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Perrier M, Fontaine M, Bertin E, Carlier C, Botsen D, Djelouah M, François E, Guilbert P, Saint A, Slimano F, Torielli P, Brugel M, Bouché O. Impact of low muscle mass and myosteatosis on treatment toxicity and survival outcomes in non-resectable pancreatic cancer patients treated with chemoradiotherapy. Eur J Clin Nutr 2025:10.1038/s41430-025-01566-5. [PMID: 39910182 DOI: 10.1038/s41430-025-01566-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 12/07/2024] [Accepted: 01/07/2025] [Indexed: 02/07/2025]
Abstract
BACKGROUND Low skeletal muscle mass and impaired muscle quality (myosteatosis) have been associated with poor outcomes in cancer patients. This study aimed to evaluate the impact of pre-therapeutic low muscle mass and myosteatosis on chemoradiotherapy (CRT)-induced toxicity and survival outcomes in patients with non-resectable pancreatic cancer (PC). METHODS In this retrospective study, pre-therapeutic CT scans were used to measure muscle mass/density. Low muscle mass was defined as a skeletal muscle index <38.5 cm²/m² (women) and <52.4 cm²/m² (men), and myosteatosis as a mean psoas density <41 HU if BMI < 25 kg/m² or <33 HU if BMI > 25 kg/m². Adverse effects were collected per week (W) of treatment. Dose-limiting toxicity (DLT) was defined as any toxicity leading to dose reduction, treatment delays or permanent discontinuation. RESULTS Among the 85 included patients, 75 (88.2%) and 18 (22.2%) had pre-therapeutic low muscle mass and myosteatosis, respectively. Only 12 patients (14.1%) experienced DLT. Patients with low muscle mass developed significantly more toxicities at W2 (p = 0.013) and W5 (p = 0.026), notably more nausea (p = 0.037) and anemia (p = 0.004). Low muscle mass was associated with poorer overall survival (HR 4.41 [1.50-12.94], p = 0.007) in multivariate Cox analysis, while myosteatosis was not associated with CRT toxicities, DLT and overall survival (p = 0.408). CONCLUSION Patients with low muscle mass experienced more toxicities and poorer outcomes during CRT for non-resectable PC.
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Affiliation(s)
- Marine Perrier
- Université Reims Champagne-Ardenne, Department of Gastroenterology and Digestive Oncology, CHU Reims, 51100, Reims, France.
| | - Marine Fontaine
- Department of Radiotherapy, Godinot Cancer Institute, 51100, Reims, France
| | - Eric Bertin
- Université Reims Champagne-Ardenne, Performance, Health, Metrology, Society Laboratory (PSMS EA 7507), Clinical Nutrition Transversal Unit (UTNC), CHU Reims, 51100, Reims, France
| | - Claire Carlier
- Université Reims Champagne-Ardenne, Department of Gastroenterology and Digestive Oncology, CHU Reims, 51100, Reims, France
- Department of Medical Oncology, Godinot Cancer Institute, 51100, Reims, France
| | - Damien Botsen
- Université Reims Champagne-Ardenne, Department of Gastroenterology and Digestive Oncology, CHU Reims, 51100, Reims, France
- Department of Medical Oncology, Godinot Cancer Institute, 51100, Reims, France
| | - Manel Djelouah
- Université Reims Champagne-Ardenne, Department of Radiology, CHU Reims, 51100, Reims, France
| | - Eric François
- Department of Medical Oncology, Antoine Lacassagne Center, 06100, Nice, France
| | - Philippe Guilbert
- Department of Radiotherapy, Godinot Cancer Institute, 51100, Reims, France
| | - Angélique Saint
- Department of Medical Oncology, Antoine Lacassagne Center, 06100, Nice, France
| | - Florian Slimano
- Université Reims Champagne-Ardenne, Department of Pharmacy, CHU Reims, 51100, Reims, France
| | - Paolo Torielli
- Department of Radiotherapy, Godinot Cancer Institute, 51100, Reims, France
| | - Mathias Brugel
- Department of Gastroenterology and Digestive Oncology, Centre Hospitalier Côte Basque, Bayonne, France
| | - Olivier Bouché
- Université Reims Champagne-Ardenne, Department of Gastroenterology and Digestive Oncology, CHU Reims, 51100, Reims, France
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Yoshimura M, Hiraoka M, Kokubo M, Sakamoto T, Karasawa K, Matsuo Y, Nakamura M, Mukumoto N, Morita S, Mizowaki T. Multi-Institutional Phase II Study on the Efficacy and Safety of Dynamic Tumor-Tracking, Moderately Hypofractionated Intensity-Modulated Radiotherapy in Patients With Locally Advanced Pancreatic Cancer. Cancer Med 2025; 14:e70648. [PMID: 39907184 DOI: 10.1002/cam4.70648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 09/22/2024] [Accepted: 01/24/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND For delivering high radiation doses to pancreatic tumors, organ motion management is indispensable; however, studies on this are limited. We aimed to evaluate the efficacy and safety of dynamic tumor tracking (DTT) moderately hypofractionated intensity-modulated radiotherapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC). METHODS Patients with histological confirmation for LAPC were included. A linac system, which was mounted with a gimbal function, was used for DTT-IMRT. The prescribed dose was 48 Gy in 15 fractions. The primary endpoint was the 1-year rate of freedom from locoregional progression (FFLP). RESULTS DTT-IMRT was successfully administered in 25 patients enrolled from four institutions. The median range of respiratory motion during DTT-IMRT was 9.8 mm (range: 3.5-27.3 mm), and the median tracking accuracy was 2.6 mm (range: 0.7-5.2 mm). With a median follow-up period of 13.9 months, the 1-year FFLP rate was 75.3% (lower limit of one-sided 80% confidence interval [CI]: 60.2%), which satisfied the predetermined primary endpoint. One-year locoregional progression-free survival, progression-free survival, and overall survival were 56.0% (95% CI: 34.8%-72.7%), 44.0% (95% CI: 24.5%-61.9%), and 60.0% (95% CI: 38.4%-76.1%), respectively. Regarding nonhematologic toxicities, grade 3 acute gastrointestinal (GI) toxicity was observed in two patients (8%), and two patients (8%) each experienced grade 3 late GI and non-GI toxicities. No grade 4 or 5 nonhematologic toxicities were observed. CONCLUSIONS DTT moderately hypofractionated IMRT shows preferable locoregional control without significant toxicity in patients with LAPC. TRIAL REGISTRATION UMIN000017521.
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Affiliation(s)
- Michio Yoshimura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masahiro Hiraoka
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masaki Kokubo
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Takashi Sakamoto
- Department of Radiation Oncology, Kyoto Katsura Hospital, Kyoto, Japan
| | - Katsuyuki Karasawa
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Yukinori Matsuo
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Mitsuhiro Nakamura
- Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Nobutaka Mukumoto
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Morita
- Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Franklin O, Sugawara T, Ross RB, Rodriguez Franco S, Colborn K, Karam S, Schulick RD, Del Chiaro M. Adjuvant Chemotherapy With or Without Radiotherapy for Resected Pancreatic Cancer After Multiagent Neoadjuvant Chemotherapy. Ann Surg Oncol 2024; 31:4966-4975. [PMID: 38789615 DOI: 10.1245/s10434-024-15157-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 02/14/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting. METHODS This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup. RESULTS Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors. CONCLUSION After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.
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Affiliation(s)
- Oskar Franklin
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden
| | - Toshitaka Sugawara
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Richard Blake Ross
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA
| | - Kathryn Colborn
- Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, CO, USA
- Surgical Outcomes and Applied Research Program, University of Colorado School of Medicine, Aurora, CO, USA
| | - Sana Karam
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, USA
| | - Richard D Schulick
- Department of Surgery, University of Colorado, Aurora, CO, USA
- University of Colorado Cancer Center, Aurora, CO, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado School of Medicine, Aurora, CO, USA.
- University of Colorado Cancer Center, Aurora, CO, USA.
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Shin JY, Chino F, Cuaron JJ, Washington C, Jablonowski M, McBride S, Gomez DR. Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center. JAMA Netw Open 2024; 7:e2416359. [PMID: 38865128 PMCID: PMC11170304 DOI: 10.1001/jamanetworkopen.2024.16359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 04/11/2024] [Indexed: 06/13/2024] Open
Abstract
Importance Insurance barriers to cancer care can cause significant patient and clinician burden. Objective To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. Design, Setting, and Participants In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Exposure Insurance denial for RT. Main Outcomes and Measures Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests. Results A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. Conclusions and Relevance In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.
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Affiliation(s)
- Jacob Y. Shin
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Fumiko Chino
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - John J. Cuaron
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Charles Washington
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Margaret Jablonowski
- Physician Billing Department, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Sean McBride
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Daniel R. Gomez
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
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Jethwa KR, Kim E, Berlin J, Anker CJ, Tchelebi L, Abood G, Hallemeier CL, Jabbour S, Kennedy T, Kumar R, Lee P, Sharma N, Small W, Williams V, Russo S. Executive Summary of the American Radium Society Appropriate Use Criteria for Neoadjuvant Therapy for Nonmetastatic Pancreatic Adenocarcinoma: Systematic Review and Guidelines. Am J Clin Oncol 2024; 47:185-199. [PMID: 38131628 DOI: 10.1097/coc.0000000000001076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2023]
Abstract
For patients with locoregionally confined pancreatic ductal adenocarcinoma (PDAC), margin-negative surgical resection is the only known curative treatment; however, the majority of patients are not operable candidates at initial diagnosis. Among patients with resectable disease who undergo surgery alone, the 5-year survival remains poor. Adjuvant therapies, including systemic therapy or chemoradiation, are utilized as they improve locoregional control and overall survival. There has been increasing interest in the use of neoadjuvant therapy to obtain early control of occult metastatic disease, allow local tumor response to facilitate margin-negative resection, and provide a test of time and biology to assist with the selection of candidates most likely to benefit from radical surgical resection. However, limited guidance exists regarding the relative effectiveness of treatment options. In this systematic review, the American Radium Society multidisciplinary gastrointestinal expert panel convened to develop Appropriate Use Criteria evaluating the evidence regarding neoadjuvant treatment for patients with PDAC, including surgery, systemic therapy, and radiotherapy, in terms of oncologic outcomes and quality of life. The evidence was assessed using the Population, Intervention, Comparator, Outcome, and Study (PICOS) design framework and "Preferred Reporting Items for Systematic Reviews and Meta-analyses" 2020 methodology. Eligible studies included phases 2 to 3 trials, meta-analyses, and retrospective analyses published between January 1, 2012 and December 30, 2022 in the Ovid Medline database. A summary of recommendations based on the available literature is outlined to guide practitioners in the management of patients with PDAC.
