Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer in Complete Remission
ABSTRACT Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival. It has been suggested that this treatment may increase neuropsychological syndromes and brain abnormalities indicated by computed tomography scans. However, other retrospective data suggested a beneficial effect on overall survival for patients in complete remission.
Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis, overall survival, and late-occurring toxic effects in patients with small-cell lung cancer in complete remission.
We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete remission. The patients were randomly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days (treatment group) or no prophylactic cranial irradiation (control group). A neuropsychological examination and a computed tomography scan of the brain were performed at the time of random assignment and repeatedly assessed at 6, 18, 30, and 48 months. Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse, using a competing-risk approach.
Two hundred ninety-four patients who did not have brain metastases at the time of random assignment were analyzed. The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45% in the control group and 19% in the treatment group (P < 10(-6)). The total 2-year rate of brain metastasis was 67% and 40%, respectively (relative risk = 0.35; P < 10(-13)). The 2-year overall survival rate was 21.5% in the control group and 29% in the treatment group (relative risk = 0.83; P = .14). There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans.
Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications. A possible beneficial effect on overall survival should be tested with a higher statistical power.
The results of the trial favor, at present, the indication of prophylactic cranial irradiation for patients who are in complete remission. A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects. The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission, and a meta-analysis of similar trials is recommended.
- SourceAvailable from: Alessandro Morabito
- "In the early 1970s, the brain was assumed to be a pharmacologic sanctuary and it was suggested that cranial irradiation might prevent the development of clinically evident brain metastases. These hypotheses led to several clinical trials that evaluated the role of prophylactic cranial irradiation in patients with SCLC: the results of these trials showed a significant decrease in the incidence of brain metastasis, with no increase in neuropsychological complications , but were inconclusive with regard to the benefit in terms of overall survival  . A meta-analysis based on individual data of 987 patients with SCLC in complete remission who took part in seven trials evaluated the role of prophylactic cranial irradiation in prolonging survival . "
Article: Treatment of Small Cell Lung Cancer[Show abstract] [Hide abstract]
ABSTRACT: Treatment of small cell lung cancer (SCLC) remains a significant challenge for the oncologists. Attemps to improve the results of first-line treatment have all failed so far and no real progress has been made in last years, emphasizing the need for novel strategies of treatment and the development of validated biomarkers. Patients with limited disease and good performance status should be considered for concomitant chemoradiotherapy, followed by prophylactic cranial irradiation. Patients with extensive disease should be treated with a platinum-based chemotherapy (cisplatin or carboplatin); chest radiotherapy can be considered in patients achieving extra-thoracic complete response and prophylactic cranial irradiation is recommended for patients responsive to initial chemotherapy. A large number of molecular-targeted drugs and immunomodulators are currently in clinical development: however, only a better understanding of molecular biology of SCLC and the identification of molecular markers predictive of response to targeted agents will lead to advances in the treatment of SCLC.Critical reviews in oncology/hematology 09/2014; 91(3). DOI:10.1016/j.critrevonc.2014.03.003 · 4.05 Impact Factor
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- "The TRT rate in the Sundstrom study was higher in both arms (83 and 88%). Prophylactic cranial irradiation has been shown to be associated with a survival advantage in LD and ED patients responding to chemotherapy (Auperin et al, 1999) (Slotman et al, 2007). In this study, 33% of LD patients receiving PE and 23% of those receiving ACE went on to have PCI. "
ABSTRACT: This randomised trial compared platinum-based to anthracycline-based chemotherapy in patients with small-cell lung cancer (limited or extensive stage) and <or=2 adverse prognostic factors. Patients were randomised to receive six cycles of either ACE (doxorubicin 50 mg/m(2) i.v., cyclophosphamide 1 g/m(2) i.v. and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) or PE (cisplatin 80 mg/m(2) and etoposide 120 mg/m(2) i.v. on day 1, then etoposide 240 mg/m(2) orally for 2 days) given for every 3 weeks. For patients where cisplatin was not suitable, carboplatin (AUC6) was substituted. A total of 280 patients were included (139 ACE, 141 PE). The response rates were 72% for ACE and 77% for PE. One-year survival rates were 34 and 38% (P=0.497), respectively and 2-year survival was the same (12%) for both arms. For LD patients, the median survival was 10.9 months for ACE and 12.6 months for PE (P=0.51); for ED patients median survival was 8.3 months and 7.5 months, respectively. More grades 3 and 4 neutropenia (90 vs 57%, P<0.005) and grades 3 and 4 infections (73 vs 29%, P<0.005) occurred with ACE, resulting in more days of hospitalisation and greater i.v. antibiotic use. ACE was associated with a higher risk of neutropenic sepsis than PE and with a trend towards worse outcome in patients with LD, and should not be studied further in this group of patients.British Journal of Cancer 09/2008; 99(3):442-7. DOI:10.1038/sj.bjc.6604480 · 4.82 Impact Factor
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