scholarly journals Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastasis

2016 ◽  
Vol 34 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Kimberly L. Johung ◽  
Norman Yeh ◽  
Neil B. Desai ◽  
Terence M. Williams ◽  
Tim Lautenschlaeger ◽  
...  

Purpose We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non–small-cell lung cancer (NSCLC) and brain metastasis. Patients and Methods A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. Results Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). Conclusion Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.

2020 ◽  
Vol 38 (14) ◽  
pp. 1505-1517 ◽  
Author(s):  
Shirish Gadgeel ◽  
Delvys Rodríguez-Abreu ◽  
Giovanna Speranza ◽  
Emilio Esteban ◽  
Enriqueta Felip ◽  
...  

PURPOSE In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680 ). METHODS Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis. RESULTS As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups. CONCLUSION First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.


2020 ◽  
Vol 66 (5) ◽  
pp. 540-548
Author(s):  
M. Girshovich ◽  
O. Ponomareva ◽  
Yu. Melnik ◽  
S. Novikov ◽  
Ye. Khrapovitskaya ◽  
...  

In 5 year 180 patients (89 men and 91 women) underwent radiosurgery of brain metastases. Most patients had breast cancer and less than 5 lesions. Median overall survival (MOS) was 12,5 months, median progression free survival (MPFS) - 6,1 months. Both values were higher in patients with solitary lesions: 22.5 vs 10 months (р=0.00703) and 9 vs 6 months (р=0.02787), respectively.MOS was 18 in women with breast cancer, 12 months in patients with non small cell lung cancer. 8 - with melanoma and only 4 months - for small cell lung cancer. MPFS was significantly shorter for lesions volumes above 15 cm3. In field progression was detected in 37 (2-24 months after treatment) of 180 cases (20,5%). Second radiosurgery was performed in 24 cases.


1990 ◽  
Vol 8 (6) ◽  
pp. 1042-1049 ◽  
Author(s):  
M P Dearing ◽  
S M Steinberg ◽  
R Phelps ◽  
M J Anderson ◽  
J L Mulshine ◽  
...  

In a study of 411 patients with small-cell lung cancer (SCLC) entered on therapeutic clinical trials between 1973 and 1987, we analyzed whether changes in the prognostic importance of pretreatment factors had occurred during the 14-year time period. After adjusting for other prognostic factors, brain involvement was associated with shorter survival in patients treated before December 1979 (P = .024) but not in patients treated thereafter (P = .54). The patients diagnosed before 1979 had brain metastases documented by radionuclide scan while computed cranial tomography (CCT) was more commonly used after 1979. Patients who had brain metastases diagnosed by radionuclide scan lived a shorter period of time than patients who had the diagnosis made by the more sensitive CCT scan (P = .031). In contrast, Cox proportional hazards modeling showed that liver metastases in patients were associated with shorter survival in patients treated after 1979 (P = .0007) but not in patients treated before then (P = .30). A larger proportion of patients had a routine liver biopsy before 1979 than after 1979 when more patients had the liver staged with less sensitive imaging studies and biochemical parameters. Patients with SCLC whose cancer was confined to the thorax but had medical or anatomic contraindications to intensive chest radiotherapy had similar survival compared with patients with limited-stage SCLC who were treated with combination chemotherapy alone (P = .68). From these data we conclude: (1) the sensitivity of the staging procedures used can affect the impact on survival of cancer involvement of a given site; and (2) patients with cancer confined to their chest with medical or anatomic contraindications to chest radiotherapy do not have a shorter survival than patients with limited-stage disease treated with chemotherapy alone.


2018 ◽  
Vol 10 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Chunhua She ◽  
Ruixia Wang ◽  
Changhong Lu ◽  
Zengfeng Sun ◽  
Peng Li ◽  
...  

2014 ◽  
Vol 76 (5) ◽  
pp. 218 ◽  
Author(s):  
Myoung-Rin Park ◽  
Yeon-Hee Park ◽  
Jae-Woo Choi ◽  
Dong-Il Park ◽  
Chae-Uk Chung ◽  
...  

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