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Affiliation(s)
- Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, MN
| | - Ed Kim
- Department of Radiation Oncology, University of Washington, Seattle, WA
| | - Jordan Berlin
- Department of Medicine, Division of Hematology-Oncology, Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - Christopher J Anker
- Department of Radiation Oncology, University of Vermont Larner College of Medicine, Burlington, VT
| | - Leila Tchelebi
- Department of Radiation Oncology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead
| | | | | | | | - Timothy Kennedy
- Department of Surgery, Rutgers Cancer Institute, New Brunswick, NJ
| | - Rachit Kumar
- Department of Radiation Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Sibley Memorial Hospital, Washington DC
| | - Percy Lee
- Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA
| | - Navesh Sharma
- Department of Radiation Oncology, WellSpan Cancer Center, York, PA
| | - William Small
- Department of Radiation Oncology, Loyola University Stritch School of Medicine, Maywood, IL
| | - Vonetta Williams
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, NY
| | - Suzanne Russo
- Department of Radiation Oncology, University Hospitals Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH
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Kamel R, Zhang T, Comino S, Dennis K. A 15-Year Single-Institution Retrospective Study of Primary Pancreatic Cancer Treated with Non-Ablative Palliative Radiotherapy. Cancers (Basel) 2024; 16:881. [PMID: 38473242 DOI: 10.3390/cancers16050881] [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: 01/25/2024] [Revised: 02/16/2024] [Accepted: 02/18/2024] [Indexed: 03/14/2024] Open
Abstract
We studied the use of palliative radiotherapy (RT) among patients with primary, non-curable, locally advanced pancreatic cancer. In this subset of patients, with very poor survival, various palliative RT dose fractionation schemes are used; but, in the absence of a guideline, practice patterns vary, and dose choice is mainly based on the physician's intuition. We divided the patients into three groups, according to the dose fractionation schedules received: low (A), intermediate (B), and high (C) dose groups, to study the potential differences in outcome between the different dose prescriptions. Cohort: n = 184. Median age: 69 years. Male: n = 105 (57%), female: n = 79 (43%). Stage IV: n = 117 (64%). T4: n = 127 (69%). Tumor location: head: n = 109 (59%), body: n = 37 (20%), tail: n = 25 (14%), neck: n = 11 (6%), and uncinate: n = 2 (1%). Prior systemic therapy: n = 66 (36%). Most common dose fractionations received: 20 Gy in five fractions n = 67 (36%), 30 Gy in 10 fractions n = 49 (27%), and 8 Gy in one fraction n = 23 (13%). Group A: n = 33 (18%), median overall survival (OS) 19 days (95% CI 4-33). Group B: n = 84 (46%), median OS 52 days (95% CI 43-60). Group C: n = 67 (36%), median OS 126 days (95% CI 77-174). Median days to in-field progression: Group A 59 days (range 7-109), Group B 96 days (range 19-173), and Group C 97 days (range 13-475). To our knowledge, this is the largest reported retrospective cohort of patients receiving non-ablative palliative RT to treat their primary pancreatic tumors. Most patients had metastatic disease, T4 tumors of the pancreatic head and had not received prior systemic therapy. A significant survival benefit was seen favoring the high dose/longer RT fractionation group, presumably due to appropriate patient selection rather than an RT effect. Despite the relatively short median overall survival, one fifth of the patients were found to experience an in-field progression following RT.
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Affiliation(s)
- Randa Kamel
- Department of Radiation Oncology, UZ Brussel, Vrije Universiteit Brussel, Jette, 1090 Brussels, Belgium
| | - Tinghua Zhang
- Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
| | - Suzanne Comino
- Radiation Medicine Program, The Ottawa Hospital, Ottawa, ON K1H 8L6, Canada
| | - Kristopher Dennis
- Division of Radiation Oncology, The Ottawa Hospital, The University of Ottawa, Ottawa, ON K1H 8L6, Canada
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Pourali G, Donyadideh G, Mehrabadi S, Hamid F, Hassanian SM, Ferns GA, Khazaei M, Avan A. Clinical practice guidelines for interventional treatment of pancreatic cancer. RECENT ADVANCES IN NANOCARRIERS FOR PANCREATIC CANCER THERAPY 2024:345-373. [DOI: 10.1016/b978-0-443-19142-8.00008-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2025]
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Chen YR, Zhao RT, Xu YF, Ma YJ, Hu SB, Wang XH, Fan BB, Zhou YJ, Huang YB, Robinson N, Liu JP, Liu ZL. Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis. Integr Med Res 2023; 12:101004. [PMID: 38033651 PMCID: PMC10681939 DOI: 10.1016/j.imr.2023.101004] [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: 07/25/2023] [Revised: 10/22/2023] [Accepted: 10/25/2023] [Indexed: 12/02/2023] Open
Abstract
Background Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. Methods We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Results Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). Conclusions CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. Protocol registration PROSPERO, CRD42023396828.
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Affiliation(s)
- Yun-Ru Chen
- Centre for Evidence-based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Ruo-Tong Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yi-Fang Xu
- Department of Oncology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China
| | - Yin-Jie Ma
- Wangjing Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, China
| | - Shao-Bo Hu
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing, China
| | - Xue-Hui Wang
- Centre for Evidence-based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Bing-Bing Fan
- Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yan-Ji Zhou
- Health Management Department, Aerospace Center Hospital, Beijing, China
| | - Yu-Bei Huang
- Department of Epidemiology and Biostatistics, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Nicola Robinson
- Centre for Evidence-based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
- School of Health and Social Care, London South Bank University, London, UK
| | - Jian-Ping Liu
- Centre for Evidence-based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Zhao-Lan Liu
- Centre for Evidence-based Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
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Jiang L, Ramesh P, Neph R, Sheng K. Technical note: Multi-MATE, a high-throughput platform for automated image-guided small-animal irradiation. Med Phys 2023; 50:7383-7389. [PMID: 37341036 PMCID: PMC10733545 DOI: 10.1002/mp.16563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 06/07/2023] [Indexed: 06/22/2023] Open
Abstract
BACKGROUND Small animal irradiation is essential to study the radiation response of new interventions before or parallel to human therapy. Image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) are recently adopted in small animal irradiation to more closely mimic human treatments. However, sophisticated techniques require exceedingly high time, resources, and expertize that are often impractical. PURPOSE We propose a high throughput and high precision platform named Multiple Mouse Automated Treatment Environment (Multi-MATE) to streamline image-guided small animal irradiation. METHODS Multi-MATE consists of six parallel and hexagonally arranged channels, each equipped with a transfer railing, a 3D-printed immobilization pod, and an electromagnetic control unit, computer-controlled via an Arduino interface. The mouse immobilization pods are transferred along the railings between the home position outside the radiation field and the imaging/irradiation position at the irradiator isocenter. All six immobilization pods are transferred to the isocenter in the proposed workflow for parallel CBCT scans and treatment planning. The immobilization pods are then sequentially transported to the imaging/therapy position for dose delivery. The positioning reproducibility of Multi-MATE are evaluated using CBCT and radiochromic films. RESULTS While parallelizing and automating the image-guided small animal radiation delivery, Multi-MATE achieved the average pod position reproducibility of 0.17 ± 0.04 mm in the superior-inferior direction, 0.20 ± 0.04 mm in the left-right direction, and 0.12 ± 0.02mm in the anterior-posterior direction in repeated CBCT tests. Additionally, in image-guided dose delivery tasks, Multi-MATE demonstrated the positioning reproducibility of 0.17 ± 0.06 mm in the superior-inferior direction, 0.19 ± 0.06 mm in the left-right direction. CONCLUSIONS We designed, fabricated, and tested a novel automated irradiation platform, Multi-MATE to accelerate and automate image-guided small animal irradiation. The automated platform minimizes human operation and achieves high setup reproducibility and image-guided dose delivery accuracy. Multi-MATE thus removes a major barrier to implementing high-precision preclinical radiation research.
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Affiliation(s)
- Lu Jiang
- Department of Radiation Oncology, University of California, Los Angeles, 90095, USA
| | - Pavitra Ramesh
- Department of Radiation Oncology, University of California, Los Angeles, 90095, USA
| | - Ryan Neph
- Department of Radiation Oncology, University of California, Los Angeles, 90095, USA
| | - Ke Sheng
- Department of Radiation Oncology, University of California, San Francisco, 94115, USA
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Zhou B, Zhang SR, Chen G, Chen P. Developments and challenges in neoadjuvant therapy for locally advanced pancreatic cancer. World J Gastroenterol 2023; 29:5094-5103. [PMID: 37744290 PMCID: PMC10514760 DOI: 10.3748/wjg.v29.i35.5094] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 07/19/2023] [Accepted: 08/31/2023] [Indexed: 09/14/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries. Despite advances in cancer treatment, the 5-year survival rate for patients with PDAC remains less than 5%. In recent years, neoadjuvant therapy (NAT) has emerged as a promising treatment option for many cancer types, including locally advanced PDAC, with the potential to improve patient outcomes. To analyze the role of NAT in the setting of locally advanced PDAC over the past decade, a systematic literature search was conducted using PubMed and Web of Science. The results suggest that NAT may reduce the local mass size, promote tumor downstaging, and increase the likelihood of resection. These findings are supported by the latest evidence-based medical literature and the clinical experience of our center. Despite the potential benefits of NAT, there are still challenges that need to be addressed. One such challenge is the lack of consensus on the optimal timing and duration of NAT. Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT. In conclusion, NAT has emerged as a promising treatment option for locally advanced PDAC. However, further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease. With continued advances in cancer treatment, there is hope of improving the outcomes of patients with PDAC in the future.
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Affiliation(s)
- Bo Zhou
- Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Shi-Ran Zhang
- Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Geng Chen
- Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
| | - Ping Chen
- Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
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11
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Falco M, Masojć B, Sulikowski T. Radiotherapy in Pancreatic Cancer: To Whom, When, and How? Cancers (Basel) 2023; 15:3382. [PMID: 37444492 DOI: 10.3390/cancers15133382] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/17/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The diagnosis rate of pancreatic cancer is steadily increasing. The average age of onset is close to 70 years. In most cases, the disease is diagnosed at an advanced stage. The indications for and techniques of radiotherapy are changing over time. The aim of this thesis is to present the role and possibilities of radiotherapy from the perspective of radiation oncologist. The most common cause of treatment failure in pancreatic cancer remains generalisation. The implementation of new systemic treatment regimens contributes to improved treatment outcomes regardless of the stage of the disease. With improved treatment outcomes in terms of the incidence of distant metastases, the impact of local curability on the length and quality of life of patients increases. Modern radiotherapy offers the opportunity to achieve high local cure rates. Postoperative radiotherapy in combination with chemotherapy seems justified in the group of postoperative pancreatic cancer patients with pT3 and pN+ features. In the group of patients with borderline resectable pancreatic cancer, the impact of radiotherapy in combination with the latest chemotherapy regimens is difficult to define clearly. In the setting of a diagnosis of advanced pancreatic cancer, radiotherapy, especially stereotactic radiotherapy, in combination with chemotherapy, contributes to improved local curability and allows to achieve a significantly reduced level of pain.
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Affiliation(s)
- Michał Falco
- Radiation Oncology Department, West Pomeranian Oncology Center, Strzałowska 22, 71-730 Szczecin, Poland
- Hospicjum Św. Jana Ewnagelisty, Pokoju 77, 71-740 Szczecin, Poland
| | - Bartłomiej Masojć
- Radiation Oncology Department, West Pomeranian Oncology Center, Strzałowska 22, 71-730 Szczecin, Poland
| | - Tadeusz Sulikowski
- Department of General, Minimally Invasive, and Gastroenterological Surgery, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland
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12
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Ogawa A, Yoshimura M, Nakamura M, Adachi T, Iwai T, Ashida R, Mizowaki T. Impact of planning organ at risk volume margins and matching method on late gastrointestinal toxicity in moderately hypofractionated IMRT for locally advanced pancreatic ductal adenocarcinoma. Radiat Oncol 2023; 18:103. [PMID: 37337247 PMCID: PMC10280835 DOI: 10.1186/s13014-023-02288-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 05/24/2023] [Indexed: 06/21/2023] Open
Abstract
BACKGROUND This study examined the differences in late gastrointestinal (GI) toxicities in moderately hypofractionated intensity-modulated radiation therapy (IMRT) for locally advanced pancreatic ductal adenocarcinoma (LA-PDAC) by changing the planning organs at risk volume (PRV) margin and the target matching method and assessed the causes of adverse events. METHODS We examined 37 patients with LA-PDAC who underwent moderately hypofractionated IMRT between 2016 and 2020 at our institution; 23 patients were treated with wide PRV margins and soft tissue matching (Protocol A) and 14 with narrow PRV margins and fiducial marker matching (Protocol B). The GI toxicities, local control (LC) rate, and overall survival (OS) were assessed for each protocol. The initially planned and daily doses to the gross tumor volume (GTV), stomach, and duodenum, reproduced from cone-beam computed tomography, were evaluated. RESULTS The late GI toxicity rate of grades 3-4 was higher in Protocol B (42.9%) than in Protocol A (4.3%). Although the 2-year LC rates were significantly higher in Protocol B (90.0%) than in Protocol A (33.3%), no significant difference was observed in OS rates. In the initial plan, no deviations were found for the stomach and duodenum from the dose constraints in either protocol. In contrast, daily dose evaluation for the stomach to duodenal bulb revealed that the frequency of deviation of V3 Gy per session was 44.8% in Protocol B, which was significantly higher than the 24.3% in Protocol A. CONCLUSIONS Reducing PRV margins with fiducial marker matching increased GI toxicities in exchange for improved LC. Daily dose analysis indicated the trade-off between the GTV dose coverage and the irradiated doses to the GI. This study showed that even with strict matching methods, the PRV margin could not be reduced safely because of GI inter-fractional error, which is expected to be resolved with online adaptive radiotherapy.
