Surgical management and clinical outcomes of cerebellar liponeurocytomas-a report of 7 cases and a pooled analysis of individual patient data

Abstract Objective Cerebellar liponeurocytomas (CLPNs) are very rare. Limited studies described this disease and their treatment protocol remain unclear. To better understand the disease, we review the clinical features and outcomes, and propose a treatment protocol based on previously reported cases and cases from our institute. Methods The clinical data were obtained from 7 patients with pathologically confirmed CLPNs, who accepted surgical treatment in our institute between November 2011 and June 2021. We also reviewed the literature and 75 patients with CLPNs were identified between September 1993 and June 2021. Risk factors for Progression-free survival (PFS) were evaluated in the pooled cohort. Results The authors’ cohort included 4 males and 3 females with a mean age of 43.9±14.5 (range: 29-64 years). 3 cases are located in lateral ventricle and 4 cases are located in cerebellum. All 7 cases achieved gross total resection (GTR) and radiotherapy was administered to 2 cases. After a mean follow-up of 44.9±44.4 months, all patients remained well with no recurrence or death. For the reported 75 patients, there are 35 males and 40 females with a mean age of 46.2±13.6 years (range: 6-77 years). Biopsy, gross total resection (GTR) and non-GTR were achieved in 1 (1.3%), 50 (66.7%), and 24 (32%) patients, respectively. Radiotherapy was administered to 16 cases and chemotherapy was administered to only 1 case. After a mean follow-up of 47.5±51.5 months, 3 patients died and tumor recurrence occurred in 17 patients. Multivariate Cox analysis revealed that non-GTR predicted a poor PFS (p=0.030). Kaplan-Meier analysis showed that GTR was significantly associated with better PFS (p=0.0084). PFS rates at 1, 5, 10 years were 92.7%, 78.0%, 23.8% respectively. Conclusions Cerebellar liponeurocytomas (CLPNs) are very rare brain tumors. Although they have favorable clinical prognosis, the recurrence is relatively high. GTR should be the first choice and close follow-up is necessary. Postoperative radiotherapy could not improve PFS in this study. A larger cohort is needed to verify our findings.

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The Long-term Outcome After Resection of Intraspinal Nerve Sheath Tumors

Neurosurgery ◽

10.1227/neu.0000000000000890 ◽

2015 ◽

Vol 77 (4) ◽

pp. 585-593 ◽

Cited By ~ 10

Author(s):

Charlotte Marie Halvorsen ◽

Pål Rønning ◽

John Hald ◽

Tom Børge Johannesen ◽

Frode Kolstad ◽

...

Keyword(s):

Clinical Outcome ◽

Progression Free Survival ◽

Gross Total Resection ◽

Subtotal Resection ◽

Total Resection ◽

Free Survival ◽

Nerve Sheath Tumors ◽

Nerve Sheath

Abstract BACKGROUND: The existing literature on recurrence rates and long-term clinical outcome after resection of intraspinal nerve sheath tumors is limited. OBJECTIVE: To evaluate progression-free survival, overall survival, and long-term clinical outcome in a consecutive series of 131 patients with symptomatic intraspinal nerve sheath tumors. METHODS: Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status. RESULTS: Follow-up data are 100% complete; median follow-up time was 6.1 years. All patients (100%) had surgery as the first line of treatment; gross total resection was performed in 112 patients (85.5%) and subtotal resection in 19 patients (14.5%). Five-year progression-free survival was 89%. The following risk factors for recurrence were identified: neurofibroma, malignant peripheral nerve sheath tumor, subtotal resection, neurofibromatoses/schwannomatosis, and advancing age at diagnosis. More than 95% of patients had neurological function compatible with an independent life at follow-up. The rate of tumor recurrence in nonneurofibromatosis patients undergoing total resection of a single schwannoma was 3% (3/93), in comparison with a recurrence rate of 32% (12/38) in the remaining patients. CONCLUSION: Gross total resection is the gold standard treatment for patients with intraspinal nerve sheath tumors. In a time of limited health care resources, we recommend that follow-up be focused on the subgroup of patients with a high risk of recurrence. The benefit of long-term, yearly magnetic resonance imaging follow-up with respect to recurrence in nonneurofibromatosis patients undergoing gross total resection of a single schwannoma is, in our opinion, questionable.

