Ra-SBRT is Potential Immune Adjuvant for Innate Immune Cell Populations in Advance Stage NSCLC Patients


  • Arun Chairmadurai Jaypee Hospital, Sector -128, NOIDA, UP, India
  • Harish Chandra Goel Amity Centre for Radiation Biology, Amity University, Uttar Pradesh, Sector -125, NOIDA, India
  • Sandeep Jain Department of Radiotherapy, The Brunei Cancer Centre, Pantai Jerudong Specialist centre, Brunei
  • Aklank Jain Department of Zoology, Central University of Punjab, Bhatinda, Punjab, India
  • Hridayesh Prakash Amity Institute of Virology and Immunology, Amity University, Uttar Pradesh, Sector -125, NOIDA, India




SBRT, lung cancer, iNOS macrophage, Eosinophils, Innate Immunity.


Bystander toxicity and tissue fibrosis are the major complications with conventional radiation therapy for cancer patients. In this context, we here propose RapidArc - Stereotactic Body Radiation Therapy (Ra-SBRT) as a non-invasive and immune adjuvant approach for the successful eradication of advance stage NSCLC. Ra-SBRT is highly focused and capable of destroying tumors with high grade metastatic lesions and spared normal tissues. Follow up of stage 4th NSCLC patient revealed that Ra-SBRT is potentially immunogenic which was evident by increased number of iNOS+ Tumor Associated macrophages (M1-TAM), Siglac-8+ eosinophils, basophils and subsequent prolongation of disease free survival of 4th stage NSCLC patients by 3 years. This study demonstrated M1 retuning potential of Ra-SBRT which is a pre-requisite of effective management of inoperable and highly metastatic tumors of lung with least or no bystander impact.


Tubin S, Popper HH, Brcic L. Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects. Radiat Oncol 2019; 14: 21. https://doi.org/10.1186/s13014-019-1227-y DOI: https://doi.org/10.1186/s13014-019-1227-y

Marin A, Martin M, Linan O, Alvarenga F, Lopez M, Fernandez L, Buchser D, Cerezo L. Bystander effects and radiotherapy. Rep Pract Oncol Radiother 2015; 20: 12-21. https://doi.org/10.1016/j.rpor.2014.08.004 DOI: https://doi.org/10.1016/j.rpor.2014.08.004

Sroussi HY, Epstein JB, Bensadoun RJ, Saunders DP, Lalla RV, Migliorati CA, Heaivilin N, Zumsteg ZS. Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med 2017; 6: 2918-2931. https://doi.org/10.1002/cam4.1221 DOI: https://doi.org/10.1002/cam4.1221

Avraham T, Yan A, Zampell JC, Daluvoy SV, Haimovitz-Friedman A, Cordeiro AP, Mehrara BJ. Radiation therapy causes loss of dermal lymphatic vessels and interferes with lymphatic function by TGF-beta1-mediated tissue fibrosis. Am J Physiol Cell Physiol 2010; 299: C589-C605. https://doi.org/10.1152/ajpcell.00535.2009 DOI: https://doi.org/10.1152/ajpcell.00535.2009

Gunn GB, Anderson KE, Patel AJ, Gallegos J, Hallberg CK, Sood G, Hatch SS, Sanguineti G. Severe radiation therapy-related soft tissue toxicity in a patient with porphyria cutanea tarda: a literature review. Head Neck 2010; 32: 1112-1117. https://doi.org/10.1002/hed.21161 DOI: https://doi.org/10.1002/hed.21161

Kumar S, Kolozsvary A, Kohl R, Lu M, Brown S, Kim JH. Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis. Radiat Oncol 2008; 3: 40. https://doi.org/10.1186/1748-717X-3-40 DOI: https://doi.org/10.1186/1748-717X-3-40

Baumann R, Chan MKH, Pyschny F, Stera S, Malzkuhn B, Wurster S, Huttenlocher S, Szucs M, Imhoff D, Keller C, Balermpas P, Rades D, Rodel C, Dunst J, Hildebrandt G, Blanck O. Clinical Results of Mean GTV Dose Optimized Robotic-Guided Stereotactic Body Radiation Therapy for Lung Tumors. Front Oncol 2018; 8: 171. https://doi.org/10.3389/fonc.2018.00171 DOI: https://doi.org/10.3389/fonc.2018.00171

Guckenberger M. Dose and Fractionation in Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer: Lessons Learned and Where Do We Go Next? Int J Radiat Oncol Biol Phys 2015; 93: 765-768. https://doi.org/10.1016/j.ijrobp.2015.08.025 DOI: https://doi.org/10.1016/j.ijrobp.2015.08.025

Xia T, Li H, Sun Q, Wang Y, Fan N, Yu Y, Li P, Chang JY. Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2006; 66: 117-125. https://doi.org/10.1016/j.ijrobp.2006.04.013 DOI: https://doi.org/10.1016/j.ijrobp.2006.04.013

