Top

Strahlentherapie und Onkologie

Published in:

01-03-2014 | Original article

Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer

Authors: R. Bütof, K. Kirchner, S. Appold, S. Löck, A. Rolle, G. Höffken, Prof. Dr. M. Krause, M. Baumann

Published in: Strahlentherapie und Onkologie | Issue 3/2014

Abstract

Aim

The aim of this analysis was to investigate the impact of tumour-, treatment- and patient-related cofactors on local control and survival after postoperative adjuvant radiotherapy in patients with non-small cell lung cancer (NSCLC), with special focus on waiting and overall treatment times.

Patients and methods

For 100 NSCLC patients who had received postoperative radiotherapy, overall, relapse-free and metastases-free survival was retrospectively analysed using Kaplan–Meier methods. The impact of tumour-, treatment- and patient-related cofactors on treatment outcome was evaluated in uni- and multivariate Cox regression analysis.

Results

No statistically significant difference between the survival curves of the groups with a short versus a long time interval between surgery and radiotherapy could be shown in uni- or multivariate analysis. Multivariate analysis revealed a significant decrease in overall survival times for patients with prolonged overall radiotherapy treatment times exceeding 42 days (16 vs. 36 months) and for patients with radiation-induced pneumonitis (8 vs. 29 months).

Conclusion

Radiation-induced pneumonitis and prolonged radiation treatment times significantly reduced overall survival after adjuvant radiotherapy in NSCLC patients. The negative impact of a longer radiotherapy treatment time could be shown for the first time in an adjuvant setting. The hypothesis of a negative impact of longer waiting times prior to commencement of adjuvant radiotherapy could not be confirmed.

Alberg AJ, Ford JG, Samet JM (2007) Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132:29S–55SPubMedCrossRef

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

Baumann M, Dubois W, Suit HD (1990) Response of human squamous cell carcinoma xenografts of different sizes to irradiation: relationship of clonogenic cells, cellular radiation sensitivity in vivo, and tumor rescuing units. Radiat Res 123:325–330PubMedCrossRef

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 100:76–85PubMedCrossRef

Baumann M, Krause M, Hill R (2008) Exploring the role of cancer stem cells in radioresistance. Nat Rev Cancer 8:545–554PubMedCrossRef

Baumann M, Liertz C, Baisch H et al (1994) Impact of overall treatment time of fractionated irradiation on local control of human FaDu squamous cell carcinoma in nude mice. Radiother Oncol 32:137–143PubMedCrossRef

Beck-Bornholdt HP, Omniczynski M, Theis E et al (1991) Influence of treatment time on the response of rat rhabdomyosarcoma R1H to fractionated irradiation. Acta Oncol 30:57–63PubMedCrossRef

Bentzen SM, Thames HD (1991) Clinical evidence for tumor clonogen regeneration: interpretations of the data. Radiother Oncol 22:161–166PubMedCrossRef

Bentzen SM, Thames HD (1996) Tumor volume and local control probability: clinical data and radiobiological interpretations. Int J Radiat Oncol Biol Phys 36:247–251PubMedCrossRef

10.

Bese NS, Hendry J, Jeremic B (2007) Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys 68:654–661PubMedCrossRef

11.

Blumenthal DT, Won M, Mehta MP et al (2009) Short delay in initiation of radiotherapy may not affect outcome of patients with glioblastoma: a secondary analysis from the radiation therapy oncology group database. J Clin Oncol 27:733–739PubMedCentralPubMedCrossRef

12.

Bourhis J, Overgaard J, Audry H et al (2006) Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet 368:843–854PubMedCrossRef

13.

Bütof R, Baumann M (2013) Time in radiation oncology—Keep it short! Radiother Oncol

14.

Chen Z, King W, Pearcey R et al (2008) The relationship between waiting time for radiotherapy and clinical outcomes: a systematic review of the literature. Radiother Oncol 87:3–16PubMedCrossRef

15.

Dai H, Hui Z, Ji W et al (2011) Postoperative radiotherapy for resected pathological stage IIIA-N2 non-small cell lung cancer: a retrospective study of 221 cases from a single institution. Oncologist 16:641–650PubMedCentralPubMedCrossRef

16.

Du F, Yuan Z, Wang J et al (2009) The role of postoperative radiotherapy on stage N2 non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 12:1164–1168PubMed

17.

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

18.

Froud PJ, Mates D, Jackson JS et al (2000) Effect of time interval between breast-conserving surgery and radiation therapy on ipsilateral breast recurrence. Int J Radiat Oncol Biol Phys 46:363–372PubMedCrossRef

19.

Gazdar AF (2010) Epidermal growth factor receptor inhibition in lung cancer: the evolving role of individualized therapy. Cancer Metastasis Rev 29:37–48PubMedCentralPubMedCrossRef

20.

Giroux Leprieur E, Fernandez D, Chatellier G et al (2012) Non-small cell lung cancer: risk factors of radiation pneumonitis. Cancer Radiother 16:257–262CrossRef

21.

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. Pneumologie 65:39–59PubMedCrossRef

22.

Group PM-aT (1998) Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet 352:257–263CrossRef

23.

Guckenberger M, Kavanagh A, Partridge M (2012) Combining advanced radiotherapy technologies to maximize safety and tumor control probability in stage III non-small cell lung cancer. Strahlenther Onkol 188:894–900PubMedCrossRef

24.