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Outcomes After Surgery and Radiotherapy for Spinal Myxopapillary Ependymoma

Neurosurgery ◽

10.1227/neu.0000000000000408 ◽

2014 ◽

Vol 75 (3) ◽

pp. 205-214 ◽

Cited By ~ 20

Author(s):

Chiaojung Jillian Tsai ◽

Yucai Wang ◽

Pamela K. Allen ◽

Anita Mahajan ◽

Ian E. McCutcheon ◽

...

Keyword(s):

Cox Regression ◽

Postoperative Radiotherapy ◽

Gross Total Resection ◽

Entire Group ◽

Subtotal Resection ◽

Myxopapillary Ependymoma ◽

Adjuvant Radiation ◽

Total Resection ◽

Cox Regression Analysis

Abstract BACKGROUND: The role of radiotherapy after surgery for myxopapillary ependymoma (MPE) is unclear. OBJECTIVE: To review long-term outcomes after surgery, with or without radiation, for spinal MPE. METHODS: Fifty-one patients with spinal MPE treated from 1968 to 2007 were included. Associations between clinical variables and overall survival (OS), progression-free survival (PFS), and local control (LC) were tested with Cox regression analysis. RESULTS: The median age at diagnosis was 35 years (range, 8-63 years). Twenty patients (39%) had surgery alone, 30 (59%) had surgery plus radiotherapy (RT), and 1 (2%) had RT only. At a median follow-up of 11 years (range, 0.2-37 years), 10-year OS, PFS, and LC for the entire group were 93%, 63%, and 67%, respectively. Nineteen patients (37%) had disease recurrence, and the recurrence was mostly local (79%). Twenty-eight of 50 patients who had surgery (56%) had gross total resection; 10-year LC was 56% after surgery vs 92% after surgery and RT (log-rank P = .14); the median time of LC was 10.5 years for patients receiving gross total resection plus RT, and 4.75 years for gross total resection only (P = .03). Among 16 patients with subtotal resection and follow-up data, 10-year LC was 0% after surgery vs 65% for surgery plus RT (log-rank P = .008). On multivariate analyses adjusting for resection type, age older that 35 years at diagnosis and receipt of adjuvant radiation were associated with improved PFS (hazard ratio [HR]: 0.14, P = .003 and HR: 0.45, P = .009) and LC (HR: 0.22, P = .02 and HR: 0.45, P = .009). CONCLUSION: Postoperative radiotherapy after resection of MPE was associated with improved PFS and LC.

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Long-term Outcome After Resection of Intraspinal Ependymomas: Report of 86 Consecutive Cases

Neurosurgery ◽

10.1227/neu.0b013e3181f96d41 ◽

2010 ◽

Vol 67 (6) ◽

pp. 1622-1631 ◽

Cited By ~ 40

Author(s):

Charlotte Marie Halvorsen ◽

Frode Kolstad ◽

John Hald ◽

Tom Børge Johannesen ◽

Bård Kronen Krossnes ◽

...

Keyword(s):

Progression Free Survival ◽

Neurological Function ◽

Gross Total Resection ◽

Total Resection ◽

Long Term Outcome ◽

Free Survival ◽

Risk Of Death ◽

Primary Surgery

Abstract BACKGROUND: Objective: To evaluate progression-free survival, overall survival (OS) and long-term clinical outcome in a consecutive series of 86 patients with intraspinal ependymomas. METHODS: Medical charts were retrospectively reviewed. Surviving patients voluntarily participated in a clinical history and physical examination that focused on neurological function and current tumor status. RESULTS: Follow-up data are nearly 100% complete; mean follow-up time was 82 months. Eighty-five patients (99%) had surgery as a first-line treatment; 14 (17%) of these patients received adjuvant radiotherapy. Of the 85 patients who underwent primary surgery, gross total resection was performed in 60 patients (71%) and subtotal resection in 25 patients (29%). Ten-year progression-free survival rate was 75%; 5-year OS, 97%; and 10-year OS, 91%. Reduced preoperative neurological function and older age at diagnosis were significantly associated with increased risk of death. At follow-up, spontaneous regression of residual tumor after primary surgery may have occurred in 7 of 19 patients (37%). More than 75% of patients had neurological function compatible with an independent life at follow-up. Good preoperative neurological function was significantly associated with favorable outcome. It was not possible to evaluate the effect of radiotherapy on progression-free survival and OS. CONCLUSION: Gross total resection remains the optimal treatment for patients with spinal ependymoma. Patients should be monitored with a clinical examination and magnetic resonance imaging at regular intervals up to 10 years after surgery.

