Cai Xu1, Jian-Yue Jin2, Ming Zhang3, Amy Liu4, Jun Wang5, Radhe Mohan4, Fengming Spring Kong6, Steven H Lin7. 1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. 2. Department of Radiation Oncology, University Hospitals/Seidman Cancer Center and Case Comprehensive Cancer Center of Case Western Reserve University, USA. 3. Department of Radiation Oncology, Hebei General Hospital, Shijiazhuang, China. 4. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 5. Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. 6. Department of Radiation Oncology, UH Cleveland Medical Center, Cleveland, USA. 7. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: SHLin@mdanderson.org.
Abstract
PURPOSE: To test the hypothesis that effective dose to circulating immune cells (EDIC) impacts the severity of radiation-induced lymphopenia and clinical outcomes of esophageal cancer patients treated with concurrent chemoradiotherapy (CCRT). MATERIAL AND METHODS: 488 esophageal cancer patients treated with CCRT with and without surgery were analyzed. The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose (MLD), mean heart dose (MHD), mean liver dose (MlD), and integral dose (ITD) of the body region scanned, calculated as: EDIC=0.12∗MLD+0.08∗MHD+0.15∗0.85∗MlD∗n451/2+0.45+0.35∗0.85∗nk1/2∗ITD62∗103 Where n is the fraction number. Correlations of EDIC with overall survival (OS), progression free survival (PFS), distant metastasis free survival (DMFS), and locoregional control (LRC) rates were analyzed using both univariable and multivariable Cox models. Lymphopenia during CCRT was graded according to Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Grade 4 lymphopenia resulted in inferior clinical outcomes, including OS, PFS, and DMFS. The median EDIC was 3.6 Gy (range, 0.8-6.0 Gy). Higher EDIC was strongly associated with severe lymphopenia, particularly when EDIC was above 4 Gy. Patients with EDIC > 4.0 Gy had more G4 lymphopenia than those with EDIC ≤ 4.0 Gy (67.3% vs. 40.8%; P < 0.001). On multivariate analysis, increasing EDIC was independently and inversely associated with worse OS, PFS, and DMFS. CONCLUSION: EDIC can be recommended as a useful tool to predict lymphopenia and inferior clinical outcomes, and it should be minimized below 4 Gy.
PURPOSE: To test the hypothesis that effective dose to circulating immune cells (EDIC) impacts the severity of radiation-induced lymphopenia and clinical outcomes of esophageal cancerpatients treated with concurrent chemoradiotherapy (CCRT). MATERIAL AND METHODS: 488 esophageal cancerpatients treated with CCRT with and without surgery were analyzed. The EDIC model considers the exposure of circulating immune cells as the proportion of blood flow to lung, heart, liver, and the volume of the exposed area of the body, with the basis of mean lung dose (MLD), mean heart dose (MHD), mean liver dose (MlD), and integral dose (ITD) of the body region scanned, calculated as: EDIC=0.12∗MLD+0.08∗MHD+0.15∗0.85∗MlD∗n451/2+0.45+0.35∗0.85∗nk1/2∗ITD62∗103 Where n is the fraction number. Correlations of EDIC with overall survival (OS), progression free survival (PFS), distant metastasis free survival (DMFS), and locoregional control (LRC) rates were analyzed using both univariable and multivariable Cox models. Lymphopenia during CCRT was graded according to Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Grade 4 lymphopenia resulted in inferior clinical outcomes, including OS, PFS, and DMFS. The median EDIC was 3.6 Gy (range, 0.8-6.0 Gy). Higher EDIC was strongly associated with severe lymphopenia, particularly when EDIC was above 4 Gy. Patients with EDIC > 4.0 Gy had more G4 lymphopenia than those with EDIC ≤ 4.0 Gy (67.3% vs. 40.8%; P < 0.001). On multivariate analysis, increasing EDIC was independently and inversely associated with worse OS, PFS, and DMFS. CONCLUSION: EDIC can be recommended as a useful tool to predict lymphopenia and inferior clinical outcomes, and it should be minimized below 4 Gy.
