Skip to main content

Advertisement

SpringerLink
Log in

Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer

A systematic review

Prädiktiver und prognostischer Wert des Tumorvolumens und seiner Veränderungen während radikaler Strahlentherapie beim nicht-kleinzelligen Bronchialkarzinom im Stadium III

Ein systematischer Review

  • Review Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

Purpose

Lung cancer remains the leading cause of cancer-related mortality worldwide. Stage III non-small cell lung cancer (NSCLC) includes heterogeneous presentation of the disease including lymph node involvement and large tumour volumes with infiltration of the mediastinum, heart or spine. In the treatment of stage III NSCLC an interdisciplinary approach including radiotherapy is considered standard of care with acceptable toxicity and improved clinical outcome concerning local control. Furthermore, gross tumour volume (GTV) changes during definitive radiotherapy would allow for adaptive replanning which offers normal tissue sparing and dose escalation.

Methods

A literature review was conducted to describe the predictive value of GTV changes during definitive radiotherapy especially focussing on overall survival. The literature search was conducted in a two-step review process using PubMed®/Medline® with the key words “stage III non-small cell lung cancer” and “radiotherapy” and “tumour volume” and “prognostic factors”.

Results

After final consideration 17, 14 and 9 studies with a total of 2516, 784 and 639 patients on predictive impact of GTV, GTV changes and its impact on overall survival, respectively, for definitive radiotherapy for stage III NSCLC were included in this review. Initial GTV is an important prognostic factor for overall survival in several studies, but the time of evaluation and the value of histology need to be further investigated. GTV changes during RT differ widely, optimal timing for re-evaluation of GTV and their predictive value for prognosis needs to be clarified. The prognostic value of GTV changes is unclear due to varying study qualities, re-evaluation time and conflicting results.

Conclusion

The main findings were that the clinical impact of GTV changes during definitive radiotherapy is still unclear due to heterogeneous study designs with varying quality. Several potential confounding variables were found and need to be considered for future studies to evaluate GTV changes during definitive radiotherapy with respect to treatment outcome.

Zusammenfassung

Zielsetzung

Das Bronchialkarzinom ist die häufigste Ursache krebsbedingter Mortalität weltweit. Das Stadium III des nicht-kleinzelligen Bronchialkarzinoms (NSCLC) präsentiert sich als heterogene Patientengruppe mit Lymphknotenbeteiligung und großen Tumoren mit Infiltration von Mediastinum, Herz und Wirbelsäule. Ein interdisziplinäres Behandlungskonzept mit Strahlentherapie ist Therapiestandard in der Behandlung des Stadium III mit akzeptabler Toxizität und verbessertem klinischen Ergebnis hinsichtlich lokaler Kontrolle. Veränderungen des Tumorvolumens (GTV) unter Strahlentherapie ermöglichen eine adaptive Bestrahlungsplanung mit Normalgewebeschonung und Dosiseskalation.

Methoden

Durchgeführt wurde eine Literaturrecherche zum prädiktiven Wert von GTV-Veränderungen unter Strahlentherapie mit dem Endpunkt „Gesamtüberleben“. Die Recherche wurde in einem zweistufigen Verfahren unter Verwendung von Medline/Pubmed mit den Stichwörtern „stage III non-small cell lung cancer“ und „radiotherapy“ und „tumour volume“ und „prognostic factors“ durchgeführt.

Ergebnisse

Nach finaler Bewertung blieben 17, 14 und 9 Studien mit 2516, 784 und 639 Patienten zum prädiktiven Einfluss von GTV, GTV-Veränderung und dessen Einfluss auf das Gesamtüberleben übrig und wurden in den Review aufgenommen. Das initiale GTV war in verschiedenen Studien ein wichtiger prognostischer Faktor für das Gesamtüberleben. Zeitpunkt der Evaluation und Einfluss der Histologie müssen jedoch weiter untersucht werden. GTV-Veränderungen unter Strahlentherapie variieren sehr. Der optimale Zeitpunkt für eine Reevaluation des GTVs für den prädiktiven Wert auf die Prognose ist unklar. Der prognostische Wert von GTV-Veränderungen ist aufgrund unterschiedlicher Studienqualität und Reevaluationszeitpunkte sowie widersprüchlicher Ergebnisse nicht eindeutig.