Timmerman R, Heinzerling J, Abdulrahman R, Choy H, Meyer JL. Stereotactic body radiation therapy for thoracic cancers: recommendations for patient selection, setup and therapy. Front Radiat Ther Oncol 2011; 43: 395-411. https://doi.org/10.1159/000322503 DOI: https://doi.org/10.1159/000322503

Lagerwaard FJ, Haasbeek CJ, Smit EF, Slotman BJ, Senan S. Outcomes of risk-adapted fractionated stereotactic radiotherapy for stage I non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2008; 70: 685-692. https://doi.org/10.1016/j.ijrobp.2007.10.053 DOI: https://doi.org/10.1016/j.ijrobp.2007.10.053

Solda F, Lodge M, Ashley S, Whitington A, Goldstraw P, Brada M. Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; systematic review and comparison with a surgical cohort. Radiother Oncol 2013; 109: 1-7. https://doi.org/10.1016/j.radonc.2013.09.006 DOI: https://doi.org/10.1016/j.radonc.2013.09.006

Zheng X, Schipper M, Kidwell K, Lin J, Reddy R, Ren Y, Chang A, Lv F, Orringer M, Spring Kong FM. Survival outcome after stereotactic body radiation therapy and surgery for stage I non-small cell lung cancer: a meta-analysis. Int J Radiat Oncol Biol Phys 2014; 90: 603-611. https://doi.org/10.1016/j.ijrobp.2014.05.055 DOI: https://doi.org/10.1016/j.ijrobp.2014.05.055

Zhang B, Zhu F, Ma X, Tian Y, Cao D, Luo S, Xuan Y, Liu L, Wei Y. Matched-pair comparisons of stereotactic body radiotherapy (SBRT) versus surgery for the treatment of early stage non-small cell lung cancer: a systematic review and meta-analysis. Radiother Oncol 2014; 112: 250-255. https://doi.org/10.1016/j.radonc.2014.08.031 DOI: https://doi.org/10.1016/j.radonc.2014.08.031

Chairmadurai A, Goel HC, Jain SK, Kumar P. Radiobiological analysis of stereotactic body radiation therapy for an evidence-based planning target volume of the lung using multiphase CT images obtained with a pneumatic abdominal compression apparatus: a case study. Radiol Phys Technol 2017; 10: 525-534. https://doi.org/10.1007/s12194-017-0431-4 DOI: https://doi.org/10.1007/s12194-017-0431-4

Ruggieri R, Stavrev P, Naccarato S, Stavreva N, Alongi F, Nahum AE. Optimal dose and fraction number in SBRT of lung tumours: A radiobiological analysis. Phys Med 2017; 44: 188-195. https://doi.org/10.1016/j.ejmp.2016.12.012 DOI: https://doi.org/10.1016/j.ejmp.2016.12.012

Kim MS, Kim W, Park IH, Kim HJ, Lee E, Jung JH, Cho LC, Song CW. Radiobiological mechanisms of stereotactic body radiation therapy and stereotactic radiation surgery. Radiat Oncol J 2015; 33: 265-275. https://doi.org/10.3857/roj.2015.33.4.265 DOI: https://doi.org/10.3857/roj.2015.33.4.265

Kutcher GJ, Burman C. Calculation of complication probability factors for non-uniform normal tissue irradiation: the effective volume method. Int J Radiat Oncol Biol Phys 1989; 16: 1623-1630. https://doi.org/10.1016/0360-3016(89)90972-3 DOI: https://doi.org/10.1016/0360-3016(89)90972-3

Kutcher GJ, Burman C, Brewster L, Goitein M, Mohan R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int J Radiat Oncol Biol Phys 1991; 21: 137-146. https://doi.org/10.1016/0360-3016(91)90173-2 DOI: https://doi.org/10.1016/0360-3016(91)90173-2

Seppenwoolde Y, Lebesque JV, De JK, Belderbos JS, Boersma LJ, Schilstra C, Henning GT, Hayman JA, Martel MK, Ten Haken RK. Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability. Int J Radiat Oncol Biol Phys 2003; 55: 724-735. https://doi.org/10.1016/S0360-3016(02)03986-X DOI: https://doi.org/10.1016/S0360-3016(02)03986-X

Chapet O, Kong FM, Lee JS, Hayman JA, Ten Haken RK. Normal tissue complication probability modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer. Radiother Oncol 2005; 77: 176-181. https://doi.org/10.1016/j.radonc.2005.10.001 DOI: https://doi.org/10.1016/j.radonc.2005.10.001

