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Original Research

Open Access Special Issue

Precision radiotherapy by SPECT lung functional imaging in NSCLC

  • Carlo Greco1
  • Michele Fiore1,*,
  • Venanzio Valenza2
  • Cristina Di Venanzio1
  • Guido Rovera2
  • Edy Ippolito1
  • Mariella Zollino2
  • Rolando Maria D’Angelillo3
  • Alessandro Giordano2
  • Sara Ramella1

1Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy

2Nuclear Medicine Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy

3Radioterapia, Dipartimento di Biomedicina e Prevenzione, Università degli Studi di Roma Tor Vergata, 00133 Roma, Italy

DOI: 10.31083/j.jomh1804101 Vol.18,Issue 4,April 2022 pp.1-7

Submitted: 15 November 2021 Accepted: 13 January 2022

Published: 30 April 2022

(This article belongs to the Special Issue Lung Cancer: The Changing Paradigm)

*Corresponding Author(s): Michele Fiore E-mail:


Background: Single Photon Emission Computed Tomography (SPECT) could be used to avoid the non-affected perfusion areas in patients with non-small-cell lung cancer (NSCLC) and to potentially reduce lung toxicity. The aim of this study is to compare dosimetric differences between two different 3D-conformal treatment plans, with and without CT/SPECT contribution. Methods: Simulation Computed tomography (CT) scans were accurately co-registered with SPECT scans and three different areas, based on SPECT intensity perfusion, were contoured: low perfusion (LP), medium perfusion (MP) and high perfusion (HP). Two different 3D-conformal plans, with co-planar and nonco-planar fields, were generated; one without SPECT information (anatomic plan), and one using the perfusion area identified with functional imaging (functional plan). Results: 9 patients were planned and a total of 18 plans were available for analysis. Anatomical and functional plans resulted in comparable planning target volume (PTV) coverage. In the functional plans, a significant reduction of dose in high perfusion areas was reported. The reduction of HP-V20 Gy values ranged from 15% to 8% (p = 0.046), the ipsiHP-V20 Gy from 38% to 22% (p = 0.028) and ipsiHP-Dmean reduction from 16 Gy to 12 Gy (p = 0.039). No significant differences in other organs at risk (OARs) metrics were reported between anatomical and functional plans. Conclusions: Despite the few cases reported, the strength of our study lies in the reported benefit of functional lung information in 3D conformal radiation planning, without compromising target coverage or worsening dose distribution to the OARs. There is an urgent need for prospective clinical and randomized trials in order to define the role of lung functional imaging in reducing toxicity in clinical practice.


pecision medicine; functional imaging; NSCLC; radiotherapy

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Carlo Greco,Michele Fiore,Venanzio Valenza,Cristina Di Venanzio,Guido Rovera,Edy Ippolito,Mariella Zollino,Rolando Maria D’Angelillo,Alessandro Giordano,Sara Ramella. Precision radiotherapy by SPECT lung functional imaging in NSCLC. Journal of Men's Health. 2022. 18(4);1-7.


[1] Schaake-Koning C, van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, et al. Effects of Concomitant Cis-platin and Radiotherapy on Inoperable Non-Small-Cell Lung Cancer. New England Journal of Medicine. 1992; 326: 524–530.

[2] Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S. Hyper-fractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study. Journal of Clinical Oncology. 1996; 14: 1065–1070.

[3] Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, et al. Phase III Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination with Mitomycin, Vin-desine, and Cisplatin in Unresectable Stage III Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. 1999; 17: 2692–2692.

[4] Albain KS, Swann RS, Rusch VW, Turrisi AT, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or with-out surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. The Lancet. 2009; 374: 379–386.

[5] Curran WJ, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, et al. Sequential vs Concurrent Chemoradiation for Stage III Non- Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410. JNCI Journal of the National Cancer Institute. 2011; 103: 1452–1460.

[6] Bradley JD, Paulus R, Komaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consol-idation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung can-cer (RTOG 0617): a randomized, two-by-two factorial phase 3 study. The Lancet Oncology. 2015; 16: 187–199.

[7] Senan S, Brade A, Wang L, Vansteenkiste J, Dakhil S, Biesma B, et al. PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Ther-apy Followed by Consolidation Chemotherapy in Locally Ad-vanced Nonsquamous Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. 2016; 34: 953–962.

[8] Graham MV, Purdy JA, Emami B, Harms W, Bosch W, Lock-ett MA, et al. Clinical dose–volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung can-cer (NSCLC). International Journal of Radiation Oncology-Biology-Physics. 1999; 45: 323–329.

[9] Hernando ML, Marks LB, Bentel GC, Zhou S, Hollis D, Das SK, et al. Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Interna-tional Journal of Radiation Oncology-Biology-Physics. 2001; 51: 650–659.

