Influence of genetic variants of genes potentially associated with colorectal brain metastases on overall survival.

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.

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4653-4653
Author(s):  
T. Nelius ◽  
T. Klatte ◽  
F. Reiher ◽  
S. Filleur ◽  
R. Yap ◽  
...  

4653 Background: D-based chemotherapy is a burgeoning option for men with advanced HRPC. Alone or in combination with E, D has been shown to improve median survival. In this study we tested the combination of D with two different doses of E in patients (pts) with HRPC to improve response rates and to lower side effects. Methods: 72 metastatic HRPC pts were randomly assigned to receive D (70 mg/m2 IV, d2, q3w) and E (3 × 280 mg/d PO starting 1 day prior to D, for 5 consecutive days) for arm A or E (3 x 140 mg/d PO starting 1 day prior to D, for 3 consecutive days) for arm B. Premedication with oral DX at a total daily dose of 16 mg, in divided doses two times a day was administered in arm A on day 1 to 5 and in arm B on day 1 to 3. Initially, 6 cycles were administered and repeated after significant PSA rise. Pts were monitored for PSA response, time to progression (TTP), survival and toxicity. Results: PSA declines of ≥75%, ≥50% and ≤50% were 36.8%, 55.3% and 44.7% in arm A and 38.2%, 67.6% and 32.4% in arm B, respectively (P = .442). TTP in Arm A and Arm B were 11 months (95% CI, 7–14) versus 14 months (95% CI, 8–19), P = .6911) and overall survival 21 months (95% CI, 6–35) versus 22 months (95% CI, 18–27), respectively, (P = .4149). The primary treatment-related side effects observed in arm A and arm B were granulocytopenia (34% and 29%, P = .663) and thrombotic complications caused by E (four pts (11%) and one pt (3%), respectively, P = .206). Associated baseline factors with overall survival in univariate analysis were ECOG performance status (P < .001), hemoglobin level (P < .001), bone pain (P < .001), and PSA (P < .097) and in multivariate analysis ECOG performance status (95% CI, 2.9–13.9) and bone pain (95% CI, 3.2–20.1), (P < .001). Conclusions: In this randomized phase II study the combination of D and E had substantial activity in HRPC. We did not find a statistically significant difference of higher dose of E in combination with D compared to a lower dose of E and D regarding PSA response, TTP and survival. However, there was a tendency of higher toxicity in the high dose E group. These treatment-related toxicities were mainly hematologic and manageable. The results of this study support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. No significant financial relationships to disclose.


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 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.


Neurosurgery ◽  
2017 ◽  
Vol 80 (6) ◽  
pp. 871-879 ◽  
Author(s):  
Rupesh Kotecha ◽  
Nicholas Damico ◽  
Jacob A. Miller ◽  
John H. Suh ◽  
Erin S. Murphy ◽  
...  

Abstract BACKGROUND: Although patients with brain metastasis are treated with primary stereotactic radiosurgery (SRS), the use of salvage therapies and their consequence remains understudied. OBJECTIVE: To study the intracranial recurrence patterns and salvage therapies for patients who underwent multiple SRS courses. METHODS: A retrospective review was performed of 59 patients with brain metastases who underwent ≥3 SRS courses for new lesions. Cox regression analyzed factors predictive for overall survival. RESULTS: The median age at diagnosis was 52 years. Over time, patients underwent a median of 3 courses of SRS (range: 3-8) to a total of 765 different brain metastases. The 6-month risk of distant intracranial recurrence after the first SRS treatment was 64% (95% confidence interval: 52%-77%). Overall survival was 40% (95% confidence interval: 28%-53%) at 24 months. Only 24 patients (41%) had a decline in their Karnofsky Performance Status ≤70 at last office visit. Quality of life was preserved among 77% of patients at 12 months, with 45% experiencing clinically significant improvement during clinical follow-up. Radiation necrosis developed in 10 patients (17%). On multivariate analysis, gender (males, Hazard Ratio [HR]: 2.0, P &lt; .05), Karnofsky Performance Status ≤80 (HR 3.2, P &lt; .001), extracranial metastases (HR: 3.6, P &lt; .001), and a distant intracranial recurrence ≤3 months from initial to repeat SRS (HR: 3.8, P &lt; .001) were associated with a poorer survival. CONCLUSION: In selected patients, performing ≥3 SRS courses controls intracranial disease. Patients may need salvage SRS for distant intracranial relapse, but focal retreatments are associated with modest toxicity, do not appear to negatively affect a patient's performance status, and help preserve quality of life.


