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Alfaifi S, Pareek V, Kim J, Rathod S, Hunter W, Leylek A, Ahmed N, Venkataraman S, Venugopal N, Chowdhury A, Dubey A, Kakumanu S, Bashir B. Moving towards single fraction peripheral lung stereotactic body radiation therapy: patient care during and after the global COVID-19 pandemic. Lung Cancer Manag 2024:2367369. [PMID: 39883102 DOI: 10.1080/17581966.2024.2367369] [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: 04/14/2023] [Accepted: 05/31/2024] [Indexed: 01/31/2025] Open
Abstract
Aim/objectives: Single-fraction stereotactic body radiation therapy (SF-SBRT) for peripheral lung tumors was reviewed. Materials & methods: Medically inoperable peripheral lung tumors eligible for SF-SBRT 34 Gray were treated. Patient characteristics, treatment and toxicity parameters were retrospectively collected, and toxicities were evaluated. Results: A total of 26 patients were assessed with median age of 74 years. Ninety-six percent had early-stage cancer and 35% were treated as per the SABR-BRIDGE protocol. Twenty-six peripheral lesions were treated (median maximal dimension 1.7 cm). Sixty-five percent had grade ≤2 toxicities with radiation pneumonitis (42.3%) and chest wall pain (35%). Radiation pneumonitis and chest wall pain rates were higher in patients with tumor diameters more than 1.5 cm. Conclusion: SF-SBRT is practical and effective treatment technique.
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Affiliation(s)
- Salem Alfaifi
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
- Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA
| | - Vibhay Pareek
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - Julian Kim
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - Shrinivas Rathod
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - William Hunter
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - Ahmet Leylek
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - Naseer Ahmed
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | | | - Niranjan Venugopal
- Department of Medical Physics, University of Manitoba, Winnipeg, MB, Canada
| | - Amitava Chowdhury
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - Arbind Dubey
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - Saranya Kakumanu
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
| | - Bashir Bashir
- Department of Radiation Oncology, University of Manitoba, Winnipeg, MB, Canada
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Iovoli AJ, Prasad S, Ma SJ, Fekrmandi F, Malik NK, Fung-Kee-Fung S, Farrugia MK, Singh AK. Long-Term Survival and Failure Outcomes of Single-Fraction Stereotactic Body Radiation Therapy in Early Stage NSCLC. JTO Clin Res Rep 2023; 4:100598. [PMID: 38124792 PMCID: PMC10730364 DOI: 10.1016/j.jtocrr.2023.100598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 10/12/2023] [Accepted: 10/30/2023] [Indexed: 12/23/2023] Open
Abstract
INTRODUCTION This study aims to report our 13-year institutional experience with single-fraction stereotactic body radiation therapy (SF-SBRT) for early stage NSCLC. METHODS A single-institutional retrospective review of patients with biopsy-proven peripheral cT1-2N0M0 NSCLC undergoing definitive SF-SBRT between September 2008 and May 2022 was performed. All patients were treated to 27 Gy with heterogeneity corrections or 30 Gy without. Primary outcomes were overall survival and progression-free survival. Secondary outcomes included local failure, nodal failure, distant failure, and second primary lung cancer. RESULTS Among 263 eligible patients, the median age was 76 years (interquartile range [IQR]: 70-81 y) and median follow-up time was 27.2 months (IQR: 14.25-44.9 mo). Median tumor size was 1.9 cm (IQR: 1.4-2.6 cm), and 224 (85%) tumors were T1. There were 92 patients (35%) alive at the time of analysis with a median follow-up of 34.0 months (IQR: 16.6-50.0 mo). Two- and five-year overall survival was 65% and 26%, respectively. A total of 74 patients (28%) developed disease progression. Rates of five-year local failure, nodal failure, distant failure, and second primary lung cancer were 12.7%, 14.7%, 23.5%, and 12.0%, respectively. CONCLUSIONS Consistent with multiple prospective randomized trials, in a large real-world retrospective cohort, SF-SBRT for peripheral early stage NSCLC was an effective treatment approach.
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Affiliation(s)
- Austin J. Iovoli
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Sharan Prasad
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York
| | - Sung Jun Ma
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Fatemeh Fekrmandi
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Nadia K. Malik
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Simon Fung-Kee-Fung
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Mark K. Farrugia
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Anurag K. Singh
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
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Zarębska I, Harat M. An optimal dose-fractionation for stereotactic body radiotherapy in peripherally, centrally and ultracentrally located early-stage non-small lung cancer. Thorac Cancer 2023; 14:2813-2820. [PMID: 37691151 PMCID: PMC10542466 DOI: 10.1111/1759-7714.15071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 09/12/2023] Open
Abstract
Stereotactic body radiotherapy (SBRT), also known as stereotactic ablative radiotherapy (SABR), is commonly used in inoperable patients with early-stage non-small lung cancer (NSCLC). This treatment has good outcomes and low toxicity in peripherally located tumors. However, in lesions which are located close to structures such as the bronchial tree or mediastinum the risk of severe toxicity increases. This review summarizes the evidence of dose-fractionation in SBRT of NSCLC patients in various locations.