Schlussfolgerung

Der klinische Einfluss von GTV-Veränderungen unter definitiver Strahlentherapie bleibt aufgrund des heterogenen Studiendesigns und der variablen Studienqualität unklar. Verschiedene potenziell beeinflussende Faktoren wurden gefunden, die in weiteren Studien zur Klärung des prognostischen Werts von GTV-Veränderungen unter Strahlentherapie berücksichtigt werden sollten.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Goldstraw P, Crowley J, Chansky K et al (2007) The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2:706–714

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics 2016. CA Cancer J Clin 66:7–30

    Article  PubMed  Google Scholar 

  3. Bosmans G, van Baardwijk A, Dekker A et al (2006) Intra-patient variability of tumor volume and tumor motion during conventionally fractionated radiotherapy for locally advanced non-small-cell lung cancer: a prospective clinical study. Int J Radiat Oncol Biol Phys 66:748–753

    Article  PubMed  Google Scholar 

  4. Fox J, Ford E, Redmond K et al (2009) Quantification of tumor volume changes during radiotherapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 74:341–348

    Article  PubMed  Google Scholar 

  5. Agrawal V, Coroller TP, Hou Y et al (2016) Radiologic-pathologic correlation of response to chemoradiation in resectable locally advanced NSCLC. Lung Cancer 102:1–8

    Article  PubMed  Google Scholar 

  6. Dehing-Oberije C, Yu S, De Ruysscher D et al (2009) Development and external validation of prognostic model for 2‑year survival of non–small-cell lung cancer patients treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys 74:355–362

    Article  PubMed  Google Scholar 

  7. 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

    Article  PubMed  Google Scholar 

  8. Zehentmayr F, Wurstbauer K, Deutschmann H et al (2015) DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. Strahlenther Onkol 191:256–263

    Article  PubMed  Google Scholar 

  9. Fleckenstein J, Kremp K, Kremp S et al (2016) IMRT and 3D conformal radiotherapy with or without elective nodal irradiation in locally advanced NSCLC. Strahlenther Onkol 192:75–82

    Article  PubMed  Google Scholar 

  10. 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 Trans-Tasman Radiation Oncology Group (TROG 99.05). Radiother Oncol 106:305–311

    Article  PubMed  Google Scholar 

  11. 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 64:449–454

    Article  PubMed  Google Scholar 

  12. Bradley JD, Ieumwananonthachai 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 52:49–57

    Article  PubMed  Google Scholar 

  13. Dehing-Oberije C, De Ruysscher D, van der Weide H et al (2008) Tumor volume combined with number of positive lymph node stations is a more important prognostic factor than TNM stage for survival of non-small-cell lung cancer patients treated with (chemo) radiotherapy. Int J Radiat Oncol Biol Phys 70:1039–1044

    Article  PubMed  Google Scholar 

  14. Dubben H‑H, Thames HD, Beck-Bornholdt H‑P (1998) Tumor volume: a basic and specific response predictor in radiotherapy. Radiother Oncol 47:167–174

    Article  CAS  PubMed  Google Scholar 

  15. 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 53:835–846

    Article  PubMed  Google Scholar 

  16. Ding X, Li H, Wang Z et al (2013) A clinical study of shrinking field radiation therapy based on 18F-FDG PET/CT for stage III non-small cell lung cancer. Technol Cancer Res Treat 12:251–257

    Article  CAS  PubMed  Google Scholar 

  17. Bral S, Duchateau M, De Ridder M et al (2009) Volumetric response analysis during chemoradiation as predictive tool for optimizing treatment strategy in locally advanced unresectable NSCLC. Radiother Oncol 91:438–442

    Article  PubMed  Google Scholar 

  18. Martel MK, Strawderman M, Hazuka MB et al (1997) Volume and dose parameters for survival of non-small cell lung cancer patients. Radiother Oncol 44:23–29

    Article  CAS  PubMed  Google Scholar 

  19. 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 51:56–61

    Article  CAS  PubMed  Google Scholar 

  20. 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 52:382–389

    Article  PubMed  Google Scholar 

  21. Stinchcombe TE, Morris DE, Moore DT, al at (2006) Post-chemotherapy gross tumor volume is predictive of survival in patients with stage III non-small cell lung cancer treated with combined modality therapy. Lung Cancer 52:67–74

    Article  PubMed  Google Scholar 

  22. 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 70:385–390

    Article  PubMed  Google Scholar 

  23. Wurstbauer K, Deutschmann H, Dagn K et al (2013) DART-bid (Dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily) — a novel approach for non-resected NSCLC: final results of a prospective study, correlating radiation dose to tumor volume. Radiat Oncol 8:49

    Article  PubMed  PubMed Central  Google Scholar 

  24. Koo TR, Moon SH, Lim YJ 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 9:283

    Article  PubMed  PubMed Central  Google Scholar 

  25. Jeong J‑U, Chung W‑K, Nam T‑K et al (2014) Early metabolic response on 18 F-Fluorodeoxyglucose — positron-emission tomography/computed tomography after concurrent chemoradiotherapy for advanced stage III non-small cell lung cancer is correlated with local tumor control and survival. Anticancer Res 34:2517–2523

    PubMed  Google Scholar 

  26. Kong M, Hong SE (2016) Comparison of survival rates between 3D conformal radiotherapy and intensity-modulated radiotherapy in patients with stage iii non-small cell lung cancer. Onco Targets Ther 9:7227–7234

