What is the lowest effective biologic dose for prophylactic cranial irradiation?

Between January 1974 and September 1984, 327 consecutive patients with small cell carcinoma of the lung (SCCL) free of clinical and brain scan (radionuclide or computed tomography) evidence of brain metastasis were treated at the Medical College of Wisconsin Affiliated Hospitals. All patients received single agent chemotherapy, consisting of cyclophosphamide or methotrexate (1974-1975), or combination chemotherapy with cyclophosphamide, doxorubicin, and vincristine with or without methotrexate and leukovorin (1976-1984). Between January 1974 and December 1974, 82 patients were treated with chemotherapy without prophylactic cranial irradiation (PCI). Between 1978 and 1984, all patients received PCI during the first week after diagnosis, simultaneous with their first cycle of chemotherapy. Chest irradiation was given to the complete responders to the chemotherapy. During the first 31/3 years of the study with PCI (January 1978-May 1981), 51 patients received 30 Gray (Gy) in 10 fractions in 2 weeks and five of them (10%) developed brain metastasis. Thereafter, 25 Gy in 10 fractions was consistently administered for PCI. Six of 194 patients (3%) developed brain metastasis. The cumulative (time corrected) probability of brain metastasis was approximately 10% at 1 year and was similar for patients who received 25 Gy and those who received 30 Gy. Although detailed neuropsychological testing has not been performed, clinically apparent late sequelae that might be attributed to PCI have not been seen. Nonetheless, the dose fractionation regimen of 25 Gy in 10 fractions with combination chemotherapy, cyclophosphamide, doxorubicin (or methotrexate), and vincristine is as effective in eliminating subclinical metastasis to the brain. It can be recommended for future trials until more data become available about late sequelae of treatment of SCCL and the patient characteristics and treatment factors that may contribute.