Authors: P van Hagen; M C C M Hulshof; J J B van Lanschot; E W Steyerberg; M I van Berge Henegouwen; B P L Wijnhoven; D J Richel; G A P Nieuwenhuijzen; G A P Hospers; J J Bonenkamp; M A Cuesta; R J B Blaisse; O R C Busch; F J W ten Kate; G-J Creemers; C J A Punt; J T M Plukker; H M W Verheul; E J Spillenaar Bilgen; H van Dekken; M J C van der Sangen; T Rozema; K Biermann; J C Beukema; A H M Piet; C M van Rij; J G Reinders; H W Tilanus; A van der Gaast Journal: N Engl J Med Date: 2012-05-31 Impact factor: 91.245
Authors: Michael A Postow; Margaret K Callahan; Christopher A Barker; Yoshiya Yamada; Jianda Yuan; Shigehisa Kitano; Zhenyu Mu; Teresa Rasalan; Matthew Adamow; Erika Ritter; Christine Sedrak; Achim A Jungbluth; Ramon Chua; Arvin S Yang; Ruth-Ann Roman; Samuel Rosner; Brenna Benson; James P Allison; Alexander M Lesokhin; Sacha Gnjatic; Jedd D Wolchok Journal: N Engl J Med Date: 2012-03-08 Impact factor: 91.245
Authors: Rajayogesh Davuluri; Wen Jiang; Penny Fang; Cai Xu; Ritsuko Komaki; Daniel R Gomez; James Welsh; James D Cox; Christopher H Crane; Charles C Hsu; Steven H Lin Journal: Int J Radiat Oncol Biol Phys Date: 2017-06-01 Impact factor: 7.038
Authors: Mian Xi; Cai Xu; Zhongxing Liao; Joe Y Chang; Daniel R Gomez; Melenda Jeter; James D Cox; Ritsuko Komaki; Reza Mehran; Mariela A Blum; Wayne L Hofstetter; Dipen M Maru; Manoop S Bhutani; Jeffrey H Lee; Brian Weston; Jaffer A Ajani; Steven H Lin Journal: Int J Radiat Oncol Biol Phys Date: 2017-06-27 Impact factor: 7.038
Authors: Robert T Dess; Yilun Sun; Martha M Matuszak; Grace Sun; Payal D Soni; Latifa Bazzi; Venkatesh L Murthy; Jason W D Hearn; Feng-Ming Kong; Gregory P Kalemkerian; James A Hayman; Randall K Ten Haken; Theodore S Lawrence; Matthew J Schipper; Shruti Jolly Journal: J Clin Oncol Date: 2017-03-16 Impact factor: 44.544
Authors: Scott J Antonia; Augusto Villegas; Davey Daniel; David Vicente; Shuji Murakami; Rina Hui; Takashi Yokoi; Alberto Chiappori; Ki H Lee; Maike de Wit; Byoung C Cho; Maryam Bourhaba; Xavier Quantin; Takaaki Tokito; Tarek Mekhail; David Planchard; Young-Chul Kim; Christos S Karapetis; Sandrine Hiret; Gyula Ostoros; Kaoru Kubota; Jhanelle E Gray; Luis Paz-Ares; Javier de Castro Carpeño; Catherine Wadsworth; Giovanni Melillo; Haiyi Jiang; Yifan Huang; Phillip A Dennis; Mustafa Özgüroğlu Journal: N Engl J Med Date: 2017-09-08 Impact factor: 91.245
Authors: Susannah Yovino; Lawrence Kleinberg; Stuart A Grossman; Manisha Narayanan; Eric Ford Journal: Cancer Invest Date: 2013-02 Impact factor: 2.176
Authors: Stuart A Grossman; Susannah Ellsworth; Jian Campian; Aaron T Wild; Joseph M Herman; Dan Laheru; Malcolm Brock; Ani Balmanoukian; Xiaobu Ye Journal: J Natl Compr Canc Netw Date: 2015-10 Impact factor: 11.908
Authors: Aaron T Wild; Xiaobu Ye; Susannah G Ellsworth; Jessica A Smith; Amol K Narang; Tanu Garg; Jian Campian; Daniel A Laheru; Lei Zheng; Christopher L Wolfgang; Phuoc T Tran; Stuart A Grossman; Joseph M Herman Journal: Am J Clin Oncol Date: 2015-06 Impact factor: 2.339
Authors: Hao Yu; Fang Chen; Ka-On Lam; Li Yang; Yang Wang; Jian-Yue Jin; Aya Ei Helali; Feng-Ming Spring Kong Journal: Front Immunol Date: 2022-06-21 Impact factor: 8.786
Authors: Jungwook Shin; Shu Xing; Lucas McCullum; Abdelkhalek Hammi; Jennifer Pursley; Camilo A Correa; Julia Withrow; Sean Domal; Wesley Bolch; Harald Paganetti; Clemens Grassberger Journal: Phys Med Biol Date: 2021-08-03 Impact factor: 4.174
Authors: Gyu Sang Yoo; Jeong Il Yu; Sungkoo Cho; Youngyih Han; Yoonjin Oh; Do Hoon Lim; Hee Rim Nam; Ji-Won Lee; Ki-Woong Sung; Hyung Jin Shin Journal: Cancer Res Treat Date: 2021-10-15 Impact factor: 5.036
Authors: Anirudh Yalamanchali; Hong Zhang; Ke Colin Huang; Radhe Mohan; Steven H Lin; Cong Zhu; Stuart A Grossman; Jian-Yue Jin; Susannah G Ellsworth Journal: Adv Radiat Oncol Date: 2020-08-10
Authors: Jack M Qian; Elliot Akama-Garren; Jungwook Shin; Lauren Gunasti; Andrew Bang; Luke R G Pike; Clemens Grassberger; Jonathan D Schoenfeld Journal: Adv Radiat Oncol Date: 2021-12-24
Authors: Jian-Yue Jin; Chen Hu; Ying Xiao; Hong Zhang; Rebecca Paulus; Susannah G Ellsworth; Steven E Schild; Jeffrey A Bogart; Michael Chris Dobelbower; Vivek S Kavadi; Samir Narayan; Puneeth Iyengar; Cliff Robinson; Joel S Greenberger; Christopher Koprowski; Mitchell Machtay; Walter Curran; Hak Choy; Jeffrey D Bradley; Feng-Ming Spring Kong Journal: Cancers (Basel) Date: 2021-12-08 Impact factor: 6.639