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Affiliation(s)
- Ayaka Ogawa
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Michio Yoshimura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Mitsuhiro Nakamura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
- Department of Advanced Medical Physics, Graduate School of Medicine, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takanori Adachi
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Takahiro Iwai
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Ryo Ashida
- Department of Radiation Oncology, Kobe City Medical Center General Hospital, 2-1-1, Minatojima Minamimachi, Chuo-ku, Kobe, 650-0047, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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13
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Umezawa R, Nakagawa K, Mizuma M, Katsuta Y, Tanaka S, Kadoya N, Suzuki Y, Takeda K, Takahashi N, Yamamoto T, Unno M, Jingu K. Comparison of acute gastrointestinal toxicities between 3-dimensional conformal radiotherapy and intensity-modulated radiotherapy including prophylactic regions in chemoradiotherapy with S-1 for pancreatic cancer-importance of dose volume histogram parameters in the stomach as the predictive factors. JOURNAL OF RADIATION RESEARCH 2022; 63:856-865. [PMID: 35993332 PMCID: PMC9726699 DOI: 10.1093/jrr/rrac049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 04/28/2022] [Indexed: 06/15/2023]
Abstract
The purpose of this study was to compare acute gastrointestinal (GI) toxicities in patients who underwent 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in chemoradiotherapy (CRT) with S-1 including prophylactic regions for pancreatic cancer. We also investigated the predictive factor of acute GI toxicities in dose volume histogram (DVH) parameters. Patients who received CRT with S-1 for pancreatic cancer between January 2014 and March 2021 were included. Radiotherapy (RT) with a total dose of 50-54 Gy was delivered. We examined the differences in the frequencies of acute GI toxicity of grade 2 or higher and DVH parameters of the stomach (ST) and duodenum (DU) between the 3DCRT group and the IMRT group. The RT-related predictive factors of acute GI toxicities were investigated by univariate and multivariate analyses. There were 25 patients in the 3DCRT group and 31 patients in the IMRT group. The frequencies of acute GI toxicity of G2 or higher were 36% in the 3DCRT group and 9.7% in the IMRT group (p = 0.035). ST V50 was the most predictive factor (p = 0.001), and the incidences of acute GI toxicity of G2 or higher in ST V50 ≥ 4.1 cc and < 4.1cc were 43.7% and 7.7%, respectively. ST V40 was also a significant predictive factor of acute GI toxicity (p = 0.002). IMRT could reduce acute GI toxicities in CRT with S-1 including prophylactic regions for pancreatic cancer. Acute GI toxicities may be affected by moderate to high doses to the ST.
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Affiliation(s)
- Rei Umezawa
- Corresponding author. Department of Radiation Oncology, Tohoku University Graduate School of Medicine, 1-1, Seiryou-machi, Aobaku, Sendai 980-8574, Japan. Tel: +81-22-717-7312; Fax: +81-22-717-7316; E-mail:
| | - Kei Nakagawa
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yoshiyuki Katsuta
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Shohei Tanaka
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Noriyuki Kadoya
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yu Suzuki
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Kazuya Takeda
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Noriyoshi Takahashi
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takaya Yamamoto
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Keiichi Jingu
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan
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14
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Jiang L, Lyu Q, Abdelhamid AMH, Hui S, Sheng K. An efficient rectangular optimization method for sparse orthogonal collimator based small animal irradiation. Phys Med Biol 2022; 67:10.1088/1361-6560/ac910b. [PMID: 36084625 PMCID: PMC9595432 DOI: 10.1088/1361-6560/ac910b] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 09/09/2022] [Indexed: 11/11/2022]
Abstract
Objective.Intensity-modulated radiotherapy (IMRT) is widely used in clinical radiotherapy, treating varying malignancies with conformal doses. As the test field for clinical translation, preclinical small animal experiments need to mimic the human radiotherapy condition, including IMRT. However, small animal IMRT is a systematic challenge due to the lack of corresponding hardware and software for miniaturized targets.Approach.The sparse orthogonal collimators (SOC) based on the direct rectangular aperture optimization (RAO) substantially simplified the hardware for miniaturization. This study investigates and evaluates a significantly improved RAO algorithm for complex mouse irradiation using SOC. Because the Kronecker product representation of the rectangular aperture is the main limitation of the computational performance, we reformulated matrix multiplication in the data fidelity term using multiplication with small matrices instead of the Kronecker product of the dose loading matrices. Solving the optimization problem was further accelerated using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA).Main results.Four mouse cases, including a liver, a brain tumor, a concave U-target, and a complex total marrow irradiation (TMI) case, were included in this study with manually delineated targets and OARs. Seven coplanar-field SOC IMRT (sIMRT) plans were compared with idealistic fluence map based IMRT (iIMRT) plans. For the first three cases with simpler and smaller targets, the differences between sIMRT plans and iIMRT plans in the planning target volumes (PTV) statistics are within 1%. For the TMI case, the sIMRT plans are superior in reducing hot spots (also termedDmax) of PTV, kidneys, lungs, heart, and bowel by 20.5%, 31.5%, 24.67%, 20.13%, and 17.78%, respectively. On average, in four cases in this study, the sIMRT plan conformity is comparable to that of the iIMRT's with lightly increased R50 and Integral Dose by 2.23% and 2.78%.Significance.The significantly improved sIMRT optimization method allows fast plan creation in under 1 min for smaller targets and makes complex TMI planning feasible while achieving comparable dosimetry to idealistic IMRT with fluence map optimization.
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Affiliation(s)
- Lu Jiang
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, United States of America
| | - Qihui Lyu
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, United States of America
| | - Amr M H Abdelhamid
- Department of Radiation Oncology, City of Hope Medical Center, Duarte, CA, United States of America
| | - Susanta Hui
- Department of Radiation Oncology, City of Hope Medical Center, Duarte, CA, United States of America
| | - Ke Sheng
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, United States of America
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15
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Naumann M, Czempiel T, Lößner AJ, Pape K, Beyreuther E, Löck S, Drukewitz S, Hennig A, von Neubeck C, Klink B, Krause M, William D, Stange DE, Bütof R, Dietrich A. Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids. Cancers (Basel) 2022; 14:cancers14153781. [PMID: 35954444 PMCID: PMC9367296 DOI: 10.3390/cancers14153781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 07/27/2022] [Accepted: 07/29/2022] [Indexed: 02/01/2023] Open
Abstract
To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and proton irradiation and combined RCT. Therapy response was subsequently measured via viability assays. In addition, treatment-naive PDOs were characterized via whole exome sequencing and tumorigenicity was investigated in NMRI Foxn1nu/nu mice. We found a mutational pattern containing common mutations associated with PDAC within the PDOs. Although we could unravel potential complications of the viability assay for PDOs in radiobiology, distinct synergistic effects of gemcitabine and 5FU with proton irradiation were observed in two PDO lines that may lead to further mechanistical studies. We could demonstrate that PDOs are a powerful tool for translational proton radiation research.
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Affiliation(s)
- Max Naumann
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany; (M.N.); (E.B.); (S.L.); (C.v.N.); (M.K.); (R.B.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
| | - Tabea Czempiel
- Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany; (T.C.); (S.D.); (B.K.); (D.W.)
| | - Anna Jana Lößner
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; (A.J.L.); (K.P.); (A.H.); (D.E.S.)
| | - Kristin Pape
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; (A.J.L.); (K.P.); (A.H.); (D.E.S.)
| | - Elke Beyreuther
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany; (M.N.); (E.B.); (S.L.); (C.v.N.); (M.K.); (R.B.)
- Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf, 01328 Dresden, Germany
| | - Steffen Löck
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany; (M.N.); (E.B.); (S.L.); (C.v.N.); (M.K.); (R.B.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany
- Institute of Radiooncology—OncoRay, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany
| | - Stephan Drukewitz
- Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany; (T.C.); (S.D.); (B.K.); (D.W.)
- Institute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany
| | - Alexander Hennig
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; (A.J.L.); (K.P.); (A.H.); (D.E.S.)
- National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
| | - Cläre von Neubeck
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany; (M.N.); (E.B.); (S.L.); (C.v.N.); (M.K.); (R.B.)
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany
- Clinic for Particle Therapy, University Hospital Essen, Universität Duisburg Essen, 45147 Essen, Germany
| | - Barbara Klink
- Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany; (T.C.); (S.D.); (B.K.); (D.W.)
- Department of Genetics, Laboratoire National de Santé, 3555 Dudelange, Luxembourg
- Institute for Clinical Genetics, University Hospital Carl Gustav Carus, Technische Universität Dresden, ERN-GENTURIS, Hereditary Cancer Syndrome Center Dresden, 01307 Dresden, Germany
| | - Mechthild Krause
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany; (M.N.); (E.B.); (S.L.); (C.v.N.); (M.K.); (R.B.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany
- Institute of Radiooncology—OncoRay, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany
| | - Doreen William
- Core Unit for Molecular Tumor Diagnostics (CMTD), National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany; (T.C.); (S.D.); (B.K.); (D.W.)
- Institute for Clinical Genetics, University Hospital Carl Gustav Carus, Technische Universität Dresden, ERN-GENTURIS, Hereditary Cancer Syndrome Center Dresden, 01307 Dresden, Germany
| | - Daniel E. Stange
- Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; (A.J.L.); (K.P.); (A.H.); (D.E.S.)
- National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
| | - Rebecca Bütof
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany; (M.N.); (E.B.); (S.L.); (C.v.N.); (M.K.); (R.B.)
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany
- National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany
- Institute of Radiooncology—OncoRay, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany
| | - Antje Dietrich
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden—Rossendorf, 01307 Dresden, Germany; (M.N.); (E.B.); (S.L.); (C.v.N.); (M.K.); (R.B.)
- German Cancer Consortium (DKTK), Partner Site Dresden, German Cancer Research Center (DKFZ), 69192 Heidelberg, Germany
- Correspondence:
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16
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Turner KM, Delman AM, Kharofa JR, Smith MT, Choe KA, Olowokure O, Wilson GC, Patel SH, Sohal D, Ahmad SA. Radiation therapy in borderline resectable pancreatic cancer: A review. Surgery 2022; 172:284-290. [PMID: 35034793 DOI: 10.1016/j.surg.2021.12.013] [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: 10/07/2021] [Revised: 11/11/2021] [Accepted: 12/14/2021] [Indexed: 11/17/2022]
Abstract
BACKGROUND Borderline resectable pancreatic cancer constitutes a complex clinical entity, presenting the clinician with a locally aggressive disease that has a proclivity for distant spread. The benefits of radiation therapy, such as improved local control and improved survival, have been questioned. In this review we seek to summarize the existing evidence on radiation therapy in borderline resectable pancreatic cancer and highlight future areas of research. METHODS A comprehensive review of PubMed for clinical studies reporting outcomes in borderline resectable pancreatic cancer was performed in June 2021, with an emphasis placed on prospective studies. RESULTS Radiologic "downstaging" in borderline resectable pancreatic cancer is a rare event, although some evidence shows increased clinical response to neoadjuvant chemotherapy over radiation therapy. Margin status seems to be equivalent between regimens that use neoadjuvant chemotherapy alone and regimens that include neoadjuvant radiation therapy. Local control in borderline resectable pancreatic cancer is likely improved with radiation therapy; however, the benefit of improved local control in a disease marked by systemic failure has been questioned. Although some studies have shown improved survival with radiation therapy, differences in the delivery and tolerance of chemotherapy between the neoadjuvant and adjuvant setting confound these results. When the evidence is evaluated as a whole, there is no clear survival benefit of radiation therapy in borderline resectable pancreatic cancer. CONCLUSION Once considered a staple of therapy, the role of radiation therapy in borderline resectable pancreatic cancer is evolving as systemic therapy regimens continues to improve. Increased clinical understanding of disease phenotype and response are needed to accurately tailor therapy for individual patients and to improve outcomes in this complex patient population.