    Article  PubMed  PubMed Central  Google Scholar 

  27. 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

    Article  CAS  PubMed  Google Scholar 

  28. Kim YH, Ahn SJ, Kim YC, al at (2006) Predictive factors for survival and correlation to toxicity in advanced stage III non-small cell lung cancer patients with concurrent chemoradiation. Jpn J Clin Oncol 46:144–151

    Google Scholar 

  29. Alexander BM, Othus M, Caglar HB et al (2011) Tumor volume is a prognostic factor in non-small-cell lung cancer treated with chemoradiotherapy. Int J Radiat Oncol Biol Phys 79:1381–1387

    Article  PubMed  Google Scholar 

  30. Erridge SC, Seppenwoolde Y, Muller SH et al (2003) Portal imaging to assess set-up errors, tumor motion and tumor shrinkage during conformal radiotherapy of non-small cell lung cancer. Radiother Oncol 66:75–85

    Article  PubMed  Google Scholar 

  31. Siker ML, Tomé WA, Mehta MP (2006) Tumor volume changes on serial imaging with megavoltage CT for non-small-cell lung cancer during intensity-modulated radiotherapy: how reliable, consistent, and meaningful is the effect? Int J Radiat Oncol Biol Phys 66:135–141

    Article  PubMed  Google Scholar 

  32. Woodford C, Yartsev S, Dar AR et al (2007) Adaptive radiotherapy planning on decreasing gross tumor volumes as seen on megavoltage computed tomography images. Int J Radiat Oncol Biol Phys 69:1316–1322

    Article  PubMed  Google Scholar 

  33. Gillham C, Zips D, Pönisch F et al (2008) Additional PET/CT in week 5–6 of radiotherapy for patients with stage III non-small cell lung cancer as a means of dose escalation planning? Radiother Oncol 88:335–341

    Article  PubMed  Google Scholar 

  34. 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 12:3449–3456

    Article  PubMed  PubMed Central  Google Scholar 

  35. Elsayad K, Kriz J, Reinartz G et al (2016) Cone-beam CT-guided radiotherapy in the management of lung cancer. Strahlenther Onkol 192:83–91

    Article  PubMed  Google Scholar 

  36. van Elmpt W, Öllers M, Dingemans A‑MC et al (2012) Response assessment using 18 F-FDG PET early in the course of chemo-radiotherapy is correlated with survival in advanced stage non-small cell lung cancer. J Nucl Med 53:1514–1520

    Article  PubMed  PubMed Central  Google Scholar 

  37. Usmanij EA, de Geus-Oei L‑F, Troost EG et al (2013) 18 F-FDG PET early response evaluation of locally advanced non-small cell lung cancer treated with concomitant chemoradiotherapy. J Nucl Med 54:1528–1534

    Article  CAS  PubMed  Google Scholar 

  38. Vera P, Mezzani-Saillard S, Edet-Sanson A et al (2014) FDG PET during radiochemotherapy is predictive of outcome at 1 year in non-small-cell lung cancer patients: a prospective multicentre study (RTEP2). Eur J Nucl Med Mol Imaging 41:1057–1065

    Article  CAS  PubMed  Google Scholar 

  39. Huang W, Liu B, Fan M et al (2015) The early predictive value of a decrease of metabolic tumor volume in repeated 18 F-FDG PET/CT for recurrence of locally advanced non-small cell lung cancer with concurrent radiochemotherapy. Eur J Radiol 84:482–488

    Article  PubMed  Google Scholar 

  40. Dong X, Sun X, Sun L et al (2016) Early change in metabolic tumor heterogeneity during chemoradiotherapy and its prognostic value for patients with locally advanced non-small cell lung cancer. PLOS ONE 11:e157836

    Article  PubMed  PubMed Central  Google Scholar 

  41. Dehing-Oberije C, Aerts H, Yu S et al (2011) Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325). Int J Radiat Oncol Biol Phys 81:360–368

    Article  PubMed  Google Scholar 

  42. Jeremić B (2015) Standard treatment option in stage III non-small-cell lung cancer: case against trimodal therapy and consolidation drug therapy. Clin Lung Cancer 16:80–85

    Article  PubMed  Google Scholar 

  43. Eberhardt WEE, Pöttgen C, Gauler TC et al (2015) Phase III study of surgery versus definitive concurrent chemoradiotherapy boost in patients with resectable stage IIIA (N2) and selected IIIB non-small-cell lung cancer after induction chemotherapy and concurrent chemoradiotherapy (ESPATUE). J Clin Oncol 33:4194–4201

    Article  CAS  PubMed  Google Scholar 

  44. Park J, Ahn YC, Kim H et al (2003) A phase II trial of concurrent chemoradiation therapy followed by consolidation chemotherapy with oral etoposide and cisplatin for locally advanced inoperable non-small cell lung cancers. Lung Cancer 42:227–235

    Article  PubMed  Google Scholar 

  45. Oshita F, Ohe M, Honda T et al (2010) Phase II study of nedaplatin and irinotecan with concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Br J Cancer 103:1325–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The study is partly funded by the Arbeitsgemeinschaft Radioonkologie (ARO).