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Affiliation(s)
- Izabela Zarębska
- Department of Neurooncology and RadiosurgeryFranciszek Lukaszczyk Oncology CenterBydgoszczPoland
- Department of RadiotherapyFranciszek Lukaszczyk Oncology CenterBydgoszczPoland
| | - Maciej Harat
- Department of Neurooncology and RadiosurgeryFranciszek Lukaszczyk Oncology CenterBydgoszczPoland
- Center of Medical SciencesUniversity of Science and TechnologyBydgoszczPoland
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Huang K, Prasad S, Ma SJ, Yu H, Iovoli AJ, Farrugia MK, Dexter EU, Demmy TL, Malik NK, Singh AK. Association of neutrophil-lymphocyte ratio with survival in peripheral early-stage non-small cell lung cancer after stereotactic body radiation therapy. BMC Cancer 2023; 23:254. [PMID: 36932396 PMCID: PMC10024425 DOI: 10.1186/s12885-023-10719-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Accepted: 03/08/2023] [Indexed: 03/19/2023] Open
Abstract
BACKGROUND The role of neutrophil-lymphocyte ratio (NLR) as a predictor for survival in single fraction SBRT-treated non-small cell lung cancer (NSCLC) patients remains unclear. We performed an observational cohort study to determine the role of pretreatment NLR in predicting survival of early-stage NSCLC patients after single fraction SBRT. METHODS A single-institution database of peripheral early-stage NSCLC patients treated with SBRT from February 2007 to May 2022 was queried. Optimal threshold of neutrophil-lymphocyte ratio (NLR) was defined based on maximally selected rank statistics. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate outcomes. RESULTS A total of 286 patients were included for analysis with median follow up of 19.7 months. On Cox multivariate analysis, as a continuous variable, NLR was shown to be an independent predictor of OS (adjusted hazards ratio [aHR] 1.06, 95% CI 1.02-1.10, p = 0.005) and PFS (aHR 1.05, 95% CI 1.01-1.09, p = 0.013). In addition, NLR was associated with DF (aHR 1.11, 95% CI 1.05-1.18, p < 0.001). Maximally selected rank statistics determined 3.28 as the cutoff point of high NLR versus low NLR. These findings were confirmed upon propensity matching. CONCLUSIONS Pretreatment NLR is an independent predictor for survival outcomes of peripheral early-stage NSCLC patients after single fraction SBRT.
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Affiliation(s)
- Karen Huang
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA
| | - Sharan Prasad
- Cornell University, 410 Thurston Avenue, Ithaca, NY, 14850, USA
| | - Sung Jun Ma
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA
| | - Han Yu
- Department of Biostatistics and Bioinformatics, Elm and Carlton Streets, Buffalo, NY, 14263, USA
| | - Austin J Iovoli
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA
| | - Mark K Farrugia
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA
| | - Elizabeth U Dexter
- Department of Thoracic Surgery, Elm and Carlton Streets, Buffalo, NY, 14263, USA
| | - Todd L Demmy
- Department of Thoracic Surgery, Elm and Carlton Streets, Buffalo, NY, 14263, USA
| | - Nadia K Malik
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA
| | - Anurag K Singh
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm Street, Buffalo, NY, 14203, USA.
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Zhang R, Kang J, Ren S, Xing L, Xu Y. Comparison of stereotactic body radiotherapy and radiofrequency ablation for early-stage non-small cell lung cancer: a systematic review and meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:104. [PMID: 35282118 PMCID: PMC8848429 DOI: 10.21037/atm-21-6256] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 01/12/2022] [Indexed: 12/25/2022]
Abstract
Background Stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) are recommended for patients with inoperable early-stage non-small cell lung cancer (NSCLC), with both offering promising results. However, it is largely unknown which of these two treatment modalities provides superior benefits for patients. Therefore, this systematic review and meta-analysis compared clinical outcomes and safety between SBRT and RFA in patients with inoperable early-stage NSCLC. Methods Eligible studies published between 2001 and 2020 were obtained through a comprehensive search of the PubMed, Medline, Embase, and Cochrane Library databases. Original English-language studies on the treatment of early-stage NSCLC with SBRT or RFA were included. Local control (LC) rates, overall survival (OS) rates, and adverse events were obtained by pooled analyses. Results Eighty-seven SBRT studies (12,811 patients) and 18 RFA studies (1,535 patients) met the eligibility criteria. For SBRT, the LC rates (with 95% confidence intervals) at 1, 2, 3, and 5 years were 98% (97-98%), 95% (95-96%), 92% (91-93%), and 92% (91-93%), respectively, which were significantly higher than those for RFA [75% (69-82%), 31% (22-39%), 67% (58-76%), and 41% (30-52%), respectively] (P<0.01). There were no significant differences in short-term OS between SBRT and RFA [1-year OS rate: 87% (86-88%) versus 89% (88-91%), P=0.07; 2-year OS rate: 71% (69-72%) versus 69% (64-74%), P=0.42]. Regarding long-term OS, the 3- and 5-year OS rates for SBRT were 58% (56-59%) and 39% (37-40%), respectively, which were significantly (P<0.01) superior to those for RFA [48% (45-51%) and 21% (19-23%), respectively]. The most common complication of SBRT was radiation pneumonitis (grade ≥2), making up 9.1% of patients treated with SBRT, while pneumothorax was the most common complication of RFA, making up 27.2% of patients treated with RFA. Discussion Compared with RFA, SBRT has superior LC and long-term OS rates but similar short-term OS rates. Prospective randomized trials with large sample sizes comparing the efficacy of SBRT and RFA are warranted.
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Affiliation(s)
- Ran Zhang
- Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.,Department of Medical Oncology, Shanghai Pulmonary Hospital & Institute of Thoracic Cancer, School of Medicine, Tongji University, Shanghai, China
| | - Jingjing Kang
- Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shengxiang Ren
- Department of Medical Oncology, Shanghai Pulmonary Hospital & Institute of Thoracic Cancer, School of Medicine, Tongji University, Shanghai, China
| | - Ligang Xing
- Department of Radiation Oncology, Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yaping Xu
- Department of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
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Bartl AJ, Mahoney M, Hennon MW, Yendamuri S, Videtic GMM, Stephans KL, Siva S, Farrugia MK, Ma SJ, Singh AK. Systematic Review of Single-Fraction Stereotactic Body Radiation Therapy for Early Stage Non-Small-Cell Lung Cancer and Lung Oligometastases: How to Stop Worrying and Love One and Done. Cancers (Basel) 2022; 14:790. [PMID: 35159057 PMCID: PMC8834253 DOI: 10.3390/cancers14030790] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/26/2022] [Accepted: 02/01/2022] [Indexed: 02/06/2023] Open
Abstract
Adoption of single-fraction lung stereotactic body radiation therapy (SBRT) for patients with medically inoperable early stage non-small-cell lung cancer (NSCLC) or oligometastatic lung disease, even during the coronavirus disease 2019 (COVID-19) pandemic, was limited despite encouraging phase II trial results. Barriers to using single-fraction SBRT may include lack of familiarity with the regimen and lack of clarity about the expected toxicity. To address these concerns, we performed a systematic review of prospective literature on single-fraction SBRT for definitive treatment of early stage and oligometastatic lung cancer. A PubMed search of prospective studies in English on single-fraction lung SBRT was conducted. A systematic review was performed of the studies that reported clinical outcomes of single-fraction SBRT in the treatment of early stage non-small-cell lung cancer and lung oligometastases. The current prospective literature including nine trials supports the use of single-fraction SBRT in the definitive treatment of early stage peripheral NSCLC and lung oligometastases. Most studies cite local control rates of >90%, mild toxicity profiles, and favorable survival outcomes. Most toxicities reported were grade 1-2, with grade ≥3 toxicity in 0-17% of patients. Prospective trial results suggest potential consideration of utilizing single-fraction SBRT beyond the COVID-19 pandemic.