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Affiliation(s)
- Kevin M Turner
- Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Aaron M Delman
- Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Jordan R Kharofa
- Department of Radiation Oncology, University of Cincinnati College of Medicine, OH
| | - Milton T Smith
- Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati College of Medicine, OH
| | - Kyuran A Choe
- Department of Radiology, University of Cincinnati College of Medicine, OH
| | - Olugbenga Olowokure
- Division of Hematology & Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, OH
| | - Gregory C Wilson
- Department of Surgery, University of Cincinnati College of Medicine, OH; Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, OH; Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, OH
| | - Davendra Sohal
- Division of Hematology & Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, OH
| | - Syed A Ahmad
- Department of Surgery, University of Cincinnati College of Medicine, OH; Division of Surgical Oncology, Department of Surgery, University of Cincinnati College of Medicine, OH.
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17
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Choi SH, Rim CH, Shin IS, Yoon WS, Koom WS, Seong J. Benefit of adjuvant radiotherapy for gallbladder cancer: a comparability-based meta-analysis. Hepatol Int 2022; 16:712-727. [PMID: 35532861 DOI: 10.1007/s12072-022-10343-6] [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] [Received: 02/07/2022] [Accepted: 04/13/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND AND PURPOSE The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies. METHODS PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm). RESULTS Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 (p = 0.111) neither favoring ART or non-ART arms. In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p = 0.008) among comparability group 1 studies, whereas it was 1.03 (p = 0.865) in comparability group 2 studies. The pooled rate of 5-year OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR 0.21, p = 0.001) but not in distant metastasis (OR 1.32, p = 0.332) was noted. CONCLUSION ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results suggest the more active application of ART in GBC treatment. PROTOCOL REGISTRATION This study is registered in PROSPERO (CRD42021240624, available at: https://www.crd.york.ac.uk/ ).
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, 123 Jeokgeum-ro, Danwon-gu, Ansan, Gyeonggi-do, 15355, Republic of Korea.
| | - In-Soo Shin
- Graduate School of Education, AI Convergence Education, Dongguk University, Seoul, Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, 123 Jeokgeum-ro, Danwon-gu, Ansan, Gyeonggi-do, 15355, Republic of Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Korea
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18
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Masui T, Nagai K, Anazawa T, Sato A, Uchida Y, Nakano K, Yogo A, Kaneda A, Nakamura N, Yoshimura M, Mizowaki T, Uza N, Fukuda A, Matsumoto S, Kanai M, Isoda H, Mizumoto M, Seo S, Hata K, Taura K, Kawaguchi Y, Takaori K, Uemoto S, Hatano E. Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution. BMC Cancer 2022; 22:119. [PMID: 35093003 PMCID: PMC8800301 DOI: 10.1186/s12885-022-09244-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 01/27/2022] [Indexed: 11/10/2022] Open
Abstract
Background Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). Methods A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. Results Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19–9 (CA19-9) > 400 U/ml before NACIMRT. Conclusions NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. Trial Registration UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013,
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Affiliation(s)
- Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Asahi Sato
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuichiro Uchida
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kenzo Nakano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akitada Yogo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akihiro Kaneda
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Naoto Nakamura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Michio Yoshimura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Norimitsu Uza
- Department of Gastroenterology and Hepatology, Kyoto University, Kyoto, Japan
| | - Akihisa Fukuda
- Department of Gastroenterology and Hepatology, Kyoto University, Kyoto, Japan
| | - Shigemi Matsumoto
- Department of Real World Data Research and Development, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masashi Kanai
- Department of Clinical Oncology, Kyoto University, Kyoto, Japan
| | - Hiroyoshi Isoda
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University, Kyoto, Japan
| | - Masaki Mizumoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoru Seo
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Koichiro Hata
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yoshiya Kawaguchi
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kyoichi Takaori
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Lutsyk M, Turgeman I, Bar-Sela G. Rapid Initiation of Neoadjuvant Chemoradiotherapy After Diagnosis is Associated With Improved Pathologic Response in Locally Advanced Rectal Cancer. Am J Clin Oncol 2022; 45:1-8. [PMID: 34857697 DOI: 10.1097/coc.0000000000000872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
INTRODUCTION In rectal cancer, neoadjuvant chemoradiation (NCRT) is preferred because of toxicity profile, improved resectability and sphincter preservation, although with no impact on overall survival. Pathologic complete response (pCR) to NCRT has been linked with longer disease-free survival (DFS). The study purpose was to evaluate an association between clinical factors and treatment schedule with tumor response and treatment outcome, among patients with locally advanced rectal cancer. PATIENTS AND METHODS In this single-center retrospective study, conducted over 9 years (2011 to 2020), patients with stage II to III rectal cancer who had received NCRT were enrolled. The standard radiotherapy was 45 Gy to the pelvis, with a simultaneous integrated 50 Gy boost to the primary tumor. Continuous 5-Fluorouracil or oral capecitabine was administered concurrently. Surgery was preplanned within 6 to 8 weeks. Multinomial logistic regressions for evaluation of clinical factors, Kaplan-Meier method for DFS estimation, and receiver operating characteristic analysis for determination of the optimal timeframe were used. RESULTS Of 279 cases, pCR was observed in 72 (25.8%). In 207 cases, pTis-4N-negative was obtained in 137 (66.2%), pT0N-positive in 6 (2.9%), and pTis-4N-positive in 64 (30.9%). The pCR group had shorter diagnosis-NCRT time (P<0.01) and on-treatment time (P=0.05). DFS was longer for pCR and partial responders with clinical stage II and III (P<0.0001). Diagnosis-NCRT time was shown different between pCR and non-pCR groups. receiver operating characteristic analysis (P<0.01) showed that a diagnosis-NCRT time of <4.5 weeks predicts pCR with a sensitivity of 88% and specificity of 81% accuracy. CONCLUSION The time elapsed between rectal cancer diagnosis and NCRT initiation is significantly associated with pCR. Reducing this time may increase the probability of achieving pCR.
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Affiliation(s)
| | | | - Gil Bar-Sela
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa
- Cancer Center, Emek Medical Center, Afula, Israel
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20
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Spiliopoulos S, Zurlo MT, Casella A, Laera L, Surico G, Surgo A, Fiorentino A, de'Angelis N, Calbi R, Memeo R, Inchingolo R. Current status of non-surgical treatment of locally advanced pancreatic cancer. World J Gastrointest Oncol 2021; 13:2064-2075. [PMID: 35070042 PMCID: PMC8713317 DOI: 10.4251/wjgo.v13.i12.2064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 06/28/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is the 7th leading cause of death due to cancer in industrialized countries and the 11th most common cancer globally, with 458918 new cases (2.5% of all cancers) and 432242 deaths (4.5% of all cancer deaths) in 2018. Unfortunately, 80% to 90% of the patients present with unresectable disease, and the reported 5-year survival rate range between 10% and 25%, even after successful resection with tumor-free margins. Systemic chemotherapy, radiotherapy, and minimally invasive image-guided procedures that have emerged over the past years, are used for the management of non-operable PC. This review focuses on currently available non-surgical options of locally advanced pancreatic cancer.
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Affiliation(s)
- Stavros Spiliopoulos
- 2nd Radiology Department, Interventional Radiology Unit, National and Kapodistrian University of Athens, Athens 12461, Greece
| | - Maria Teresa Zurlo
- Interventional Radiology Unit, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Annachiara Casella
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Letizia Laera
- Department of Oncology, General Regional Hospital “F. Miulli”, Acquaviva delle Fonti 70021, Italy
| | - Giammarco Surico
- Department of Oncology, General Regional Hospital “F. Miulli”, Acquaviva delle Fonti 70021, Italy
| | - Alessia Surgo
- Department of Radiation Oncology, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Alba Fiorentino
- Department of Radiation Oncology, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Nicola de'Angelis
- Unit of Minimally Invasive and Robotic Digestive Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Roberto Calbi
- Department of Radiology, General Regional Hospital “F. Miulli”, Acquaviva delle Fonti 70021, Italy
| | - Riccardo Memeo
- Unit of Hepato-Pancreatic-Biliary Surgery, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
| | - Riccardo Inchingolo
- Interventional Radiology Unit, “F. Miulli” Regional General Hospital, Acquaviva delle Fonti 70021, Italy
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21
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Xing J, Yang B, Hou X, Jia N, Gong X, Li X, Zhou N, Cheng Y, Bai C. Prognostic Factors and Effect of Adjuvant Chemoradiation Following Chemotherapy in Resected Pancreatic Cancer Patients With Lymph Node Metastasis or R1 Resection. Front Oncol 2021; 11:660215. [PMID: 34631515 PMCID: PMC8493064 DOI: 10.3389/fonc.2021.660215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 09/06/2021] [Indexed: 12/17/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor prognosis. In resectable PDAC, the recurrence rate is still high even when surgery and adjuvant chemotherapy (CT) are applied. Regional lymph node metastasis and positive margins are associated with higher recurrence risk and worse survival. Adjuvant radiotherapy has been explored, but its efficacy remains controversial. In recent years, some characteristics have been reported to stratify patients who may benefit from adjuvant chemoradiation (CRT), such as lymph node metastasis and margin status. Adjuvant chemotherapy followed by chemoradiation (CT-CRT) was also proposed. A total of 266 patients with resectable PDAC who have lymph node metastasis or R1 resection after surgery were enrolled. In multivariate Cox regression analyses, pancreatic body or tail tumor location (HR 0.433, p<0.0001, compared with pancreatic head) and adjuvant CT predicted a better survival, while there were no significant differences among the different CT regimens. Higher T stage indicated poor survival (stage I: reference; stage II: HR 2.178, p=0.014; stage III: HR 3.581, p=0.001). Propensity score matching was applied in 122 patients to explore the role of CRT. A cohort of 51 patients (31 and 20 patients in the CT and CT-CRT groups, respectively) was generated by matching. Further analyses revealed adjuvant CT-CRT was associated with prolonged survival compared with CT alone (HR 0.284, p=0.014) and less frequent local recurrences (56.5% vs. 21.4% in the CT and CT-CRT group, respectively). However, no significant differences in disease-free survival among these two groups were observed.
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Affiliation(s)
- Jiazhang Xing
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Bo Yang
- Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaorong Hou
- Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ning Jia
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaolei Gong
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaoyuan Li
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Na Zhou
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuejuan Cheng
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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22
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Choi SH, Rim CH, Shin IS, Yoon WS, Koom WS, Seong J. Adjuvant Radiotherapy for Extrahepatic Cholangiocarcinoma: A Quality Assessment-Based Meta-Analysis. Liver Cancer 2021; 10:419-432. [PMID: 34721505 PMCID: PMC8527906 DOI: 10.1159/000518298] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 07/05/2021] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION The benefits of adjuvant radiotherapy (ART) for extrahepatic cholangiocarcinoma are uncertain largely because existing publications lack clear comparisons between ART and non-ART arms. METHODS PubMed, Medline, Embase, and the Cochrane library were systematically searched until December 2020. The primary endpoint was overall survival (OS). Sensitivity analysis was performed for studies with reliable comparability (i.e., no favorable prognosticators in the ART arm that could skew the data). RESULTS Twenty-three studies involving 1,731 patients with extrahepatic cholangiocarcinoma were reviewed. The overall median of all median prescribed doses was 50.4 Gy; brachytherapy or an intraoperative boost of 10-21 Gy was applied in 5 studies. The pooled 1-, 3-, and 5-year OS rates in the non-ART and ART arms were 69.2% versus 81.0%, p = 0.035; 34.3% versus 44.7%, p = 0.025; 25.6% versus 31.7%, p = 0.115, respectively. The corresponding pooled locoregional recurrence rates were 52.1% versus 34.9% (p = 0.014). The pooled rate of grade ≥3 gastrointestinal complications was 9.8%. Sensitivity analysis performed on 14 eligible studies showed that the ART arms had a lower pooled R0 rate (36.8% vs. 63.2%, p = 0.02) and a higher rate of positive lymph nodes (47.4% vs. 34.9%, p = 0.08). The pooled 1-, 3-, and 5-year OS rates in the non-ART versus ART arms of the selected studies were 78.2% versus 84.9%, p = 0.143; 38.5% versus 49.2%, p = 0.026; and 27.8% versus 34.5%, p = 0.11, respectively. CONCLUSIONS ART was shown to improve OS in all studies and in those selected for their reliable comparability.
