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Zhou Z, Guan B, Lin J, Zheng R, Xu B. Will personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) or split-course SBRT based on systemic therapy (3S) be future directions in the Field of SBRT? Int Immunopharmacol 2025; 146:113689. [PMID: 39721852 DOI: 10.1016/j.intimp.2024.113689] [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: 02/19/2024] [Revised: 10/30/2024] [Accepted: 11/19/2024] [Indexed: 12/28/2024]
Abstract
The combined use of stereotactic body radiotherapy (SBRT) and immunotherapy is a promising new development. However, the optimal modality for combining SBRT with immunotherapy needs further study. Timmerman and colleagues reported that the time split between radiotherapy and α-PD-L1 therapy can affect the therapeutic effect and introduced a new SBRT paradigm-personalized ultrafractionated stereotactic adaptive radiation therapy (PULSAR). Split-course SBRT based on systemic therapy (3S), which is a concept similar to PULSAR, was introduced. We focus on the underlying mechanisms and advantages of PULSAR or 3S. Notably, the partial results of two relevant clinical trials initiated by our clinical research center are reported here. Moreover, some directions that warrant further investigation are emphasized.
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Affiliation(s)
- Zihan Zhou
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Bingjie Guan
- Department of Radiation Oncology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
| | - Junjian Lin
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
| | - Rong Zheng
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China; Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Fuzhou, Fujian, China; Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou, Fujian, China.
| | - Benhua Xu
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China; Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Fuzhou, Fujian, China; Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou, Fujian, China.
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Price AT, Schiff JP, Silberstein A, Beckert R, Zhao T, Hugo GD, Samson PP, Laugeman E, Henke LE. Feasibility of simulation free abdominal stereotactic adaptive radiotherapy using an expedited pre-plan workflow. Phys Imaging Radiat Oncol 2024; 31:100611. [PMID: 39253730 PMCID: PMC11382001 DOI: 10.1016/j.phro.2024.100611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 07/02/2024] [Accepted: 07/09/2024] [Indexed: 09/11/2024] Open
Abstract
Background and Purpose Improved hounsfield-unit accuracy of on-board imaging may lead to direct-to-unit treatment approaches We aimed to demonstrate the feasibility of using only a diagnostic (dx) computed tomography (CT)-defined target pre-plan in an in silico study of simulation-free abdominal stereotactic adaptive radiotherapy (ART). Materials and Methods Eight patients with abdominal treatment sites (five pancreatic cancer, three oligometastases) were treated using an integrated adaptive O-Ring gantry system. Each patient's target was delineated on a dxCT. The target only pre-plan served primarily to seed the ART process. During the ART session, all structures were delineated. All simulated cases were treated to 50 Gy in 5 fractions to a planning target optimization structure (PTV_OPT) to allow for dose escalation within the planning target volume. Timing of steps during this workflow was recorded. Plan quality was compared between ART treatment plans and a plan created on a CT simulation scan using the traditional planning workflow. Results The workflow was feasible in all attempts, with organ-at-risk (OAR) constraints met in all fractions despite lack of initial OAR contours. Median absolute difference between the adapted plan and simulation CT plan for the PTV_Opt V95% was 2.0 %. Median absolute difference in the D0.5 cm3 between the adapted plan and simulation CT plan was -0.9 Gy for stomach, 1.2 Gy for duodenum, -5.3 Gy for small bowel, and 0.3 Gy for large bowel. Median end-to-end workflow time was 63 min. Conclusion The workflow was feasible for a dxCT-defined target-only pre-plan approach to stereotactic abdominal ART.
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Affiliation(s)
- Alex T Price
- University Hospitals Seidman Cancer Center, Department of Radiation Oncology, Cleveland, OH, USA
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Joshua P Schiff
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, USA
| | - Alice Silberstein
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, USA
| | - Robbie Beckert
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, USA
| | - Tianyu Zhao
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, USA
| | - Geoffrey D Hugo
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, USA
| | - Pamela P Samson
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, USA
| | - Eric Laugeman
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, MO, USA
| | - Lauren E Henke
- University Hospitals Seidman Cancer Center, Department of Radiation Oncology, Cleveland, OH, USA
- Case Western Reserve University School of Medicine, Cleveland, OH, USA
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Bentahila R, Bensalah K, Benziane-Ouaritini N, Barthelemy P, Rioux-Leclerc N, Correas JM, Belhomme S, Bigot P, Sargos P. Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU. THE FRENCH JOURNAL OF UROLOGY 2024; 34:102660. [PMID: 38823486 DOI: 10.1016/j.fjurol.2024.102660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 05/08/2024] [Accepted: 05/26/2024] [Indexed: 06/03/2024]
Abstract
INTRODUCTION The incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. MATERIAL AND METHODS We conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. RESULTS Studies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately -5 to -17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. CONCLUSION Stereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited. LEVEL OF EVIDENCE: 5
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Affiliation(s)
- Rita Bentahila
- Department of radiotherapy, Bergonié Institute, Bordeaux, France
| | - Karim Bensalah
- Urology Department, Rennes University Hospital, Rennes, France
| | | | - Philippe Barthelemy
- Medical Oncology Department, Institut de Cancérologie Strasbourg Europe, Strasbourg, France
| | | | | | - Sarah Belhomme
- Department of Medical Physic, Bergonié Institute, Bordeaux, France
| | - Pierre Bigot
- Urology Department, Angers University Hospital, Angers, France
| | - Paul Sargos
- Department of radiotherapy, Bergonié Institute, Bordeaux, France; Amethyst Radiotherapy Group, Paris, France.