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Affiliation(s)
- Austin J. Bartl
- Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14203, USA;
| | - Mary Mahoney
- College of Medicine, State University of New York Upstate Medical University, Syracuse, NY 13210, USA;
| | - Mark W. Hennon
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (M.W.H.); (S.Y.)
| | - Sai Yendamuri
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (M.W.H.); (S.Y.)
| | - Gregory M. M. Videtic
- Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA; (G.M.M.V.); (K.L.S.)
| | - Kevin L. Stephans
- Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA; (G.M.M.V.); (K.L.S.)
| | - Shankar Siva
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia;
| | - Mark K. Farrugia
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (M.K.F.); (S.J.M.)
| | - Sung Jun Ma
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (M.K.F.); (S.J.M.)
| | - Anurag K. Singh
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; (M.K.F.); (S.J.M.)
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Alongi F, Nicosia L, Figlia V, De Sanctis V, Mazzola R, Giaj-Levra N, Reverberi C, Valeriani M, Osti MF. A multi-institutional analysis of fractionated versus single-fraction stereotactic body radiotherapy (SBRT) in the treatment of primary lung tumors: a comparison between two antipodal fractionations. Clin Transl Oncol 2021; 23:2133-2140. [PMID: 33840047 DOI: 10.1007/s12094-021-02619-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Accepted: 04/01/2021] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Stereotactic body radiotherapy (SBRT) is a consolidate treatment for inoperable early-stage lung tumors, usually delivered in single or multi-fraction regimens. We aimed to compare these two approaches in terms of local effectiveness, safety and survival. MATERIALS AND METHODS Patients affected by medically inoperable early-stage lung tumor were treated at two Institutions with two different schedules: 70 Gy in ten fractions (TF) (BED10: 119 Gy) or 30 Gy in single fraction (SF) (BED10: 120 Gy). RESULTS 73 patients were treated with SBRT delivered with two biological equivalent schedules: SF (44) and TF (29). The median follow-up was 34 months (range 3-81 months). Three-year Overall survival (OS) was 57.9%, 3-year cancer-specific survival (CSS) was 77.2%, with no difference between treatment groups. Three-year progression-free survival (LPFS) was 88.9% and did not differs between SF and TF. Overall, four cases (5.4%) of acute grade ≥ 3 pneumonitis occurred. No differences in acute and late toxicity between the two groups were detected. CONCLUSION SF and TF seems to be equally safe and effective in the treatment of primary inoperable lung tumors especially for smaller lesion. The SF may be preferentially offered to reduce patient access to hospital with no negative impact on tumor control and survival.
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Affiliation(s)
- F Alongi
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy
- University of Brescia, Brescia, Italy
| | - L Nicosia
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy.
| | - V Figlia
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy
| | - V De Sanctis
- Department of Radiation Oncology, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy
| | - R Mazzola
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy
| | - N Giaj-Levra
- Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy
| | - C Reverberi
- Department of Radiation Oncology, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy
| | - M Valeriani
- Department of Radiation Oncology, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy
| | - M F Osti
- Department of Radiation Oncology, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy
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Farrugia M, Jun Ma S, Hennon M, Nwogu C, Dexter E, Picone A, Demmy T, Gomez-Suescun J, Fung-Kee-Fung S, Yendamuri S, Singh A. Prior Treatment for Non-small Cell Lung Cancer Is Associated With Improved Survival in Patients who Undergo Definitive Stereotactic Body Radiation Therapy for a Subsequent Lung Malignancy: A Retrospective Multivariate and Matched Pair Analysis. Am J Clin Oncol 2021; 44:18-23. [PMID: 33264123 PMCID: PMC8211287 DOI: 10.1097/coc.0000000000000778] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Despite occurring commonly, the prognoses of second early-stage non-small cell lung cancers (NSCLC) are not well known. METHODS The authors retrospectively reviewed the charts of inoperable patients who underwent thoracic stereotactic body radiation therapy (SBRT) from February 2007 to April 2019. Those with previous small cell lung cancers or SBRT treatments for tumors other than NSCLC were excluded. Multivariate Cox regression and a matched pair cohort analyses evaluated the prognoses of patients undergoing definitive SBRT for a new second primary. RESULTS Of 438 patients who underwent definitive SBRT for NSCLC, 84 had previously treated NSCLC. Univariate log-rank tests identified gender, Karnofksy performance status (KPS), prior lung cancer, anticoagulation use, and history of heart disease to correlate with overall survival (OS) (P<0.05). These factors were incorporated into a multivariate Cox regression model that demonstrated female sex (P=0.004, hazard ratio [HR]=0.68), KPS (P<0.001, HR=2.0), and prior lung cancer (P=0.049, HR=0.7) to be significantly associated with OS. A similar approach found only gender (P=0.017, HR=0.64) and tumor stage (P=0.02, HR=1.7) to correlate with relapse-free survival. To support the Cox regression analysis, propensity score matching was performed using gender, age, KPS, tumor stage, history of heart disease, and anticoagulation use. Kaplan-Meier survival analysis within the matched pairs found prior lung cancer to be associated with improved OS (P=0.011), but not relapse-free survival (P=0.44). CONCLUSIONS Compared with initial lung cancer SBRT inoperable cases, ablative radiotherapy for new primaries was associated with improved OS. Physicians should not be dissuaded from offering SBRT to such patients.