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Evolution of Surgical Approaches in the Treatment of Petroclival Meningiomas: A Retrospective Review

Operative Neurosurgery ◽

10.1227/01.neu.0000303218.61230.39 ◽

2007 ◽

Vol 61 (suppl_5) ◽

pp. ONS202-ONS211 ◽

Cited By ~ 36

Author(s):

Nicholas C. Bambakidis ◽

U. Kumar Kakarla ◽

Louis J. Kim ◽

Peter Nakaji ◽

Randall W. Porter ◽

...

Keyword(s):

Survival Rates ◽

Progression Free Survival ◽

Surgical Approaches ◽

Single Institution ◽

Short Term ◽

Total Resection ◽

Free Survival ◽

Petroclival Meningioma ◽

Petroclival Meningiomas

Abstract Objective: We examined the surgical approaches used at a single institution to treat petroclival meningioma and evaluated changes in method utilization over time. Methods: Craniotomies performed to treat petroclival meningioma between September of 1994 and July of 2005 were examined retrospectively. We reviewed 46 patients (mean follow-up, 3.6 yr). Techniques included combined petrosal or transcochlear approaches (15% of patients), retrosigmoid craniotomies with or without some degree of petrosectomy (59% of patients), orbitozygomatic craniotomies (7% of patients), and combined orbitozygomatic-retrosigmoid approaches (19% of patients). In 18 patients, the tumor extended supratentorially. Overall, the rate of gross total resection was 43%. Seven patients demonstrated progression over a mean of 5.9 years. No patients died. At 36 months, the progression-free survival rate for patients treated without petrosal approaches was 96%. Of 14 patients treated with stereotactic radiosurgery, none developed progression. Conclusion: Over the study period, a diminishing proportion of patients with petroclival meningioma were treated using petrosal approaches. Utilization of the orbitozygomatic and retrosigmoid approaches alone or in combination provided a viable alternative to petrosal approaches for treatment of petroclival meningioma. Regardless of approach, progression-free survival rates were excellent over short-term follow-up period.

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Long-term efficacy of surgical resection with or without adjuvant therapy for treatment of secondary glioblastoma in adults

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa098 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Ruoyu Huang ◽

Guanzhang Li ◽

Yiming Li ◽

Yinyan Wang ◽

Pei Yang ◽

...

Keyword(s):

Survival Analysis ◽

Prognostic Factors ◽

Adjuvant Therapy ◽

Clinical Outcomes ◽

Cox Regression ◽

Postoperative Radiotherapy ◽

Gross Total Resection ◽

Subtotal Resection ◽

Total Resection ◽

Secondary Glioblastoma

Abstract Background There are limited studies on treatment strategies and associated clinical outcomes in patients with secondary glioblastoma (sGBM). We sought to investigate the prognostic factors and treatment decisions in a retrospective cohort of patients with sGBM. Methods One hundred and seventy-one patients with sGBM who met the screening criteria were included in this study. Kaplan–Meier survival analysis and Cox survival analysis were used to detect prognostic factors. R (v3.5.0) and SPSS software (v25.0, IBM) were used to perform statistical analyses. Results The median overall survival was 303 days (range 23–2237 days) and the median progression-free survival was 229 days (range 33–1964 days) in patients with sGBM. When assessing the relationship between adjuvant treatment outcome and extent of resection (EOR), the results showed that patients underwent gross total resection can benefit from postoperative radiotherapy and chemotherapy, but not in patients underwent subtotal resection. In addition, we also found that aggressive adjuvant therapy can significantly improve clinical outcomes of IDH1-mutated patients but no significant prognostic value for IDH1-wildtyped patients. The univariate Cox regression analyses demonstrated that EOR, adjuvant therapy, and postoperative Karnofsky Performance Scores were prognostic factors for patients with sGBM, and multivariate COX analysis confirmed that adjuvant therapy and EOR were independent prognostic factors. Conclusions For patients with sGBM, aggressive postoperative adjuvant therapy after gross total resection was recommended. However, we did not detect a benefit in IDH1-wildtype patients in our cohort.

