Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01)

Abstract

Background: We recently published the results of the PCI99 randomised trial comparing the effect of a prophylactic cranial irradiation (PCI) at 25 or 36 Gy on the incidence of brain metastases (BM) in 720 patients with limited small-cell lung cancer (SCLC). As concerns about neurotoxicity were a major issue surrounding PCI, we report here midterm and long-term repeated evaluation of neurocognitive functions and quality of life (QoL).

Patients and methods: At predetermined intervals, the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and brain module were used for self-reported patient data, whereas the EORTC-Radiation Therapy Oncology Group Late Effects Normal Tissue-Subjective, Objective, Management, Analytic scale was used for clinicians' assessment. For each scale, the unfavourable status was analysed with a logistic model including age, grade at baseline, time and PCI dose.

Results: Over the 3 years studied, there was no significant difference between the two groups in any of the 17 selected items assessing QoL and neurological and cognitive functions. We observed in both groups a mild deterioration across time of communication deficit, weakness of legs, intellectual deficit and memory (all P < 0.005).

Conclusion: Patients should be informed of these potential adverse effects, as well as the benefit of PCI on survival and BM. PCI with a total dose of 25 Gy remains the standard of care in limited-stage SCLC.

Figures

Figure 1a.

Quality of life (QoL) evaluation according to treatment (continuous line: 25-Gy group, dotted line: 36-Gy group). Total sample size: 448, 387, 283, 143 and 92 at 0, 6, 12, 24 and 36 months, respectively. Upper curve: proportion of patients (95% confidence interval) in an unfavourable status by treatment and time (see ‘statistical methods’ section for definition). Lower histogram: proportion of patients in the three classes of unfavourable status, from better (left) to worst (right) in each arm. The P-value corresponds to the treatment effect estimated in the model of analysis. There are two scales (communication deficit and weakness of legs) that decline with time, and two scales (physical functioning and motor dysfunction) where a decline according to age at baseline, has been observed.

Figure 1a.

Quality of life (QoL) evaluation according to treatment (continuous line: 25-Gy group, dotted line: 36-Gy group). Total sample size: 448, 387, 283, 143 and 92 at 0, 6, 12, 24 and 36 months, respectively. Upper curve: proportion of patients (95% confidence interval) in an unfavourable status by treatment and time (see ‘statistical methods’ section for definition). Lower histogram: proportion of patients in the three classes of unfavourable status, from better (left) to worst (right) in each arm. The P-value corresponds to the treatment effect estimated in the model of analysis. There are two scales (communication deficit and weakness of legs) that decline with time, and two scales (physical functioning and motor dysfunction) where a decline according to age at baseline, has been observed.

Figure 2a.

Evaluation of clinical and radiological sequelae using Late Effects Normal Tissue (LENT)-Subjective, Objective, Management, Analytic (SOMA) scale according to treatment (continuous line: 25-Gy group, dotted line: 36-Gy group). Total sample size: 322, 288, 146 and 101 at 0, 12, 24 and 36 months, respectively. Upper curve: proportion of patients (95% confidence interval) in an unfavourable status by treatment and time (see ‘statistical methods’ section for definition). Lower histogram: proportion of patients in the four classes of unfavourable status [grade 1 (left), grade 2, grade 3 and grade 4 (right)] in each arm. The P-value corresponds to the treatment effect estimated in the model of analysis. Two scales (intellectual deficit and memory) decline with time, and two scales (memory and brain magnetic resonance imaging and/or computed tomography abnormalities) where a decline according to age at baseline has been observed.

Figure 2a.

Evaluation of clinical and radiological sequelae using Late Effects Normal Tissue (LENT)-Subjective, Objective, Management, Analytic (SOMA) scale according to treatment (continuous line: 25-Gy group, dotted line: 36-Gy group). Total sample size: 322, 288, 146 and 101 at 0, 12, 24 and 36 months, respectively. Upper curve: proportion of patients (95% confidence interval) in an unfavourable status by treatment and time (see ‘statistical methods’ section for definition). Lower histogram: proportion of patients in the four classes of unfavourable status [grade 1 (left), grade 2, grade 3 and grade 4 (right)] in each arm. The P-value corresponds to the treatment effect estimated in the model of analysis. Two scales (intellectual deficit and memory) decline with time, and two scales (memory and brain magnetic resonance imaging and/or computed tomography abnormalities) where a decline according to age at baseline has been observed.