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Affiliation(s)
- M.K. Farrugia
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - S. Jun Ma
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - M.W. Hennon
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - C.E. Nwogu
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - E.U. Dexter
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - A.L. Picone
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - T.L. Demmy
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - J.A. Gomez-Suescun
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - Simon Fung-Kee-Fung
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - S.S. Yendamuri
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
| | - A.K. Singh
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA
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Ng SS, Ning MS, Lee P, McMahon RA, Siva S, Chuong MD. Single-Fraction Stereotactic Body Radiation Therapy: A Paradigm During the Coronavirus Disease 2019 (COVID-19) Pandemic and Beyond? Adv Radiat Oncol 2020; 5:761-773. [PMID: 32775790 PMCID: PMC7406732 DOI: 10.1016/j.adro.2020.06.011] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/09/2020] [Accepted: 06/10/2020] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Owing to the coronavirus disease 2019 (COVID-19) pandemic, radiation oncology departments have adopted various strategies to deliver radiation therapy safely and efficiently while minimizing the risk of severe acute respiratory syndrome coronavirus-2 transmission among patients and health care providers. One practical strategy is to deliver stereotactic body radiation therapy (SBRT) in a single fraction, which has been well established for treating bone metastases, although it has been infrequently used for other extracranial sites. METHODS AND MATERIALS A PubMed search of published articles in English related to single-fraction SBRT was performed. A critical review was performed of the articles that described clinical outcomes of single-fraction SBRT for treatment of primary extracranial cancers and oligometastatic extraspinal disease. RESULTS Single-fraction SBRT for peripheral early-stage non-small cell lung cancer is supported by randomized data and is strongly endorsed during the COVID-19 pandemic by the European Society for Radiotherapy and Oncology-American Society for Radiation Oncology practice guidelines. Prospective and retrospective studies supporting a single-fraction regimen are limited, although outcomes are promising for renal cell carcinoma, liver metastases, and adrenal metastases. Data are immature for primary prostate cancer and demonstrate excess late toxicity in primary pancreatic cancer. CONCLUSIONS Single-fraction SBRT should be strongly considered for peripheral early-stage non-small cell lung cancer during the COVID-19 pandemic to mitigate the potentially severe consequences of severe acute respiratory syndrome coronavirus-2 transmission. Although single-fraction SBRT is promising for the definitive treatment of other primary or oligometastatic cancers, multi-fraction SBRT should be the preferred regimen owing to the need for additional prospective evaluation to determine long-term efficacy and safety.
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Affiliation(s)
- Sylvia S.W. Ng
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Matthew S. Ning
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Percy Lee
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ryan A. McMahon
- Department of Radiation Oncology, Peter MacCallum Cancer Center, University of Melbourne, Victoria, Australia
| | - Shankar Siva
- Department of Radiation Oncology, Peter MacCallum Cancer Center, University of Melbourne, Victoria, Australia
| | - Michael D. Chuong
- Department of Radiation Oncology, Miami Cancer Institute, Miami, Florida
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10
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Ijsseldijk MA, Shoni M, Siegert C, Wiering B, van Engelenburg AKC, Tsai TC, Ten Broek RPG, Lebenthal A. Oncologic Outcomes of Surgery Versus SBRT for Non-Small-Cell Lung Carcinoma: A Systematic Review and Meta-analysis. Clin Lung Cancer 2020; 22:e235-e292. [PMID: 32912754 DOI: 10.1016/j.cllc.2020.04.017] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/21/2020] [Accepted: 04/25/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The optimal treatment of stage I non-small-cell lung carcinoma is subject to debate. The aim of this study was to compare overall survival and oncologic outcomes of lobar resection (LR), sublobar resection (SR), and stereotactic body radiotherapy (SBRT). METHODS A systematic review and meta-analysis of oncologic outcomes of propensity matched comparative and noncomparative cohort studies was performed. Outcomes of interest were overall survival and disease-free survival. The inverse variance method and the random-effects method for meta-analysis were utilized to assess the pooled estimates. RESULTS A total of 100 studies with patients treated for clinical stage I non-small-cell lung carcinoma were included. Long-term overall and disease-free survival after LR was superior over SBRT in all comparisons, and for most comparisons, SR was superior to SBRT. Noncomparative studies showed superior long-term overall and disease-free survival for both LR and SR over SBRT. Although the papers were heterogeneous and of low quality, results remained essentially the same throughout a large number of stratifications and sensitivity analyses. CONCLUSION Results of this systematic review and meta-analysis showed that LR has superior outcomes compared to SBRT for cI non-small-cell lung carcinoma. New trials are underway evaluating long-term results of SBRT in potentially operable patients.
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Affiliation(s)
- Michiel A Ijsseldijk
- Division of Surgery, Slingeland Ziekenhuis, Doetinchem, The Netherlands; Division of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
| | - Melina Shoni
- Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA
| | - Charles Siegert
- Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA; Division of Thoracic Surgery, West Roxbury Veterans Administration, West Roxbury, MA
| | - Bastiaan Wiering
- Division of Surgery, Slingeland Ziekenhuis, Doetinchem, The Netherlands
| | | | - Thomas C Tsai
- Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA
| | - Richard P G Ten Broek
- Division of Surgery, Slingeland Ziekenhuis, Doetinchem, The Netherlands; Division of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Abraham Lebenthal
- Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA; Division of Thoracic Surgery, West Roxbury Veterans Administration, West Roxbury, MA; Harvard Medical School, Boston, MA
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11
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Pokhrel D, Visak J, Sanford L. A novel and clinically useful dynamic conformal arc (DCA)-based VMAT planning technique for lung SBRT. J Appl Clin Med Phys 2020; 21:29-38. [PMID: 32306530 PMCID: PMC7386176 DOI: 10.1002/acm2.12878] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 03/12/2020] [Accepted: 03/15/2020] [Indexed: 12/26/2022] Open
Abstract
Purpose Volumetric modulated arc therapy (VMAT) is gaining popularity for stereotactic treatment of lung lesions for medically inoperable patients. Due to multiple beamlets in delivery of highly modulated VMAT plans, there are dose delivery uncertainties associated with small‐field dosimetry error and interplay effects with small lesions. We describe and compare a clinically useful dynamic conformal arc (DCA)‐based VMAT (d‐VMAT) technique for lung SBRT using flattening filter free (FFF) beams to minimize these effects. Materials and Methods Ten solitary early‐stage I‐II non‐small‐cell lung cancer (NSCLC) patients were treated with a single dose of 30 Gy using 3–6 non‐coplanar VMAT arcs (clinical VMAT) with 6X‐FFF beams in our clinic. These clinically treated plans were re‐optimized using a novel d‐VMAT planning technique. For comparison, d‐VMAT plans were recalculated using DCA with user‐controlled field aperture shape before VMAT optimization. Identical beam geometry, dose calculation algorithm, grid size, and planning objectives were used. The clinical VMAT and d‐VMAT plans were compared via RTOG‐0915 protocol compliances for conformity, gradient indices, and dose to organs at risk (OAR). Additionally, treatment delivery efficiency and accuracy were recorded. Results All plans met RTOG‐0915 requirements. Comparing with clinical VMAT, d‐VMAT plans gave similar target coverage with better target conformity, tighter radiosurgical dose distribution with lower gradient indices, and dose to OAR. Lower total number of monitor units and small beam modulation factor reduced beam‐on time by 1.75 min (P < 0.001), on average (maximum up to 2.52 min). Beam delivery accuracy was improved by 2%, on average (P < 0.05) and maximum up to 6% in some cases for d‐VMAT plans. Conclusion This simple d‐VMAT technique provided excellent plan quality, reduced intermediate dose‐spillage, and dose to OAR while providing faster treatment delivery by significantly reducing beam‐on time. This novel treatment planning approach will improve patient compliance along with potentially reducing intrafraction motion error. Moreover, with less MLC modulation through the target, d‐VMAT could potentially minimize small‐field dosimetry errors and MLC interplay effects. If available, d‐VMAT planning approach is recommended for future clinical lung SBRT plan optimization.