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Kim H, Lee E, Cho H, Kim E, Jang WI, Yang K, Lee YJ, Kim TJ, Kim MS. Five-Day Spacing of Two Fractionated Ablative Radiotherapies Enhances Antitumor Immunity. Int J Radiat Oncol Biol Phys 2024; 118:498-511. [PMID: 37717785 DOI: 10.1016/j.ijrobp.2023.09.014] [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: 04/25/2023] [Revised: 08/10/2023] [Accepted: 09/09/2023] [Indexed: 09/19/2023]
Abstract
PURPOSE This study aimed to enhance tumor control and abscopal effects by applying diverse stereotactic ablative radiation therapy (SABR) schedules. METHODS AND MATERIALS FSaII, CT-26, and 4T1 cells were used for tumor growth delay and lung metastases analysis after 1- or 5-day intervals radiation therapy (RT) with 40, 20, and 20 Gy, respectively. Immunodeficient BALB/c-nude, immunocompetent C3H, and BALB/c mouse models were used. For immune monitoring, FSaII tumors were analyzed using flow cytometry, immunofluorescence staining, and real-time quantitative reverse transcription polymerase chain reaction. The spleens were used for the ELISpot assay and flow cytometry to determine effector CD8 T cells. For abscopal effect analysis in CT-26 tumors, the volume of the nonirradiated secondary tumors was measured after primary tumors were irradiated with 1-day or 5-day intervals. RESULTS Contrary to the high-dose 1-day interval RT, the 5-day interval RT significantly delayed tumor growth in immunocompetent mice, which was not observed in immunodeficient mice. In addition, the 5-day interval RT significantly reduced the number of lung metastases in FSaII and CT-26 tumors. Five-day spacing was more effective than 1-day interval in enhancing the antitumor immunity via increasing the secretion of tumor-specific IFN-γ, activating the CD8 T cells, and suppressing the monocytic myeloid-derived suppressor cells. The 5-day spacing inhibited nonirradiated secondary tumor growth more effectively than did the 1-day interval. CONCLUSIONS Compared with the 1-day interval RT, the 5-day interval RT scheme demonstrated enhanced antitumor immunity of CD8 T cells associated with inhibition of myeloid-derived suppressor cells. Enhancing antitumor immunity leads to significant improvements in both primary tumor control and the abscopal effect.
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Affiliation(s)
| | - Eunju Lee
- Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Korea; Department of Biochemistry and Molecular Biology, College of Medicine, Korea University, Seoul, Korea
| | - Haeun Cho
- Departments of Radiation Oncology and; Department of Radiological & Medico-Oncological Science, University of Science and Technology, Daejeon, Korea
| | - Eunji Kim
- Departments of Radiation Oncology and
| | | | | | - Yoon-Jin Lee
- Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Tae-Jin Kim
- Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, Seoul, Korea.
| | - Mi-Sook Kim
- Departments of Radiation Oncology and; Department of Radiological & Medico-Oncological Science, University of Science and Technology, Daejeon, Korea.
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Barbour AB, Kirste S, Grosu AL, Siva S, Louie AV, Onishi H, Swaminath A, Teh BS, Psutka SP, Weg ES, Chen JJ, Zeng J, Gore JL, Hall E, Liao JJ, Correa RJM, Lo SS. The Judicious Use of Stereotactic Ablative Radiotherapy in the Primary Management of Localized Renal Cell Carcinoma. Cancers (Basel) 2023; 15:3672. [PMID: 37509333 PMCID: PMC10377531 DOI: 10.3390/cancers15143672] [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: 06/16/2023] [Revised: 07/11/2023] [Accepted: 07/18/2023] [Indexed: 07/30/2023] Open
Abstract
Localized renal cell carcinoma is primarily managed surgically, but this disease commonly presents in highly comorbid patients who are poor operative candidates. Less invasive techniques, such as cryoablation and radiofrequency ablation, are effective, but require percutaneous or laparoscopic access, while generally being limited to cT1a tumors without proximity to the renal pelvis or ureter. Active surveillance is another management option for small renal masses, but many patients desire treatment or are poor candidates for active surveillance. For poor surgical candidates, a growing body of evidence supports stereotactic ablative radiotherapy (SABR) as a safe and effective non-invasive treatment modality. For example, a recent multi-institution individual patient data meta-analysis of 190 patients managed with SABR estimated a 5.5% five-year cumulative incidence of local failure with one patient experiencing grade 4 toxicity, and no other grade ≥3 toxic events. Here, we discuss the recent developments in SABR for the management of localized renal cell carcinoma, highlighting key concepts of appropriate patient selection, treatment design, treatment delivery, and response assessment.
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Affiliation(s)
- Andrew B Barbour
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Simon Kirste
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK) Partner Site Freiburg, 79085 Freiburg, Germany
| | - Anca-Liga Grosu
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK) Partner Site Freiburg, 79085 Freiburg, Germany
| | - Shankar Siva
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Center, University of Melbourne, Parkville, VIC 3052, Australia
| | - Alexander V Louie
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Hiroshi Onishi
- Department of Radiology, School of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
| | - Anand Swaminath
- Division of Radiation Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON L8V 5C2, Canada
| | - Bin S Teh
- Department of Radiation Oncology, Cancer Center and Research Institute, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sarah P Psutka
- Department of Urology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Emily S Weg
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Jonathan J Chen
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Jing Zeng
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - John L Gore
- Department of Urology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Evan Hall
- Department of Medical Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Jay J Liao
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
| | - Rohann J M Correa
- Department of Radiation Oncology, London Health Sciences Centre, London, ON N6A 5W9, Canada
| | - Simon S Lo
- Department of Radiation Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98195, USA
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Gogineni E, Chen H, Istl AC, Johnston FM, Narang A, Deville C. Comparative In Silico Analysis of Ultra-Hypofractionated Intensity-Modulated Photon Radiotherapy (IMRT) Versus Intensity-Modulated Proton Therapy (IMPT) in the Pre-Operative Treatment of Retroperitoneal Sarcoma. Cancers (Basel) 2023; 15:3482. [PMID: 37444592 DOI: 10.3390/cancers15133482] [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: 06/20/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND While pre-operative radiation did not improve abdominal recurrence-free survival for retroperitoneal sarcoma (RPS) in the randomized STRASS trial, it did reduce rates of local recurrence. However, the risk of toxicity was substantial and the time to surgery was prolonged. A combination of hypofractionation and proton therapy may reduce delays from the initiation of radiation to surgery and limit the dose to surrounding organs at risk (OARs). We conducted a dosimetric comparison of the pre-operative ultra-hypofractionated intensity-modulated photon (IMRT) and proton radiotherapy (IMPT). METHODS Pre-operative IMRT and IMPT plans were generated on 10 RPS patients. The prescription was 25 Gy radiobiological equivalents (GyEs) (radiobiological effective dose of 1.1) to the clinical target volume and 30 GyEs to the margin at risk, all in five fractions. Comparisons were made using student T-tests. RESULTS The following endpoints were significantly lower with IMPT than with IMRT: mean doses to liver, bone, and all genitourinary and gastrointestinal OARs; bowel, kidney, and bone V5-V20; stomach V15; liver V5; maximum doses to stomach, spinal canal, and body; and whole-body integral dose. CONCLUSIONS IMPT maintained target coverage while significantly reducing the dose to adjacent OARs and integral dose compared to IMRT. A prospective trial treating RPS with pre-operative ultra-hypofractionated IMPT at our institution is currently being pursued.