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Lübeck, Lübeck, Germany

    Lukas Käsmann

  2. Department of Radiation Oncology, LMU Munich, Munich, Germany

    Maximilian Niyazi, Chukwuka Eze & Daniel Fleischmann

  3. German Cancer Consortium (DKTK), partner site Munich, Munich, Germany

    Maximilian Niyazi & Daniel Fleischmann

  4. Department of Radiation Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany

    Oliver Blanck & René Baumann

  5. Department of Radiotherapy, University Hospital of Cologne, Cologne, Germany

    Christian Baues, Lisa Klook, Johannes Rosenbrock & Maike Trommer-Nestler

  6. Department of Radiation Oncology, Technische Universität München, Munich, Germany

    Sophie Dobiasch

  7. Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Tobias Gauer & Yvonne Goy

  8. Department of Radiation Oncology, University Medical Center Mannheim, Mannheim, Germany

    Frank A. Giordano & Lisa Sautter

  9. Department of Radiation Oncology, University Medical Center Düsseldorf, Düsseldorf, Germany

    Jan Hausmann

  10. Department of Radiation and Special Oncology, Hannover Medical School, Hannover, Germany

    Christoph Henkenberens

  11. Department of Radiation Oncology, Charité School of Medicine and University Hospital, Campus Virchow-Klinikum, Berlin, Germany

    David Kaul & Alexander H. Thieme

  12. Department of Radiation Oncology, University Hospital Heidelberg and National Center for Radiation Research in Oncology (NCRO) and Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany

    David Krug & Daniela Schmitt

  13. Department of Radiation Oncology, University Medical Center Jena, Jena, Germany

    Matthias Mäurer

  14. Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland

    Cédric M. Panje

  15. Department of Radiation Oncology, University Medical Center Regensburg, Regensburg, Germany

    Christoph Süß

  16. Department of Radiation Oncology, University Medical Center Erlangen, Erlangen, Germany

    Sonia Ziegler

  17. Department of Radiation Oncology, University Medical Center Dresden, Dresden, Germany

    Nadja Ebert

  18. Department of Radiation Oncology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany

    Daniel Medenwald &  Christian Ostheimer

  19. Klinik und Poliklinik für Strahlentherapie, Ernst-Grube-Straße 40, 06120, Universitätsklinikum Halle (Saale), Germany

    Christian Ostheimer

  20. German Cancer Research Center (DKFZ), Heidelberg, Germany

    Maximilian Niyazi & Daniel Fleischmann

  21. OncoRay—National Center for Radiation Research in Oncology, Dresden, Germany

    Nadja Ebert

Authors
  1. Lukas Käsmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maximilian Niyazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oliver Blanck
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Christian Baues
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. René Baumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sophie Dobiasch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chukwuka Eze
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daniel Fleischmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tobias Gauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Frank A. Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yvonne Goy
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jan Hausmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Christoph Henkenberens
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. David Kaul
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Lisa Klook
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. David Krug
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Matthias Mäurer
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Cédric M. Panje
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Johannes Rosenbrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Lisa Sautter
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Daniela Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Christoph Süß
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Alexander H. Thieme
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Maike Trommer-Nestler
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Sonia Ziegler
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Nadja Ebert
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Daniel Medenwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Christian Ostheimer
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Young DEGRO Trial Group

Corresponding author

Correspondence to Christian Ostheimer.

Ethics declarations

Conflict of interest

L. Käsmann, M. Niyazi, O. Blanck, C. Baues, R. Baumann, S. Dobiasch, C. Eze, D. Fleischmann, T. Gauer, F.A. Giordano, Y. Goy, J. Hausmann, C. Henkenberens, D. Kaul, L. Klook, D. Krug, M. Mäurer, C.M. Panje, J. Rosenbrock, L. Sautter, D. Schmitt, C. Süß, A.H. Thieme, M. Trommer-Nestler, S. Ziegler, N. Ebert, D. Medenwald and C. Ostheimer; YoungDEGROTrialGroup declare that they have no competing interests.

Additional information

D. Medenwald and C. Ostheimer shared corresponding/senior authorship.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Käsmann, L., Niyazi, M., Blanck, O. et al. Predictive and prognostic value of tumor volume and its changes during radical radiotherapy of stage III non-small cell lung cancer. Strahlenther Onkol 194, 79–90 (2018). https://doi.org/10.1007/s00066-017-1221-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-017-1221-y

Keywords

Schlüsselwörter

Search

Navigation