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Affiliation(s)
- Damodar Pokhrel
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA.,Department of Radiation Medicine, University of Kentucky, Markey Cancer Center, Lexington, KY, USA
| | - Justin Visak
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Lana Sanford
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
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12
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Pokhrel D, Halfman M, Sanford L. A simple, yet novel hybrid-dynamic conformal arc therapy planning via flattening filter-free beam for lung stereotactic body radiotherapy. J Appl Clin Med Phys 2020; 21:83-92. [PMID: 32243704 PMCID: PMC7324700 DOI: 10.1002/acm2.12868] [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: 07/18/2019] [Revised: 02/23/2020] [Accepted: 03/09/2020] [Indexed: 12/25/2022] Open
Abstract
Purpose Due to multiple beamlets in the delivery of highly modulated volumetric arc therapy (VMAT) plans, dose delivery uncertainties associated with small‐field dosimetry and interplay effects can be concerns in the treatment of mobile lung lesions using a single‐dose of stereotactic body radiotherapy (SBRT). Herein, we describe and compare a simple, yet clinically useful, hybrid 3D‐dynamic conformal arc (h‐DCA) planning technique using flattening filter‐free (FFF) beams to minimize these effects. Materials and Methods Fifteen consecutive solitary early‐stage I‐II non‐small‐cell lung cancer (NSCLC) patients who underwent a single‐dose of 30 Gy using 3–6 non‐coplanar VMAT arcs with 6X‐FFF beams in our clinic. These patients’ plans were re‐planned using a non‐coplanar hybrid technique with 2–3 differentially‐weighted partial dynamic conformal arcs (DCA) plus 4–6 static beams. About 60–70% of the total beam weight was given to the DCA and the rest was distributed among the static beams to maximize the tumor coverage and spare the organs‐at‐risk (OAR). The clinical VMAT and h‐DCA plans were compared via RTOG‐0915 protocol for conformity and dose to OAR. Additionally, delivery efficiency, accuracy, and overall h‐DCA planning time were recorded. Results All plans met RTOG‐0915 requirements. Comparison with clinical VMAT plans h‐DAC gave better target coverage with a higher dose to the tumor and exhibited statistically insignificance differences in gradient index, D2cm, gradient distance and OAR doses with the exception of maximal dose to skin (P = 0.015). For h‐DCA plans, higher values of tumor heterogeneity and tumor maximum, minimum and mean doses were observed and were 10%, 2.8, 1.0, and 2.0 Gy, on average, respectively, compared to the clinical VMAT plans. Average beam on time was reduced by a factor of 1.51. Overall treatment planning time for h‐DCA was about an hour. Conclusion Due to no beam modulation through the target, h‐DCA plans avoid small‐field dosimetry and MLC interplay effects and resulting in enhanced target coverage by improving tumor dose (characteristic of FFF‐beam). The h‐DCA simplifies treatment planning and beam on time significantly compared to clinical VMAT plans. Additionally, h‐DCA allows for the real time target verification and eliminates patient‐specific VMAT quality assurance; potentially offering cost‐effective, same or next day SBRT treatments. Moreover, this technique can be easily adopted to other disease sites and small clinics with less extensive physics or machine support.
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Affiliation(s)
- Damodar Pokhrel
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Matthew Halfman
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Lana Sanford
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
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Pokhrel D, Sanford L, Dhanireddy B, Molloy J, Randall M, McGarry RC. Flattening filter free VMAT for a stereotactic, single-dose of 30 Gy to lung lesion in a 15-min treatment slot. J Appl Clin Med Phys 2020; 21:6-12. [PMID: 32039544 PMCID: PMC7170282 DOI: 10.1002/acm2.12829] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 12/10/2019] [Accepted: 12/18/2019] [Indexed: 12/26/2022] Open
Abstract
Cone‐beam CT‐guided single dose of lung stereotactic body radiotherapy (SBRT) treatment with a flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a safe and highly effective treatment modality for selective small lung lesions. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB algorithm for heterogeneity corrections. 6X‐FFF beam produced highly conformal radiosurgical dose distribution to the target and reduced lung SBRT fraction duration to less than 10 min for a single dose of 30 Gy, significantly improving patient comfort and clinic workflow. Early follow‐up CT imaging results (mean, 8 months) show high local control rates (100%) with no acute lung or rib toxicity. Longer clinical follow‐up in a larger patient cohort managed in this fashion is underway to further validate this treatment approach.
