Prophylactic cranial irradiation (PCI) has a detrimental effect on the overall survival (OS) of patients (pts) with extensive disease small cell lung cancer (ED-SCLC): Results of a Japanese randomized phase III trial.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 7503-7503 ◽  
Author(s):  
Takashi Seto ◽  
Toshiaki Takahashi ◽  
Takeharu Yamanaka ◽  
Hideyuki Harada ◽  
Hiroshi Nokihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Detrimental Effect ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Extensive Disease ◽  
Phase Iii Trial

Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study

2021 ◽  
pp. JCO.21.00639
Author(s):  
Núria Rodríguez de Dios ◽  
Felipe Couñago ◽  
Mauricio Murcia-Mejía ◽  
Mikel Rico-Oses ◽  
Patricia Calvo-Crespo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Free Recall ◽  
Brain Metastases ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Phase Iii Trial ◽  
Hippocampal Avoidance

PURPOSE Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.

Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer

2006 ◽  
Vol 24 (13) ◽  
pp. 2038-2043 ◽  
Author(s):  
Nasser Hanna ◽  
Paul A. Bunn ◽  
Corey Langer ◽  
Lawrence Einhorn ◽  
Troy Guthrie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Febrile Neutropenia ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Extensive Disease ◽  
Phase Iii Trial ◽  
Grade 3

Purpose Etoposide and cisplatin (EP) has been a standard treatment for extensive-disease small-cell lung cancer (SCLC). An earlier phase III trial reported improved survival for patients receiving irinotecan plus cisplatin (IP) versus EP. Our trial was designed to determine if a modified weekly regimen of IP would provide superior survival with less toxicity than EP. Patients and Methods The primary objective was to compare overall survival in extensive-disease SCLC patients randomly assigned to receive IP (n = 221) or EP (n = 110). Patients were randomly assigned in 2:1 ratio to cisplatin 30 mg/m2 intravenously (IV) + irinotecan 65 mg/m2 IV on days 1 and 8 every 21 days, or cisplatin 60 mg/m2 IV on day 1, and etoposide 120 mg/m2 IV on days 1 to 3 every 21 days for at least four cycles, until progressive disease, or until intolerable toxicity resulted. Results Selected grade 3/4 toxicities for IP/EP were: neutropenia (36.2% v 86.5%; P < .01), febrile neutropenia (3.7% v 10.4%; P = .06), anemia (4.8% v 11.5%; P = .02), thrombocytopenia (4.3% v 19.2%; P < .01), vomiting (12.5% v 3.8%; P = .04), and diarrhea (21.3% v 0%; P < .01). There was no significant difference in response rates (48% v 43.6%), median time to progression (4.1 v 4.6 months), or overall survival (median survival time, 9.3 months v 10.2 months; P = .74). Conclusion Treatment with this dose and schedule of IP did not result in improved survival when compared with EP. Fewer patients receiving IP had grade 3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with patients receiving EP, but more had grade 3/4 diarrhea and vomiting.

A randomized trial of prophylactic cranial irradiation (PCI) versus no PCI in extensive disease small cell lung cancer after a response to chemotherapy (EORTC 08993–22993)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
B. Slotman ◽  
C. Faivre-Finn ◽  
G. Kramer ◽  
E. Rankin ◽  
M. Snee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cumulative Incidence ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Extensive Disease

