Surgical Indication Optimization of Brain Metastases Based on the Evolutionary Analysis of Karnofsky Performance Status

2021 ◽  
Author(s):  
Jorge Rasmussen ◽  
Pablo Ajler ◽  
Daniela Massa ◽  
Pedro Plou ◽  
Matteo Baccanelli ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Functional Status ◽  
Surgical Resection ◽  
Pharmacological Treatment ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Cohort Analysis ◽  
Surgical Indication ◽  
Evolutionary Analysis ◽  
Survival Curves

Abstract Background and Objective Surgical resection of brain metastases (BM) offers the highest rates of local control and survival; however, it is reserved for patients with good functional status. In particular, the presence of BM tends to oversize the detriment of the overall functional status, causing neurologic deterioration, potentially reversible following symptomatic pharmacological treatment. Thus, a timely indication of surgical resection may be dismissed. We propose to identify and quantify these variations in the functional status of patients with symptomatic BM to optimize the indication of surgical resection. Patients and Methods Historic, retrospective cohort analysis of adult patients undergoing BM microsurgical resection, consecutively from January 2012 to May 2016, was conducted. The Karnofsky performance status (KPS) variation was recorded according to the symptomatic evolution of each patient at specific moments of the diagnostic–therapeutic algorithm. Finally, survival curves were delineated for the main identified factors. Results One hundred and nineteen resection surgeries were performed. The median overall survival was 243 days, while on average it was 305.7 (95% confidence interval [CI]: 250.6–360.9) days. The indication of surgical resection of 10% of the symptomatic patients in our series (7.5% of overall) could have been initially rejected due to pharmacologically reversible neurologic impairment. Survival curves showed statistically significant differences when KPS was stratified following pharmacological symptomatic treatment (p < 0.0001), unlike when they were estimated at the time of BM diagnosis (p = 0.1128). Conclusion The preoperative determination of the functional status by KPS as an evolutive parameter after the nononcologic symptomatic pharmacological treatment allowed us to optimize the surgical indication of patients with symptomatic BM.

scholarly journals Stereotactic Radiosurgery for Renal Cancer Brain Metastasis: Prognostic Factors and the Role of Whole-Brain Radiation and Surgical Resection

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Franziska M. Ippen ◽  
Anand Mahadevan ◽  
Eric T. Wong ◽  
Erik J. Uhlmann ◽  
Soma Sengupta ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Surgical Resection ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Patient Treatment ◽  
Consecutive Series ◽  
Additional Surgery

Background. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection.Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed.Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31–85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60–100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively.Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate.

scholarly journals Cyberknife® hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases

2021 ◽  
Author(s):  
Sergej Telentschak ◽  
Daniel Ruess ◽  
Stefan Grau ◽  
Roland Goldbrunner ◽  
Niklas von Spreckelsen ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Poor Prognosis ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Salvage Treatment ◽  
Treatment Modalities ◽  
Large Tumor ◽  
Fractionated Radiotherapy ◽  
Hypofractionated Stereotactic Radiosurgery

Abstract Purpose The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature. Methods All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE). Results We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%. The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively. Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1–3 were observed in 12%. Conclusion Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.

scholarly journals Clinicopathologic Features and Early Surgical Outcome of Astrocytomas in Eldoret, Kenya

2018 ◽  
Vol 09 (03) ◽  
pp. 363-369
Author(s):  
Clifford C. Mwita ◽  
Florentius Koech ◽  
Titus Sisenda ◽  
Kirtika Patel ◽  
Benson Macharia ◽  
...  
Keyword(s):  
Functional Status ◽  
Tumor Size ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Neurological Deficits ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Short Term ◽  
Duration Of Illness ◽  
Mri Score

ABSTRACT Background: Astrocytomas are primary central nervous system tumors arising from astrocytes and accounting for up to 37.8% of all brain tumors seen in hospital-based studies from Africa. Despite being common, their patterns and short-term outcomes remain poorly studied in Kenya. Materials and Methods: A prospective, descriptive study involving consecutive patients with a histological diagnosis of astrocytoma seen in three hospitals located in Eldoret, Kenya. Clinicopathologic characteristics and outcomes were recorded and patients followed up for 12 weeks. Results: Thirty-one patients were recruited over a 1-year period. Majority of them were female (51.6%). Headache (83.9%) and focal neurological deficits (64.5%) were the most common presenting features. Among patients with high-grade tumors, mean duration of illness was 106.03 ± 162.16 days, median functional status was Karnofsky performance status (KPS) score 50, mean tumor size was 110.22 ± 46.16 cm3, and median magnetic resonance imaging (MRI) score was 17. Among patients with low-grade astrocytomas, mean duration of illness was 213.03 ± 344.93 days, median functional status was KPS score 40, mean tumor size was 53.49 ± 54.96 cm3 and median MRI score was 9. Glioblastoma multiforme (GBM) (71%) and diffuse astrocytoma (22.6%) were the predominant histological subtypes. The median Ki-67 proliferative index was 6% for pilocytic astrocytoma, 1.6% for diffuse astrocytoma, and 60% for GBM. Systemic and regional surgical complications occurred in 6.5% and 38.7% of patients, respectively. In-hospital mortality was 19.4% and increased to 25.8% at 12 weeks. The KPS score at discharge was 50 and improved to 60 at 12 weeks. Only 9.7% of patients had acceptable functional status at 12 weeks follow-up. Conclusions: In this locality, headache, focal neurological deficits, and reduced functional status are the most common presenting features of astrocytomas while GBM is the most common histological subtype. Tumors are highly proliferative and in the short-term, both surgical and functional outcome are suboptimal.