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Affiliation(s)
- Emile Gogineni
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Hao Chen
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Alexandra C Istl
- Department of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Amol Narang
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Curtiland Deville
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
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Zheng R, Wang BS, Li Z, Chi P, Xu B. Combining chemotherapy and tislelizumab with preoperative split-course hypofraction radiotherapy for locally advanced rectal cancer: study protocol of a prospective, single-arm, phase II trial. BMJ Open 2023; 13:e066976. [PMID: 36927585 PMCID: PMC10030573 DOI: 10.1136/bmjopen-2022-066976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/18/2023] Open
Abstract
INTRODUCTION Short-course radiotherapy (SCRT) with systemic therapy has the potential to further improve the long-term efficacy in patients with locally advanced rectal cancer (LARC). To maximise the benefits of neoadjuvant therapy for improved prognosis, it is important to determine the optimal mix of chemotherapy, immunotherapy and SCRT. METHODS AND ANALYSIS Fifty treatment-naïve patients with operable LARC (T3-4 and/or N+) will be recruited. Patients will be synchronously treated with capecitabine plus oxaliplatin (CAPOX) chemotherapy, tislelizumab and preoperative split-course hypofraction radiotherapy (SCHR) (5×7 Gy) before surgery. Chemotherapy for CAPOX starts on day 1 of every 21-day cycle: on day 1, oxaliplatin 130 mg/m2 will be injected intravenously. On days 1-14, capecitabine 1000 mg/m2 was ingested two times a day. Simultaneously, tocilizumab 200 mg will be given intravenously on the first day of every 21-day cycle. A single 7 Gy SCHR treatment (day 7 of each 21-day cycle) will be delivered five times during the seventh day of treatment. The primary endpoint will be pathological complete response. The secondary outcomes will be the 3-year disease-free survival, local recurrence rate, overall survival, sphincter-sparing surgery rate, R0 resection rate, predictive biomarkers and quality of life. ETHICS AND DISSEMINATION The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (XAHFMU) (No. 2021YF025-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER NCT05176964.
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Affiliation(s)
- Rong Zheng
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Fuzhou, Fujian, People's Republic of China
- Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive,Hematological and Breast Malignancies), Fuzhou, Fujian, People's Republic of China
| | - Bi-Si Wang
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
| | - Zhihua Li
- Department of Oncology, The Second Hospital of Zhangzhou, Zhangzhou, People's Republic of China
| | - Pan Chi
- Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
| | - Benhua Xu
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China
- Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Fuzhou, Fujian, People's Republic of China
- Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive,Hematological and Breast Malignancies), Fuzhou, Fujian, People's Republic of China
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Schiff JP, Stowe HB, Price A, Laugeman E, Hatscher C, Hugo GD, Badiyan SN, Kim H, Robinson CG, Henke LE. In Silico Trial of Computed Tomography-Guided Stereotactic Adaptive Radiotherapy (CT-STAR) for the Treatment of Abdominal Oligometastases. Int J Radiat Oncol Biol Phys 2022; 114:1022-1031. [PMID: 35768023 DOI: 10.1016/j.ijrobp.2022.06.078] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 05/25/2022] [Accepted: 06/13/2022] [Indexed: 11/17/2022]
Abstract
PURPOSE We conducted a prospective, in silico clinical imaging study (NCTXXXX) to evaluate the feasibility of cone-beam computed tomography-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of abdominal oligometastases. We hypothesized that CT-STAR produces improved dosimetry compared to non-adapted CT-stereotactic body radiotherapy (SBRT). METHODS/MATERIALS Eight patients receiving SBRT for abdominal oligometastatic disease received five additional kV cone beam CTs (CBCTs) on the ETHOS system. These additional CBCTs were used for imaging during an emulator treatment session. Initial plans were created based on their simulation (PI) and emulated adaptive plans (PA) were based on anatomy-of-the-day. The prescription was 50 Gy/5 fractions. Organ-at-risk (OAR) constraints were prioritized over planning target volume coverage under a strict isotoxicity approach. The PI was applied to the patient's anatomy-of-the-day and compared to the re-optimized PA using dose volume histogram metrics, with selection of the superior plan. Feasibility was defined as completion of the adaptive workflow and compliance with strict OAR constraints in ≥80% of fractions. Fractions were performed under time pressures by a physician and physicist to mimic the adaptive process. RESULTS CT-STAR was feasible, with successful workflow completion in 38/40 (95%) fractions. PI application to daily anatomy created OAR constraint violations in 30/40 (75%) fractions. There were 8 stomach, 18 duodenum, 16 small bowel, and 11 large bowel PI OAR constraint violations. In contrast, OAR violations occurred in 2/40 (5%) PA (both small bowel violations, both improved from the PI). CT-STAR also improved GTV V100 and D95 coverage in 25/40 (63%) and 20/40 (50%) fractions, respectively. 0/40 (0%) fractions were deemed non-feasible due to poor image quality and/or inability to delineate structures. Adaptation time per fraction was a median of 22.59 minutes (10.97-47.23). CONCLUSIONS CT-STAR resolved OAR hard constraint violations and/or improved target coverage in silico when compared to non-adapted CT-guided SBRT for the ablation of abdominal oligometastatic disease. While limitations of this study include its small sample size and in silico design, the consistently high quality CBCT images captured and comparable timing metrics to prior adaptive studies suggest that CT- STAR is a viable treatment paradigm for the ablation of abdominal oligometastatic disease. Clinical trials are in development to further evaluate CT-STAR in the clinic.
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Affiliation(s)
- Joshua P Schiff
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA.
| | - Hayley B Stowe
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Alex Price
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Eric Laugeman
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Casey Hatscher
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Geoffrey D Hugo
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Shahed N Badiyan
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Hyun Kim
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Clifford G Robinson
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA
| | - Lauren E Henke
- Washington University School of Medicine in St. Louis, Department of Radiation Oncology, St. Louis, Missouri, USA.
