Early Prophylactic Cranial Irradiation Research Articles

Prophylactic cranial irradiation in 399 patients with limited-stage small cell lung cancer.

The benefit of prophylactic cranial irradiation (PCI) in limited-stage small-cell lung cancer (LS-SCLC) was established in a meta-analysis performed in 1999. Since then, considerable progress has been made in the diagnosis, staging and treatment of LS-SCLC, including chemotherapy and radiotherapy, which led to a longer survival time in patients. Therefore, the magnitude of the benefit of PCI should be re-evaluated. Furthermore, the optimum timing of PCI for LS-SCLC treatment has not been established and more data is required to demonstrate this. In the present retrospective study, the cases of patients that were diagnosed with LS-SCLC between March 2005 and December 2010 were reviewed. The main eligibility criteria of patients were a diagnosis of LS-SCLC and the achievement of a complete response (CR) or near CR subsequent to receiving ≥3 cycles of cisplatin-based chemotherapy, with or without advanced thoracic radiotherapy. Early and late PCI groups were separated using the median time interval between the start of primary chemotherapy and the start of PCI. In total, 80 patients were excluded from the analysis, including 9 patients that developed brain metastases, 2 during primary chemotherapy and 7 during radiotherapy. The remaining 399 patients were deemed eligible. PCI was administered to 185 patients; 92 patients were in the early PCI group and 93 were in the late PCI group. PCI significantly decreased the incidence of brain metastases [P<0.001; HR, 0.24; 95% confidence interval (CI), 0.15-0.39] and improved the overall survival time of the patients (median survival time, 21.5-38.8 months; P<0.001; HR, 0.60; 95% CI, 0.45-0.79). However, no significant difference was identified between the early and late PCI groups, either in the incidence of brain metastases (P=0.875) or the overall survival time (P=0.361). Multivariate analysis revealed that PCI (P=0.004) and thoracic radiotherapy (P=0.023) were the only 2 independent favorable prognostic factors of overall survival time. The present study demonstrates that PCI may be of considerable benefit to increase the survival rate and time of patients, and early PCI is as effective as late PCI. However, the present study recommends that PCI should be offered as soon as primary chemotherapy is completed, since there is a greater risk of developing brain metastases during thoracic radiotherapy.

Results of a Phase II Study of High-Dose Thoracic Radiation Therapy With Concurrent Cisplatin and Etoposide in Limited-Stage Small-Cell Lung Cancer (NCCTG 95-20-53)

To evaluate the outcome of patients with limited-stage small-cell lung cancer (L-SCLC) treated with cisplatin and etoposide (PE), early prophylactic cranial irradiation (PCI), and high-dose twice-daily thoracic radiotherapy (bid RT). A total of 76 assessable patients were treated on this phase II trial, which included six cycles of PE. PCI (25 Gy/10 fractions) was delivered during cycle 3 to responding patients. Cycles 4 and 5 included concurrent chemotherapy and thoracic RT (30 Gy/20 bid fractions, a 2-week break, and another 30 Gy/20 bid fractions). Of the 76 assessable patients, 74 patients (97%) suffered grade 3 or greater (3+) toxicity and 61 patients (80%) had grade 4 or greater (4+) toxicity. Of these adverse events, grade 3+ hematologic toxicity occurred in 72 patients (95%), and grade 3+ nonhematologic toxicity occurred in 55 patients (72%). Only one (2%) of the 61 patients who received PCI experienced treatment failure in the brain. The 5-year survival rate of the 76 assessable patients was 24% (median, 20 months). The 5-year survival rate of the 64 patients who received thoracic RT was 29% (median, 22 months). The 5-year cumulative incidence of in-field treatment failure was 34%. This regimen included a high total dose of bid TRT, which resulted in a favorable 5-year survival rate. Local failure remains a problem that will require additional investigation. Newer technology should allow the safe administration of greater doses of RT, which should improve patient outcome. Data from eight trials were combined to demonstrate a relationship between RT dose fractionation and 5-year survival.

2195 High dose thoracic radiation therapy with concomitant cisplatin/etoposide and early prophylactic cranial irradiation in limited stage small cell lung cancer

2195 High dose thoracic radiation therapy with concomitant cisplatin/etoposide and early prophylactic cranial irradiation in limited stage small cell lung cancer

Dose–Response Relationship for Prophylactic Cranial Irradiation in Small Cell Lung Cancer

Purpose: To determine the dose–response relationship for prophylactic cranial irradiation (PCI) in small cell lung cancer, to quantify the growth kinetics of subclinical metastases, and to determine the influence of time-delay in initiating PCI on its utility. Methods and Materials: Published reports of brain relapse rates in small cell lung cancer with and without PCI were collected. The reduction in brain relapse rate as a function of radiation dose was analyzed. The time interval between treatment of the primary tumor and the initiation of PCI was analyzed as a factor potentially influencing dose–response. Results: A shallow dose–response curve without any threshold in the dose intercept was demonstrated for control of subclinical brain metastases in “early PCI” (delay between initiation of treatment for primary tumor and PCI less than 60 days). By contrast “late PCI” (delay over 60 days) was associated with a significant displacement of the dose intercept. Doses over 30–35 Gy in 2-Gy fractions did not result in a further reduction in brain relapse rate, but there were too few high-dose studies to draw any definite conclusion. Conclusions: The nearly linear dose–response relationship for reduction in brain relapses demonstrated for “early PCI” in the range of doses from zero up to 35 Gy given in 2-Gy fractions supports the model of a fairly logarithmically uniform distribution of metastatic cell number within a series of patients. When PCI is delayed, a significant threshold in dose–response was observed, consistent with a fast growth rate of untreated subclinical brain metastases from small cell lung cancer. The exact shape and locations of dose–response curves is not well established by this retrospective analysis of diverse data. A high probability of eliminating brain relapses following PCI requires a dose of about 30–35 Gy in 2-Gy fractions. Control rates in brain can be enhanced if PCI is applied early.