Herrmann T, Baumann M (2005) Prolongation of latency or overall treatment time by unplanned radiation pauses. The clinical importance of compensation. Strahlenther Onkol 181:65–76PubMedCrossRef

25.

Hessel F, Petersen C, Zips D et al (2003) Impact of increased cell loss on the repopulation rate during fractionated irradiation in human FaDu squamous cell carcinoma growing in nude mice. Int J Radiat Biol 79:479–486PubMedCrossRef

26.

Huang J, Barbera L, Brouwers M et al (2003) Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol 21:555–563PubMedCrossRef

27.

Jobsen JJ, Palen J van der, Baum M et al (2013) Timing of radiotherapy in breast-conserving therapy: a large prospective cohort study of node-negative breast cancer patients without adjuvant systemic therapy. Br J Cancer 108:820–825PubMedCentralPubMedCrossRef

28.

Lally BE, Zelterman D, Colasanto JM et al (2006) Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 24:2998–3006PubMedCrossRef

29.

Le Pechoux C (2011) Role of postoperative radiotherapy in resected non-small cell lung cancer: a reassessment based on new data. Oncologist 16:672–681CrossRef

30.

Manapov F, Klocking S, Niyazi M et al (2012) Chemoradiotherapy duration correlates with overall survival in limited disease SCLC patients with poor initial performance status who successfully completed multimodality treatment. Strahlenther Onkol 188:29–34PubMedCrossRef

31.

Mantovani C, Giaj Levra N, Filippi AR et al (2012) Postoperative radiotherapy for patients with completely resected pathologic N2 non-small-cell lung cancer: a retrospective analysis. Clin Lung Cancer

32.

Overgaard J, Mohanti BK, Begum N et al (2010) Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial. Lancet Oncol 11:553–560PubMedCrossRef

33.

Pirker R, Filipits M (2011) Monoclonal antibodies against EGFR in non-small cell lung cancer. Crit Rev Oncol Hematol 80:1–9PubMedCrossRef

34.

Pirker R, Pereira JR, Szczesna A et al (2009) Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet 373:1525–1531PubMedCrossRef

35.

Roeder F, Friedrich J, Timke C et al (2010) Correlation of patient-related factors and dose-volume histogram parameters with the onset of radiation pneumonitis in patients with small cell lung cancer. Strahlenther Onkol 186:149–156PubMedCrossRef

36.

RTOG0617 (2013) A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy with or without cetuximab for stage III non-small cell lung cancer: results on radiation dose in RTOG 0617. J Clin Oncol 31 (suppl; abstr 7501)

37.

Saunders M, Dische S, Barrett A et al (1997) Continuous hyperfractionated accelerated radiotherapy (CHART) versus conventional radiotherapy in non-small-cell lung cancer: a randomised multicentre trial. CHART Steering Committee. Lancet 350:161–165PubMedCrossRef

38.

Sobin LH, Fleming ID (1997) TNM classification of malignant tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 80:1803–1804PubMedCrossRef

39.

Soliman M, Yaromina A, Appold S et al (2013) GTV differentially impacts locoregional control of non-small cell lung cancer (NSCLC) after different fractionation schedules: subgroup analysis of the prospective randomized CHARTWEL trial. Radiother Oncol

40.

Thames HD, Kuban D, Levy LB et al (2010) The role of overall treatment time in the outcome of radiotherapy of prostate cancer: an analysis of biochemical failure in 4839 men treated between 1987 and 1995. Radiother Oncol 96:6–12PubMedCrossRef

41.

Turrisi AT 3rd, Kim K, Blum R et al (1999) Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 340:265–271PubMedCrossRef

42.

Wurschmidt F, Bunemann H, Ehnert M, Heilmann HP (1997) Is the time interval between surgery and radiotherapy important in operable nonsmall cell lung cancer? A retrospective analysis of 340 cases. Int J Radiat Oncol Biol Phys 39:553–559PubMedCrossRef

43.

Zhang X, Li L, Mu X, Wang S (2004) ZD1839 (Iressa) in the treatment of non-small cell lung cancer patients. Zhongguo Fei Ai Za Zhi 7:309–312PubMed

Title: Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer
Authors: R. Bütof
K. Kirchner
S. Appold
S. Löck
A. Rolle
G. Höffken
Prof. Dr. M. Krause
M. Baumann
Publication date: 01-03-2014
Publisher: Springer-Verlag
Published in: Strahlentherapie und Onkologie / Issue 3/2014
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-013-0501-4

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer

Abstract

Aim

Patients and methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Aim

Patients and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2014

Mitteilungen der Fachgesellschaften

Concomitant chemoradiotherapy versus induction chemotherapy followed by chemoradiotherapy as definitive, first line treatment of squamous cell carcinoma of the head and neck

A pilot study on potential plasma hypoxia markers in the radiotherapy of non-small cell lung cancer

Gemcitabin- oder Capecitabin-basierte Radiochemotherapie beim lokal fortgeschrittenen Pankreaskarzinom (SCALOP)

Erratum to: Androgen receptor expression

Survival and prognostic factors after moderately hypofractionated palliative thoracic radiotherapy for non-small cell lung cancer