment changes to compare the different treatment schedules radiobiologically. RESULTS Regardless of the treatment type, a high regression coefficient during radiotherapy predicted for a significantly prolonged cause-specific local progression free-survival (p = 0.05). Significant differences were found in the response during radiotherapy. The significant difference in volumetric treatment response between radiotherapy with concurrent chemotherapy and radiotherapy plus induction chemotherapy translated to a superior long-term local progression-free survival for concurrent chemotherapy (p = 0.03). An enhancement ratio of 1.3 was measured for the used platinum/taxane doublet in comparison with radiotherapy alone. CONCLUSION Contouring on daily megavoltage computed tomography images during radiotherapy enabled us to predict the efficacy of a given treatment. The significant differences in volumetric response between treatment strategies makes it a possible tool for future schedule comparison.
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Affiliation(s)
- Samuel Bral
- Department of Radiation Oncology, Oncology Center, Universitair Ziekenhuis Brussel, Brussels, Belgium.
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