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, Seoul, Republic of Korea,*Chai Hong Rim,
| | - In-Soo Shin
- Graduate School of Education, AI Convergence Education, Dongguk University, Seoul, Republic of Korea
| | - Won Sup Yoon
- Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, Seoul, Republic of Korea
| | - Woong Sub Koom
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Republic of Korea
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23
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Tchelebi LT, Zaorsky NG, Rosenberg JC, Sharma NK, Tuanquin LC, Mackley HB, Ellis RJ. Reducing the Toxicity of Radiotherapy for Pancreatic Cancer With Magnetic Resonance-guided Radiotherapy. Toxicol Sci 2021; 175:19-23. [PMID: 32053201 DOI: 10.1093/toxsci/kfaa021] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Pancreatic cancer is a highly fatal malignancy for which surgery is currently considered to be the only curative treatment. However, less than a quarter of patients have disease amenable to definitive surgical resection. Local treatment with radiation therapy is a promising alternative to surgery for those patients with unresectable disease. However, conventional radiation techniques with computed tomography (CT)-guided therapy have yielded disappointing results due to the inability to deliver ablative doses of ionizing radiation, while sparing the radiosensitive adjacent organs at risk. Magnetic resonance-guided radiotherapy (MRgRT) has emerged as an alternative to CT-guided radiation treatment which allows for the delivery of higher doses of radiation with low toxicity to surrounding structures. Further study into the use of MRgRT and dose escalation for locally advanced unresectable pancreatic cancer is needed.
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Affiliation(s)
| | - Nicholas G Zaorsky
- Department of Radiation Oncology, Penn State Cancer Institute.,Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania 17033
| | | | - Navesh K Sharma
- Department of Radiation Oncology, Penn State Cancer Institute
| | | | - Heath B Mackley
- Department of Radiation Oncology, Penn State Cancer Institute
| | - Rodney J Ellis
- Department of Radiation Oncology, Penn State Cancer Institute
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24
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Brunner TB, Haustermans K, Huguet F, Morganti AG, Mukherjee S, Belka C, Krempien R, Hawkins MA, Valentini V, Roeder F. ESTRO ACROP guidelines for target volume definition in pancreatic cancer. Radiother Oncol 2021; 154:60-69. [DOI: 10.1016/j.radonc.2020.07.052] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 02/08/2023]
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25
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Afifi ANAM, Powerski M, Jechorek D, Brunner TB, Weigt J, Venerito M. Radiation-induced damage in the upper gastrointestinal tract: clinical presentation, diagnostic tests and treatment options. Best Pract Res Clin Gastroenterol 2020; 48-49:101711. [PMID: 33317797 DOI: 10.1016/j.bpg.2020.101711] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 11/05/2020] [Accepted: 11/09/2020] [Indexed: 01/31/2023]
Abstract
Radiation-induced damage of the upper gastrointestinal (GI) tract results from radiation of GI tumors or structures adjacent to the GI tract. Radiation-induced damages of the upper GI tract may be acute or delayed, and ranges from lack of appetite, mucosal inflammation (i.e. esophagitis, gastritis, duodenitis) to ulcers, which may be complicated by perforation, penetration, bleeding and stenosis. Radiation-related factors as well as individual patient predisposing factors may increase susceptibility to post-radiation damage. High quality evidence for the treatment of radiation-induced GI damage is scarce and the management is often extrapolated from studies on GI lesions of different etiology. Treatment depends on severity and localization of the radiation-induced damage, and ranges from supportive and dietary measures to endoscopic interventions or surgery. Modern radiation techniques may decrease the incidence and severity of the radiation-induced upper gastrointestinal disease.
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Affiliation(s)
- Ahmed N A M Afifi
- Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Germany
| | - Maciej Powerski
- Universitätsklinik für Radiologie und Nuklearmedizin, Germany
| | | | - Thomas B Brunner
- Universitätsklinik für Strahlentherapie, Otto-von-Guericke Universitätsklinikum Magdeburg, Germany
| | - Jochen Weigt
- Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Germany
| | - Marino Venerito
- Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Germany.
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Patient-Reported Quality of Life Before and After Chemoradiation for Intact Pancreas Cancer: A Prospective Registry Study. Pract Radiat Oncol 2020; 11:e63-e69. [PMID: 32712461 DOI: 10.1016/j.prro.2020.06.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 05/04/2020] [Accepted: 06/28/2020] [Indexed: 01/13/2023]
Abstract
PURPOSE Our purpose was to determine the effect of chemoradiotherapy (CRT) on patient-reported quality of life (QOL) for patients with intact pancreas cancer. METHODS AND MATERIALS We reviewed a prospective QOL registry for patients with intact, clinically localized pancreatic ductal adenocarcinoma treated with CRT between June 2015 and November 2018. QOL was assessed pre-CRT (immediately before CRT, after neoadjuvant chemotherapy) and at the completion of CRT with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and its component parts: FACT-General (FACT-G) and hepatobiliary cancer subscore (HCS). A minimally important difference from pre-CRT was defined as ≥ 6, 5, and 8 points for FACT-G, HCS, and FACT-Hep, respectively. RESULTS Of 157 patients who underwent CRT, 100 completed both pre- and post-CRT surveys and were included in the primary analysis. Median age at diagnosis was 65 years (range, 23-90). National Comprehensive Cancer Network resectability status was resectable (3%), borderline resectable (40%), or locally advanced (57%). Folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) (75%) or gemcitabine and nab-paclitaxel (42%) were given for a median of 6 cycles (range, 0-42) before CRT. Radiation therapy techniques included 3-dimensional conformal (22%), intensity modulated photon (55%), and intensity modulated proton (23%) radiation therapy to a median dose of 50 Gy (range, 36-62.5). Concurrent chemotherapy was most commonly capecitabine (82%). Sixty-three patients (63%) had surgery after CRT. The mean decline in FACT-G, HCS subscale, and FACT-Hep from pre- to post-CRT was 3.5 (standard deviation [SD], 13.7), 1.7 (SD 7.8), and 5.2 (SD 19.4), respectively. Each of these changes were statistically significant, but did not meet the minimally important difference threshold. Pancreatic head tumor location was associated with decline in FACT-Hep. Nausea was the toxicity with the greatest increase from pre- to post-CRT by both physician-assessment and patient-reported QOL. CONCLUSIONS For patients with intact pancreatic adenocarcinoma, modern CRT is well tolerated with minimal decline in QOL during treatment.
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Bouchart C, Navez J, Closset J, Hendlisz A, Van Gestel D, Moretti L, Van Laethem JL. Novel strategies using modern radiotherapy to improve pancreatic cancer outcomes: toward a new standard? Ther Adv Med Oncol 2020; 12:1758835920936093. [PMID: 32684987 PMCID: PMC7343368 DOI: 10.1177/1758835920936093] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Accepted: 05/22/2020] [Indexed: 12/11/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive solid tumours with an estimated 5-year overall survival rate of 7% for all stages combined. In this highly resistant disease that is located in the vicinity of many radiosensitive organs, the role of radiotherapy (RT) and indications for its use in this setting have been debated for a long time and are still under investigation. Although a survival benefit has yet to be clearly demonstrated for RT, it is the only technique, other than surgery, that has been demonstrated to lead to local control improvement. The adjuvant approach is now strongly challenged by neoadjuvant treatments that could spare patients with rapidly progressive systemic disease from unnecessary surgery and may increase free margin (R0) resection rates for those eligible for surgery. Recently developed dose-escalated RT treatments, designed either to maintain full-dose chemotherapy or to deliver a high biologically effective dose, particularly to areas of contact between the tumour and blood vessels, such as hypofractionated ablative RT (HFA-RT) or stereotactic body RT (SBRT), are progressively changing the treatment landscape. These modern strategies are currently being tested in prospective clinical trials with encouraging preliminary results, paving the way for more effective treatment combinations using novel targeted therapies. This review summarizes the current literature regarding the use of RT for the treatment of primary PDAC, describes the limitations of conventional RT, and discusses the emerging role of dose-escalated RT and heavy-particle RT.
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Affiliation(s)
- Christelle Bouchart
- Department of Radiation-Oncology, Institut Jules Bordet, Boulevard de Waterloo, 121, Brussels, 1000, Belgium
| | - Julie Navez
- Department of Hepato-Biliary-Pancreatic Surgery, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Jean Closset
- Department of Hepato-Biliary-Pancreatic Surgery, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - Alain Hendlisz
- Department of Gastroenterology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Dirk Van Gestel
- Department of Radiation-Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Luigi Moretti
- Department of Radiation-Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Jean-Luc Van Laethem
- Department of Gastroenterology, Hepatology and Digestive Oncology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium
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Could Protons and Carbon Ions Be the Silver Bullets Against Pancreatic Cancer? Int J Mol Sci 2020; 21:ijms21134767. [PMID: 32635552 PMCID: PMC7369903 DOI: 10.3390/ijms21134767] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 06/30/2020] [Accepted: 07/01/2020] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer is a very aggressive cancer type associated with one of the poorest prognostics. Despite several clinical trials to combine different types of therapies, none of them resulted in significant improvements for patient survival. Pancreatic cancers demonstrate a very broad panel of resistance mechanisms due to their biological properties but also their ability to remodel the tumour microenvironment. Radiotherapy is one of the most widely used treatments against cancer but, up to now, its impact remains limited in the context of pancreatic cancer. The modern era of radiotherapy proposes new approaches with increasing conformation but also more efficient effects on tumours in the case of charged particles. In this review, we highlight the interest in using charged particles in the context of pancreatic cancer therapy and the impact of this alternative to counteract resistance mechanisms.
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Raturi VP, Hojo H, Hotta K, Baba H, Takahashi R, Rachi T, Nakamura N, Zenda S, Motegi A, Tachibana H, Ariji T, Motegi K, Nakamura M, Okumura M, Hirano Y, Akimoto T. Radiobiological model-based approach to determine the potential of dose-escalated robust intensity-modulated proton radiotherapy in reducing gastrointestinal toxicity in the treatment of locally advanced unresectable pancreatic cancer of the head. Radiat Oncol 2020; 15:157. [PMID: 32571379 PMCID: PMC7310413 DOI: 10.1186/s13014-020-01592-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 06/03/2020] [Indexed: 12/31/2022] Open
Abstract
Background The purpose of this study was to determine the potential of escalated dose radiation (EDR) robust intensity-modulated proton radiotherapy (ro-IMPT) in reducing GI toxicity risk in locally advanced unresectable pancreatic cancer (LAUPC) of the head in term of normal tissue complication probability (NTCP) predictive model. Methods For 9 patients, intensity-modulated radiotherapy (IMRT) was compared with ro-IMPT. For all plans, the prescription dose was 59.4GyE (Gray equivalent) in 33 fractions with an equivalent organ at risk (OAR) constraints. Physical dose distribution was evaluated. GI toxicity risk for different endpoints was estimated using published NTCP Lyman Kutcher Burman (LKB) models for stomach, duodenum, small bowel, and combine stomach and duodenum (Stoduo). A Wilcoxon signed-rank test was used for dosimetry parameters and NTCP values comparison. Result The dosimetric results have shown that, with similar target coverage, ro-IMPT achieves a significant dose-volume reduction in the stomach, small bowel, and stoduo in low to high dose range in comparison to IMRT. NTCP evaluation for the endpoint gastric bleeding of stomach (10.55% vs. 13.97%, P = 0.007), duodenum (1.87% vs. 5.02%, P = 0.004), and stoduo (5.67% vs. 7.81%, P = 0.008) suggest reduced toxicity by ro-IMPT compared to IMRT. ∆NTCP IMRT – ro-IMPT (using parameter from Pan et al. for gastric bleed) of ≥5 to < 10% was seen in 3 patients (33%) for stomach and 2 patients (22%) for stoduo. An overall GI toxicity relative risk (NTCPro-IMPT/NTCPIMRT) reduction was noted (0.16–0.81) for all GI-OARs except for duodenum (> 1) with endpoint grade ≥ 3 GI toxicity (using parameters from Holyoake et al.). Conclusion With similar target coverage and better conformity, ro-IMPT has the potential to substantially reduce the risk of GI toxicity compared to IMRT in EDR of LAUPC of the head. This result needs to be further evaluated in future clinical studies.