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Grozman V, Onjukka E, Wersäll P, Lax I, Tsakonas G, Nyren S, Lewensohn R, Lindberg K. Extending hypofractionated stereotactic body radiotherapy to tumours larger than 70cc - effects and side effects. Acta Oncol 2021; 60:305-311. [PMID: 33448899 DOI: 10.1080/0284186x.2020.1866776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
BACKGROUND AND PURPOSE Stereotactic body radiotherapy (SBRT) for tumours ≥5 cm is poorly studied and its utility and feasibility is uncertain. We here report the Karolinska experience of SBRT in this setting. MATERIAL AND METHODS All patients had a gross tumour volume (GTV) ≥70 cc, a prescribed physical dose of at least 40 Gy and received treatment between 1995-2012. RESULTS We included 164 patients with 175 tumours located in the thorax (n = 86), the liver (n = 27) and the abdomen (n = 62) and treated with a median prescribed dose (BEDα/β 10Gy) of 80 Gy (71.4-113). One- and 2- year local control rates were 82% and 61%. In multivariate analyses, minimum dose to the GTV and histological subtype were associated with local control. Renal cell carcinoma (RCC) histology showed the most favourable local control - 94% at 2 years for all histologies. Thirty-seven patients experienced grade 3-5 toxicity most likely related to SBRT. Seven of the ten patients with grade 5 toxicity, had a centrally located tumour in the thorax. CONCLUSION SBRT of tumours >5 cm in diameter may be an option for peripherally located lung and abdominal tumours. Histological origin and tumour location should be considered before treatment.
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Affiliation(s)
- Vitali Grozman
- Section of Thoracic Radiology, Department of Imaging and Physiology, Karolinska University Hospital, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Eva Onjukka
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
- Section of Radiotherapy Physics and Engineering, Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Wersäll
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
- Section of Radiotherapy, Department of Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Ingmar Lax
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
- Section of Radiotherapy Physics and Engineering, Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Georgios Tsakonas
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
- Section of Head, Neck, Lung and Skin tumours, Department of Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Sven Nyren
- Section of Thoracic Radiology, Department of Imaging and Physiology, Karolinska University Hospital, Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
| | - Rolf Lewensohn
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
- Section of Head, Neck, Lung and Skin tumours, Department of Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Karin Lindberg
- Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
- Section of Head, Neck, Lung and Skin tumours, Department of Cancer, Karolinska University Hospital, Stockholm, Sweden
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10
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Zheng R, Wang C, Huang X, Lin Q, Huang D, Li XB, Huang H, Xu B. Chemotherapy-based split stereotactic body radiation therapy for borderline resectable and locally advanced pancreatic cancer: study protocol of a prospective, single-arm phase II trial. BMJ Open 2020; 10:e039900. [PMID: 33154057 PMCID: PMC7646341 DOI: 10.1136/bmjopen-2020-039900] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
INTRODUCTION The question of how to administer adequate chemotherapy to synchronise stereotactic body radiation therapy (SBRT) treatment strategy to maximise the benefits of neoadjuvant therapy for the improved prognosis of patients with borderline resectable (BRPC) and locally advanced (LAPC) pancreatic cancer is a challenging and debatable issue. No studies have yet evaluated the efficacy of split-course SBRT as the neoadjuvant chemoradiotherapy regimen. We aimed to study whether neoadjuvant chemotherapy plus split-course SBRT results in better outcomes in BRPC and LAPC patients. METHODS AND ANALYSIS Treatment-naïve patients with radiographically confirmed BRPC or LAPC, supporting biopsy results and no severe comorbidities will be enrolled. They will be treated with nab-paclitaxel plus gemcitabine (nab-P+Gem) chemotherapy plus split-course SBRT, followed by an investigator's choice of continuation of treatment with nab-P+Gem or surgery. nab-P+Gem chemotherapy will commence on day 1 for each of six cycles: nab-paclitaxel 125 mg/m2 intravenous infusion over approximately 30-45 min, followed by gemcitabine 1000 mg/m2 intravenous infusion over about 30 min on days 1 and 15 of each 28-day cycle. During the first and second cycles of chemotherapy, SBRT will be given as a single irradiation of 10 Gy four times (days 2 and 16 of each 28-day cycle). The primary endpoint is progression-free survival; while the secondary outcomes are the time to treatment failure, disease control rate, overall response rate, overall survival, R0 resection rate and incidence of adverse effects. ETHICS AND DISSEMINATION The study protocol was approved by the Ethics Committee of Xiehe Affiliated Hospital of Fujian Medical University (No. 2019YF015-01). Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER NCT04289792.
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Affiliation(s)
- Rong Zheng
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Congfei Wang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Xiaoxue Huang
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Qingliang Lin
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Daxin Huang
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Xiao-Bo Li
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Heguang Huang
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Benhua Xu
- Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
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11
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Park J, Park JW, Kang MK. Current status of stereotactic body radiotherapy for the treatment of hepatocellular carcinoma. Yeungnam Univ J Med 2019; 36:192-200. [PMID: 31620633 PMCID: PMC6784649 DOI: 10.12701/yujm.2019.00269] [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: 07/03/2019] [Revised: 07/22/2019] [Accepted: 07/30/2019] [Indexed: 12/19/2022] Open
Abstract
Stereotactic body radiotherapy (SBRT) is an advanced form of radiotherapy (RT) with a growing interest on its application in the treatment of hepatocellular carcinoma (HCC). It can deliver ablative radiation doses to tumors in a few fractions without excessive doses to normal tissues, with the help of advanced modern RT and imaging technologies. Currently, SBRT is recommended as an alternative to curative treatments, such as surgery and radiofrequency ablation. This review discusses the current status of SBRT to aid in the decision making on how it is incorporated into the HCC management.
