Brain metastases in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 326-326
Author(s):  
H. Alharbi ◽  
T. K. Choueiri ◽  
C. K. Kollmannsberger ◽  
S. North ◽  
M. J. MacKenzie ◽  
...  

326 Background: Patients with brain metastases from advanced RCC treated in the targeted therapy era are not well characterized. Methods: Data from patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium from 6 centers. Results: One hundred six out of 705 (15%) patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-VEGF therapy and the rest developed metastases during follow-up. Of the patients with brain metastases, 6%, 68%, and 26% were in the favorable, intermediate and poor prognosis groups, respectively, per the Heng et al JCO 2009 criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 40% had a Karnofsky performance status (KPS) <80%, and 81% had symptoms of brain metastases. The median largest size and number of brain metastases was 1.8 cm (range 0.2–6.6) and 1 (range 1–20), respectively. Patients were treated with first-line sunitinib (n=77), sorafenib (n=23), bevacizumab (n=5), and temsirolimus (n=1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). The brain metastases of 59 patients were evaluable and based on the local treatment and/or targeted therapy achieved 7 (12%) complete responses, 23 (39%) partial responses, 14 (24%) patients with stable disease, and 15 (25%) patients with progressive disease in the brain metastases. Patients with more than 4 brain metastases vs. those with no more than 4 have an overall survival time from diagnosis of brain metastasis of 3.9 vs. 15.4 months (p=0.0051). Previous nephrectomy, sarcomatoid, and non-clear cell histology are not associated with development of brain metastases. On multivariable analysis, KPS<80% (p=0.0139), diagnosis to treatment with targeted therapy <1 year (p=0.0012), and higher number of brain metastases (p=0.0311) were associated with worse survival from diagnosis of brain metastases. Conclusions: In patients with brain metastases from RCC, KPS at start of therapy, diagnosis to treatment time and number of brain metastases may be prognostic factors for overall survival. [Table: see text]

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS9106-TPS9106
Author(s):  
Minesh P. Mehta ◽  
Vinai Gondi ◽  
Paul D. Brown

TPS9106 Background: Tumor Treating Fields (TTFields) are non-invasive regional anti-mitotic treatment modality, based on low intensity alternating electric fields. Efficacy of TTFields in non-small cell lung cancer (NSCLC) has been demonstrated in multiple in vitro and in vivo models, and in a phase I/II clinical study. TTFields treatment to the brain was shown to be safe and to extend overall survival in newly-diagnosed glioblastoma patients. Methods: 270 patients with 1-10 brain metastases (BM) from NSCLC will be randomized in a ratio of 1:1 to receive stereotactic radio surgery (SRS) followed by either TTFields or supportive care alone. Patients are followed-up every two months until 2nd cerebral progression. Patients in the control arm may cross over to receive TTFields at the time of 2st cerebral progression. Objectives: To test the efficacy, safety and neurocognitive outcomes of TTFields in this patient population. Endpoints: Time to 1st cerebral progression based on the RANO-BM Criteria or neurological death (primary); time to neurocognitive failure based on the following tests: HVLT, COWAT and TMT; overall survival; radiological response rate; quality of life; adverse events severity and frequency (secondary). Main eligibility criteria: Karnofsky performance status (KPS) of 70 or above, 1 inoperable or 2-10 brain lesions amenable to SRS, optimal standard therapy for the extracranial disease, no brain-directed therapy, no signs of significantly increased intracranial pressure, no electronic implantable devices in the brain. Treatment: Continuous TTFields at 150 kHz for at least 18 hours per day will be applied to the brain within 7 days of SRS. The treatment system is a portable medical device allowing normal daily activities. The device delivers TTFields to the brain using 4 Transducer Arrays, which may be covered by a wig or a hat for cosmetic reasons. Patients will receive the best standard of care for their systemic disease. Statistical Considerations: This is a prospective, randomized, multicenter study for 270 patients. The sample size was calculated using a log-rank test (based on Lakatos 1988 and 2002) and has 80% power at a two sided alpha of 0.05 to detect a hazard ratio of 0.57. Clinical trial information: NCT02831959.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7153-7153
Author(s):  
G. M. Videtic ◽  
C. A. Reddy ◽  
S. T. Chao ◽  
T. W. Rice ◽  
D. J. Adelstein ◽  
...  

