Ultrarapid High-Dose Course of Prophylactic Cranial Irradiation in Small-Cell Lung Cancer

Abstract

Despite the reduction in the incidence of brain metastases following prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), the use of this modality is still controversial due to the lack of improvement in survival and the appearance of neurotoxicity in long-term survivors. Moreover, the optimum dose, fraction size, and timing are not known. From 1980 to 1988, 70 patients with limited stage SCLC underwent PCI after or during multimodality treatment of their primary tumor. Most of these patients (75.7%) received an unconventional ultrarapid high-dose course of 17 Gy in two fractions over 3 days. Long-term (range 60-138 months) survivors (n = 16) were invited to have a complete neurological evaluation including computed cranial tomography (CCT), 99mTc-HMPAO single photon emission computerized tomography (SPECT) scan, electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychometry. Delayed neurologic complications or psychometric impairment was observed in 46% of patients. One or more abnormalities were detected by CCT in all patients, and the presence of neurologic complications seemed to correlate with periventricular and subcortical white matter changes. A strong correlation was found between CCT and SPECT periventricular white matter changes. Although the incidence of late neurologic toxicity following this rapid course of irradiation was high, clinical findings were less severe than expected, and all the patients were capable of self-care.

Primary Analysis of a Phase II Randomized Trial Radiation Therapy Oncology Group (RTOG) 0212: Impact of Different Total Doses and Schedules of Prophylactic Cranial Irradiation on Chronic Neurotoxicity and Quality of Life for Patients With Limited-Disease Small-Cell Lung Cancer

“…Several factors in the literature have been reported as being associated with the risk of long-term neurotoxicity, including age greater than 60 years [25], a daily fraction size of greater than 3 Gy [25, 26, 27, 28, 29], and concurrent use of chemotherapy during PCI [25, 26, 28, 30, 31, 32, 33]. In RTOG 0212, age as a continuous variable was the most significant predictor of CNt (p = 0.005).…”

Prophylactic cranial irradiation in elderly patients with small cell lung cancer: Findings from a North Central Cancer Treatment Group pooled analysis

“…Both of these practices were fraught with an increased risk of potentially serious long-term neurologic sequelae. (9–16) Modern PCI doses have decreased significantly and the delivery of concurrent PCI and chemotherapy is not advocated.…”

Controversies in small cell carcinoma of the head and neck: Prophylactic cranial irradiation (PCI) after primary complete initial remission

“…Age greater than 60 years and daily doses of more than 3 Gy are the most significant predictors of chronic neurotoxicity. Of note, data on the development of chronic neurotoxicity and deterioration in quality of life are extrapolated from international PCI trials conducted in lung SmCC, suggesting a beneficial effect on survival without deleterious neurological effect [35][36][37][38]. In detail cognitive function and quality of life have been examined in two prospective studies [39][40].…”