Strahlentherapie und Onkologie

, Volume 194, Issue 2, pp 107–115 | Cite as

Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

  • Olarn Roengvoraphoj
  • Cherylina Wijaya
  • Chukwuka Eze
  • Minglun Li
  • Maurice Dantes
  • Julian Taugner
  • Amanda Tufman
  • Rudolf Maria Huber
  • Claus Belka
  • Farkhad Manapov
Original Article
  • 134 Downloads

Abstract

Purpose

Positron emission tomography with 2‑deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG-PET/CT) has an established role in the initial diagnosis and staging of lung cancer. However, a prognostic value of PET/CT during multimodality treatment has not yet been fully clarified. This study evaluated the role of primary tumor metabolic volume (PT-MV) changes on PET/CT before, during, and after chemoradiotherapy (CRT).

Methods

A total of 65 patients with non-small-cell lung cancer (NSCLC) UICC stage IIIA/B (TNM 7th Edition) were treated with definitive chemoradiotherapy (sequential or concurrent setting). PET/CT was acquired before the start, at the end of the third week, and 6 weeks following CRT.

Results

Median overall survival (OS) for the entire cohort was 16 months (95% confidence interval [CI]: 12–20). In all, 60 (92.3%) patients were eligible for pre-treatment (pre-PT-MV), 28 (43%) for mid-treatment (mid-PT-MV), and 53 (81.5%) for post-treatment (post-PT-MV) volume analysis. Patients with pre-PT-MV >63 cm3 had worse OS (p < 0.0001). A reduction from mid-PT-MV to post-PT-MV of >15% improved OS (p = 0.001). In addition, patients with post-PT-MV > 25 cm3 had significantly worse outcome (p = 0.001). On multivariate analysis, performance status (p = 0.002, hazard ratio [HR] 0.007; 95% CI 0.00–0.158), pre-PT-MV1 < 63 cm3 (p = 0.027, HR 3.98; 95% CI 1.17–13.49), post-PT-MV < 25 cm3 (p = 0.013, HR 11.90; 95% CI 1.70–83.27), and a reduction from mid-PT-MV to post-PT-MV > 15% (p = 0.004, HR 0.25; 95% CI 0.02–0.31) correlated with improved OS.

Conclusions

Our results demonstrated that pre- and post-treatment PT-MV, as well as an at least 15% reduction in mid- to post-PT-MV, significantly correlates with OS in patients with inoperable locally advanced NSCLC.

Keywords

Chemoradiotherapy Positron emission tomography/computed tomography Metabolic volume NSCLC Survival 

Analyse des metabolischen Primärtumorvolumens im Verlauf der Radiochemotherapie bei lokal fortgeschrittenem nichtkleinzelligem Lungenkarzinom

Zusammenfassung

Zielsetzung

Die kombinierte Positronenemissionstomographie (PET) mit 18F-2-Fluor-2-desoxy-D-Glukose und Computertomographie (18F-FDG-PET/CT) hat sich in der initialen Diagnostik und im Staging des Lungenkarzinoms bewährt. Jedoch wurde der prognostische Wert der PET/CT-Untersuchung während der multimodalen Therapie noch nicht vollständig aufgeklärt. In dieser Studie wurde die Rolle der Änderung des metabolischen Primärtumorvolumens („primary tumor metabolic volume“ [PT-MV]) in der PET/CT vor, während und nach der definitiven Radiochemotherapie untersucht.

Methoden

Insgesamt 65 Patienten mit nichtkleinzelligem Lungenkarzinom (NSCLC) des UICC-Stadiums IIIA/B (TNM, 7. Version) wurden mit definitiver Radiochemotherapie behandelt (sequenziell oder gleichzeitig). Eine PET/CT wurde vor dem Start, am Ende der dritten Behandlungswoche und 6 Wochen nach dem Abschluss der Radiochemotherapie durchgeführt.