Postoperative ischemic changes following brain metastasis resection as measured by diffusion-weighted magnetic resonance imaging

2013 ◽  
Vol 119 (6) ◽  
pp. 1395-1400 ◽  
Author(s):  
Jens Gempt ◽  
Julia Gerhardt ◽  
Vivien Toth ◽  
Stefanie Hüttinger ◽  
Yu-Mi Ryang ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Neurological Deficit ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Neurological Status ◽  
Neurological Deficits ◽  
Brain Irradiation ◽  
Diffusion Weighted ◽  
The Mean

Object Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits. Methods Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded. Results One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21–89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0–338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003). Conclusions This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.

scholarly journals Factors influencing the outcome of stereotactic radiosurgery in patients with five or more brain metastases

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
E. Hamel-Perreault ◽  
D. Mathieu ◽  
L. Masson-Cote
Keyword(s):  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Nonsmall Cell Lung Cancer ◽  
Factors Influencing ◽  
Treatment Volume ◽  
Extracranial Disease

Background Stereotactic radiosurgery (srs) for patients with 5 or more brain metastases (bmets) is a matter of debate. We report our results with that approach and the factors influencing outcome.Methods In the 103 patients who underwent srs for the treatment of 5 or more bmets, primary histology was nonsmall- cell lung cancer (57% of patients). All patients were grouped by Karnofsky performance status and recursive partitioning analysis (rpa) classification. In our cohort, 72% of patients had uncontrolled extracranial disease, and 28% had stable or responding systemic disease. Previous irradiation for 1–4 bmets had been given to 56 patients (54%). The mean number of treated bmets was 7 (range: 5–19), and the median cumulative bmets volume was 2 cm3 (range: 0.06–28 cm3).Results Multivariate analyses showed that stable extracranial disease (p < 0.001) and rpa (p = 0.022) were independent prognostic factors for overall survival (os). Moreover, a cumulative treated bmets volume of less than 6 cm3 (adjusted hazard ratio: 2.54; p = 0.006; 95% confidence interval: 1.30 to 4.99) was associated with better os. The total number of bmets had no effect on survival (p = 0.206). No variable was found to be predictive of local control. The rpa was significant (p = 0.027) in terms of distant recurrence.Conclusions Our study suggests that srs is a reasonable option for the management of patients with 5 or more bmets, especially with a cumulative treatment volume of less than 6 cm3.

Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review

Neurosurgery ◽  
2017 ◽  
Vol 83 (1) ◽  
pp. 128-136 ◽  
Author(s):  
E Emily Bennett ◽  
Michael A Vogelbaum ◽  
Gene H Barnett ◽  
Lilyana Angelov ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Early Death ◽  
Tumor Type ◽  
Prognostic Groups ◽  
Prior Surgery

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival. OBJECTIVE To evaluate prognostic factors, which may predict early death (within 90 d) after SRS. METHODS A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices. RESULTS Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable. CONCLUSION Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.

Do gender and race influence survival in patients with non-small cell lung cancer brain metastases? An outcomes study utilizing the RTOG RPA class stratification

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 ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Recursive Partitioning ◽  
Multivariable Analysis ◽  
Class I ◽  
Class Iii ◽  
Gender And Race ◽  
Class Stratification

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.

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 ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Local Treatment ◽  
Multivariable Analysis ◽  
First Line ◽  
The Brain

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]

A multicentered population-based analysis of outcomes of patients with metastatic renal cell carcinoma (mRCC) who do not meet eligibility criteria for clinical trials.

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 ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Clear Cell ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Exclusion Criteria ◽  
Eligibility Criteria ◽  
Number Of Patients

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]

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 ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Genetic Variants ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Nucleotide Polymorphisms ◽  
Primary Tumor Site ◽  
Prognostic Effect ◽  
Significant Difference

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.

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