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Affiliation(s)
- Damodar Pokhrel
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Lana Sanford
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Bhaswanth Dhanireddy
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Janelle Molloy
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Marcus Randall
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
| | - Ronald C McGarry
- Department of Radiation Medicine, Medical Physics Graduate Program, University of Kentucky, Lexington, KY, USA
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Singh AK, Gomez-Suescun JA, Stephans KL, Bogart JA, Hermann GM, Tian L, Groman A, Videtic GM. One Versus Three Fractions of Stereotactic Body Radiation Therapy for Peripheral Stage I to II Non-Small Cell Lung Cancer: A Randomized, Multi-Institution, Phase 2 Trial. Int J Radiat Oncol Biol Phys 2019; 105:752-759. [PMID: 31445956 PMCID: PMC7043929 DOI: 10.1016/j.ijrobp.2019.08.019] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 07/31/2019] [Accepted: 08/05/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE Stereotactic body radiation therapy for early stage non-small cell lung cancer is a standard of care for medically inoperable patients. Our aim was to compare Common Terminology Criteria for Adverse Events thoracic grade 3 or higher adverse events (AEs) of 30 Gy in 1 fraction (arm 1) versus 60 Gy in 3 fractions (arm 2). METHODS AND MATERIALS This was a randomized multi-institutional, phase 2, 2-arm clinical trial. Medically inoperable patients with biopsy-proven peripheral T1/T2N0M0 non-small cell lung cancer were enrolled. Patients were randomized to arm 1 or arm 2 and stratified by performance status. The primary endpoint was Common Terminology Criteria for Adverse Events thoracic grade 3 or higher AEs. Secondary endpoints were local control (LC), progression-free survival (PFS), overall survival (OS), and quality of life. RESULTS Between September 2008 and April 2015, 98 patients were randomized. Median follow-up was 53.8 months. Ten patients were lost to follow-up, 1 in arm 1 and 9 in arm 2. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no grade 4 or 5 AEs. There were no differences in LC, PFS, or OS (P = .68, .86, and .94, respectively). Arm 1 reported better social functioning (P = .006) with less dyspnea (P = .016) in follow-up at 6 months. CONCLUSIONS This randomized phase 2 study demonstrated that 30 Gy in 1 fraction was equivalent to 60 Gy in 3 fractions in terms of toxicity, LC, PFS, and OS. Quality of life measures of social functioning and dyspnea favored single-fraction SBRT.
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Affiliation(s)
- Anurag K Singh
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
| | - Jorge A Gomez-Suescun
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Kevin L Stephans
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Jeffrey A Bogart
- Department of Radiation Oncology, State University of New York Upstate Medical University, Syracuse, New York
| | - Gregory M Hermann
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Lili Tian
- Department of Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Adrienne Groman
- Department of Biostatistics, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Gregory M Videtic
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio
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15
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Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial. Breast 2019; 49:55-62. [PMID: 31734589 PMCID: PMC7375645 DOI: 10.1016/j.breast.2019.10.016] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 10/24/2019] [Accepted: 10/28/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Stereotactic ablative body radiotherapy (SABR) is an emerging noninvasive approach for the treatment of oligometastases. Limited prospective evidence is available in breast cancer. OBJECTIVES To determine the safety and feasibility of single fraction SABR for patients with bone only oligometastatic breast cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity and response assessment. METHODS AND MATERIALS In this single institution prospective trial we screened patients with computed tomography, bone scan, and sodium fluoride positron emission tomography. Eligible patients had one to three bone only oligometastases. All patients were treated at a dose of 20Gy in 1 fraction to each metastasis. Kaplan-Meier methods were used to determine local and distant progression free survival (LPFS and DPFS). Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. RESULTS 15 eligible patients were recruited to the study. Median follow-up time was 24 months. The treatment was feasible in 12 (80%) of patients with 3 (20%) of patients having treatment delayed by more than 3 days. 10 (67%) of patients experienced grade 1 treatment related toxicity, 4 (27%) experienced grade 2 toxicity and no patients experienced grade 3 or 4 treatment related toxicity. The two-year LPFS was 100%, DPFS was 67%. CONCLUSION We observed that SABR is feasible, well tolerated and effective in this cohort with two thirds of patients disease-free at two years. In selected patients with bone-only oligometastatic disease, SABR could be considered a treatment option. Randomised trials are required to assess the impact of SABR on overall survival when compared to the standard of care.
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16
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Long term results of single high dose Stereotactic Body Radiotherapy in the treatment of primary lung tumors. Sci Rep 2019; 9:15498. [PMID: 31664125 PMCID: PMC6820864 DOI: 10.1038/s41598-019-51900-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 09/24/2019] [Indexed: 12/19/2022] Open
Abstract
Stereotactic body radiotherapy (SBRT) is a standard treatment for inoperable early-stage NSCLC, with local control rates comparable to surgical series. Promising results have been achieved utilizing a high single-dose schedule. The aim of our study was to evaluate long-term local control and toxicity in a series of patients treated with SBRT delivered in a single dose of 30 Gy. 44 patients affected by early stage NSCLC were treated with SBRT delivered in a single dose of 30 Gy. Survival and prognostic factors were retrospectively evaluated. Median follow-up was 34 months (range 3-81). Three- and 5-year local progression-free survival (LPFS) were 87.8% and 87.8% respectively (median 30 months; range 6-81 months), 3- and 5-year OS and CSS were 64.9% and 36.9%, 80.9% and 65.5%, respectively. Two (4.6%) cases of grade 3 pneumonitis occurred. At the univariate analysis lesion diameter ≤ 25 mm was predictive of better 5-year LPFS (95.8% versus 56.3%; p = 0.003) and 5-year PFS (69.8% versus 27.8%; p = 0.002). The results of our study indicated a high local control, survival and tolerability after a long-term follow-up with the use of SBRT 30 Gy single dose. Further prospective studies could better define the role of this regimen.
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17
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Kjellsson Lindblom E, Ureba A, Dasu A, Wersäll P, Even AJG, van Elmpt W, Lambin P, Toma-Dasu I. Impact of SBRT fractionation in hypoxia dose painting - Accounting for heterogeneous and dynamic tumor oxygenation. Med Phys 2019; 46:2512-2521. [PMID: 30924937 DOI: 10.1002/mp.13514] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 02/18/2019] [Accepted: 03/13/2019] [Indexed: 12/11/2022] Open
Abstract
PURPOSE Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on 18 F-HX4 positron emission tomography (PET) imaging of NSCLC. METHODS Positron emission tomography imaging data based on the hypoxia tracer 18 F-HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO2 ) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy. RESULTS Gross target volumes ranged between 6.2 and 859.6 cm3 , and the hypoxic fraction < 10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO2 , HTV doses were calculated as 43.6-48.4 Gy for a three-fraction schedule, 51.7-57.6 Gy for five fractions, and 59.5-66.4 Gy for eight fractions. For patients in whom the HTV pO2 distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single-fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions. CONCLUSIONS The method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on 18 F-HX4-PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume.