Yang Y, Catalano S, Kelsey CR, Yoo DS, Yin FF, Cai J. Dosimetric effects of rotational offsets in stereotactic body radiation therapy (SBRT) for lung cancer. Med Dosim 2014; 39: 117-121. https://doi.org/10.1016/j.meddos.2013.11.002 DOI: https://doi.org/10.1016/j.meddos.2013.11.002

Cozzi L, Dinshaw KA, Shrivastava SK, Mahantshetty U, Engineer R, Deshpande DD, Jamema SV, Vanetti E, Clivio A, Nicolini G, Fogliata A. A treatment planning study comparing volumetric arc modulation with RapidArc and fixed field IMRT for cervix uteri radiotherapy. Radiother Oncol 2008; 89: 180-191. https://doi.org/10.1016/j.radonc.2008.06.013 DOI: https://doi.org/10.1016/j.radonc.2008.06.013

Zhai DY, Yin Y, Gong GZ, Liu TH, Chen JH, Ma CS, Lu J. RapidArc radiotherapy for whole pelvic lymph node in cervical cancer with 6 and 15 MV: a treatment planning comparison with fixed field IMRT. J Radiat Res 2013; 54: 166-173. https://doi.org/10.1093/jrr/rrs066 DOI: https://doi.org/10.1093/jrr/rrs066

Qiao L, Cheng J, Liang N, Xie J, Luo H, Zhang J. A comparative dosimetric study of volumetric-modulated arc therapy vs. fixed field intensity-modulated radiotherapy in postoperative irradiation of stage IB-IIA high-risk cervical cancer. Oncol Lett 2016; 11: 959-964. https://doi.org/10.3892/ol.2015.3998 DOI: https://doi.org/10.3892/ol.2015.3998

Ling CC, Gerweck LE, Zaider M, Yorke E. Dose-rate effects in external beam radiotherapy redux. Radiother Oncol 2010; 95: 261-268. https://doi.org/10.1016/j.radonc.2010.03.014 DOI: https://doi.org/10.1016/j.radonc.2010.03.014

Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, Klapproth K, Schakel K, Garbi N, Jager D, Weitz J, Schmitz-Winnenthal H, Hammerling GJ, Beckhove P. Low-dose irradiation programs macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 2013; 24: 589-602. https://doi.org/10.1016/j.ccr.2013.09.014 DOI: https://doi.org/10.1016/j.ccr.2013.09.014

Prakash H, Klug F, Nadella V, Mazumdar V, Schmitz-Winnenthal H, Umansky L. Low doses of gamma irradiation potentially modifies immunosuppressive tumor microenvironment by retuning tumor-associated macrophages: lesson from insulinoma. Carcinogenesis 2016; 37: 301-313. https://doi.org/10.1093/carcin/bgw007 DOI: https://doi.org/10.1093/carcin/bgw007

Carretero R, Sektioglu IM, Garbi N, Salgado OC, Beckhove P, Hammerling GJ. Corrigendum: Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol 2016; 17: 214. https://doi.org/10.1038/ni0216-214b DOI: https://doi.org/10.1038/ni0216-214b

Arpaci F, Dogru T, Ozturk B, Komurcu S, Ozet A, Yilmaz MI, Beyzadeoglu M, Turan M, Sengul A, Yalcin A. Changes in immunological recovery in patients who received post-transplant G-CSF or GM-CSF after autologous peripheral blood stem cell transplantation (PBSCT). Haematologia (Budap) 2002; 32: 253-264. https://doi.org/10.1163/15685590260461066 DOI: https://doi.org/10.1163/15685590260461066

de Gast GC, Vyth-Dreese FA, Nooijen W, van den Bogaard CJ, Sein J, Holtkamp MM, Linthorst GA, Baars JW, Schornagel JH, Rodenhuis S. Reinfusion of autologous lymphocytes with granulocyte-macrophage colony-stimulating factor induces rapid recovery of CD4+ and CD8+ T cells after high-dose chemotherapy for metastatic breast cancer. J Clin Oncol 2002; 20: 58-64. https://doi.org/10.1200/JCO.20.1.58 DOI: https://doi.org/10.1200/JCO.2002.20.1.58

Lachmann G, von HC, Kurth J, Yuerek F, Spies C. Innate immunity recovers earlier than acquired immunity during severe postoperative immunosuppression. Int J Med Sci 2018; 15: 1-9. https://doi.org/10.7150/ijms.21433 DOI: https://doi.org/10.7150/ijms.21433




How to Cite

Arun Chairmadurai, Harish Chandra Goel, Sandeep Jain, Aklank Jain, & Hridayesh Prakash. (2019). Ra-SBRT is Potential Immune Adjuvant for Innate Immune Cell Populations in Advance Stage NSCLC Patients . Journal of Analytical Oncology, 8, 71–76. https://doi.org/10.30683/1927-7229.2019.08.10