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Affiliation(s)
- Vijay P Raturi
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan.,Course of Advanced Clinical Research of Cancer, Graduate school of Medicine, Juntendo University, Tokyo, Japan
| | - Hidehiro Hojo
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Kenji Hotta
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Hiromi Baba
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Ryo Takahashi
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Toshiya Rachi
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Naoki Nakamura
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Sadamoto Zenda
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Atsushi Motegi
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Hidenobu Tachibana
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Takaki Ariji
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Kana Motegi
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Masaki Nakamura
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Masayuki Okumura
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Yasuhiro Hirano
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan
| | - Tetsuo Akimoto
- Division of Radiation Oncology and Particle therapy, National Cancer Center Hospital East, 6-5-1 chome, Kashiwanoha, Kashiwa-shi, Chiba-ken, 277-8577, Japan. .,Course of Advanced Clinical Research of Cancer, Graduate school of Medicine, Juntendo University, Tokyo, Japan.
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Martin-Perez E, Domínguez-Muñoz JE, Botella-Romero F, Cerezo L, Matute Teresa F, Serrano T, Vera R. Multidisciplinary consensus statement on the clinical management of patients with pancreatic cancer. Clin Transl Oncol 2020; 22:1963-1975. [PMID: 32318964 PMCID: PMC7505812 DOI: 10.1007/s12094-020-02350-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 04/01/2020] [Indexed: 12/14/2022]
Abstract
Pancreatic cancer (PC) remains one of the most aggressive tumors with an increasing incidence rate and reduced survival. Although surgical resection is the only potentially curative treatment for PC, only 15–20% of patients are resectable at diagnosis. To select the most appropriate treatment and thus improve outcomes, the diagnostic and therapeutic strategy for each patient with PC should be discussed within a multidisciplinary expert team. Clinical decision-making should be evidence-based, considering the staging of the tumor, the performance status and preferences of the patient. The aim of this guideline is to provide practical and evidence-based recommendations for the management of PC.
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Affiliation(s)
- E Martin-Perez
- Department of Surgery, Hospital Universitario de La Princesa, Diego de Leon 62, 28006, Madrid, Spain.
| | - J E Domínguez-Muñoz
- Department of Gastroenterology and Hepatology, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - F Botella-Romero
- Department of Endocrinology, Hospital General Universitario, Albacete, Spain
| | - L Cerezo
- Department of Radiation Oncology, Hospital Universitario de La Princesa, Madrid, Spain
| | - F Matute Teresa
- Department of Radiology, Hospital Clínico San Carlos, Madrid, Spain
| | - T Serrano
- Department of Pathology, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.,Oncology Program, CIBEREHD National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, Madrid, Spain
| | - R Vera
- Department of Medical Oncology, Complejo Hospitalario de Navarra, Pamplona, Spain
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Meduri B, Gregucci F, D'Angelo E, Alitto AR, Ciurlia E, Desideri I, Marino L, Borghetti P, Fiore M, Fiorentino A. Volume de-escalation in radiation therapy: state of the art and new perspectives. J Cancer Res Clin Oncol 2020; 146:909-924. [PMID: 32072318 DOI: 10.1007/s00432-020-03152-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 02/10/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE New RT techniques and data emerging from follow-up for several tumor sites suggest that treatment volume de-escalation may permit to minimize therapy-related side effects and/or obtain better clinical outcomes. Here, we summarize the main evidence about volume de-escalation in RT. METHOD The relevant literature from PubMed was reviewed in this article. The ClinicalTrials.gov database was searched for clinical trials related to the specific topic. RESULTS In Lymphoma, large-volume techniques (extended- and involved-field RT) are being successfully replaced by involved-site RT and involved-node RT. In head and neck carcinoma, spare a part of elective neck is controversial. In early breast cancer, partial breast irradiation has been established as a treatment option in low-risk patients. In pancreatic cancer stereotactic body radiotherapy may be used to dose escalation. Stereotactic radiosurgery should be the treatment choice for patients with oligometastatic brain disease and a life expectancy of more than 3 months, and it should be considered an alternative to WBRT for patients with multiple brain metastases. CONCLUSION Further clinical trials are necessary to improve the identification of suitable patient cohorts and the extent of possible volume de-escalation that does not compromise tumor control.
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Affiliation(s)
- Bruno Meduri
- Radiation Oncology Unit, University Hospital of Modena, Via del pozzo, 71, 41124, Modena, Italy
| | - Fabiana Gregucci
- Radiotherapy Oncology Department, General Regional Hospital "F. Miulli", Acquaviva delle Fonti, Bari, Italy
| | - Elisa D'Angelo
- Radiation Oncology Unit, University Hospital of Modena, Via del pozzo, 71, 41124, Modena, Italy.
| | - Anna Rita Alitto
- Radiotherapy Oncology Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Radioterapia, Rome, Italy
| | - Elisa Ciurlia
- Radiotherapy Oncology Department, Vito Fazzi Hospital, Lecce, Italy
| | - Isacco Desideri
- Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Section of Radiation Oncology, University of Florence, Firenze, Italy
| | - Lorenza Marino
- Radiotherapy Oncology Department, REM, Viagrande, Catania, Italy
| | - Paolo Borghetti
- Radiation Oncology Department University and Spedali Civili, Brescia, Italy
| | - Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, Rome, Italy
| | - Alba Fiorentino
- Radiotherapy Oncology Department, General Regional Hospital "F. Miulli", Acquaviva delle Fonti, Bari, Italy
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Rutenberg MS, Nichols RC. Proton beam radiotherapy for pancreas cancer. J Gastrointest Oncol 2020; 11:166-175. [PMID: 32175120 PMCID: PMC7052755 DOI: 10.21037/jgo.2019.03.02] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 03/07/2019] [Indexed: 12/17/2022] Open
Abstract
Pancreatic carcinoma is a challenging malignancy to manage with a very poor prognosis. Despite continued difficulties in its management, there have been incremental improvements in outcomes over the past several decades. Achieving the best oncologic outcomes requires a multimodality approach including surgery, chemotherapy, and radiotherapy. Proton radiotherapy enables the delivery of high-dose radiotherapy to the tumor or resection bed while sparing nearby critical organs. Due to their unique physical properties, protons can deliver radiotherapy dose distributions that are not achievable with photons (X-rays) even with advanced photon delivery techniques (e.g., intensity-modulated radiotherapy). Improved dose distributions can lead to reduced treatment toxicity and enable treatment intensification. As better chemotherapy regimens lead to better systemic disease control, it will become increasingly important that local-regional control is achieved. This will in part be accomplished by combining better radiotherapy with more active chemotherapies. Proton radiotherapy provides an excellent means for achieving this.
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Affiliation(s)
- Michael S Rutenberg
- Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL, USA
| | - Romaine C Nichols
- Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, FL, USA
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Boldrini L, Cusumano D, Cellini F, Azario L, Mattiucci GC, Valentini V. Online adaptive magnetic resonance guided radiotherapy for pancreatic cancer: state of the art, pearls and pitfalls. Radiat Oncol 2019; 14:71. [PMID: 31036034 PMCID: PMC6489212 DOI: 10.1186/s13014-019-1275-3] [Citation(s) in RCA: 91] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 04/11/2019] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND Different studies have proved in recent years that hypofractionated radiotherapy (RT) improves overall survival of patients affected by locally advanced, unresectable, pancreatic cancer. The clinical management of these patients generally leads to poor results and is considered very challenging, due to different factors, heavily influencing treatment delivery and its outcomes. Firstly, the dose prescribed to the target is limited by the toxicity that the highly radio-sensitive organs at risk (OARs) surrounding the disease can develop. Treatment delivery is also complicated by the significant inter-fractional and intra-fractional variability of therapy volumes, mainly related to the presence of hollow organs and to the breathing cycle. The recent introduction of magnetic resonance guided radiotherapy (MRgRT) systems leads to the opportunity to control most of the aforementioned sources of uncertainty influencing RT treatment workflow in pancreatic cancer. MRgRT offers the possibility to accurately identify radiotherapy volumes, thanks to the high soft-tissue contrast provided by the Magnetic Resonance imaging (MRI), and to monitor the tumour and OARs positions during the treatment fraction using a high-temporal cine MRI. However, the main advantage offered by the MRgRT is the possibility to online adapt the RT treatment plan, changing the dose distribution while the patient is still on couch and successfully addressing most of the sources of variability. SHORT CONCLUSION Aim of this study is to present and discuss the state of the art, the main pitfalls and the innovative opportunities offered by online adaptive MRgRT in pancreatic cancer treatment.
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Affiliation(s)
- Luca Boldrini
- Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, UOC Radioterapia Oncologica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italia
| | - Davide Cusumano
- Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, UOC Fisica Sanitaria, Fondazione Policlinico Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italia
| | - Francesco Cellini
- Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, UOC Radioterapia Oncologica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italia
| | - Luigi Azario
- Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, UOC Fisica Sanitaria, Fondazione Policlinico Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italia
| | - Gian Carlo Mattiucci
- Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, UOC Radioterapia Oncologica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italia
| | - Vincenzo Valentini
- Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, UOC Radioterapia Oncologica, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma, Italia
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Bohoudi O, Bruynzeel AM, Meijerink MR, Senan S, Slotman BJ, Palacios MA, Lagerwaard FJ. Identification of patients with locally advanced pancreatic cancer benefitting from plan adaptation in MR-guided radiation therapy. Radiother Oncol 2019; 132:16-22. [DOI: 10.1016/j.radonc.2018.11.019] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 11/27/2018] [Accepted: 11/28/2018] [Indexed: 12/11/2022]
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Grimm M. Pankreaskarzinom. STRAHLENTHERAPIE KOMPAKT 2019:101-105. [DOI: 10.1016/b978-3-437-23292-3.00009-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Nakamura A, Hiraoka M, Itasaka S, Nakamura M, Akimoto M, Ishihara Y, Mukumoto N, Goto Y, Kishi T, Yoshimura M, Matsuo Y, Yano S, Mizowaki T. Evaluation of Dynamic Tumor-tracking Intensity-modulated Radiotherapy for Locally Advanced Pancreatic Cancer. Sci Rep 2018; 8:17096. [PMID: 30459454 PMCID: PMC6244273 DOI: 10.1038/s41598-018-35402-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 11/05/2018] [Indexed: 12/25/2022] Open
Abstract
Intensity-modulated radiotherapy (IMRT) is now regarded as an important treatment option for patients with locally advanced pancreatic cancer (LAPC). To reduce the underlying tumor motions and dosimetric errors during IMRT as well as the burden of respiratory management for patients, we started to apply a new treatment platform of the dynamic tumor dynamic tumor-tracking intensity-modulated radiotherapy (DTT-IMRT) using the gimbaled linac, which can swing IMRT toward the real-time tumor position under patients' voluntary breathing. Between June 2013 and March 2015, ten patients were treated, and the tumor-tracking accuracy and the practical benefits were evaluated. The mean PTV size in DTT-IMRT was 18% smaller than a conventional ITV-based PTV. The root-mean-squared errors between the predicted and the detected tumor positions were 1.3, 1.2, and 1.5 mm in left-right, anterior-posterior, and cranio-caudal directions, respectively. The mean in-room time was 24.5 min. This high-accuracy of tumor-tracking with reasonable treatment time are promising and beneficial to patients with LAPC.