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Affiliation(s)
- Jongmoo Park
- Department of Radiation Oncology, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Jae Won Park
- Department of Radiation Oncology, Yeungnam University College of Medicine, Daegu, Korea
| | - Min Kyu Kang
- Department of Radiation Oncology, School of Medicine, Kyungpook National University, Daegu, Korea
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12
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Cho I, Park JW, Cho B, Kwak J, Yoon SM, Nesseler JP, Park J, Kim JH. Dosimetric analysis of stereotactic rotational versus static intensity-modulated radiation therapy for pancreatic cancer. Cancer Radiother 2018; 22:754-762. [PMID: 30322818 DOI: 10.1016/j.canrad.2018.01.007] [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: 11/21/2017] [Revised: 01/20/2018] [Accepted: 01/24/2018] [Indexed: 02/06/2023]
Abstract
PURPOSE Stereotactic body radiation therapy is a promising treatment modality for locally advanced pancreatic cancer. To determine the optimal radiation treatment, we compared the plan characteristics of volumetric-modulated arc therapy and intensity-modulated radiation therapy when administered with stereotactic body radiation therapy to treat pancreatic cancer. PATIENTS AND METHODS Fifteen patients with locally advanced pancreatic cancer were treated by stereotactic body radiation therapy at a dose of 24-32Gy in four fractions with marker-guided gated volumetric-modulated arc therapy. Four dimensional-computed tomography scans were used to assess the target and surrounding normal organs. The same images, contours, and dose constraints were used for dual-arc volumetric-modulated arc therapy and 9-field intensity-modulated radiation therapy planning. Plans were compared using dosimetric parameters and treatment performance. RESULTS Volumetric-modulated arc therapy required significantly lower monitor units (1726 vs. 4188; P<0.001) and shorter treatment delivery time in comparison with intensity-modulated radiation therapy (22.5min vs. 52.4min; P<0.001). Regarding target volume coverage, both modalities demonstrated comparable results (V95%, 99.3% vs. 99.4%; P=0.796). Both modalities satisfied the dosimetric determinants for duodenal toxicity and the maximum and mean doses administered to normal organ were also statistically similar. CONCLUSION In comparison with 9-field intensity-modulated radiation therapy, volumetric-modulated arc therapy significantly reduces the number of monitoring units and treatment delivery times while administering similar dosimetric quality. Based on these results, volumetric-modulated arc therapy might be an appropriate treatment for locally advanced pancreatic cancer when combined with stereotactic body radiation therapy.
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Affiliation(s)
- I Cho
- Division of Heavy-ion Clinical Research, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Republic of Korea
| | - J W Park
- Department of Radiation Oncology, Yeungnam University College of Medicine, 170, Hyeonchung-ro, Nam-gu, Daegu, Republic of Korea
| | - B Cho
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, 05505 Songpa-gu, Seoul, Republic of Korea
| | - J Kwak
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, 05505 Songpa-gu, Seoul, Republic of Korea
| | - S M Yoon
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, 05505 Songpa-gu, Seoul, Republic of Korea
| | - J P Nesseler
- Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - J Park
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, 05505 Songpa-gu, Seoul, Republic of Korea.
| | - J H Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, 05505 Songpa-gu, Seoul, Republic of Korea
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13
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Paik EK, Kim MS, Seo YS, Jang WI, Kang JK, Cho CK, Yoo HJ. Feasibility of split-course stereotactic ablative radiotherapy for oligometastases. Jpn J Clin Oncol 2018; 48:548-554. [PMID: 29722825 PMCID: PMC5974783 DOI: 10.1093/jjco/hyy062] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 04/12/2018] [Indexed: 12/25/2022] Open
Abstract
Background There is growing interest in the use of stereotactic ablative radiotherapy (SABR) for oligometastases. However, extreme caution should be exercised in treating tumors closely located to organs at risk (OARs) with SABR. To reduce complications, we have applied split-course SABR to oligometastases closely located to OARs or to those being retreated with radiotherapy. Methods We retrospectively reviewed the records of patients with oligometastases who were treated with planned split-course SABR between January 2012 and December 2016. Results A total of 23 patients with 29 oligometastatic lesions were enrolled. The primary diagnoses were bone and soft tissue cancers in 13 lesions, liver cancers in 12 lesions, and colorectal cancers in four lesions. The median tumor volume was 78 cm3 (range, 4-1781 cm3). The lesions were treated with 1-3 fractions in the first stage of SABR (first SABR), and one or two fractions in the second stage of SABR (second SABR). The time interval between the two stages was about 4 weeks. A partial response was noted in 16 lesions (55%) after the first SABR, and practical reductions in the doses to OARs were observed in the second SABR compared with the first SABR. The 1-, 2- and 3-year local control rates were 92%, 65% and 43%, respectively. No Grade 4 or 5 toxicities were observed during or after treatment. Conclusion Split-course SABR appeared to be feasible for the treatment of oligometastases closely located to OARs.
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Affiliation(s)
- Eun Kyung Paik
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences
| | - Young-Seok Seo
- Department of Radiation Oncology, Seoul National University Hospital
| | - Won Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences
| | - Jin-Kyu Kang
- National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
| | - Chul-Koo Cho
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences
| | - Hyung Jun Yoo
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences
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14
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Zhang X, Niedermann G. Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response. Int J Radiat Oncol Biol Phys 2018. [PMID: 29534901 DOI: 10.1016/j.ijrobp.2018.01.094] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment. METHODS AND MATERIALS In mice bearing 2 B16-CD133 melanoma tumors, the primary tumor was irradiated with 3 × 9.18 Gy in 3 or 5 days or with 5 × 6.43 Gy in 10 days; an anti-PD1 antibody was given weekly. The mice were monitored for tumor growth and survival. T-cell responses were determined on days 8 and 15 of treatment. The role of regional lymph nodes was studied by administering FTY720, which blocks lymph node egress of activated T cells. Tumor growth measurements after combination treatment using short or extended hRT and control treatment were also performed in the wild-type B16 melanoma and 4T1 breast carcinoma models. RESULTS In the B16-CD133 model, growth inhibition of irradiated primary and nonirradiated secondary tumors and overall survival were similar with all 3 hRT/anti-PD1 combinations, superior to hRT and anti-PD1 monotherapy, and was strongly dependent on CD8+ T cells. TIL infiltration and local and systemic tumor-specific CD8+ T-cell responses were also similar, regardless of whether short or extended hRT was used. Administration of FTY720 accelerated growth of both primary and secondary tumors, strongly reduced their TIL infiltration, and increased tumor-specific CD8+ T cells in the lymph nodes draining the irradiated tumor. In the 4T1 model, local and abscopal tumor control was also similar, regardless of whether short or extended hRT was used, although the synergy between hRT and anti-PD1 was weaker. No synergies were found in the B16 wild-type model lacking an exogenous antigen. CONCLUSIONS Our data suggest that combination therapy with hRT schedules extending into the period during which treatment-induced T cells infiltrate the irradiated tumor can provoke local and systemic antitumor effects similar to those with therapy using shorter schedules, if the regional lymph nodes supply sufficient tumor-specific T cells. This has implications for planning clinical RT/immune checkpoint blockade trials.