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.


2003 ◽  
Vol 2 (3) ◽  
pp. 267-272 ◽  
Author(s):  
Deepak Khuntia ◽  
Ratna Sajja ◽  
Mark A. Chidel ◽  
Shih-Yuan Lee ◽  
Thomas W. Rice ◽  
...  

There are over 200,000 cases of brain metastases (BrM) every year, but very few are from esophageal cancer primaries. In order to determine predictors for outcome of these patients, the authors conducted a retrospective review of twenty-seven patients with BrM from esophageal carcinoma diagnosed at the Cleveland Clinic Foundation between 1991 and 2001. For the entire cohort, median follow-up and median survival was 3.6 months and 3.6 months, respectively. On univariate analysis, patients with Karnofsky Performance Status (KPS) ≥ 70, low recursive partitioning analysis score, single BrM, no systemic disease, and aggressive treatment [surgery, stereotactic radiosurgery (SRS) + whole brain radiation (WBRT), SRS + surgery + WBRT, surgery + WBRT)] had a significantly improved survival. In a multivariate model, patients with higher KPS and aggressive treatment had improved survival. The 1-year survival for the WBRT alone group and the aggressive treatment group was 6%, and 36% respectively. We conclude that based on the data presented here, patients with BrM from esophageal cancer have poor outcome. Aggressive treatment and favorable KPS are associated with longer survival for selected patients. We recommend esophageal cancer patients with BrM be enrolled in clinical trials to better delineate the role of treatment and potentially improve results.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 844
Author(s):  
Kerstin Riecke ◽  
Volkmar Müller ◽  
Rudolf Weide ◽  
Marcus Schmidt ◽  
Tjoung-Won Park-Simon ◽  
...  

Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded-prognostic-assessment (GPA)-scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients (n = 197) had triple-negative, 33.4% (n = 295) luminal A like, 25.1% (n = 221) luminal B/HER2-enriched like and 19.2% (n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple-negative subtype and low Karnofsky-Performance-Status (KPS) were all associated with worse overall survival (OS) in univariate analysis (p < 0.001 each). All three GPA-scores were associated with OS. The breast-GPA showed the highest probability of classifying patients with survival above 12 months in the best prognostic group (specificity 68.7% compared with 48.1% for the updated breast-GPA and 21.8% for the original GPA). Sensitivities for predicting 3 months survival were very low for all scores. In this analysis, all GPA-scores showed only moderate diagnostic accuracy in predicting the OS of BC patients with BM.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi15-vi15
Author(s):  
Yanwei Liu ◽  
Xia Shan ◽  
Xiaoguang Qiu

Abstract Our previous data showed that WHO grade II/III gliomas with isocitrate dehydrogenase wide-type (IDH-wt) and telomerase reverse transcriptase promoter mutation (TERTp-mut) have dismal prognosis as glioblastoma. This study compared concurrent chemoradiotherapy(CRT) with radiotherapy(RT) alone on the outcome of these patients. Between September 2016 and November 2018, 30 eligible grade II/III glioma patients with IDH-wt and TERTp-mut were randomly assigned to receive either RT (60 Gy in 30 daily fractions for 6 weeks) alone (n=15) or concurrent CRT with daily temozolomide and adjuvant temozolomide (n=15). The median follow-up duration was 15.5 months. The median age was 51 years (range, 24–66 years). The median Karnofsky performance status (KPS) score at randomization was 80 (range, 60–80). Surgery was the primary treatment. The characteristics of the two treatment groups were well balanced at baseline. The 1-year OS rate was significant difference between CRT group (92.3%; 95% CI: 77.8–100) and RT alone group(71.1%; 95% CI: 47.0–95.2) (p = 0.019). Local, distant, and combined tumor recurrence patterns were observed in 4 (26.7%), 1 (6.7%), and 3 patients (20%) in the CRT group and 4 (26.7%), 3 (20%), and 3 patients (20%) in the RT alone group. Those treated with RT alone had shorter median PFS (9 vs 18 months, HR: 0.517; 95% CI: 0.193 to 1.386; p = 0.19). CRT with temozolomide and extent of resection were statistically significant predictors for survival on univariate analysis. Multivariate analysis showed that CRT was associated with a significantly better OS compared with RT alone (OR=0.195; 95% CI, 0.044 to 0.867; p=0.032). Consequently, concurrent CRT with daily temozolomide and adjuvant temozolomide for newly diagnosed IDHwt/TERTp-mut grade II/III gliomas had significantly better OS compared with RT alone. A large multi-center prospective randomized trial is warranted. The trial has been registered at ClinicalTrials.gov (NCT02766270).