4 Background: Prophylactic cranial irradiation (PCI) significantly reduces the risk of brain metastases (BM) and improves survival in patients with limited disease small cell lung cancer. Development of BM is often accompanied by deterioration of physical and psychological functioning and response to therapy is poor. Patients with extensive disease (ED SCLC) are at high risk for BM. This randomized study assesses PCI in patients with ED SCLC. Methods: Patients (18–75 years; WHO=2) with confirmed ED SCLC and any response to 4–6 cycles of chemotherapy, were randomized to receive PCI (doses ranging from 20 Gy/5 fr to 30 Gy/12 fr) or no PCI. The primary endpoint was the cumulative incidence of symptomatic BM. CT or MRI of the brain was performed whenever any of the pre-defined “key-symptoms” was present at baseline or during follow-up. The study was sized to detect a hazard ratio of 0.44 with 80% power and 2-sided 5% significance (52 events, 287 patients). Results: Between Feb ’01 and Mar ’06, 286 patients entered the trial, 76% with residual disease in the thorax and 71% at distant sites. Baseline characteristics were well balanced. Only 6% of patients in the PCI arm were not treated and 3% interrupted treatment. Acute toxicity was mild: nausea/vomiting was reported by about 30% of PCI-treated cases and about 30% reported late reactions (mostly mild headache). PCI significantly reduced the risk of symptomatic brain metastases (Gray P<0.0001, HR=0.27, CI: 0.16–0.44). The 1-year cumulative incidence of symptomatic BM was 14.6% on PCI (CI 8.3–20.9) versus 40.4% in controls (CI 32.1–48.6). PCI had no impact on extra-cranial progression rates (Gray P>0.1), but it significantly prolonged progression-free survival time (P=0.0218, HR=0.76, CI: 0.59–0.96) and overall survival (P=0.0033, HR=0.68, CI: 0.52–0.88). The 1-year survival rate was 27.1% for the PCI and 13.3% for the control arm. Conclusions: PCI significantly reduces the risk of symptomatic brain metastases, and significantly improves both disease-free and overall survival in patients with ED SCLC. PCI should be offered to all ED patients showing a response to initial chemotherapy. No significant financial relationships to disclose.

Thoracic twice-daily radiotherapy and brain metastasis in patients with small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8560-8560
Author(s):  
Haiyan Zeng ◽  
Rui Li ◽  
Chen Hu ◽  
Guoqin Qiu ◽  
Hong Ge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Cranial Irradiation ◽  
Prophylactic Cranial Irradiation ◽  
Small Cell ◽  
Small Cell Lung

8560 Background: Although thoracic twice-daily radiotherapy (TDRT) is one of standards of care for small cell lung cancer, its impact on brain metastases remains unknown. This study aimed to compare TDRT with once-daily radiotherapy (ODRT) for the brain metastases rate after prophylactic cranial irradiation in patients with small cell lung cancer. Methods: Consecutive patients received TDRT (45Gy/30f)/ODRT(50-66Gy/25-33f), chemotherapy and prophylactic cranial irradiation were retrieved from eight hospitals’ databases between 2003 and 2016. The endpoints included brain metastases, progression-free survival and overall survival. Brain metastases rate was evaluated using competing risk analysis. A 1:1 propensity score matching approach was used to control confounding between these two groups. Confounding covariates included eight demographic variables and eight treatment related covariates. Results: Of the 778 eligible patients with median age of 55-year (IQR, 48-61), 204 (26.2%) were female. At a median follow-up time of 23.6 months (IQR, 14.2- 38.2), 131 (16.8%) experienced brain metastases. The rates in TDRT were significantly higher than ODRT (3-year, 26.0% vs. 16.9%; HR = 1.55, 95%CI 1.06-2.26, P = 0.03). Of the 338 matched patients (169 in ODRT vs. 169 in TDRT), 60 (17.8%) experienced brain metastases with 3-year rate of 14.9% in ODRT vs 26.0% in TDRT (HR = 1.71, 95%CI 1.02-2.88, P = 0.04). Progression-free survival was similar in both the whole cohort and the matched one. Overall survival in ODRT tended to be significantly longer after matching (median, 47.2 months in ODRT vs. 32.8 months in TDRT; HR = 1.41, 95%CI 0.99-2.01, P = 0.06). When jointly evaluated biologically effective dose (BED), start of any therapy to the end of radiotherapy (SER) and TDRT/ODRT in the multivariable analysis, the impact of ODRT/TDRT on overall survival become more significant (HR = 1.69, 95%CI 1.05-2.71, P = 0.03). Conclusions: Patients with small cell lung cancer who were treated with thoracic TDRT appeared to have higher risk of brain metastases than those with ODRT, which strongly supports the need for further prospective randomized clinical trials, especially in China or other parts of Asia.

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