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MESH Headings
- Animals
- Antibodies/therapeutic use
- CD8-Positive T-Lymphocytes/cytology
- CD8-Positive T-Lymphocytes/drug effects
- CD8-Positive T-Lymphocytes/immunology
- CD8-Positive T-Lymphocytes/radiation effects
- Combined Modality Therapy
- Fingolimod Hydrochloride/pharmacology
- Flow Cytometry
- Humans
- Immunosuppressive Agents/pharmacology
- Immunotherapy, Adoptive/methods
- Interferon-gamma/analysis
- Lymphocyte Activation/immunology
- Lymphocyte Activation/radiation effects
- Lymphocytes, Tumor-Infiltrating/cytology
- Lymphocytes, Tumor-Infiltrating/drug effects
- Lymphocytes, Tumor-Infiltrating/immunology
- Lymphocytes, Tumor-Infiltrating/radiation effects
- Melanoma, Experimental/immunology
- Melanoma, Experimental/mortality
- Melanoma, Experimental/pathology
- Melanoma, Experimental/radiotherapy
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Programmed Cell Death 1 Receptor/immunology
- Radiation Dose Hypofractionation
- Relative Biological Effectiveness
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Affiliation(s)
- Xuanwei Zhang
- Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium, partner site Freiburg, and German Cancer Research Center, Heidelberg, Germany; Department of Radiation Oncology, First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, Shaan Xi, People's Republic of China
| | - Gabriele Niedermann
- Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium, partner site Freiburg, and German Cancer Research Center, Heidelberg, Germany.
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15
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Franzese C, Fogliata A, Comito T, Tozzi A, Iftode C, Clerici E, Franceschini D, Navarria P, Ascolese AM, Di Brina L, De Rose F, D'Agostino GR, Cozzi L, Scorsetti M. Stereotactic/hypofractionated body radiation therapy as an effective treatment for lymph node metastases from colorectal cancer: an institutional retrospective analysis. Br J Radiol 2017; 90:20170422. [PMID: 28869396 DOI: 10.1259/bjr.20170422] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE The colorectal cancer (CRC) might present loco-regional recurrence, including lymph-node metastasis. Stereotactic body radiotherapy (SBRT) is a non-invasive and well-tolerated ablative treatment. Aim of the present study is to evaluate efficacy and toxicity of SBRT with volumetric modulated arc therapy (VMAT) in this setting. METHODS 35 patients presenting a total of 47 nodal recurrences from CRC, treated with VMAT-SBRT from 2008 to 2015, were selected. About three fourth of the treatments delivered 45 Gy in 6 daily fractions. End-points were the detection of toxicities, overall survival (OS), local control (LC), disease progression free incidence (DPFI) and disease free survival (DFS). Tumour response was assessed according to the RECIST criteria. RESULTS Only Grade 1 and 2 toxicities were recorded. Median follow-up was 15 months (range 2-68). Local relapse was reported in 6 patients, regional relapse in 10 patients. Complete remission was reported in 20 cases (53%), partial remission in 14 (37%). Rates of LC at 1, 2 and 3 years were 85.3, 75.0 and 75.0%, respectively. At 1 year the actuarial OS was 100%, at 2 and 3 years was 81.4%. Median DFS was estimated in 16 months, with an incidence of 69.4, 33.3 and 19.4% at 1, 2 and 3 years, respectively. CONCLUSION The use of the VMAT-SBRT in lymph-node recurrence of CRC could prevent severe complications and achieve satisfying rates of disease control. Advances in knowledge: The use of VMAT-SBRT is a viable approach for lymph-node recurrence of CRC.
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Affiliation(s)
- Ciro Franzese
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Antonella Fogliata
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Tiziana Comito
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Angelo Tozzi
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Cristina Iftode
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Elena Clerici
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Davide Franceschini
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Pierina Navarria
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Anna Maria Ascolese
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Lucia Di Brina
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Fiorenza De Rose
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Giuseppe R D'Agostino
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy
| | - Luca Cozzi
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy.,2 Department of Biomedical Sciences, Humanitas University, Milan-Rozzano, Italy
| | - Marta Scorsetti
- 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan-Rozzano, Italy.,2 Department of Biomedical Sciences, Humanitas University, Milan-Rozzano, Italy
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16
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Qing SW, Ju XP, Cao YS, Zhang HJ. Dose escalation of Stereotactic Body Radiotherapy (SBRT) for locally advanced unresectable pancreatic cancer patients with CyberKnife: protocol of a phase I study. Radiat Oncol 2017; 12:6. [PMID: 28069017 PMCID: PMC5223403 DOI: 10.1186/s13014-016-0760-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Accepted: 12/28/2016] [Indexed: 01/01/2023] Open
Abstract
Background Dose escalation of SBRT for locally advanced pancreatic cancer patients had been reported in several studies in one or three fractions, and phase I protocol was developed to investigate the maximum tolerated dose with CyberKnife for locally advanced unresectable pancreatic cancer patients in five fractions. Methods The study is designed as a mono-center phase I study. The primary endpoint is to determine the maximum tolerated dose by frequency of III/IV GI (gastrointestinal) toxicity. Adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Doses of 7 Gy, 7.5 Gy, 8 Gy, 8.5 Gy, 9 Gy, 9.5Gy x 5 respectively would be delivered while meeting with normal tissue constraints. A minimum of three patients will be included for each dosage level. And an interval is 4 weeks from the first patient treatment to the next patient treatment at each dose level. The maximal tolerated dose will be defined as the dose for which at least two patients in three, or at least three patients in nine, will present with a limiting toxicity. Discussion Since the dose and fractions of SBRT treatment for locally advanced pancreatic cancer patients are still unknown, we propose to conduct a Phase I study determining the maximum tolerated dose of CyberKnife SBRT for the treatment of locally advanced pancreatic tumor based on a 5 fractions treatment regimen. This trial protocol has been approved by the Ethics committee of Changhai hospital. The ethics number is 2016-030-01. Trial registration Clinical trials number: NCT02716207. Date of registration: 20 March 2016.
