Advertisement

Strahlentherapie und Onkologie

, Volume 191, Issue 3, pp 256–263 | Cite as

DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily

High local control in early stage (I/II) non-small-cell lung cancer
  • Franz Zehentmayr
  • Karl Wurstbauer
  • Heinz Deutschmann
  • Christoph Fussl
  • Peter Kopp
  • Karin Dagn
  • Gerd Fastner
  • Peter Porsch
  • Michael Studnicka
  • Felix Sedlmayer
Original article

Abstract

Background

While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid).

Patients and methods

Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for <  2.5 cm, 79.2 Gy for 2.5–4.5 cm, 84.6 Gy for 4.5–6 cm, 90 Gy for > 6 cm.

Results

The median follow-up was 28.5 months (range 2–108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤  grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis.

Conclusion

DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts.

Keywords

Carcinoma, non-small-cell lung NSCLC Radiation dose fractionation Toxicity Treatment outcome 

DART-bid: dosisdifferenzierte akzelerierte Radiotherapie, 2 × 1,8 Gy täglich

Hohe lokale Kontrolle bei nichtkleinzelligem Bronchialkarzinom im Frühstadium (I/II)

Zusammenfassung

Hintergrund

Die Standardbehandlung für nichtkleinzellige Bronchialkarzinome (NSCLC) im Stadium I/II ist die Operation, wobei Radiotherapie für Patienten, die nicht operabel sind oder die Operation ablehnen, als Alternative akzeptiert ist. Internationale Leitlinien empfehlen verschiedene Therapieoptionen, darunter Körperstereotaxie für kleine Tumoren, konventionelle Radiotherapie ≥ 60 Gy für größere insbesondere zentral gelegene Tumoren oder eine Behandlung nach dem CHART("continuous hyperfractionated accelerated radiotherapy")-Regime. Diese Studie zeigt klinische Ergebnisse und Toxizität nach akzelerierter Radiotherapie mit 2 × 1,8 Gy täglich (DART-bid).

Patienten und Methoden

Von 04/2002 bis 12/2010 wurden 54 Patienten (medianes Alter 71 Jahre, medianer Karnofsky-Index 70 %) mit NSCLC im Frühstadium behandelt. Die Gesamtdosis wurde nach Tumordurchmesser verordnet: 73,8 Gy (< 2,5 cm), 79,2 Gy (2,5–4 cm), 84,6 Gy (4,5–6 cm), 90 Gy (> 6 cm).

Ergebnisse

Die mediane Nachsorgedauer aller Patienten betrug 28,5 Monate (2–108), die aktuarische Lokalkontrolle (LC) nach 2 und 3 Jahren 88 % und die regionäre Kontrolle 100 %. Tumorbedingt verstarben 10/54 (19 %) Patienten, 18/54 (33 %) an kardiovaskulären oder pulmonalen Erkrankungen. Interkurrent verstarben 11/54 (20 %) Patienten, wobei die Tumorerkrankung zum Zeitpunkt der letzten Nachsorge kontrolliert war und keine therapieassoziierte Toxizität feststellbar war; 15/54 (28 %) Patienten leben noch. Sieben Patienten erlitten eine akute Ösophagitis ≤ Grad 2, 2 eine chronische Lungenfibrose Grad 2.

Schlussfolgerung

DART-bid ermöglicht eine hohe Lokalkontrollrate ohne wesentliche Toxizität. Insbesondere für zentral gelegene und/oder große (> 5 cm) Tumoren, bei denen eine Körperstereotaxie nicht durchführbar ist, könnte diese Methode als mögliche radiotherapeutische Alternative zu den derzeit gültigen Empfehlungen dienen, mit der Notwendigkeit der Validierung in größeren Kohorten.

Schlüsselwörter

Nicht-kleinzelliges Bronchuskarzinom Toxizität NSCLC Radiation dose fractionation Therapie-Outcome 

Notes

Compliance with ethical guidelines

Conflict of interest

F. Zehentmayr, K. Wurstbauer, H. Deutschmann, C. Fussl, P. Kopp, K. Dagn, G. Fastner, P. Porsch, M. Studnicka, and F. Sedlmayer state that there are no conflicts of interest.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients.