2020 ◽  
Author(s):  
Morgan Guénolé ◽  
François Lucia ◽  
Vincent Bourbonne ◽  
Gurvan Dissaux ◽  
Emmanuelle Reygagne ◽  
...  

Abstract Background: The aim of this study was to determine the safety and efficacy of fractionated stereotactic radiotherapy (SRT) in combination with systemic therapies (ST) for brain metastases (BM). Methods: 99 patients (171 BM) received SRT and concurrent ST (group 1) and 95 patients (131 BM) received SRT alone without concurrent ST (group 2). SRT was planned on a linear accelerator, using volumetric modulated arc therapy. All ST were allowed including chemotherapy (CT), immunotherapy (IT), targeted therapy (TT) and hormonotherapy (HT). Treatment was considered to be concurrent if the timing between the drug administration and SRT did not exceed 1 month. IT was used concurrently with SRT in 30 patients. Local control (LC), freedom for distant brain metastases (FFDBM), overall survival (OS) and radionecrosis (RN) were evaluated. Variables analyzed included histology, age, gender, diagnosis-specific Graded Prognostic Assessment score, recursive partitioning analysis score, number of BM, presence of extracranial metastases, tumor volume, Karnofsky performance status and the timing of ST. Results: After a median follow-up of 11.9 months (range 0.7-29.7), there was no significant difference between the two groups. However, patients who received concurrent IT had better 1-year LC, FFDBM and RN rate compared to patient who did not: 96% versus 78% (p=0.02), 76% versus 53% (p=0.004) and 80% versus 90% (p=0.03), respectively. In multivariate analysis, concurrent IT (p=0.022) and tumor volume <2.07cc (p=0.039) were significantly correlated with improvement of LC. The addition of IT to SRT compared to SRT alone was associated with an increased risk of RN (p=0.03).Conclusion: SRT delivered concurrently with IT improved LC, FFDBM, OS with a higher RN rate.


2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv12-iv13
Author(s):  
Mark Noble ◽  
Jeng Ching ◽  
Enrico Clarke

Abstract Aims Since 2016, the University Hospital Southampton NHS Foundation Trust (UHSFT) has been commissioned by NHS England to deliver SRST to brain metastases. At UHSFT, all referrals are discussed at the Wessex Neurosciences multidisciplinary team meeting. Referrals that satisfy the criteria set by NHS England (estimated prognosis greater than 6 months, absence or controlled extracranial disease or potentially controllable extracranial disease with a Karnofsky Performance Status &gt;70%) will be offered SRST. This retrospective study was performed to assess overall survival rates of patients with brain metastases treated with SRST with further tumour subtype analysis. We also benchmarked our results with other SRST centres. Method Retrospective data collection was performed for all the patients who have been treated with SRST. Patients who received SRST to a single metastasis, multiple metastases and/or to the resection cavity between 01/01/2017 to 30/09/2019 were included in this study. All treatment was delivered using a LINAC based SRST platform. Prescription doses ranged from 13.5 Gy to 21 Gy in a single fraction, 21 to 24 Gy in 3 fractions and 25 Gy in 5 fractions. Patients are treated using a stereotactic thermoplastic immobilisation shell and dynamic conformal arc therapy with ExacTrac TM and Cone Beam CT imaging. Dates of death were obtained from the NHS Digital Spine and survival analysis using median overall survival was performed using the Kaplan Meier Method. Results 277 patients were treated between 01/01/17 and 30/9/2019. The median overall survival from the Kaplan Meier Method was shown to be 14.7 months and the 6-month overall survival was 71% for all patients. Sub-group analysis of individual tumour sites showed: lung (n=110) median OS 12.1 months, melanoma (n=58) median OS 26.4 months, breast (n=46) median OS not reached (67% still alive) but 18 months survival was 70%, renal (n=22) median OS 15.4 months and colorectal (n=19) median OS 6 months. “Other” tumour sites (n=22) included patients with ovarian, neuroendocrine, sarcoma, testis, oesophagus, unknown primary and gallbladder which were grouped together due to small patient numbers. 41% of patients treated were alive at the time of analysis. Conclusion Patients with brain metastases treated with SRST at UHFST have similar outcomes compared to other SRST centres. These patients have a median overall survival of 14.7 months. However, 29% of patients analysed did not survive more than 6 months. Further collection and analysis of the data might improve patient selection and their outcomes.


Sign in / Sign up

Export Citation Format

Share Document