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Affiliation(s)
- Akira Nakamura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masahiro Hiraoka
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
| | - Satoshi Itasaka
- Department of Radiation Oncology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Mitsuhiro Nakamura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Mami Akimoto
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yoshitomo Ishihara
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Nobutaka Mukumoto
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yoko Goto
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takahiro Kishi
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Michio Yoshimura
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yukinori Matsuo
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shinsuke Yano
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Oh ES, Kim TH, Woo SM, Lee WJ, Lee JH, Youn SH, Han SS, Park SJ, Kim DY. Effectiveness and feasibility of concurrent chemoradiotherapy using simultaneous integrated boost-intensity modulated radiotherapy with and without induction chemotherapy for locally advanced pancreatic cancer. Radiat Oncol J 2018; 36:200-209. [PMID: 30309211 PMCID: PMC6226140 DOI: 10.3857/roj.2018.00073] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 07/23/2018] [Indexed: 11/09/2022] Open
Abstract
Purpose To evaluate the effectiveness and feasibility of chemoradiotherapy (CRT) using simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in locally advanced pancreatic cancer (LAPC) patients. Materials and Methods Between January 2011 and May 2015, 47 LAPC patients received CRT using SIB-IMRT. Prior to SIB-IMRT, 37 patients (78.7%) received induction chemotherapy (IC-CRT group) and remaining 10 patients (21.3%) did not received induction chemotherapy (CRT group). During SIB-IMRT, all patients received concomitant chemotherapy, with gemcitabine (n = 37) and capecitabine (n = 10). Results At the time of analysis, 45 patients had died and 2 patients remained alive and the median follow-up time was 14.2 months (range, 3.3 to 51.4 months). For all patients, the median times of local progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were 18.1, 10.3, and 14.2 months, respectively. The median time of LPFS between IC-CRT and CRT groups was similar (18.1 months vs. 18.3 months, p = 0.711). IC-CRT group had a higher trend in PFS (10.9 months vs. 4.1 months, p = 0.054) and had significantly higher OS (15.4 months vs. 9.5 months, p = 0.007) than CRT group. In multivariate analysis, the use of induction chemotherapy and tumor response were significant factors associated with OS (p < 0.05, each). During SIBIMRT, toxicity of grade ≥3 was observed in 7 patients (14.9%) in all patients. Conclusions CRT using SIB-IMRT is feasible and promising in LAPC patients.
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Affiliation(s)
- Eun Sang Oh
- Proton Therapy Center, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
| | - Tae Hyun Kim
- Proton Therapy Center, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
- Correspondence: Tae Hyun Kim, MD, Proton Therapy Center, National Cancer Center Research Institute and Hospital, National Cancer Institute, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea. Tel: +82-31-920-1725, Fax: +82-31-920-0149, E-mail:
| | - Sang Myung Woo
- Center for Liver Cancer, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
| | - Woo Jin Lee
- Center for Liver Cancer, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
| | - Ju Hee Lee
- Center for Liver Cancer, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
| | - Sang Hee Youn
- Proton Therapy Center, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
| | - Sung Sik Han
- Center for Liver Cancer, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
| | - Sang Jae Park
- Center for Liver Cancer, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
| | - Dae Yong Kim
- Proton Therapy Center, National Cancer Center Research Institute and Hospital, National Cancer Institute, Goyang, Korea
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Ng SP, Koay EJ. Current and emerging radiotherapy strategies for pancreatic adenocarcinoma: stereotactic, intensity modulated and particle radiotherapy. ACTA ACUST UNITED AC 2018; 1. [PMID: 30198024 DOI: 10.21037/apc.2018.07.03] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The role of radiotherapy for locally advanced pancreatic cancer (LAPC) is unclear based on studies that used conventional doses and fractionation schedules. Modern radiotherapy techniques have not been studied in depth, however. We reviewed the literature on emerging methods of delivering higher doses of conformal radiotherapy using stereotactic body radiation, intensity modulated radiation, and particle beam radiation, highlighting clinical outcomes and toxicities. The literature review suggests low rates of acute and late toxicities when higher doses of radiation are given with careful attention to normal tissue dose constraints, including for stereotactic body radiotherapy (SBRT), escalated doses with intensity modulated radiation therapy (IMRT), and particle-based therapy. Retrospective evidence suggests prolonged survival for patients who receive biological equivalent doses above 70 Gy. Prospective trials that evaluate modern radiotherapy techniques are warranted for LAPC.
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Affiliation(s)
- Sweet Ping Ng
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Eugene J Koay
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Chuong M, Badiyan SN, Yam M, Li Z, Langen K, Regine W, Morris C, Snider J, Mehta M, Huh S, Rutenberg M, Nichols RC. Pencil beam scanning versus passively scattered proton therapy for unresectable pancreatic cancer. J Gastrointest Oncol 2018; 9:687-693. [PMID: 30151265 DOI: 10.21037/jgo.2018.03.14] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Background With an increasing number of proton centers capable of delivering pencil beam scanning (PBS), understanding the dosimetric differences in PBS compared to passively scattered proton therapy (PSPT) for pancreatic cancer is of interest. Methods Optimized PBS plans were retrospectively generated for 11 patients with locally advanced pancreatic cancer previously treated with PSPT to 59.4 Gy on a prospective trial. The primary tumor was targeted without elective nodal coverage. The same treatment couch, target coverage and normal tissue dose objectives were used for all plans. A Wilcoxon t-test was performed to compare various dosimetric points between the two plans for each patient. Results All target volume coverage goals were met in all PBS and passive scattering (PS) plans, except for the planning target volume (PTV) coverage goal (V100% >95%) which was not met in one PS plan (range, 81.8-98.9%). PBS was associated with a lower median relative dose (102.4% vs. 103.8%) to 10% of the PTV (P=0.001). PBS plans had a lower median duodenal V59.4 Gy (37.4% vs. 40.4%; P=0.014), lower small bowel median V59.4 Gy (0.11% vs. 0.37%; P=0.012), lower stomach median V59.4 Gy (0.01% vs. 0.1%; P=0.023), and lower median dose to 0.1 cc of the spinal cord {35.0 vs. 38.7 Gy [relative biological effectiveness (RBE)]; P=0.001}. Liver dose was higher in PBS plans for median V5 Gy (24.1% vs. 20.2%; P=0.032), V20 Gy (3.2% vs. 2.8%; P=0.010), and V25 Gy (2.6% vs. 2.2%; P=0.019). There was no difference in kidney dose between PBS and PS plans. Conclusions Proton therapy for locally advanced pancreatic cancer using PBS was not clearly associated with clinically meaningful reductions in normal tissue dose compared to PS. Some statistically significant improvements in PTV coverage were achieved using PBS. PBS may offer improved conformality for the treatment of irregular targets, and further evaluation of PBS and PS incorporating elective nodal irradiation should be considered.
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Affiliation(s)
- Michael Chuong
- Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA
| | - Shahed N Badiyan
- University of Maryland Medical School of Medicine, Baltimore, MD, USA
| | - Man Yam
- Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA
| | - Zuofeng Li
- University of Florida Proton Therapy Institute, Jacksonville, FL, USA
| | - Katja Langen
- University of Maryland Medical School of Medicine, Baltimore, MD, USA
| | - William Regine
- University of Maryland Medical School of Medicine, Baltimore, MD, USA
| | | | - James Snider
- University of Maryland Medical School of Medicine, Baltimore, MD, USA
| | - Minesh Mehta
- Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA
| | - Soon Huh
- University of Florida Proton Therapy Institute, Jacksonville, FL, USA
| | - Michael Rutenberg
- University of Florida Proton Therapy Institute, Jacksonville, FL, USA
| | - Romaine C Nichols
- University of Florida Proton Therapy Institute, Jacksonville, FL, USA
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Clinical evaluation of intensity-modulated radiotherapy for locally advanced pancreatic cancer. Radiat Oncol 2018; 13:118. [PMID: 29940984 PMCID: PMC6019294 DOI: 10.1186/s13014-018-1063-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2017] [Accepted: 06/14/2018] [Indexed: 01/05/2023] Open
Abstract
Background The purpose was to retrospectively evaluate the effect of intensity-modulated radiotherapy (IMRT) on gastrointestinal (GI) toxicities and outcomes compared to three-dimensional conformal radiotherapy (3DCRT) for locally advanced pancreatic cancer (LAPC). Methods We included 107 consecutive patients who underwent CRT for LAPC from September 2001 to March 2015; 80 patients underwent 3DCRT and 27 patients underwent IMRT. They were compared for GI toxicities, locoregional progression free survival (LRPFS), distant metastasis free survival (DMS), and overall survival (OS). Results Median radiation dose and fractions for 3DCRT and IMRT were 54 Gy/30 fr. and 48 Gy/15 fr. The regimens of CRT consisted of weekly gemcitabine 250 mg/m2 (for 3DCRT) or 1000 mg/m2 (for IMRT). Acute GI toxicity ≥grade 2 occurred in 32 patients (40%) treated with 3DCRT compared with five patients (19%) treated with IMRT. Late GI toxicity of grade 3 occurred in 10 patients (12%) treated with 3DCRT and one patient (4%) treated with IMRT. Patients who underwent IMRT had superior 1-year LRPFS (73.1% vs. 63.2%, p = 0.035) and 1-year OS (92.3% vs. 68.2%, p = 0.037) as compared with those treated with 3DCRT. Multivariate analysis showed that in IMRT patients, higher dose (≥45 Gy) was an independent factor for better LRPFS and OS. Conclusions LAPC patients treated with hypofractionated full-dose gemcitabine IMRT had improved OS and LRPFS without increased GI toxicities when compared to those of patients treated with conventionally fractionated low dose gemcitabine 3DCRT. In IMRT patients, higher dose was an independent favorable prognostic factor for better LRPFS and OS, which suggests that dose escalation with IMRT for LAPC is a promising strategy.
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Goto Y, Ashida R, Nakamura A, Itasaka S, Shibuya K, Akimoto M, Mukumoto N, Matsumoto S, Kanai M, Isoda H, Masui T, Kodama Y, Nakamura M, Takaori K, Mizowaki T, Hiraoka M. Clinical results of dynamic tumor tracking intensity-modulated radiotherapy with real-time monitoring for pancreatic cancers using a gimbal mounted linac. Oncotarget 2018; 9:23628-23635. [PMID: 29805762 PMCID: PMC5955105 DOI: 10.18632/oncotarget.25310] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 04/14/2018] [Indexed: 12/25/2022] Open
Abstract
Objectives We performed dynamic tumor-tracking IMRT (DTT-IMRT) in locally advanced pancreatic cancer (LAPC) patients using a gimbaled linac of Vero4DRT. The purpose of this study is to report the first clinical results. Methods From June 2013 to June 2015, eleven LAPC patients enrolled in this study and DTT-IMRT was successfully performed. The locoregional progression free survival (LRPFS), distant metastasis free survival (DMFS), overall survival (OS), hematologic and gastrointestinal (GI) toxicities were evaluated. Oncologic outcomes were estimated using Kaplan-Meier analysis, and toxicities using CTCAE v4.0. Results The median radiation dose was 48 Gy (range, 45-51) in 15 fractions. Concurrent chemoradiotherapy (CCRT) was performed using gemcitabine in 9 patients and S-1 in one, while one patient refused. With a median follow-up of 22.9 months, 1-year LRPFS, DMFS, and OS rates were 90.9%, 70.7%, and 100%, respectively. Median survival time was 23.6 months. Grade-3 leucopenia and neutropenia were observed in two (18%) and one patient (9%), respectively. Grade-2 acute GI toxicity occurred in 2 patients (18%) and late grade-3 in 1 patient (9%). Conclusions Preliminarily application of DTT-IMRT using a gimbaled linac on CCRT in LAPC patients resulted in excellent locoregional control and OS without severe toxicity.