7153 Background: To explore gender, race and their interactions in the setting of NSCLC brain metastases only, a single-institution brain database was analyzed, using the RTOG recursive partitioning analysis (RPA) brain metastases classification. Methods: From 1/82 to 9/04, 831 NSCLC pts with brain metastases were registered. RPA criteria for analysis were: class I- Karnofsky performance status (KPS) ≥ 70, age<65 years, primary tumor controlled, no extracranial metastases; class III- KPS<70; class II- all others. Results: Median follow-up was 5.4 months (m) (range 0–122.9). Median age was 62.4 (range 25–90). Median KPS was 80 (range 20–100). There were 485 males [M] (58.4%) and 346 females [F] (41.6%). 824 pts (99%) were either African-American (AA; n = 142[17%]) or White (W; n = 682[83%]). Pts characteristics were balanced when stratified by RPA class and by treatments. Median survival (MS) in months from time of brain metastasis diagnosis for all pts was 5.8. MS in months by gender [F vs. M] and race [W vs. AA] was: 6.3 vs. 5.5, p = 0.013; 6.0 vs. 5.2, p = 0.08, respectively. By RPA class for gender, MS trends (in months) favored F over M in classes I and II but not III: 17.1 vs. 9.5 (p = 0.11); 6.8 vs. 6.0 (p = 0.09), 2.7 vs. 2.5 (p = 0.42), respectively. By RPA class for gender and race, MS trends (in months) favored AAF over AAM in classes I and II but not III: 30.0 vs. 12.4, p = 0.50; 11.2 vs. 4.6, p = 0.021; 3.2 vs. 3.2, p = 0.64, respectively; and WF over WM in classes I but not II or III: 14.4 vs. 9.5, p = 0.11; 6.6 vs. 6.3, p = 0.38; 2.4 vs. 2.3, p = 0.49, respectively. On multivariable analysis, significant variables were gender (p = 0.041; RR 0.83); RPA class (p < 0.0001; RR 0.28, for I vs. III; p < 0.0001; RR 0.51, for II vs. III). Conclusions: Gender significantly influences NSCLC brain metastasis survival while race trends to significance. MS trends by RTOG RPA class suggest race may interact with genderprimarily in class I but pt numbers limited significance. Further characterization of these factors is warranted. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 353-353 ◽  
Author(s):  
Daniel Yick Chin Heng ◽  
Toni K. Choueiri ◽  
Jae-Lyun Lee ◽  
Lauren Christine Harshman ◽  
Georg A. Bjarnason ◽  
...  

353 Background: Clinical trials have strict eligibility criteria to maintain internal validity. These criteria exclude many patients to whom the trial results are later applied to in clinical practice. Patients that do not meet eligibility criteria are poorly characterized. Methods: mRCC patients treated with VEGF targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky Performance Status (KPS) < 70%, brain metastases, non-clear cell histology, hemoglobin ≤ 9 g/dL, creatinine > 2x the upper limit of normal, platelet count of < 100x103/uL, neutrophil count < 1500/mm3 or corrected calcium ≤ 12 mg/dL. Results: 894/2076 (43%) patients were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression free survival (PFS) and median overall survival of first-line targeted therapy were 21% vs 29%, 5.2 vs 8.8 months and 14.5 vs 28.8 months (all p < 0.0001), respectively. Second-line PFS (if applicable) was 3.2 months in the trial ineligible vs 4.4 months in the trial eligible patients (p = 0.0074). When adjusted by the Heng et al prognostic categories, the hazard ratio for death between trial ineligible vs trial eligible patients was 1.621 (95% CI = 1.431–1.836, p < 0.0001). If only KPS, brain metastases and non-clear cell histology were used as exclusion criteria, 672 (32%) patients were excluded and the results were similar. Conclusions: The number of patients that are ineligible for clinical trials is high and their outcomes are inferior. Designing more inclusive clinical trials for this “ineligible” patient population are needed. [Table: see text]


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15546-e15546
Author(s):  
David Naskhletashvili ◽  
Vera Gorbunova ◽  
Mark Bychkov ◽  
Ali Bekyashev ◽  
Vladislav Karahan ◽  
...  