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Radiosurgical Treatment of Cavernous Sinus Meningiomas: Experience with 122 Treated Patients

Neurosurgery ◽

10.1097/00006123-200211000-00009 ◽

2002 ◽

Vol 51 (5) ◽

pp. 1153-1161 ◽

Cited By ~ 110

Author(s):

Antonio Nicolato ◽

Roberto Foroni ◽

Franco Alessandrini ◽

Albino Bricolo ◽

Massimo Gerosa

Keyword(s):

Adjuvant Therapy ◽

Cavernous Sinus ◽

Growth Control ◽

Progression Free Survival ◽

Morbidity Rate ◽

Eligibility Criteria ◽

Neurological Improvement ◽

First Choice ◽

High Operative Risk

Abstract OBJECTIVE To evaluate the efficacy of gamma knife (GK) radiosurgery, in terms of neurological improvement and tumor growth control (TGC), for a large series of patients with cavernous sinus meningiomas. METHODS Between February 1993 and January 2002, 156 patients with cavernous sinus meningiomas (35 male and 121 female patients; mean age, 56.1 yr) were treated with GK radiosurgery in our department. GK radiosurgery was used as a first-choice treatment for 75 of 156 patients and as postoperative adjuvant therapy for 81 of 156 patients (all with Grade I meningiomas). Eligibility criteria for radiosurgery were as follows: symptomatic meningiomas and/or documented tumor progression on magnetic resonance imaging scans, conditions of high operative risk, patient refusal of microsurgery or reoperation, tumor volume of <20 cm3, and location no less than 2 mm from the optic pathways. RESULTS Follow-up data for at least 12 months were available for 122 patients (median follow-up period, 48.9 mo). Clinical conditions were improved or stable for 118 of 122 patients (97%). Neurological recovery was observed for 78.5% of patients treated with GK radiosurgery alone and for 60.5% of patients treated with adjuvant therapy (P < 0.05). Adequate TGC was documented for 119 of 122 tumors (97.5%), with shrinkage/disappearance in 75 of 122 cases (61.5%) and no variation in volume in 44 of 122 cases (36%); the overall actuarial progression-free survival rate at 5 years was 96.5%. Tumor size regression was observed for 80% of patients with follow-up periods of more than 30 months, compared with 43.5% of patients with follow-up periods of less than 30 months (P < 0.0002). Radiosurgical sequelae were transient in 4 of 122 cases (3.0%) and permanent in 1 case (1%). CONCLUSION For the follow-up periods in our series (median, >4 yr), GK radiosurgery seems to be both safe (permanent morbidity rate, 1%) and effective (97% neurological improvement/stability, 97.5% overall TGC, and 96.5% actuarial TGC at 5 yr). GK radiosurgery might be considered a first-choice treatment for selected patients with cavernous sinus meningiomas.

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The impact of adjuvant stereotactic radiosurgery on atypical meningioma recurrence following aggressive microsurgical resection

Journal of Neurosurgery ◽

10.3171/2012.12.jns12414 ◽

2013 ◽

Vol 119 (2) ◽

pp. 475-481 ◽

Cited By ~ 72

Author(s):

Douglas A. Hardesty ◽

Andrew B. Wolf ◽

David G. Brachman ◽

Heyoung L. McBride ◽

Emad Youssef ◽

...

Keyword(s):

Radiation Therapy ◽

Stereotactic Radiosurgery ◽

Recurrence Rate ◽

Tumor Recurrence ◽

Gross Total Resection ◽

Adjuvant Radiation ◽

Total Resection ◽

Microsurgical Resection ◽

Atypical Meningiomas

Object Patients with atypical meningioma often undergo gross-total resection (GTR) at initial presentation, but the role of adjuvant radiation therapy remains unclear. The increasing prevalence of stereotactic radiosurgery (SRS) in the modern neurosurgical era has led to the use of routine postoperative radiation therapy in the absence of evidence-based guidelines. This study sought to define the long-term recurrence rate of atypical meningiomas and identify the value of SRS in affecting outcome. Methods The authors identified 228 patients with microsurgically treated atypical meningiomas who underwent a total of 257 resections at the Barrow Neurological Institute over the last 20 years. Atypical meningiomas were diagnosed according to current WHO criteria. Clinical and radiographic data were collected retrospectively. Results Median clinical and radiographic follow-up was 52 months. Gross-total resection, defined as Simpson Grade I or II resection, was achieved in 149 patients (58%). The median proliferative index was 6.9% (range 0.4%–20.6%). Overall 51 patients (22%) demonstrated tumor recurrence at a median of 20.2 months postoperatively. Seventy-one patients (31%) underwent adjuvant radiation postoperatively, with 32 patients (14%) receiving adjuvant SRS and 39 patients (17%) receiving adjuvant intensity modulated radiation therapy (IMRT). The recurrence rate for patients receiving SRS was 25% (8/32) and for IMRT was 18% (7/39), which was not significantly different from the overall group. Gross-total resection was predictive of progression-free survival (PFS; relative risk 0.255, p < 0.0001), but postoperative SRS was not associated with improved PFS in all patients or in only those with subtotal resections. Conclusions Atypical meningiomas are increasingly irradiated, even after complete or near-complete microsurgical resection. This analysis of the largest patient series to date suggests that close observation remains reasonable in the setting of aggressive microsurgical resection. Although postoperative adjuvant SRS did not significantly affect tumor recurrence rates in this experience, a larger cohort study with longer follow-up may reveal a therapeutic benefit in the future.

