Prophylactic Cranial Irradiation for Patients With Small-Cell Lung Cancer in Complete Remission
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.
Available 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 . "
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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.
Available from: Shoji Yomo
- "Brain metastases (BM) are a significant threat to quality of life in patients with SCLC . Given that the cumulative incidence of BM from SCLC at 2 years is approximately 50% [1,3], prophylactic cranial irradiation (PCI) combined with systemic chemotherapy, which moderately prolongs overall survival (OS) by reducing the incidence of delayed BM, has historically been recommended as the treatment for this aggressive disease in most patients [4-8]. "
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Although the efficacy of prophylactic or therapeutic whole brain radiotherapy (WBRT) for brain metastases (BM) from small cell lung cancer (SCLC) is well established, the role of stereotactic radiosurgery (SRS) has yet to be determined. In the present retrospective analysis, we investigated whether upfront SRS might be an effective treatment option for patients with BM from SCLC.
We analyzed 41 consecutive patients with a limited number of BM (≤ 10) from SCLC who received SRS as the initial treatment. No prophylactic and therapeutic WBRT was given prior to SRS. The median patient age was 69 years and the median Karnofsky performance status (KPS) score was 90. Repeat SRS was given for new distant lesions detected on follow-up neuroradiological imaging, as necessary. Overall survival, neurological death, and local and distant BM recurrence rates were analyzed. The survival results were tested with three prognostic scoring systems validated for SCLC: Diagnosis-specific graded prognostic assessment (DS-GPA), Radiation therapy oncology group -recursive partitioning analysis and Rades’s survival score.
One- and 2-year overall survival rates were 44% and 17%, respectively. The median survival time was 8.1 months. Survival results replicated the DS-GPA (P = 0.022) and Rades’s survival score (P = 0.034). On multivariate analysis, patients with high KPS (hazard ratio (HR): 0.308, P = 0.009) and post-SRS chemotherapy (HR: 0.324, P = 0.016) had better overall survival. In total, 95/121 tumors (79%) in 34 patients (83%) with sufficient radiological follow-up data were evaluated. Six- and 12-month rates of local control failure were 0% and 14%, respectively. Six- and 12-month distant BM rates were 22% and 44%, respectively. Repeat SRS, salvage WBRT and microsurgery were subsequently required in 18, 7 and one patient, respectively. Symptomatic radiation injury developed in two patients and both were treated conservatively.
Our survival analyses with the validated prognostic grading systems suggested upfront SRS for limited BM from SCLC to be a potential treatment option, with patient survival being slightly more than eight months after SRS. Although SRS provided durable local tumor control, repeat treatment was needed in nearly half of patients to achieve control of distant BM.
Available from: Apar Kishor Ganti
- "Almost 25 per cent of patients will have brain metastases at presentation66. Furthermore, of the patients who obtain a complete response with initial therapy, approximately 45 per cent will present with brain metastases as the only site of relapse at 2 years6768. CNS relapse is associated with greater deterioration in performance status, and an increased need for hospitalization69. Hence prevention of CNS relapse would be a good option in order to decrease the suffering caused by CNS metastases. "
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ABSTRACT: Small cell lung cancer (SCLC) has a clinical course that is distinct from its more common counterpart non-small cell lung cancer. SCLC continues to be a major clinical problem, with an aggressive clinical course and short disease-free duration after initial therapy. Current optimal treatment consists of chemotherapy with platinum-etoposide, given concurrently with thoracic irradiation in patients with limited stage disease and chemotherapy alone in those with extensive stage. Prophylactic cranial irradiation (PCI) is recommended for patients who have responded to initial therapy, as it not only decreases the risk of brain metastases and but also improves overall survival. Newer targeted agents are currently being evaluated for this disease.
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