e15546 Background: About 2–11% of all patients (pts) with RCC develop BM, leading to a poor prognosis and a median survival of <6 months after whole brain radiotherapy. The role of targeted therapy in the management of BM is controversial. This study was designed to evaluate EGFR TKIs in RCC pts with BM. Methods: eligible pts had confirmed RCC and BM (≥1 lesion of ≥10mm diameter) aged >18 years with ECOG performanse status (PS) of 0–2. From June 2009 to January 2013, 11 pts with RCC and BM were enrolled in this study. 10 pts (91%) had extracranial metastases. 6 pts received sunitinib (50mg/day, 4 weeks, every cycle), 4 pts received sorafenib (800 mg/day) and 1 patient received pazopanib (800 mg/day) until radiologically-verified progressive disease. The primary endpoints were objective response rate (ORR) - complete and partial response in the brain and in the extracranial lesions, progressive-free survival (PFS) and overall survival. Demographics were: median age - 59 years (range 44–74 years); male/female - 10/1; PS 1/2 - 7/4; previously treated/untreated - 10/1; number of BM: ≤3/>3 - 6/5. Previous treatment: nephrectomy – 10 pts (91%), cytokines – 6 pts (54,5%), targeted therapy (before BM) – 4 pts (36,4%). Local control of BM: previous neurosurgery – 2 pts (18,2%), radiosurgery – 4 pts (36,4%), previous neurosurgery + radiosurgery – 2 pts (18,2%). Results: ORR in the brain was 27,3% (3 partial responses). All partial responses in the brain achieved in patients who received targeted therapy and radiosurgery. Stable disease in the brain was 54,5% (6 pts). 1 patient with stable in the brain received targeted therapy and radiosurgery, 5 pts received targeted therapy. ORR in the extracranial lesions was 20% (2 partial responses). Stable disease in the extracranial lesions was 50% (5 pts). The median of PFS was 6 months. The median of overall survival was 10 months. Conclusions: surgery and radiotherapy, including radiosurgery, must be considered as optimal local treatment for pts with RCC and BM. Targeted drugs have demonstrated their ability to achive a clinical and X-ray verified objective effect (as stabilization in most cases) in treating of pts with disseminated RCC and BM.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 487-487
Author(s):  
Stefan Stremitzer ◽  
Anna Sophie Berghoff ◽  
Nico Benjamin Volz ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  

487 Background: Brain metastases (BM) in colorectal cancer (CRC) are rare, developing in only 0.3-9% of the patients, and considered a late-stage manifestation of the disease. The aim of this study was to investigate whether genetic variants of genes involved in BM-related pathways, such as integrin, invasion- and adhesion-mediating, angiogenic and tumor suppressing pathways, are associated with outcome. Methods: Genomic DNA was extracted from formalin-fixed paraffin embedded resected BM from 70 patients with histologically proven CRC. Single nucleotide polymorphisms (SNP) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed by direct Sanger DNA sequencing and evaluated for association with overall survival (OS) from resection of BM. Only SNPs with an allele frequency of ≥ 10% were analyzed. Results: In univariate analysis, rs17577 (MMP9) and rs4642 (ITGB3) showed a significant difference in OS [(G/G 7.4 months, G/A 5.1 months; HR (95% CI) 1.83 (0.95-3.53), p = 0.0440) and (A/A 9.4 months, A/G 4.8 months, G/G 4.3 months; HR (95% CI) 0.81 (0.44-1.49) and 2.14 (0.98-4.67), p = 0.0354), respectively]. In multivariate analysis adjusted for baseline characteristics [primary tumor site (right colon, left colon, rectal), chemotherapy before BM (yes/no), BM location (supratentorial, infratentorial, both), Karnofsky performance status (<80, 80-100)], rs2236599 (KLF4), and rs10171481 (ITGAV) are significant in OS [(G/G 7.4 months, G/A or A/A 4.8 months; HR (95% CI) 3.19 (1.55-6.53), p = 0.0016) and (A/A 5.7 months, A/G 4.4 months, G/G 15.5 months; HR (95% CI) 0.61 (0.29-1.29) and 0.25 (0.10-0.60), p = 0.0082), respectively]. Conclusions: This study suggests for the first time a prognostic effect of the SNPs involved in the BM pathway. Further analyses are needed to confirm these findings.


2004 ◽  
Vol 22 (9) ◽  
pp. 1583-1588 ◽  
Author(s):  
W. Roa ◽  
P.M.A. Brasher ◽  
G. Bauman ◽  
M. Anthes ◽  
E. Bruera ◽  
...  

Purpose To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). Patients and Methods One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). Results All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P = .57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, −13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P = .63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (χ2 test, P = .02). Conclusion There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4538-4538
Author(s):  
Wanling Xie ◽  
Toni K. Choueiri ◽  
Jae-Lyun Lee ◽  
Lauren Christine Harshman ◽  
Georg A. Bjarnason ◽  
...  

4538 Background: Patients with mRCC have variable courses in terms of survival and response to targeted therapy. The patients at the two extremes of the survival spectrum need to be characterized. Methods: 2,161 patients with mRCC treated with targeted therapy were examined. 152 patients who survived 4 years or more after the initiation of targeted therapy (long-term) were compared with 218 patients who survived 6 months or less (short-term) over the same time period (2004-2007). Results: Long-term survivors had fewer poor prognostic factors (PFs) such as Karnofsky performance status (KPS) <80%, diagnosis to treatment interval<1 yr, hypercalcemia, anemia, thrombocytosis and neutrophilia (all p<0.0001). Patients with favorable prognosis who responded to targeted therapy were more likely to be long term survivors. For those in the intermediate risk group, patients who were long-term survivors were more likely to have only 1 poor prognostic factor (73% vs. 28%, p<0.0001) and KPS≥80% (88% vs. 69%, p=0.009) compared to those in the short term survivor group. On multivariable analysis adjusting for PFs, response to targeted therapy (PR or better) significantly predicted long term survivor status (odds ratio=6.3, 95% CI: 2.3,17.4, p=0.0004). Conclusions: Long term survivors had a higher response rate to targeted therapy, a longer treatment duration and more use of second-line targeted therapy. Baseline prognostic criteria may be able to discriminate between long- and short- term survivors. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20604-e20604 ◽  
Author(s):  
Robert H. Press ◽  
Xinyan Zhang ◽  
Richard John Cassidy ◽  
Matthew Jeffrey Ferris ◽  
Jim Zhong ◽  
...  