References

  1. 1.
    Detterbeck FC, Boffa DJ, Tanoue LT (2009) The new lung cancer staging system. Chest 136:260–271CrossRefPubMedGoogle Scholar
  2. 2.
    Mauguen A, Le Pechoux C, Saunders MI et al (2012) Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis. J Clin Oncol 30:2788–2797CrossRefPubMedGoogle Scholar
  3. 3.
    Bogart JA, Hodgson L, Seagren SL et al (2010) Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904. J Clin Oncol 28:202–206CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Cheung PC, Yeung LT, Basrur V, Ung YC, Balogh J, Danjoux CE (2002) Accelerated hypofractionation for early-stage non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 54:1014–1023CrossRefPubMedGoogle Scholar
  5. 5.
    Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC (2013) Treatment of stage I and II non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 143:e278S–313SCrossRefPubMedGoogle Scholar
  6. 6.
    Goeckenjan G, Sitter H, Thomas M et al (2011) Prevention, diagnosis, therapy, and follow-up of lung cancer. Interdisciplinary guideline of the German Respiratory Society and the German Cancer Society—abridged version. Pneumologie 65:e51–75CrossRefPubMedGoogle Scholar
  7. 7.
    Vansteenkiste J, De Ruysscher D, Eberhardt WE et al (2013) Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 24:vi89–98CrossRefGoogle Scholar
  8. 8.
    www.nccn.org. Accessed: 28 Feb. 2014
  9. 9.
    Wurstbauer K, Deutschmann H, Kopp P et al (2010) Nonresected non-small-cell lung cancer in Stages I through IIIB: accelerated, twice-daily, high-dose radiotherapy—a prospective phase I/II trial with long-term follow-up. Int J Radiat Oncol Biol Phys 77:1345–1351CrossRefPubMedGoogle Scholar
  10. 10.
    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 8:49CrossRefPubMedCentralPubMedGoogle Scholar
  11. 11.
    van Baardwijk A, Tome WA, van Elmpt W et al (2012) Is high-dose stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) overkill? A systematic review. Radiother Oncol 105:145–149CrossRefPubMedGoogle Scholar
  12. 12.
    Fowler JF, Tome WA, Fenwick JD, Mehta MP (2004) A challenge to traditional radiation oncology. Int J Radiat Oncol Biol Phys 60:1241–1256CrossRefPubMedGoogle Scholar
  13. 13.
    Deutschmann H, Steininger P, Nairz O et al (2008) “Augmented reality” in conventional simulation by projection of 3-D structures into 2-D images: a comparison with virtual methods. Strahlenther Onkol 184:93–99CrossRefPubMedGoogle Scholar
  14. 14.
    Essler M, Wantke J, Mayer B et al (2013) Positron-emission tomography CT to identify local recurrence in stage I lung cancer patients 1 year after stereotactic body radiation therapy. Strahlenther Onkol 189:495–501CrossRefPubMedGoogle Scholar
  15. 15.
    Solda F, Lodge M, Ashley S, Whitington A, Goldstraw P, Brada M (2013) Stereotactic radiotherapy (SABR) for the treatment of primary non-small cell lung cancer; systematic review and comparison with a surgical cohort. Radiother Oncol 109:1–7CrossRefPubMedGoogle Scholar
  16. 16.
    Grills IS, Mangona VS, Welsh R et al (2010) Outcomes after stereotactic lung radiotherapy or wedge resection for stage I non-small-cell lung cancer. J Clin Oncol 28:928–935CrossRefPubMedGoogle Scholar
  17. 17.
    Shirvani SM, Jiang J, Chang JY et al (2012) Comparative effectiveness of 5 treatment strategies for early-stage non-small cell lung cancer in the elderly. Int J Radiat Oncol Biol Phys 84:1060–1070CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Rowell NP, Williams CJ (2001) Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable): a systematic review. Thorax 56:628–638CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Baumann M, Herrmann T, Koch R et al (2011) Final results of the randomized phase III CHARTWEL-trial (ARO 97–1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC). Radiother Oncol 100:76–85CrossRefPubMedGoogle Scholar
  20. 20.
    Saunders M, Dische S, Barrett A, Harvey A, Griffiths G, Palmar M (1999) Continuous, hyperfractionated, accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small cell lung cancer: mature data from the randomised multicentre trial. CHART Steering committee. Radiother Oncol 52:137–148CrossRefPubMedGoogle Scholar
  21. 21.
    Saunders M, Dische S, Barrett A, Harvey A, Gibson D, Parmar M (1997) Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee. Lancet 350:161–165CrossRefPubMedGoogle Scholar
  22. 22.
    Maguire PD, Marks LB, Sibley GS et al (2001) 73.6 Gy and beyond: hyperfractionated, accelerated radiotherapy for non-small-cell lung cancer. J Clin Oncol 19:705–711PubMedGoogle Scholar
  23. 23.
    Sibley GS, Jamieson TA, Marks LB, Anscher MS, Prosnitz LR (1998) Radiotherapy alone for medically inoperable stage I non-small-cell lung cancer: the Duke experience. Int J Radiat Oncol Biol Phys 40:149–154CrossRefPubMedGoogle Scholar
