Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer (ROSEL)

• Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
• quality adjusted life years (QALYs) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
• quality adjusted life years (QALYs) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• total costs (both direct and indirect) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The standard treatment for an early stage I lung cancer is surgery. However, surgery can be associated with complications and long-term impairment of the quality of life of patients. Stereotactic radiotherapy (SRT) is a outpatient technique which allows for local control rates that are comparable to those achieved using surgery. In this study, patients with stage IA non-small cell lung cancer will be randomized to either surgery or SRT in order to study the local and regional tumor control, quality of life and treatment costs at 2- and 5-years.

• Radiation: stereotactic radiotherapy
  Either 3 fractions of 20 Gray or 5 fractions of 12 Gy
  Other Name: radiotherapy
• Procedure: primary surgery
  an anatomical surgical resection with lymph node dissection
  Other Name: operation

• Active Comparator: primary surgery
  primary surgical resection
  Intervention: Procedure: primary surgery
• Experimental: stereotactic radiotherapy
  primary stereotactic radiotherapy
  Intervention: Radiation: stereotactic radiotherapy

• Haasbeek CJ, Senan S, Smit EF, Paul MA, Slotman BJ, Lagerwaard FJ. Critical review of nonsurgical treatment options for stage I non-small cell lung cancer. Oncologist. 2008 Mar;13(3):309-19.
• Lagerwaard FJ, Haasbeek CJ, Smit EF, Slotman BJ, Senan S. Outcomes of risk-adapted fractionated stereotactic radiotherapy for stage I non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008 Mar 1;70(3):685-92. Epub 2007 Dec 31.
• Hurkmans CW, Cuijpers JP, Lagerwaard FJ, Widder J, van der Heide UA, Schuring D, Senan S. Recommendations for implementing stereotactic radiotherapy in peripheral stage IA non-small cell lung cancer: report from the Quality Assurance Working Party of the randomised phase III ROSEL study. Radiat Oncol. 2009 Jan 12;4:1.

Inclusion Criteria:

• Patients with a cytological or histological diagnosis of stage IA non-cell lung cancer diagnosed in accordance with Dutch CBO guidelines [2004]. When no pathological diagnosis is available, a patient with a new or growing pulmonary lesion with radiological features consistent with malignancy AND a lesion showing uptake on a FDG-PET scan will be eligible [Herder 2005].
• No evidence of regional or distant metastases on a standardized FDG-PET scan within 6 weeks of any protocol treatment .
• The medial extension of tumors should be least 2 cm away from main and lobar bronchi, and also minimum of 1.5 cm from large peripheral blood vessels such as the aorta and main pulmonary artery. Lesions of at least 2 cm from the mediastinal pleura will be eligible if the responsible radiation oncologist judges that the specified normal tissue tolerance doses specified in the protocol will not be exceeded.
• Patients who are judged by a multi-disciplinary team to have 2 primary lung tumors (on the basis of clinical, radiological, FDG-PET and/or cyto-pathology findings) are eligible for randomization provided that both surgery and SRT can be performed in accordance with protocol requirements.
• Patient should be fit to undergo a complete surgical resection of the lesion in accordance with Dutch CBO guidelines [2004]
• Performance score of ECOG ≤ 2 before any treatment.
• Able to comply with post-treatment follow-up
• Patients must sign and date a written Independent Ethics Committee approved informed consent form.

Exclusion Criteria:

• Prior chemotherapy or radiotherapy for the present diagnosis of NSCLC.
• History of any active malignancy (other than NSCLC) unless treated more than 3 years with curative intent and no recurrence, with the exception of non-melanoma skin cancers or in-situ cervical cancers.
• Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, severe cardiac arrhythmia requiring medication, hepatic, renal or metabolic disease).
• Concomitant treatment with any other experimental drug under investigation.
• Pregnancy
• Men and women of child-bearing potential not using effective means of contraception for 6 months after treatment has been completed.