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Affiliation(s)
- Shui-Wang Qing
- Department of Radiation Oncology, Changhai Hospital, No.168 Changhai road, Shanghai, China
| | - Xiao-Ping Ju
- Department of Radiation Oncology, Changhai Hospital, No.168 Changhai road, Shanghai, China
| | - Yang-Sen Cao
- Department of Radiation Oncology, Changhai Hospital, No.168 Changhai road, Shanghai, China
| | - Huo-Jun Zhang
- Department of Radiation Oncology, Changhai Hospital, No.168 Changhai road, Shanghai, China.
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17
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Kim SK, Wu CC, Horowitz DP. Stereotactic body radiotherapy for the pancreas: a critical review for the medical oncologist. J Gastrointest Oncol 2016; 7:479-86. [PMID: 27284482 DOI: 10.21037/jgo.2015.10.01] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
With recent advances in imaging modalities and radiation therapy, stereotactic body radiotherapy (SBRT) has allowed for the delivery of high doses of radiation with accuracy and precision. As such, SBRT has generated favorable results in the treatment of several cancers. Although the role of radiation has been controversial for the treatment of pancreatic ductal adenocarcinoma (PDAC) due to rather lackluster results in clinical trials, SBRT may offer improved outcomes, enhance the quality of life, and aid in palliative care settings for PDAC patients. This review delineates the role of SBRT in the treatment of PDAC, presents the defining principles of radiation biology and the radiation oncology work flow, and discusses the prospects of new treatment regimens involving tumor immunology and radiation therapy.
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Affiliation(s)
- Samuel K Kim
- Department of Radiation Oncology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - Cheng-Chia Wu
- Department of Radiation Oncology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
| | - David P Horowitz
- Department of Radiation Oncology, New York Presbyterian Hospital, Columbia University Medical Center, New York, NY 10032, USA
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18
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LaCouture TA, Xue J, Subedi G, Xu Q, Lee JT, Kubicek G, Asbell SO. Small Bowel Dose Tolerance for Stereotactic Body Radiation Therapy. Semin Radiat Oncol 2016; 26:157-64. [DOI: 10.1016/j.semradonc.2015.11.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Trakul N, Koong AC, Chang DT. Stereotactic body radiotherapy in the treatment of pancreatic cancer. Semin Radiat Oncol 2014; 24:140-7. [PMID: 24635871 DOI: 10.1016/j.semradonc.2013.11.008] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Most patients diagnosed with pancreatic cancer are unable to have a curative surgical resection. Chemoradiation is a standard of care treatment for patients with locally advanced unresectable disease, but local failure rates are high with conventionally fractionated radiotherapy. However, stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy offers an alternative type of radiation therapy, which allows for the delivery of high-dose, conformal radiation. The high doses and shorter overall treatment time with SBRT may provide advantages in local control, disease outcomes, quality of life, and cost-effectiveness, and further investigation is currently underway. Here, we review the technology behind SBRT for pancreatic malignancy and its future direction in the overall management of pancreatic cancer.
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Affiliation(s)
- Nicholas Trakul
- Department of Radiation Oncology, Keck School of Medicine of University of Southern California, Los Angeles, CA
| | - Albert C Koong
- Department of Radiation Oncology, Stanford University School of Medicine and Cancer Center, Stanford, CA
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford University School of Medicine and Cancer Center, Stanford, CA.
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20
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Pollom EL, Alagappan M, von Eyben R, Kunz PL, Fisher GA, Ford JA, Poultsides GA, Visser BC, Norton JA, Kamaya A, Cox VL, Columbo LA, Koong AC, Chang DT. Single- versus multifraction stereotactic body radiation therapy for pancreatic adenocarcinoma: outcomes and toxicity. Int J Radiat Oncol Biol Phys 2014; 90:918-25. [PMID: 25585785 DOI: 10.1016/j.ijrobp.2014.06.066] [Citation(s) in RCA: 74] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2014] [Revised: 06/24/2014] [Accepted: 06/25/2014] [Indexed: 01/09/2023]
Abstract
PURPOSE We report updated outcomes of single- versus multifraction stereotactic body radiation therapy (SBRT) for unresectable pancreatic adenocarcinoma. METHODS AND MATERIALS We included 167 patients with unresectable pancreatic adenocarcinoma treated at our institution from 2002 to 2013, with 1-fraction (45.5% of patient) or 5-fraction (54.5% of patients) SBRT. The majority of patients (87.5%) received chemotherapy. RESULTS Median follow-up was 7.9 months (range: 0.1-63.6). The 6- and 12-month cumulative incidence rates (CIR) of local recurrence for patients treated with single-fraction SBRT were 5.3% (95% confidence interval [CI], 0.2%-10.4%) and 9.5% (95% CI, 2.7%-16.2%), respectively. The 6- and 12-month CIR with multifraction SBRT were 3.4% (95% CI, 0.0-7.2%) and 11.7% (95% CI, 4.8%-18.6%), respectively. Median survival from diagnosis for all patients was 13.6 months (95% CI, 12.2-15.0 months). The 6- and 12- month survival rates from SBRT for the single-fraction group were 67.0% (95% CI, 57.2%-78.5%) and 30.8% (95% CI, 21.9%-43.6%), respectively. The 6- and 12- month survival rates for the multifraction group were 75.7% (95% CI, 67.2%-85.3%) and 34.9% (95% CI, 26.1%-46.8%), respectively. There were no differences in CIR or survival rates between the single- and multifraction groups. The 6- and 12-month cumulative incidence rates of gastrointestinal toxicity grade ≥3 were 8.1% (95% CI, 1.8%-14.4%) and 12.3% (95% CI, 4.7%-20.0%), respectively, in the single-fraction group, and both were 5.6% (95% CI, 0.8%-10.5%) in the multifraction group. There were significantly fewer instances of toxicity grade ≥2 with multifraction SBRT (P=.005). Local recurrence and toxicity grade ≥2 were independent predictors of worse survival. CONCLUSIONS Multifraction SBRT for pancreatic cancer significantly reduces gastrointestinal toxicity without compromising local control.