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Affiliation(s)
- Yoko Goto
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Ryo Ashida
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Akira Nakamura
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Satoshi Itasaka
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Keiko Shibuya
- Department of Radiation Oncology, Graduate School of Medicine, Yamaguchi University, Yamaguchi, Japan
| | - Mami Akimoto
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Nobutaka Mukumoto
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Shigemi Matsumoto
- Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masashi Kanai
- Department of Clinical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Hiroyoshi Isoda
- Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Toshihiko Masui
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Yuzo Kodama
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Mitsuhiro Nakamura
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Kyoichi Takaori
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Masahiro Hiraoka
- Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.,Department of Radiation Oncology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan
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Jethwa KR, Tryggestad EJ, Whitaker TJ, Giffey BT, Kazemba BD, Neben-Wittich MA, Merrell KW, Haddock MG, Hallemeier CL. Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes. Adv Radiat Oncol 2018; 3:314-321. [PMID: 30202800 PMCID: PMC6128024 DOI: 10.1016/j.adro.2018.04.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 03/25/2018] [Accepted: 04/04/2018] [Indexed: 12/22/2022] Open
Abstract
Purpose Pencil-beam scanning intensity modulated proton therapy (IMPT) may allow for an improvement in the therapeutic ratio compared with conventional techniques of radiation therapy delivery for pancreatic cancer. The purpose of this study was to describe the clinical implementation of IMPT for intact and clinically localized pancreatic cancer, perform a matched dosimetric comparison with volumetric modulated arc therapy (VMAT), and report acute adverse event (AE) rates and patient-reported outcomes (PROs) of health-related quality of life. Methods and materials Between July 2016 and March 2017, 13 patients with localized pancreatic cancer underwent concurrent capecitabine or 5-fluorouracil-based chemoradiation therapy (CRT) utilizing IMPT to a dose of 50 Gy (radiobiological effectiveness: 1.1). A VMAT plan was generated for each patient to use for dosimetric comparison. Patients were assessed prospectively for AEs and completed PRO questionnaires utilizing the Functional Assessment of Cancer Therapy-Hepatobiliary at baseline and upon completion of CRT. Results There was no difference in mean target coverage between IMPT and VMAT (P > .05). IMPT offered significant reductions in dose to organs at risk, including the small bowel, duodenum, stomach, large bowel, liver, and kidneys (P < .05). All patients completed treatment without radiation therapy breaks. The median weight loss during treatment was 1.6 kg (range, 0.1-5.7 kg). No patients experienced grade ≥3 treatment-related AEs. The median Functional Assessment of Cancer Therapy-Hepatobiliary scores prior to versus at the end of CRT were 142 (range, 113-163) versus 136 (range, 107-173; P = .18). Conclusions Pencil-beam scanning IMPT was feasible and offered significant reductions in radiation exposure to multiple gastrointestinal organs at risk. IMPT was associated with no grade ≥3 gastrointestinal AEs and no change in baseline PROs, but the conclusions are limited due to the patient sample size. Further clinical studies are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.
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Affiliation(s)
- Krishan R Jethwa
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | | | | | - Broc T Giffey
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
| | - Bret D Kazemba
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota
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Dosimetric analysis of stereotactic body radiation therapy for pancreatic cancer using MR-guided Tri- 60Co unit, MR-guided LINAC, and conventional LINAC-based plans. Pract Radiat Oncol 2018; 8:e312-e321. [PMID: 29703704 DOI: 10.1016/j.prro.2018.02.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2017] [Revised: 02/10/2018] [Accepted: 02/21/2018] [Indexed: 01/08/2023]
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Estabrook NC, Corn JB, Ewing MM, Cardenes HR, Das IJ. Dosimetric impact of gastrointestinal air column in radiation treatment of pancreatic cancer. Br J Radiol 2017; 91:20170512. [PMID: 29166133 DOI: 10.1259/bjr.20170512] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVE Dosimetric evaluation of air column in gastrointestinal (GI) structures in intensity modulated radiation therapy (IMRT) of pancreatic cancer. METHODS Nine sequential patients were retrospectively chosen for dosimetric analysis of air column in the GI apparatus in pancreatic cancer using cone beam CT (CBCT). The four-dimensional CT (4DCT) was used for target and organs at risk (OARs) and non-coplanar IMRT was used for treatment. Once a week, these patients underwent CBCT for air filling, isocentre verification and dose calculations retrospectively. RESULTS Abdominal air column variation was as great as ±80% between weekly CBCT and 4DCT. Even with such a large air column in the treatment path for pancreatic cancer, changes in anteroposterior dimension were minimal (2.8%). Using IMRT, variations in air column did not correlate dosimetrically with large changes in target volume. An average dosimetric deviation of mere -3.3% and a maximum of -5.5% was observed. CONCLUSION CBCT revealed large air column in GI structures; however, its impact is minimal for target coverage. Because of the inherent advantage of segmentation in IMRT, where only a small fraction of a given beam passes through the air column, this technique might have an advantage over 3DCRT in treating upper GI malignancies where the daily air column can have significant impact. Advances in knowledge: Radiation treatment of pancreatic cancer has significant challenges due to positioning, imaging of soft tissues and variability of air column in bowels. The dosimetric impact of variable air column is retrospectively studied using CBCT. Even though, the volume of air column changes by ± 80%, its dosimetric impact in IMRT is minimum.
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Affiliation(s)
- Neil C Estabrook
- 1 Indiana University Health Arnett Cancer Care , Lafayette, IN , USA
| | - Jonathan B Corn
- 1 Indiana University Health Arnett Cancer Care , Lafayette, IN , USA
| | - Marvene M Ewing
- 2 Department of Radiation Oncology, Indiana University School of Medicine , Indianapolis, IN , USA
| | - Higinia R Cardenes
- 3 The Arnold Center for Radiation Oncology, New York Presbyterian Queens Weill Cornell Medicine , New York, NY , USA
| | - Indra J Das
- 4 Department of Radiation Oncology, New York University Langone Medical Center , New York, NY , USA
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Fast and robust online adaptive planning in stereotactic MR-guided adaptive radiation therapy (SMART) for pancreatic cancer. Radiother Oncol 2017; 125:439-444. [PMID: 28811038 DOI: 10.1016/j.radonc.2017.07.028] [Citation(s) in RCA: 247] [Impact Index Per Article: 30.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 07/23/2017] [Accepted: 07/27/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND PURPOSE To implement a robust and fast stereotactic MR-guided adaptive radiation therapy (SMART) online strategy in locally advanced pancreatic cancer (LAPC). MATERIAL AND METHODS SMART strategy for plan adaptation was implemented with the MRIdian system (ViewRay Inc.). At each fraction, OAR (re-)contouring is done within a distance of 3cm from the PTV surface. Online plan re-optimization is based on robust prediction of OAR dose and optimization objectives, obtained by building an artificial neural network (ANN). Proposed limited re-contouring strategy for plan adaptation (SMART3CM) is evaluated by comparing 50 previously delivered fractions against a standard (re-)planning method using full-scale OAR (re-)contouring (FULLOAR). Plan quality was assessed using PTV coverage (V95%, Dmean, D1cc) and institutional OAR constraints (e.g. V33Gy). RESULTS SMART3CM required a significant lower number of optimizations than FULLOAR (4 vs 18 on average) to generate a plan meeting all objectives and institutional OAR constraints. PTV coverage with both strategies was identical (mean V95%=89%). Adaptive plans with SMART3CM exhibited significant lower intermediate and high doses to all OARs than FULLOAR, which also failed in 36% of the cases to adhere to the V33Gy dose constraint. CONCLUSIONS SMART3CM approach for LAPC allows good OAR sparing and adequate target coverage while requiring only limited online (re-)contouring from clinicians.
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de Geus SWL, Eskander MF, Kasumova GG, Ng SC, Kent TS, Mancias JD, Callery MP, Mahadevan A, Tseng JF. Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review. Cancer 2017; 123:4158-4167. [PMID: 28708929 DOI: 10.1002/cncr.30856] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 05/02/2017] [Accepted: 05/30/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND The role of conventional radiotherapy in the management of pancreatic cancer has yet to be elucidated. Over the past decade, stereotactic body radiotherapy (SBRT) has emerged as a novel therapeutic option in pancreatic cancer care. This study evaluated the survival impact of SBRT on patients with unresected pancreatic cancer. METHODS The National Cancer Data Base was queried for unresected patients who received chemotherapy for nonmetastatic pancreatic adenocarcinoma between 2004 and 2012. Four treatment groups were identified: chemotherapy alone, chemotherapy combined with external-beam radiotherapy (EBRT), chemotherapy combined with intensity-modulated radiotherapy (IMRT), and chemotherapy combined with SBRT. Propensity score models predicting the odds of receiving SBRT were created to control for potential selection bias, and patients were matched by propensity scores. The survival analysis was performed with the Kaplan-Meier method. RESULTS A total of 14,331 patients met the inclusion criteria. Chemotherapy alone was delivered to 5464 patients (38.1%); 6418 (44.8%), 322 (2.3%), and 2127 (14.8%) received chemotherapy along with EBRT, IMRT, and SBRT, respectively. The unadjusted median survival before matching was 9.9, 10.9, 12.0, and 13.9 months for patients treated with chemotherapy, EBRT, IMRT, and SBRT, respectively. In separate matched analyses, SBRT remained superior to chemotherapy alone (log-rank P < .0001) and EBRT (log-rank P = .0180). After matching, survival did not differ between patients receiving IMRT and patients receiving SBRT (log-rank P = .0492). CONCLUSIONS SBRT is associated with a significantly better outcome than chemotherapy alone or in conjunction with traditional EBRT. These results support the idea that SBRT is a promising treatment approach for patients with unresected pancreatic cancer. Cancer 2017;123:4158-4167. © 2017 American Cancer Society.
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Affiliation(s)
- Susanna W L de Geus
- Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Mariam F Eskander
- Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Gyulnara G Kasumova
- Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Sing Chau Ng
- Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Tara S Kent
- Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Joseph D Mancias
- Department of Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, Massachusetts
| | - Mark P Callery
- Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Anand Mahadevan
- Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
| | - Jennifer F Tseng
- Surgical Outcomes Analysis and Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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Chung SY, Chang JS, Lee BM, Kim KH, Lee KJ, Seong J. Dose escalation in locally advanced pancreatic cancer patients receiving chemoradiotherapy. Radiother Oncol 2017; 123:438-445. [PMID: 28464997 DOI: 10.1016/j.radonc.2017.04.010] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2017] [Revised: 03/30/2017] [Accepted: 04/05/2017] [Indexed: 12/28/2022]
Abstract
PURPOSE To investigate whether radiotherapy (RT) dose escalation would improve treatment outcomes without increasing severe toxicity in locally advanced pancreatic cancer patients. METHODS From 2005 to 2015, 497 locally advanced pancreatic cancer patients who received neoadjuvant or definitive chemoradiotherapy (CCRT) were included. Patients were divided according to the total dose (TD). Overall survival (OS), progression-free survival (PFS), local failure-free rate (LFFR), distant failure-free rate (DFFR), and toxicity rates were compared between <61Gy (n=345) and ≥61Gy groups (n=152). Additionally, propensity score matching was performed. RESULTS At a median follow-up of 19.3months (range, 4.8-128.5months), the 1-year OS, PFS, LFFR, and DFFR were significantly higher in the ≥61Gy group. After multivariate analysis, a TD of ≥61Gy remained a significant favorable factor for OS (p=0.019), PFS (p=0.001), LFFR (p=0.004), and DFFR (p=0.008). After propensity score matching, the ≥61Gy group still showed higher OS, PFS, and LFFR, but not DFFR (p=0.205). The acute and late toxicity rates showed no significant difference between the two groups. CONCLUSION Patients who received a higher RT dose showed not only improved PFS and LFFR, but also improved OS without an increase in severe toxicity. Dose-escalated CCRT can be a favorable treatment option in locally advanced pancreatic cancer patients.
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Affiliation(s)
- Seung Yeun Chung
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jee Suk Chang
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Byung Min Lee
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyung Hwan Kim
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyong Joo Lee
- Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Nagakawa Y, Hosokawa Y, Nakayama H, Sahara Y, Takishita C, Nakajima T, Hijikata Y, Kasuya K, Katsumata K, Tokuuye K, Tsuchida A. A phase II trial of neoadjuvant chemoradiotherapy with intensity-modulated radiotherapy combined with gemcitabine and S-1 for borderline-resectable pancreatic cancer with arterial involvement. Cancer Chemother Pharmacol 2017; 79:951-957. [DOI: 10.1007/s00280-017-3288-7] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 03/09/2017] [Indexed: 12/30/2022]
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