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Ependymomas in infancy: underlying genetic alterations, histological features, and clinical outcome

Child s Nervous System ◽

10.1007/s00381-020-04655-x ◽

2020 ◽

Vol 36 (11) ◽

pp. 2693-2700

Author(s):

Stephanie T. Jünger ◽

Felipe Andreiuolo ◽

Martin Mynarek ◽

Evelyn Dörner ◽

Anja zur Mühlen ◽

...

Keyword(s):

Posterior Fossa ◽

Genetic Alterations ◽

Gross Total Resection ◽

Older Children ◽

Total Resection ◽

Who Grade ◽

Chromosome 1Q ◽

Stable Genome ◽

1Q Gain

Abstract Introduction Young age is an adverse prognostic factor in children with ependymomas. Treatment of these infants is challenging since beneficial therapeutic options are limited. As ependymomas are considered a biologically heterogeneous group, we aimed to characterize infant ependymomas with regard to their histological and genetic features. Materials and methods We analyzed 28 ependymomas occurring in children younger than 18 months at diagnosis enrolled into the HIT2000-E protocols with the aim to postpone irradiation until the age of 18 months if possible. All cases underwent neuropathological review, including immunohistochemical characterization. Genome-wide copy number alterations (CNA) were assessed by molecular inversion probe assays, and RELA and YAP1 fusions were detected by RT-PCR and sequencing. Results All infant ependymomas were anaplastic (WHO grade III). Twenty-one (75%) cases were located in the posterior fossa. Gross total resection was accomplished in 12 (57%) of these cases. All posterior fossa tumors showed loss of H3-K27me3 characteristic of PFA ependymomas. CNA analysis showed a stable genome in all cases with lack of chromosome 1q gain, an adverse prognostic marker in PFA ependymomas of older children. However, after a median follow-up of 5.4 years, 15 (71%) relapsed, and 9 (43%) died. Seven ependymomas (25%) occurred in the supratentorial region. Gross total resection could be achieved in only two of these cases. Four tumors carried C11orf95-RELA fusions, and two cases had typical YAP1-MAMLD1 fusions (one case was not analyzable). The RELA-fused cases did not display CDKN2A loss as an adverse indicator of prognosis in this disease entity. Although three infants (43%) with supratentorial ependymomas relapsed, all patients survived (median follow-up, 8.0 years). Conclusion Infant ependymomas seem to fall into three biological entities, with supratentorial tumors carrying RELA or YAP fusions and PFA posterior fossa ependymomas. The latter showed a poor outcome even though chromosome 1q gain was absent.

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Factors affecting outcome following treatment of patients with cavernous sinus meningiomas

Journal of Neurosurgery ◽

10.3171/2010.3.jns091807 ◽

2010 ◽

Vol 113 (5) ◽

pp. 1087-1092 ◽

Cited By ~ 43

Author(s):

Michael E. Sughrue ◽

Martin J. Rutkowski ◽

Derick Aranda ◽

Igor J. Barani ◽

Michael W. McDermott ◽

...