[10] Ramella S, Trodella L, Mineo TC, Pompeo E, Stimato G, Gaudino D, et al. Adding Ipsilateral V20 and V30 to Con-ventional Dosimetric Constraints Predicts Radiation Pneumoni-tis in Stage IIIA–B NSCLC Treated with Combined-Modality Therapy. International Journal of Radiation Oncology-Biology-Physics. 2010; 76: 110–115.

[11] Chun SG, Hu C, Choy H, Komaki RU, Timmerman RD, Schild SE, et al. Impact of Intensity-Modulated Radiation Therapy Technique for Locally Advanced Non–Small-Cell Lung Cancer: a Secondary Analysis of the NRG Oncology RTOG 0617 Ran-domized Clinical Trial. Journal of Clinical Oncology. 2017; 35: 56–62.

[12] S. Ramella, M. Fiore, S. Silipigni, et al.Local control and toxi-city of adaptive radiotherapy using weekly CT imaging: results from the LARTIA trial in stage III NSCLC. Journal of Thoracic Oncology. 2017; 12:1122–1130.

[13] Bucknell NW, Hardcastle N, Bressel M, Hofman MS, Kron T, Ball D, et al. Functional lung imaging in radiation therapy for lung cancer: a systematic review and meta-analysis. Radiother-apy and Oncology. 2018; 129: 196–208.

[14] Wang K, Eblan MJ, Deal AM, Lipner M, Zagar TM, Wang Y, et al. Cardiac Toxicity after Radiotherapy for Stage III Non–Small-Cell Lung Cancer: Pooled Analysis of Dose-Escalation Trials Delivering 70 to 90 Gy. Journal of Clinical Oncology. 2017; 35: 1387–1394.

[15] McGuire SM, Zhou S, Marks LB, Dewhirst M, Yin F, Das SK. A methodology for using SPECT to reduce intensity-modulated radiation therapy (IMRT) dose to functioning lung. Interna-tional Journal of Radiation Oncology-Biology-Physics. 2006; 66: 1543–1552.

[16] Lavrenkov K, Singh S, Christian JA, Partridge M, Nioutsikou E, Cook G, et al. Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): an update of a planning study. Radiotherapy and Oncology. 2009; 91: 349–352.

[17] Lavrenkov K, Christian JA, Partridge M, Niotsikou E, Cook G, Parker M, et al. A potential to reduce pulmonary toxicity: the use of perfusion SPECT with IMRT for functional lung avoidance in radiotherapy of non-small cell lung cancer. Radiotherapy and Oncology. 2007; 83: 156–162.

[18] Dhami G, Zeng J, Vesselle HJ, Kinahan PE, Miyaoka RS, Patel SA, et al. Framework for radiation pneumonitis risk stratifica-tion based on anatomic and perfused lung dosimetry. Strahlen-therapie Und Onkologie. 2017; 193: 410–418.

[19] Peeters ST, Dooms C, Van Baardwijk A, Dingemans AC, Mart-inussen H, Vansteenkiste J, et al. Selective mediastinal node ir-radiation in non-small cell lung cancer in the IMRT/VMAT era: how to use E(B)us-NA information in addition to PET–CT for delineation? Radiotherapy and Oncology. 2016; 120: 273–278.

[20] Feuvret L, Noël G, Mazeron J, Bey P. Conformity index: a review. International Journal of Radiation Oncology-Biology-Physics. 2006; 64: 333–342.

[21] Carrie C, Ginestet C, Bey P, et al. Conformal radiation therapy. Fédération nationale des centres de lutte contre le cancer (FN-CLCC). Bull Cancer. 1995; 82: 325–330.

[22] Marks L B, Spencer D P, Bentel G C, et al. The utility of SPECT lung perfusion scans in minimizing and assessing the physio-logic consequences of thoracic irradiation. International Journal of Radiation Oncology-Biology-Physics. 1993; 26: 659–668.

[23] Seppenwoolde Y, Muller SH, Theuws JCM, Baas P, Belderbos JSA, Boersma LJ, et al. Radiation dose-effect relations and lo-cal recovery in perfusion for patients with non–small-cell lung cancer. International Journal of Radiation Oncology-Biology-Physics. 2000; 47: 681–690.

[24] Shioyama Y, Jang SY, Liu HH, Guerrero T, Wang X, Gayed IW, et al. Preserving Functional Lung Using Perfusion Imag-ing and Intensity-Modulated Radiation Therapy for Advanced-Stage Non–Small Cell Lung Cancer. International Journal of Ra-diation Oncology-Biology-Physics. 2007; 68: 1349–1358.

[25] Seppenwoolde Y, Engelsman M, De Jaeger K, Muller SH, Baas P, McShan DL, et al. Optimizing radiation treatment plans for lung cancer using lung perfusion information. Radiotherapy and Oncology. 2002; 63: 165–177.

[26] Palma D A, Senan S, Oberije C, et al. Predicting esophagitis after chemoradiation therapy for non-small cell lung cancer: an indi-vidual patient data meta-analysis. International Journal of Radi-ation Oncology- Biology- Physics. 2013; 87: 690–696.

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