Sites of recurrent disease and prognostic factors in SCLC patients treated with radiochemotherapy

Purpose:

Concurrent radiochemotherapy (RCHT) is the standard treatment in locally advanced small cell lung cancer (SCLC) patients. Due to conflicting results on elective nodal irradiation (ENI) or selective node irradiation (SNI) there is no clear evidence on optimal target volumes. Therefore, the aims of this study were the evaluation of sites of recurrent disease in patients with limited stage SCLC undergoing radiochemotherapy to assess the feasibility and safety of SNI versus ENI and, moreover, the extraction of prognostic factors for loco-regional control, freedom from distant metastases and overall survival.
Material and methods:
A retrospective single-institution study was performed in 54 consecutive patients treated with RCHT. After state-of-the-art staging, all patients underwent three-dimensional conformal radiotherapy to a total dose of 45 Gy in twice-daily fractions of 1.5 Gy starting concurrently with the first or second chemotherapy cycle according to Turrisi et al. [1]. The gross tumour volume (GTV) consisted of the primary tumour and SNI visualized on CT and/or FDG-PET, or confirmed by cytology. The clinical target volume (CTV) was obtained by expanding the GTV, adjusting it for anatomical boundaries, and electively adding the supraclavicular lymph node stations. Thereafter, the CTV was expanded to a planning target volume based on institutional guidelines. Follow-up consisted of a 3-monthly chest x-ray or CT-scan. All sites of loco-regional recurrences were correlated to the initial tumour and dose delivered. The impact of potential prognostic variables on outcome was evaluated using the Cox-regression model.
Results:
After a median interval of 11.5 months, 17 patients (31%) relapsed locally or regionally: six within the initial primary tumour volume, five within the initially affected lymph nodes, three metachronously within primary tumour and initially affected lymph nodes, and three both inside and outside of the initial nodal disease. All sites of loco-regional recurrence had received 92%-106% of the prescribed dose. Thirty-seven patients (69%) developed distant metastases (37.8% liver, 35% brain). Among all investigated co-factors only total GTV revealed a significant correlation with patient outcome.
Conclusion:
In our study most recurrences occurred in the initial primary tumour or lymph node volume, or distantly. We did not register any case of isolated nodal failure, suggesting the use of selective nodal irradiation, possibly with the addition of supraclavicular irradiation in patients with affected lymph nodes in the upper mediastinum, instead of ENI.
Among all investigated patient- and tumour-related co-factors only total GTV revealed a significant correlation with patient outcome. Further prospective clinical trials are needed for final determination of optimal irradiation fields in SCLC patients.