  24. 24.
    Jeremic B, Shibamoto Y, Acimovic L, Milisavljevic S (1997) Hyperfractionated radiotherapy alone for clinical stage I nonsmall cell lung cancer. Int J Radiat Oncol Biol Phys 38:521–525CrossRefPubMedGoogle Scholar
  25. 25.
    van Baardwijk A, Wanders S, Boersma L et al (2010) Mature results of an individualized radiation dose prescription study based on normal tissue constraints in stages I to III non-small-cell lung cancer. J Clin Oncol 28:1380–1386CrossRefPubMedGoogle Scholar
  26. 26.
    Baumann P, Nyman J, Hoyer M et al (2009) Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol 27:3290–3296CrossRefPubMedGoogle Scholar
  27. 27.
    Duncker-Rohr V, Nestle U, Momm F et al (2013) Stereotactic ablative radiotherapy for small lung tumors with a moderate dose. Favorable results and low toxicity. Strahlenther Onkol 189:33–40CrossRefPubMedGoogle Scholar
  28. 28.
    Timmerman R, McGarry R, Yiannoutsos C et al (2006) Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 24:4833–4839CrossRefPubMedGoogle Scholar
  29. 29.
    Soliman H, Cheung P, Yeung L et al (2011) Accelerated hypofractionated radiotherapy for early-stage non-small-cell lung cancer: long-term results. Int J Radiat Oncol Biol Phys 79:459–465CrossRefPubMedGoogle Scholar
  30. 30.
    Asai K, Shioyama Y, Nakamura K et al (2012) Radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy: risk factors and dose-volume relationship. Int J Radiat Oncol Biol Phys 84:768–773CrossRefPubMedGoogle Scholar
  31. 31.
    Lagerwaard FJ, Verstegen NE, Haasbeek CJ et al (2012) Outcomes of stereotactic ablative radiotherapy in patients with potentially operable stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys 83:348–353CrossRefPubMedGoogle Scholar
  32. 32.
    Dunlap NE, Cai J, Biedermann GB et al (2010) Chest wall volume receiving >30 Gy predicts risk of severe pain and/or rib fracture after lung stereotactic body radiotherapy. Int J Radiat Oncol Biol Phys 76:796–801CrossRefPubMedGoogle Scholar
  33. 33.
    Mutter RW, Liu F, Abreu A, Yorke E, Jackson A, Rosenzweig KE (2012) Dose-volume parameters predict for the development of chest wall pain after stereotactic body radiation for lung cancer. Int J Radiat Oncol Biol Phys 82:1783–1790CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Forquer JA, Fakiris AJ, Timmerman RD et al (2009) Brachial plexopathy from stereotactic body radiotherapy in early-stage NSCLC: dose-limiting toxicity in apical tumor sites. Radiother Oncol 93:408–413CrossRefPubMedGoogle Scholar
  35. 35.
    Ong CL, Palma D, Verbakel WF, Slotman BJ, Senan S (2010) Treatment of large stage I-II lung tumors using stereotactic body radiotherapy (SBRT): planning considerations and early toxicity. Radiother Oncol 97:431–436CrossRefPubMedGoogle Scholar
  36. 36.
    Palma D, Visser O, Lagerwaard FJ, Belderbos J, Slotman B, Senan S (2011) Treatment of stage I NSCLC in elderly patients: a population-based matched-pair comparison of stereotactic radiotherapy versus surgery. Radiother Oncol 101:240–244CrossRefPubMedGoogle Scholar
  37. 37.
    Senthi S, Haasbeek CJ, Slotman BJ, Senan S (2013) Outcomes of stereotactic ablative radiotherapy for central lung tumours: a systematic review. Radiother Oncol 106:276–282CrossRefPubMedGoogle Scholar
  38. 38.
    Jeremic B, Classen J, Bamberg M (2002) Radiotherapy alone in technically operable, medically inoperable, early-stage (I/II) non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 54:119–130CrossRefPubMedGoogle Scholar
  39. 39.
    Jeremic B (2007) Low incidence of isolated nodal failures after involved-field radiation therapy for non small-cell lung cancer: blinded by the light? J Clin Oncol 25:5543–5545CrossRefPubMedGoogle Scholar
  40. 40.
    Rosenzweig KE, Sura S, Jackson A, Yorke E (2007) Involved-field radiation therapy for inoperable non small-cell lung cancer. J Clin Oncol 25:5557–5561CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Franz Zehentmayr
    • 1
    • 2
  • Karl Wurstbauer
    • 1
    • 2
  • Heinz Deutschmann
    • 1
    • 2
  • Christoph Fussl
    • 1
  • Peter Kopp
    • 1
  • Karin Dagn
    • 1
  • Gerd Fastner
    • 1
  • Peter Porsch
    • 3
  • Michael Studnicka
    • 3
  • Felix Sedlmayer
    • 1
    • 2
  1. 1.Univ.-Klinik für Radiotherapie und Radio-Onkologie, Univ.-Klinikum der Paracelsus Medizinischen PrivatuniversitätLandeskrankenhaus SalzburgSalzburgAustria
  2. 2.Institute for Research and Development of Advanced Radiation Technologies (radART)Paracelsus Medizinische PrivatuniversitätSalzburgAustria
  3. 3.Univ.-Klinik für Pneumologie, Univ.-Klinikum der Paracelsus Medizinischen PrivatuniversitätLandeskrankenhaus SalzburgSalzburgAustria

Personalised recommendations