e20604 Background: Historically, survival in patients (pts) with NSCLC brain metastases (BM) is poor, however, improved systemic therapies are now available including targeted therapies and immunotherapy. We sought to evaluate the prevalence of genetic alterations in pts with BM from non-squamous (NS) lung cancer, and to determine clinical outcomes in the modern era. Methods: With IRB approval, pts with BM from NS-NSCLC from 1/2010-1/2016 with genetic testing were captured and retrospectively reviewed. Snapshot genotyping was performed prior to 1/2014, after which Next Generation Sequencing was utilized, along with FISH lung cancer panel. Genes examined included: EGFR, ALK, RET, ROS1, TP53, KRAS, NRAS, MET, PTEN, BRAF, FBXW7, MAP2K1, APC, PIK3CA, CTNNB1, and SMAD4. Univariable and multivariable analysis (MVA) were utilized to assess factors associated with overall survival (OS). Results: 92 pts were included. Median number of BM was 4 (range 1-45). Median age was 64 (32-90 years). 59.8% were male. 38% received targeted therapy, 11% received immunotherapy, and 70% received conventional chemotherapy. 52.2% and 47.8% received whole brain radiotherapy and stereotactic radiosurgery, respectively. Median OS from first brain radiotherapy (RT) was 10.7 months (0.1-56.4). EGFR mutation, ALK fusion, ROS1 rearrangement, and RET rearrangement occurred in 27.5%, 5.2%, 1.7%, and 0% of pts. EGFR L858 and EGFR T790 mutations occurred in 19.2% and 2.7% of all pts. TP53, KRAS, and NRAS mutations occurred in 63.9%, 28.8% and 7% of pts. All other mutations had an incidence of less than 3%. On MVA, targeted therapy (HR 0.43 95% CI 0.22-0.86), immunotherapy (HR 0.04 95% CI 0.01-0.3), surgical resection (HR 0.38 95% CI 0.18-0.81), and ECOG performance status (0.23 95% CI 0.1-0.54) were associated with improved OS. No specific genetic aberration, RT modality, or number of BM was associated with OS. Conclusions: In pts with BM from NS-NSCLC, the most common molecular aberrations include TP53, EGFR, and KRAS mutations. Treatment with brain RT and modern systemic therapies yields a median survival greater than ten months. The use of targeted therapy or immunotherapy was associated with increased OS.


2017 ◽  
Vol 13 (9) ◽  
pp. e782-e791 ◽  
Author(s):  
Lindsay L. Puckett ◽  
Eric Luitweiler ◽  
Louis Potters ◽  
Sewit Teckie

Purpose: Approximately one third of patients with cancer require palliative radiation therapy (PRT), yet no guidelines exist for optimal patient selection. We have observed that many patients who begin PRT do not complete their prescribed treatment. Our study sought to identify factors associated with discontinuation of PRT, assess for a relationship with survival, and inform patient selection. Methods: We performed an institutional review board–approved retrospective analysis of patients with cancer treated in a multicenter radiation oncology department in 2014. Of 297 patients who began PRT, 60 discontinued and 237 completed treatment. Primary end points included discontinuation and overall survival. Results: Patient factors were analyzed for association with discontinuation of PRT and overall survival, respectively, using logistic regression and Cox proportional regression models. Factors associated with discontinuation were low Karnofsky performance status (KPS) score, high number of fractions prescribed, and treatment site other than bone metastasis. The odds of discontinuing PRT decreased by approximately 52% for every 10-point increase in KPS score (odds ratio, 0.48; 95% CI, 0.36 to 0.63; P < .001). Factors associated with shorter survival included discontinuation of PRT, low KPS score, community practice location, multiple comorbidities, and treatment of brain metastases. Patients who discontinued treatment were more likely to die than patients who completed treatment, independent of other factors (hazard ratio, 3.67; 95% CI, 2.41 to 5.61; P < .001). Conclusion: Patients with low KPS scores, long treatment courses, and those treated to sites other than bone metastasis were significantly more likely to discontinue treatment. Discontinuation was predictive for poor survival. Pretreatment evaluation of KPS, comorbidities, and brain metastases can help guide appropriate patient selection for PRT.


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