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Affiliation(s)
- Emely Kjellsson Lindblom
- Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, S-17176, Sweden
| | - Ana Ureba
- Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, S-17176, Sweden
| | | | - Peter Wersäll
- Department of Oncology, Karolinska University Hospital, Stockholm, S-17176, Sweden
| | - Aniek J G Even
- Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, 6229, The Netherlands
| | - Wouter van Elmpt
- Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, 6229, The Netherlands
| | - Philippe Lambin
- Department of Radiation Oncology (MAASTRO), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, 6229, The Netherlands
| | - Iuliana Toma-Dasu
- Medical Radiation Physics, Department of Physics, Stockholm University, Stockholm, S-17176, Sweden.,Medical Radiation Physics, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, S-17176, Sweden
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18
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Videtic GM, Paulus R, Singh AK, Chang JY, Parker W, Olivier KR, Timmerman RD, Komaki RR, Urbanic JJ, Stephans KL, Yom SS, Robinson CG, Belani CP, Iyengar P, Ajlouni MI, Gopaul DD, Gomez Suescun JB, McGarry RC, Choy H, Bradley JD. Long-term Follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 2019; 103:1077-1084. [PMID: 30513377 PMCID: PMC6454873 DOI: 10.1016/j.ijrobp.2018.11.051] [Citation(s) in RCA: 209] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 11/20/2018] [Accepted: 11/23/2018] [Indexed: 11/29/2022]
Abstract
PURPOSE To present long-term results of RTOG 0915/NCCTG N0927, a randomized lung stereotactic body radiation therapy trial of 34 Gy in 1 fraction versus 48 Gy in 4 fractions. METHODS AND MATERIALS This was a phase 2 multicenter study of patients with medically inoperable non-small cell lung cancer with biopsy-proven peripheral T1 or T2 N0M0 tumors, with 1-year toxicity rates as the primary endpoint and selected failure and survival outcomes as secondary endpoints. The study opened in September 2009 and closed in March 2011. Final data were analyzed through May 17, 2018. RESULTS Eighty-four of 94 patients accrued were eligible for analysis: 39 in arm 1 and 45 in arm 2. Median follow-up time was 4.0 years for all patients and 6.0 years for those alive at analysis. Rates of grade 3 and higher toxicity were 2.6% in arm 1 and 11.1% in arm 2. Median survival times (in years) for 34 Gy and 48 Gy were 4.1 versus 4.6, respectively. Five-year outcomes (95% confidence interval) for 34 Gy and 48 Gy were a primary tumor failure rate of 10.6% (3.3%-23.1%) versus 6.8% (1.7%-16.9%); overall survival of 29.6% (16.2%-44.4%) versus 41.1% (26.6%-55.1%); and progression-free survival of 19.1% (8.5%-33.0%) versus 33.3% (20.2%-47.0%). Distant failure as the sole failure or a component of first failure occurred in 6 patients (37.5%) in the 34 Gy arm and in 7 (41.2%) in the 48 Gy arm. CONCLUSIONS No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 years were similar by arm. A median survival time of 4 years for each arm suggests similar efficacy, pending any larger studies appropriately powered to detect survival differences.
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Affiliation(s)
| | - Rebecca Paulus
- NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania
| | | | | | | | | | | | | | - James J Urbanic
- UC San Diego Moores Cancer Center Accruals-Arizona Oncology Services Foundation, San Diego, California
| | | | - Sue S Yom
- UCSF Medical Center, San Francisco, California
| | | | - Chandra P Belani
- The Pennsylvania State University Accruals-Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | | | | | - Darindra D Gopaul
- Grand River Regional Cancer Centre Accruals-London Regional Cancer Centre
| | | | - Ronald C McGarry
- University of Kentucky/Markey Cancer Center Accruals-University of Maryland Medical Systems
| | - Hak Choy
- UT Southwestern/Simmons Cancer Center-Dallas, Dallas, Texas
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Prezzano KM, Ma SJ, Hermann GM, Rivers CI, Gomez-Suescun JA, Singh AK. Stereotactic body radiation therapy for non-small cell lung cancer: A review. World J Clin Oncol 2019; 10:14-27. [PMID: 30627522 PMCID: PMC6318482 DOI: 10.5306/wjco.v10.i1.14] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 11/29/2018] [Accepted: 12/17/2018] [Indexed: 02/06/2023] Open
Abstract
Stereotactic body radiation therapy (SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer (NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility, prescription dose and delivery, and follow up duration varied widely. Three-years overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.
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Affiliation(s)
- Kavitha M Prezzano
- University at Buffalo, the State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Sung Jun Ma
- University at Buffalo, the State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Gregory M Hermann
- University at Buffalo, the State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Charlotte I Rivers
- University at Buffalo, the State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Jorge A Gomez-Suescun
- University at Buffalo, the State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
| | - Anurag K Singh
- University at Buffalo, the State University of New York, Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY 14214, United States
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, United States
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Manyam BV, Videtic GMM, Verdecchia K, Reddy CA, Woody NM, Stephans KL. Effect of Tumor Location and Dosimetric Predictors for Chest Wall Toxicity in Single-Fraction Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer. Pract Radiat Oncol 2018; 9:e187-e195. [PMID: 30529796 DOI: 10.1016/j.prro.2018.11.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 10/17/2018] [Accepted: 11/29/2018] [Indexed: 12/16/2022]
Abstract
PURPOSE Dosimetric parameters to limit chest wall toxicity (CWT) are not well defined in single-fraction (SF) stereotactic body radiation therapy (SBRT) phase 2 trials. We sought to determine the relationship of tumor location and dosimetric parameters with CWT for SF-SBRT. METHODS AND MATERIALS From a prospective registry of 1462 patients, we identified patients treated with 30 Gy or 34 Gy. Gross tumor volume was measured as abutting, ≤1 cm, 1 to 2 cm, or >2 cm from the chest wall. CWT was prospectively graded according to Common Terminology Criteria for Adverse Events version 3.0, with grade 2 requiring medical therapy, grade 3 requiring procedural intervention, and grade 4 being disabling pain. Grade 1 CWT or radiographic rib fracture was not included. Logistic regression analysis was used to identify the parameters associated with CWT and calculate the probability of CWT with dose. RESULTS This study included 146 lesions. The median follow-up time was 23.8 months. The 5-year local control, distant metastasis, and overall survival rates were 91.8%, 19.2%, and 28.7%, respectively. Grade 2 to 4 CWT was 30.6% for lesions abutting the chest wall, 8.2% for ≤1 cm from the chest wall, 3.8% for 1 to 2 cm from the chest wall, and 5.7% for >2 cm from the chest wall. Grade ≥3 CWT was 1.4%. Tumor abutment (odds ratio [OR]: 6.5; P = .0005), body mass index (OR: 1.1; P = .02), rib D1cc (OR: 1.01/Gy; P = .03), chest wall D1cc (OR: 1.08/Gy; P = .03), and chest wall D5cc (OR: 1.10/Gy; P = .01) were significant predictors for CWT on univariate analysis. Tumor abutment was significant for CWT (OR: 7.5; P = .007) on multivariate analysis. The probability of CWT was 15% with chest wall D5cc at 27.2 Gy and rib D1cc at 30.2 Gy. CONCLUSIONS The rate of CWT with SF-SBRT is similar to the rates published for fractionated SBRT, with most CWT being low grade. Tumor location relative to the chest wall is not a contraindication to SF-SBRT, but the rates increase significantly with abutment. Rib D1cc and chest wall D1cc and D5cc may be used as predictors of CWT.