Ergebnisse

Das mediane Gesamtüberleben der Kohorte betrug 16 Monate (95 %-Konfidenzintervall [KI]: 12–20 Monate). Insgesamt 60 (92,3 %) Patienten waren in die Volumenanalyse vor der Behandlung („pre-PT-MV“), 28 (43 %) in die Volumenanalyse während der Behandlung („mid-PT-MV“) und 53 (81,5 %) in die Volumenanalyse nach abgeschlossener Behandlung („post-PT-MV“) eingeschlossen. Patienten mit „pre-PT-MV“ > 63 cm3 hatten ein signifikant schlechteres Gesamtüberleben (p < 0,0001). Eine Reduktion von „mid-PT-MV“ zu „post-PT-MV“ um >15 % verbesserte das Gesamtüberleben signifikant (p = 0,001). Außerdem zeigten Patienten mit einem „post-PT-MV“ > 25 cm3 eine signifikant schlechtere Überlebensrate (p = 0,001). In der multivariaten Analyse korrelierten der Performance-Status (p = 0,002, Hazard Ratio [HR] 0,007; 95 %-KI 0,00–0,158), ein „pre-PT-MV“ < 63 cm3 (p = 0,027, HR 3,98; 95 %-KI 1,17–13,49), ein „post-PT-MV“ < 25 cm3 (p = 0,013, HR 11,90; 95 %-KI 1,70–83,27) und eine Abnahme von „mid-PT-MV“ zu „post-PT-MV“ um >15 % (p = 0,004, HR 0,25; 95 %-KI 0,02–0,31) signifikant mit einem verbesserten Gesamtüberleben.

Schlussfolgerung

Unsere Ergebnisse zeigen, dass die pre-PT-MV- und post-PT-MV-Werte sowie eine Abnahme des PT-MV zwischen der dritten Behandlungswoche und 6 Wochen nach der Radiochemotherapie um mindestens 15 % signifikant mit dem Gesamtüberleben von Patienten mit inoperablem, lokal fortgeschrittenem NSCLC korrelieren.

Schlüsselwörter

Radiochemotherapie Positronenemissionstomographie/Computertomographie Metabolisches Volumen Nichtkleinzelliges Lungenkarzinom Überleben 

Notes

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.

Conflict of interest

O. Roengvoraphoj, C. Wijaya, C. Eze, M. Li, M. Dantes, J. Taugner, A. Tufman, R.M. Huber, C. Belka, and F. Manapov declare that they have no competing interests.

