Skip to main content
Top
Published in: Strahlentherapie und Onkologie 5/2021

Open Access 01-05-2021 | NSCLC | Original Article

Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer—results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group

Authors: Dr. med. C. Ostheimer, MD, M. Mäurer, N. Ebert, D. Schmitt, D. Krug, R. Baumann, C. Henkenberens, F. A. Giordano, L. Sautter, Guerra López, D. F. Fleischmann, M. Niyazi, L. Käsmann, D. Kaul, A. H. Thieme, C. Billiet, S. Dobiasch, C. R. Arnold, M. Oertel, J. Haussmann, T. Gauer, Y. Goy, C. Suess, S. Ziegler, C. M. Panje, C. Baues, M. Trommer, T. Skripcak, D. Medenwald

Published in: Strahlentherapie und Onkologie | Issue 5/2021

Login to get access

Abstract

Background

In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT.

Methods

A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40–50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models.

Results

GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5–877) and GTV2 of 106.2 ml (95% CI: 0.5–589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12–6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9–2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0–69, 0.32–1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01–13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64–0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2.

Conclusion

Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.
Appendix
Available only for authorised users
Literature
1.
go back to reference Agrawal V, Coroller TP, Hou Y et al (2016) Radiologic-pathologic correlation of response to chemoradiation in resectable locally advanced NSCLC. Lung Cancer 102:1–8CrossRef Agrawal V, Coroller TP, Hou Y et al (2016) Radiologic-pathologic correlation of response to chemoradiation in resectable locally advanced NSCLC. Lung Cancer 102:1–8CrossRef
2.
go back to reference Martel MK, Strawderman M, Hazuka MB et al (1997) Volume and dose parameters for survival of non-small cell lung cancer patients. Radiother Oncol 44:23–29CrossRef Martel MK, Strawderman M, Hazuka MB et al (1997) Volume and dose parameters for survival of non-small cell lung cancer patients. Radiother Oncol 44:23–29CrossRef
3.
go back to reference Dubben H‑H, Thames HD, Beck-Bornholdt H‑P (1998) Tumor volume: a basic and specific response predictor in radiotherapy. Radiother Oncol 47:167–174CrossRef Dubben H‑H, Thames HD, Beck-Bornholdt H‑P (1998) Tumor volume: a basic and specific response predictor in radiotherapy. Radiother Oncol 47:167–174CrossRef
4.
go back to reference Käsmann L, Niyazi M, Blanck O, Baues C, Baumann R, Dobiasch S, Eze C, Fleischmann D, Gauer T, Giordano FA, Goy Y, Hausmann J, Henkenberens C, Kaul D, Klook L, Krug D, Mäurer M, Panje CM, Rosenbrock J, Sautter L, Schmitt D, Süß C, Thieme AH, Trommer-Nestler M, Ziegler S, Ebert N, Medenwald D, Ostheimer C, Young DEGRO Trial Group (2018) Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer: a systematic review. Strahlenther Onkol 194(2):79–90. https://doi.org/10.1007/s00066-017-1221-yCrossRefPubMed Käsmann L, Niyazi M, Blanck O, Baues C, Baumann R, Dobiasch S, Eze C, Fleischmann D, Gauer T, Giordano FA, Goy Y, Hausmann J, Henkenberens C, Kaul D, Klook L, Krug D, Mäurer M, Panje CM, Rosenbrock J, Sautter L, Schmitt D, Süß C, Thieme AH, Trommer-Nestler M, Ziegler S, Ebert N, Medenwald D, Ostheimer C, Young DEGRO Trial Group (2018) Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer: a systematic review. Strahlenther Onkol 194(2):79–90. https://​doi.​org/​10.​1007/​s00066-017-1221-yCrossRefPubMed
5.
go back to reference Bradley JD, Leumwananonthachai N, Purdy JA et al (2002) Gross tumor volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys 52:49–57CrossRef Bradley JD, Leumwananonthachai N, Purdy JA et al (2002) Gross tumor volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma. Int J Radiat Oncol Biol Phys 52:49–57CrossRef
6.
go back to reference Basaki K, Abe Y, Aoki M et al (2006) Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: impact of tumor volume. Int J Radiat Oncol Biol Phys 64:449–454CrossRef Basaki K, Abe Y, Aoki M et al (2006) Prognostic factors for survival in stage III non-small-cell lung cancer treated with definitive radiation therapy: impact of tumor volume. Int J Radiat Oncol Biol Phys 64:449–454CrossRef
7.
go back to reference Werner-Wasik M, Xiao Y, Pequignot E et al (2001) Assessment of lung cancer response after nonoperative therapy: tumor diameter, bidimensional product, and volume. A serial CT scan-based study. Int J Radiat Oncol Biol Phys 51:56–61CrossRef Werner-Wasik M, Xiao Y, Pequignot E et al (2001) Assessment of lung cancer response after nonoperative therapy: tumor diameter, bidimensional product, and volume. A serial CT scan-based study. Int J Radiat Oncol Biol Phys 51:56–61CrossRef
8.
go back to reference Werner-Wasik M, Swann RS, Bradley J et al (2008) Increasing tumor volume is predictive of poor overall and progression-free survival: secondary analysis of the Radiation Therapy Oncology Group 93–11 phase I–II radiation dose-escalation study in patients with inoperable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 70:385–390CrossRef Werner-Wasik M, Swann RS, Bradley J et al (2008) Increasing tumor volume is predictive of poor overall and progression-free survival: secondary analysis of the Radiation Therapy Oncology Group 93–11 phase I–II radiation dose-escalation study in patients with inoperable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 70:385–390CrossRef
9.