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Affiliation(s)
- Erqi L Pollom
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Muthuraman Alagappan
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Rie von Eyben
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Pamela L Kunz
- Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - George A Fisher
- Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - James A Ford
- Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - George A Poultsides
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Brendan C Visser
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Jeffrey A Norton
- Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Aya Kamaya
- Department of Radiology, Stanford University School of Medicine, Stanford, California
| | - Veronica L Cox
- Department of Radiology, Stanford University School of Medicine, Stanford, California
| | - Laurie A Columbo
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Albert C Koong
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
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21
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Thomas TO, Hasan S, Small W, Herman JM, Lock M, Kim EY, Mayr NA, Teh BS, Lo SS. The tolerance of gastrointestinal organs to stereotactic body radiation therapy: what do we know so far? J Gastrointest Oncol 2014; 5:236-46. [PMID: 24982772 PMCID: PMC4074956 DOI: 10.3978/j.issn.2078-6891.2014.024] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2014] [Accepted: 05/08/2014] [Indexed: 12/14/2022] Open
Abstract
As stereotactic body radiation therapy (SBRT) for gastrointestinal (GI) gains popularity, there is a need to optimize doses and fractionation to minimize GI toxicity. GI organs that have classically developed radiation-induced toxicity include the liver & biliary system, small bowel, esophagus, and rectum. While the literature quantifies dose restrictions for these organs under standard fractionation, there is limited data regarding toxicity with the ablative dose schedules used in SBRT. We conducted a review of the literature to identify prospective and retrospective studies that detail GI toxicities when SBRT was employed. Based on the literature, the median SBRT dose for abdominal and thoracic tumors ranged from 24 to 60 Gy, at 5 to 25 Gy per fraction. The respective observed frequencies of grade 3 and 4 toxicities for the liver, biliary system, small bowel, and esophagus were variable among different studies. Typically, patients who suffered grade 3 and 4 toxicities were more likely to have had some form of systemic therapy as well. The effect of dose, fractionation, timing, and volume on GI toxicities has been described in the literature but more data is necessary to develop uniform treatment guidelines for SBRT.
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22
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Seo Y, Kim MS, Yoo HJ, Jang WI, Rhu SY, Choi SC, Kim MH, Kim BJ, Lee DH, Cho CK. Salvage stereotactic body radiotherapy for locally recurrent uterine cervix cancer at the pelvic sidewall: Feasibility and complication. Asia Pac J Clin Oncol 2014; 12:e280-8. [PMID: 24889550 DOI: 10.1111/ajco.12185] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2014] [Indexed: 12/20/2022]
Abstract
AIMS To determine the feasibility of stereotactic body radiotherapy (SBRT) in patients with pelvic sidewall recurrence of uterine cervical cancer after radical hysterectomy or definitive radiotherapy. METHODS We retrospectively reviewed 23 patients with locally recurrent uterine cervical cancer limited to the pelvic sidewall who were treated with SBRT at our institution between January 2003 and May 2010. The SBRT dose ranged from 27 to 45 Gy (median, 39 Gy) in three fractions, and the fractional SBRT dose ranged from 9 to 15 Gy (median, 13 Gy). RESULTS The 2-year overall survival, local progression-free survival and disease progression-free survival rates were 43%, 65% and 52%, respectively. Patients with small tumors (gross tumor volume <30 cm(3) ) had a significantly longer 2-year overall survival rate and 2-year local progression-free survival rate than did patients with large tumors (overall survival rate: 89% vs 12%; P = 0.0001 and local progression-free survival: 85% vs 0%; P = 0.0199). There were three cases (13%) of severe toxicities (rectovaginal fistula). Pelvic pain relief was achieved in all patients. In particular, 10 of 14 patients (71%) achieved analgesic (nonsteroidal anti-inflammatory drug or narcotic) reduction of 50% or more from baseline. CONCLUSION SBRT is a feasible treatment option for women with pelvic sidewall tumors from recurrent uterine cervical cancer, especially for small recurrent tumors. However, SBRT should be used carefully in the treatment of large tumors, as the incidence of severe late toxicity increases with the size of the tumor.
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Affiliation(s)
- YoungSeok Seo
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Hyung-Jun Yoo
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Won-Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Sang-Young Rhu
- Department of Gynecology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Suck-Chul Choi
- Department of Gynecology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Moon-Hong Kim
- Department of Gynecology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Beob-Jong Kim
- Department of Gynecology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Dong-Han Lee
- CyberKnife Center, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
| | - Chul-Koo Cho
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
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23
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Seo YS, Kim MS, Yoo HJ, Jang WI. Stereotactic body radiotherapy for oligo-recurrence within the nodal area from colorectal cancer. World J Gastroenterol 2014; 20:2005-2013. [PMID: 24587675 PMCID: PMC3934470 DOI: 10.3748/wjg.v20.i8.2005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Revised: 09/25/2013] [Accepted: 01/08/2014] [Indexed: 02/06/2023] Open
Abstract
Recurrence of colorectal cancer (CRC) often presents as solitary metastases, oligometastases or oligo-recurrence. Surgical resection became the preferred treatment for patients with CRC lung and hepatic metastases. However, surgical treatment for oligo-recurrence within nodal area is not a widely accepted treatment due to due to their relative rarity and high postoperative morbidity. Stereotactic body radiotherapy (SBRT) is one of the emerging radiation treatment techniques in which a high radiation dose can be delivered to the tumor. High-dose SBRT can ablate the tumor with an efficacy similar to that achieved with surgery, especially for small tumors. However, there have been very few studies on SBRT for oligo-recurrence within nodal area, although several studies have evaluated the role of SBRT in the treatment of liver and lung metastases from CRC. This article reviews the current clinical status of and treatment methods for oligo-recurrence within nodal area from CRC, with particular emphasis on SBRT.
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24
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Jang WI, Kim MS, Bae SH, Cho CK, Yoo HJ, Seo YS, Kang JK, Kim SY, Lee DH, Han CJ, Kim J, Park SC, Kim SB, Cho EH, Kim YH. High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma. Radiat Oncol 2013; 8:250. [PMID: 24160944 PMCID: PMC4231524 DOI: 10.1186/1748-717x-8-250] [Citation(s) in RCA: 144] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2013] [Accepted: 10/23/2013] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC. METHODS Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0-7.0 cm), and the median dose was 51 Gy (range, 33-60 Gy). RESULTS LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45-54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT. CONCLUSIONS This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.
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Affiliation(s)
| | - Mi-Sook Kim
- Department of Radiation Oncology, Korea Institute of Radiological & Medical Science, Seoul, Republic of Korea.
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