References

  1. 1.
    Oser MG, Niederst MJ, Sequist LV, Engelman JA (2015) Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol 16:e165–e172.  https://doi.org/10.1016/S1470-2045(14)71180-5 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Crino L, Weder W, van Meerbeeck J, Felip E (2010) Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v103–v115.  https://doi.org/10.1093/annonc/mdq207 CrossRefPubMedGoogle Scholar
  3. 3.
    Le Chevalier T, Arriagada R, Quoix E et al (1991) Radiotherapy alone versus combined chemotherapy and radiotherapy in nonresectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst 83:417–423CrossRefPubMedGoogle Scholar
  4. 4.
    Flentje M, Huber RM, Engel-Riedel W et al (2016) GILT-A randomised phase III study of oral vinorelbine and cisplatin with concomitant radiotherapy followed by either consolidation therapy with oral vinorelbine and cisplatin or best supportive care alone in stage III non-small cell lung cancer. Strahlenther Onkol 192:216–222.  https://doi.org/10.1007/s00066-016-0941-8 CrossRefPubMedGoogle Scholar
  5. 5.
    Bradley JD, Paulus R, Komaki R et al (2015) Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial. Lancet Oncol 16:187–199.  https://doi.org/10.1016/S1470-2045(14)71207-0 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Delbeke D, Coleman RE, Guiberteau MJ et al (2006) Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med 47:885–895PubMedGoogle Scholar
  7. 7.
    Nappi A, Gallicchio R, Simeon V et al (2015) [F-18] FDG-PET/CT parameters as predictors of outcome in inoperable NSCLC patients. Radiol Oncol 49:320–326.  https://doi.org/10.1515/raon-2015-0043 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Pottgen C, Gauler T, Bellendorf A et al (2016) Standardized uptake decrease on [18F]-Fluorodeoxyglucose positron emission tomography after neoadjuvant chemotherapy is a prognostic classifier for long-term outcome after multimodality treatment: secondary analysis of a randomized trial for resectable st. J Clin Oncol 34:2526–2533.  https://doi.org/10.1200/JCO.2015.65.5167 CrossRefPubMedGoogle Scholar
  9. 9.
    Machtay M, Duan F, Siegel BA et al (2013) Prediction of survival by [18F]fluorodeoxyglucose positron emission tomography in patients with locally advanced non-small-cell lung cancer undergoing definitive chemoradiation therapy: results of the ACRIN 6668/RTOG 0235 trial. J Clin Oncol 31:3823–3830.  https://doi.org/10.1200/JCO.2012.47.5947 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Usmanij EA, de Geus-Oei L‑F, Troost EGC et al (2013) 18F-FDG PET early response evaluation of locally advanced non-small cell lung cancer treated with concomitant chemoradiotherapy. J Nucl Med 54:1528–1534.  https://doi.org/10.2967/jnumed.112.116921 CrossRefPubMedGoogle Scholar
  11. 11.
    van Elmpt W, Ollers M, Dingemans A‑MC et al (2012) Response assessment using 18F-FDG PET early in the course of radiotherapy correlates with survival in advanced-stage non-small cell lung cancer. J Nucl Med 53:1514–1520.  https://doi.org/10.2967/jnumed.111.102566 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Su X‑D, Xie H‑J, Liu Q‑W et al (2017) The prognostic impact of tumor volume on stage I non-small cell lung cancer. Lung Cancer 104:91–97.  https://doi.org/10.1016/j.lungcan.2016.12.013 CrossRefPubMedGoogle Scholar
  13. 13.
    Bazan JG, Duan F, Snyder BS et al (2017) Metabolic tumor volume predicts overall survival and local control in patients with stage III non-small cell lung cancer treated in ACRIN 6668/RTOG 0235. Eur J Nucl Med Mol Imaging:17–24.  https://doi.org/10.1007/s00259-016-3520-4 PubMedGoogle Scholar
  14. 14.
    Park S, Kim HJ, Choi C‑M et al (2016) Predictive factors for a long-term response duration in non-squamous cell lung cancer patients treated with pemetrexed. BMC Cancer 16:417.  https://doi.org/10.1186/s12885-016-2457-0 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Chung MK, Jeong H‑S, Park SG et al (2009) Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer. Clin Cancer Res 15:5861–5868.  https://doi.org/10.1158/1078-0432.CCR-08-3290 CrossRefPubMedGoogle Scholar
  16. 16.
    Kanzaki H, Kataoka M, Nishikawa A et al (2016) Impact of early tumor reduction on outcome differs by histological subtype in stage III non-small-cell lung cancer treated with definitive radiotherapy. Int J Clin Oncol 21:853–861.  https://doi.org/10.1007/s10147-016-0982-0 CrossRefPubMedGoogle Scholar
  17. 17.
    Halvorsen TO, Herje M, Levin N et al (2016) Tumour size reduction after the first chemotherapy-course and outcomes of chemoradiotherapy in limited disease small-cell lung cancer. Lung Cancer 102:9–14.  https://doi.org/10.1016/j.lungcan.2016.10.003 CrossRefPubMedGoogle Scholar