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Affiliation(s)
- Bindu V Manyam
- Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio.
| | | | - Kyle Verdecchia
- Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio
| | - Chandana A Reddy
- Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio
| | - Neil M Woody
- Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio
| | - Kevin L Stephans
- Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio
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Singh AK, Hennon M, Ma SJ, Demmy TL, Picone A, Dexter EU, Nwogu C, Attwood K, Tan W, Hermann GM, Fung-Kee-Fung S, Malhotra HK, Yendamuri S, Gomez-Suescun JA. A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer. BMC Cancer 2018; 18:1183. [PMID: 30497431 PMCID: PMC6267846 DOI: 10.1186/s12885-018-5039-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 11/04/2018] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. METHODS Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. RESULTS Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4-5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36-86) and 40% (90% CI 16-63), respectively. CONCLUSIONS In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. TRIAL REGISTRATION ClinicalTrials.gov identifying number NCT01781741 . Registered February 1, 2013.
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Affiliation(s)
- Anurag K. Singh
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Mark Hennon
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Sung Jun Ma
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Todd L. Demmy
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Anthony Picone
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Elizabeth U. Dexter
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Chumy Nwogu
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Kristopher Attwood
- Department of Biostatistics, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Wei Tan
- Department of Biostatistics, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Gregory M. Hermann
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Simon Fung-Kee-Fung
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Harish K. Malhotra
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Sai Yendamuri
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
| | - Jorge A. Gomez-Suescun
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, 665 Elm St, Buffalo, NY USA
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22
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Cummings MA, Ma SJ, Hermann G, Serra L, Syed Y, Malhotra HK, Chen Y, Milano MT, Gomez-Suescun JA, Singh DP, Singh AK. Comparison of Single- and Five-fraction Regimens of Stereotactic Body Radiation Therapy for Peripheral Early-stage Non-small-cell Lung Cancer: A Two-institution Propensity-matched Analysis. Clin Lung Cancer 2018; 19:511-517. [PMID: 30131257 DOI: 10.1016/j.cllc.2018.07.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Revised: 07/17/2018] [Accepted: 07/20/2018] [Indexed: 12/20/2022]
Abstract
PURPOSE To evaluate differences in local control (LC), disease-specific (DC), and overall survival (OS) of patients with early-stage non-small-cell lung cancer (NSCLC) treated with single- (SF) versus 5-fraction (FF) stereotactic body radiation therapy (SBRT) at 2 institutions. PATIENTS AND METHODS Peripheral early-stage NSCLC cases treated with a median dose of 30 Gy in SF or a median dose of 50 Gy in FF were included per institutional practice. Kaplan-Meier and Cox models were used to assess survival. A matched-pair analysis was performed to account for imbalances. Toxicities including Common Terminology Criteria for Adverse Events (CTCAE) grade 3 pneumonitis, chest wall pain requiring long-acting narcotics, and hospitalization for respiratory events 6 months posttreatment were recorded. RESULTS A total of 163 lesions were treated between 2007 and 2015; 65 received SF SBRT and 98 received FF SBRT. Most tumors were T1 (n = 92) and T2 (n = 34) lesions and had adenocarcinoma (n = 77) and squamous cell carcinoma (n = 46) histologies, respectively. In the matched cohort, there were no differences in OS, LC, DC, or progression-free survival between the groups. LC and OS at 1 year in the matched cohort was 95% and 88%, and 87% and 84% in the SF and FF cohorts, respectively. There was 1 grade 3 pneumonitis in the FF group, and 9 total hospitalizations post-SBRT, 3 (5%) in the SF group and 6 (6%) in the FF group. CONCLUSIONS No statistically significant differences were seen in LC or DC following SF or FF SBRT in this matched cohort of peripheral lesions. No grade 4 or higher toxicities were reported.
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Affiliation(s)
- Michael A Cummings
- Department of Radiation Oncology, Wilmot Cancer Institute, Rochester, NY.
| | - Sung Jun Ma
- University at Buffalo, The State University of New York Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY; Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Gregory Hermann
- University at Buffalo, The State University of New York Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY; Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Lucas Serra
- University at Buffalo, The State University of New York Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY; Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Yusef Syed
- University at Buffalo, The State University of New York Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY; Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Harish K Malhotra
- Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Yuhchyau Chen
- Department of Radiation Oncology, Wilmot Cancer Institute, Rochester, NY
| | - Michael T Milano
- Department of Radiation Oncology, Wilmot Cancer Institute, Rochester, NY
| | - Jorge A Gomez-Suescun
- University at Buffalo, The State University of New York Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY; Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
| | - Deepinder P Singh
- Department of Radiation Oncology, Wilmot Cancer Institute, Rochester, NY
| | - Anurag K Singh
- University at Buffalo, The State University of New York Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY; Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY
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