go back to reference Stinchcombe TE, Morris DE, Moore DT et al (2006) Postchemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy. Lung Cancer 52:67–74CrossRef Stinchcombe TE, Morris DE, Moore DT et al (2006) Postchemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy. Lung Cancer 52:67–74CrossRef
10.
go back to reference Dehing-Oberije C, De Ruysscher D, van der Weide H et al (2008) Tumor volume combined with number of positive lymph node stationsisa more important prognostic factor thanTNM stage for survival of non-small-cell lung cancer patients treated with (chemo) radiotherapy. Int J Radiat Oncol Biol Phys 70:1039–1044CrossRef Dehing-Oberije C, De Ruysscher D, van der Weide H et al (2008) Tumor volume combined with number of positive lymph node stationsisa more important prognostic factor thanTNM stage for survival of non-small-cell lung cancer patients treated with (chemo) radiotherapy. Int J Radiat Oncol Biol Phys 70:1039–1044CrossRef
11.
go back to reference Ball DL, Fisher RJ, Burmeister BH et al (2013) The complex relationship between lung tumor volume and survival in patients with non-small cell lung cancer treated by definitive radiotherapy: a prospective, observational prognostic factor study of the TransTasman Radiation Oncology Group (TROG 99.05). Radiother Oncol 106:305–311CrossRef Ball DL, Fisher RJ, Burmeister BH et al (2013) The complex relationship between lung tumor volume and survival in patients with non-small cell lung cancer treated by definitive radiotherapy: a prospective, observational prognostic factor study of the TransTasman Radiation Oncology Group (TROG 99.05). Radiother Oncol 106:305–311CrossRef
12.
go back to reference Etiz D, Marks LB, Zhou S‑M et al (2002) Influence of tumor volume on survival in patients irradiated for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 53:835–846CrossRef Etiz D, Marks LB, Zhou S‑M et al (2002) Influence of tumor volume on survival in patients irradiated for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 53:835–846CrossRef
13.
go back to reference Willner J, Baier K, Caragiani E et al (2002) Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 52:382–389CrossRef Willner J, Baier K, Caragiani E et al (2002) Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 52:382–389CrossRef
15.
go back to reference Kanzaki H, Kataoka M, Nishikawa A et al (2016) Impact of early tumorreduction onoutcomediffers byhistological subtype instage III non-small-cell lung cancer treated with definitive radiotherapy. Int J Clin Oncol 21:853–861CrossRef Kanzaki H, Kataoka M, Nishikawa A et al (2016) Impact of early tumorreduction onoutcomediffers byhistological subtype instage III non-small-cell lung cancer treated with definitive radiotherapy. Int J Clin Oncol 21:853–861CrossRef
16.
go back to reference Kupelian PA, Ramsey C, Meeks SL (2005) Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: observations on tumor regression during treatment. Int J Radiat Oncol Biol Phys 63(4):1024–1028CrossRef Kupelian PA, Ramsey C, Meeks SL (2005) Serial megavoltage CT imaging during external beam radiotherapy for non-small-cell lung cancer: observations on tumor regression during treatment. Int J Radiat Oncol Biol Phys 63(4):1024–1028CrossRef
17.
go back to reference Fox J, Ford E, Redmond K et al (2009) Quantification of tumor volumechangesduringradiotherapy fornon-small-cell lungcancer. Int J Radiat Oncol Biol Phys 74:341–348CrossRef Fox J, Ford E, Redmond K et al (2009) Quantification of tumor volumechangesduringradiotherapy fornon-small-cell lungcancer. Int J Radiat Oncol Biol Phys 74:341–348CrossRef
18.
go back to reference Ostheimer C, Schweyer F, Reese T et al (2016) The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer. Oncol Lett 12:3449–3456CrossRef Ostheimer C, Schweyer F, Reese T et al (2016) The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer. Oncol Lett 12:3449–3456CrossRef
19.
go back to reference Koo TR, Moon SH, Lim Y et al (2014) The effect of tumor volume and its change on survival in stage III non-small cell lung cancer treated with definitive concurrent chemoradiotherapy. Radiat Oncol 9:283CrossRef Koo TR, Moon SH, Lim Y et al (2014) The effect of tumor volume and its change on survival in stage III non-small cell lung cancer treated with definitive concurrent chemoradiotherapy. Radiat Oncol 9:283CrossRef
20.
go back to reference van Elmpt W, Öllers M, Dingemans A‑MC et al (2012) Response assessment using 18F-FDG PET early in the course of chemo-radiotherapy is correlated with survival in advanced stage non-small cell lung cancer. J Nucl Med 53:1514–1520CrossRef van Elmpt W, Öllers M, Dingemans A‑MC et al (2012) Response assessment using 18F-FDG PET early in the course of chemo-radiotherapy is correlated with survival in advanced stage non-small cell lung cancer. J Nucl Med 53:1514–1520CrossRef
Metadata
Title
Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer—results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group
Authors
Dr. med. C. Ostheimer, MD
M. Mäurer
N. Ebert
D. Schmitt
D. Krug
R. Baumann
C. Henkenberens
F. A. Giordano
L. Sautter
Guerra López
D. F. Fleischmann
M. Niyazi
L. Käsmann
D. Kaul
A. H. Thieme
C. Billiet
S. Dobiasch
C. R. Arnold
M. Oertel
J. Haussmann
T. Gauer
Y. Goy
C. Suess
S. Ziegler
C. M. Panje
C. Baues
M. Trommer
T. Skripcak
D. Medenwald
Publication date
01-05-2021
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 5/2021
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-020-01727-4

Other articles of this Issue 5/2021

Strahlentherapie und Onkologie 5/2021 Go to the issue