  18. 18.
    Jabbour SK, Kim S, Haider SA et al (2015) Reduction in tumor volume by cone beam computed tomography predicts overall survival in non-small cell lung cancer treated with chemoradiation therapy. Int J Radiat Oncol Biol Phys 92:627–633.  https://doi.org/10.1016/j.ijrobp.2015.02.017 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    van Timmeren JE, Leijenaar RTH, van Elmpt W et al (2017) Survival prediction of non-small cell lung cancer patients using radiomics analyses of cone-beam CT images. Radiother Oncol 123:363–369.  https://doi.org/10.1016/j.radonc.2017.04.016 CrossRefPubMedGoogle Scholar
  20. 20.
    Huber RM, Borgmeier A, Flentje M et al (2010) Concurrent chemoradiation therapy with docetaxel/cisplatin followed by docetaxel consolidation therapy in inoperable stage IIIA/B non-small-cell lung cancer: results of a phase I study. Clin Lung Cancer 11:45–50.  https://doi.org/10.3816/CLC.2010.n.007 CrossRefPubMedGoogle Scholar
  21. 21.
    Huber RM, Flentje M, Schmidt M et al (2006) Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage IIIA or IIIB non-small-cell lung cancer: study CTRT99/97 by the Bronchial Carcinoma Therapy Group. J Clin Oncol 24:4397–4404.  https://doi.org/10.1200/JCO.2005.05.4163 CrossRefPubMedGoogle Scholar
  22. 22.
    Huang W, Zhou T, Ma L et al (2011) Standard uptake value and metabolic tumor volume of (1)(8)F-FDG PET/CT predict short-term outcome early in the course of chemoradiotherapy in advanced non-small cell lung cancer. Eur J Nucl Med Mol Imaging 38:1628–1635.  https://doi.org/10.1007/s00259-011-1838-5 CrossRefPubMedGoogle Scholar
  23. 23.
    Nagamachi S (2014) The problem of metabolic tumor volume in FDG/PET for evaluating cancers – determination of threshold and use of Methionine-PET. J Radiol Radiat Ther 2(2):1029Google Scholar
  24. 24.
    Ohri N, Piperdi B, Garg MK et al (2015) Pre-treatment FDG-PET predicts the site of in-field progression following concurrent chemoradiotherapy for stage III non-small cell lung cancer. Lung Cancer 87:23–27.  https://doi.org/10.1016/j.lungcan.2014.10.016 CrossRefPubMedGoogle Scholar
  25. 25.
    Ohri N, Duan F, Snyder BS et al (2016) Pretreatment 18F-FDG PET textural features in locally advanced non-small cell lung cancer: secondary analysis of ACRIN 6668/RTOG 0235. J Nucl Med 57:842–848.  https://doi.org/10.2967/jnumed.115.166934 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ohri N, Bodner WR, Halmos B et al (2017) 18F-Fluorodeoxyglucose/positron emission tomography predicts patterns of failure after definitive chemoradiation therapy for locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys 97:372–380.  https://doi.org/10.1016/j.ijrobp.2016.10.031 CrossRefPubMedGoogle Scholar
  27. 27.
    Markovina S, Duan F, Snyder BS et al (2015) Regional lymph node uptake of [(18)F]Fluorodeoxyglucose after definitive chemoradiation therapy predicts local-regional failure of locally advanced non-small cell lung cancer: results of ACRIN 6668/RTOG 0235. Int J Radiat Oncol Biol Phys 93:597–605.  https://doi.org/10.1016/j.ijrobp.2015.04.026 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Manapov F, Eze C (2017) Survival advantage for etoposide/cisplatin over paclitaxel/carboplatin concurrent chemoradiation in patients with inoperable stage III NSCLC: a subgroup analysis for ECOG 2 patients would be of great interest. Ann Oncol 28(9):2319–2320.  https://doi.org/10.1093/annonc/mdx254 CrossRefPubMedGoogle Scholar
  29. 29.
    Liang J, Bi N, Wu S et al (2017) Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol 28:777–783.  https://doi.org/10.1093/annonc/mdx009 PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland 2017

Authors and Affiliations

  • Olarn Roengvoraphoj
    • 1
  • Cherylina Wijaya
    • 2
  • Chukwuka Eze
    • 1
  • Minglun Li
    • 1
  • Maurice Dantes
    • 1
  • Julian Taugner
    • 1
  • Amanda Tufman
    • 3
    • 4
  • Rudolf Maria Huber
    • 3
    • 4
  • Claus Belka
    • 1
    • 4
  • Farkhad Manapov
    • 1
    • 4
  1. 1.Department of Radiation Oncology, University HospitalLMU MunichMunichGermany
  2. 2.Department of PulmonologyAsklepios Fachkliniken München-GautingMunichGermany
  3. 3.Respiratory Medicine and Thoracic Oncology, Internal Medicine VLudwig-Maximilians-University of Munich and Thoracic Oncology Centre MunichMunichGermany
  4. 4.members of the German Centre for Lung Research (DZL CPC-M)-Germany

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