Keyword(s):

Cavernous Sinus ◽

Postoperative Radiotherapy ◽

Meta Analysis ◽

Survival Rates ◽

Extent Of Resection ◽

Gross Total Resection ◽

Cranial Neuropathy ◽

Tumor Control ◽

Subtotal Resection ◽

Total Resection

Object Although there is a considerable volume of literature available on the treatment of patients with cavernous sinus meningiomas (CSMs), most of the data regarding tumor control and survival come from case studies or single-institution series. The authors performed a meta-analysis of reported tumor control and survival rates of patients described in the published literature, with an emphasis on specific prognostic factors. Methods The authors systematically analyzed the published literature and found more than 3000 patients treated for CSMs. Separate meta-analyses were performed to calculate pooled rates of recurrence and cranial neuropathy after 1) gross-total resection, 2) subtotal resection without adjuvant postoperative radiotherapy or radiosurgery, and 3) stereotactic radiosurgery (SRS) alone. Results were expressed as pooled proportions, and random-effects models were used to incorporate any heterogeneity present to generate a pooled proportion. Individual studies were weighted using the inverse variance method, and 95% CIs for each group were calculated from the pooled proportions. Results A total of 2065 nonduplicated patients treated for CSM met inclusion criteria for the analysis. Comparisons of the 95% CIs for recurrence of these 3 cohorts revealed that SRS-treated patients experienced improved rates of recurrence (3.2% [95% CI 1.9–4.5%]) compared with either gross-total resection (11.8% [95% CI 7.4–16.1%]) or subtotal resection alone (11.1% [95% CI 6.6–15.7%]) (p < 0.01). The authors found that the pooled mixed-effects rate of cranial neuropathy was markedly higher in patients undergoing resection (59.6% [95% CI 50.3–67.5%]) than for those undergoing SRS alone (25.7% [95% CI 11.5–38.9%]) (p < 0.05). Conclusions Radiosurgery provided improved rates of tumor control compared with surgery alone, regardless of the subjective extent of resection.

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Pharmacogenetics revisits bevacizumab in breast cancer patients: An ancillary analysis of the UCBG trial COMET—A French multicentric prospective study from R&D UNICANCER.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.1079 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 1079-1079

Author(s):

Gerard A. Milano ◽

Jean-Yves Pierga ◽

Jocelyn Gal ◽

Laurence Llorca ◽

Coraline Dubot ◽

...

Keyword(s):

Breast Cancer ◽

Gene Polymorphisms ◽

Low Cost ◽

Progression Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

Pcr Rflp ◽

Cox Analysis ◽

Clinical Trial Information

1079 Background: Bevacizumab (Beva) is no longer unanimously recommended in the management of breast cancer (BC). Given the absence of faithful predictors of Beva treatment outcome, we made the hypothesis that constitutional gene polymorphisms could play a role in this context. We report the pharmacogenetic ancillary study of the prospective COMET trial conducted in advanced BC patients (pts) receiving first-line Beva associated with paclitaxel. Methods: Relevant targeted gene polymorphisms were analyzed (blood) in 203 prospective pts (mean age 55.3, median follow-up 24 months). VEGFA at positions -2578C > A (rs699947), -1498T > C (rs833061), -634G > C (rs2010963), and 936C > T (rs3025039) were analyzed by PCR-RFLP. VEGFR1 319A > C (rs9582036), VEGFR2 at positions 604C > T (rs2071559), 1192C > T (rs2305948), 1416T > A (rs1870377), IL8 251T > A (rs4073), CYP2C8 139C > T (rs1572080), 399T > C (rs10509681) and ABCB1 at positions 1199 C > TA (rs2229109), 2677G > TAC (rs2032582) were analyzed by Mass-Array Agena. ABCB1 1236C > T (rs1128503) and 3435T > C (rs1045642) were analyzed by pyrosequencing. All fitted HWE. Results: Median progression-free survival (PFS) was 10.8 months. VEGFR1 319A allele was associated with longer PFS (p = 0.03). The VEGFA-1498T allele was significantly associated with both longer overall survival (OS) (p = 0.005) and PFS (p = 0.065). The VEGFA -2578C allele was associated with greater OS (p = 0.002) and PFS (p = 0.071). These two VEGFA polymorphisms were in linkage disequilibrium (p < 0.0001). Multivariate Cox analysis showed that VEGFA -2578 (p = 0.001) and VEGFR2 1416 (p = 0.025) were significant predictors of OS: the score of favorable alleles (VEGFA -2575C and VEGFR2 1416T) was highly associated with OS (p = 0.0003), with median survival at 24 months being 30% for score 0 (95%CI 15-61), 65% for score 1 (95%CI 55-75) and 90% for score 2 (95%CI 67-90). Conclusions: Application of an easy-to-perform low-cost genotyping test may identify strong predictors of Beva outcome in metastatic BC pts. In the current era of precision medicine, a pharmacogenetic-based personalized Beva therapy deserves to be prospectively validated in BC pts. Clinical trial information: 2012-A00244-39.

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