Stereotactic radiosurgery for recurrent malignant gliomas.

PURPOSE To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.

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

Current Oncology ◽

10.3747/co.26.4244 ◽

2019 ◽

Vol 26 (1) ◽

Cited By ~ 4

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.

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Factors Influencing the Outcome of Stereotactic Radiosurgery in Patients With Five or More Brain Metastases

Current Oncology ◽

10.3747/co.25.4244 ◽

2019 ◽

Vol 26 (1) ◽

pp. 64-69 ◽

Cited By ~ 3

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 ◽

Distant Recurrence ◽

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 non-small-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.

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Hypofractionated stereotactic radiosurgery with concurrent bevacizumab for recurrent malignant gliomas: the University of Alabama at Birmingham experience

Neuro-Oncology Practice ◽

10.1093/nop/npu028 ◽

2014 ◽

Vol 1 (4) ◽

pp. 172-177 ◽

Cited By ~ 5

Author(s):

Grant M. Clark ◽

Andrew M. McDonald ◽

Louis B. Nabors ◽

Hassan Fathalla-Shaykh ◽

Xiaosi Han ◽

...

Keyword(s):

Malignant Glioma ◽

Stereotactic Radiosurgery ◽

Karnofsky Performance Status ◽

Performance Status ◽

Malignant Gliomas ◽

Concurrent Chemotherapy ◽

Who Grade ◽

Volume Delineation ◽

Grade 3 ◽

Hypofractionated Stereotactic Radiosurgery

Abstract Background Nearly all patients with malignant glioma will have disease recurrence. Our purpose was to define the treatment toxicity and efficacy of concurrent bevazicumab (BVZ) with hypofractionated stereotactic radiosurgery (SRS) of relatively larger targets for patients with recurrent MG. Methods A retrospective review of 21 patients with recurrent malignant glioma (18 glioblastoma, 3 WHO grade III glioma), treated at initial diagnosis with surgery and standard chemoradiation, was performed. All patients had concurrent BVZ with hypofractionatedSRS, 30 Gy in 5 fractions, with or without concurrent chemotherapy (temozolomide or CCNU). Results Median patient age was 54 years, median Karnofsky Performance Status was 80, and median target size was 4.3 cm (range, 3.4–7.5 cm). Eleven patients (52%) had previously failed BVZ. One patient had grade 3 toxicities (seizures, dysphasia), which resolved with inpatient admission and intravenous steroids/antiepileptics. Treatment-related toxicities were grade 3 (n = 1), grade 2 (n = 9), and grade 0–1 (n = 11). Kaplan-Meier median progression-free survival and overall survival estimates (calculated from start of SRS) for GBM patients (n = 18) were 11.0 and 12.5 months, respectively. Concurrent chemotherapy did not appear to show any statistically significant efficacy benefit or have any propensity for toxicity. Conclusion BVZ concurrent with hypofractionated SRS was well tolerated by this cohort of patients with relatively larger targets. Ongoing randomized trials with more moderate radiotherapy dosing may help establish the efficacy of this regimen, though intricacies of this approach, including patient selection, radiation target volume delineation/size, and optimal radiation dose, will need further evaluation.

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Accelerator-Based Stereotactic Radiosurgery for Brainstem Metastases

Neurosurgery ◽

10.1227/neu.0b013e31823c40fe ◽

2011 ◽

Vol 70 (4) ◽

pp. 953-958 ◽

Cited By ~ 24

Author(s):

Chun-Shu Lin ◽

Michael T. Selch ◽

Steve P. Lee ◽

Jeffrey K. Wu ◽

Furen Xiao ◽

...

Keyword(s):

Los Angeles ◽

Survival Time ◽

Stereotactic Radiosurgery ◽

Local Control ◽

Complication Rate ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Local Control Rate ◽

Prescription Dose

Abstract BACKGROUND: Stereotactic radiosurgery represents a noninvasive alternative treatment for intracranial metastases. OBJECTIVE: To investigate the treatment outcome of linear accelerator-based stereotactic radiosurgery (linac-SRS) for brainstem metastases. METHODS: We retrospectively reviewed our database of patients who were diagnosed with brainstem metastases and underwent linac-SRS between 1997 and 2008 at the University of California, Los Angeles. RESULTS: A total of 45 patients with 48 brainstem metastases were treated. The median target volume was 0.40 mL (range, 0.02-5.70 mL), and median prescription dose was 14 Gy (range, 10–17 Gy) at 90% isodose curve. The median survival time was 11.6 months. Longer survival time was associated with higher Karnofsky performance status. The local control rate was 92% at 6 months and 88% at 1 year. Univariate analysis demonstrated a significant relationship between local control and tumor volume (⩽0.4 mL vs >0.4 mL, P = .023) and SRS mode (conventional circular arc vs dynamic conformal arc, P = .044). There was a trend toward improved local control and prescription dose >14 Gy (P = .059). Two patients had brainstem complications following treatment, and the complication rate was 4.7% at 2 years. Serious morbidity occurred with 17 Gy. CONCLUSION: Linac-SRS using a median dose of 14 Gy provided excellent local control in patients with brainstem metastases less than 0.4 mL with relatively low serious morbidity. The results of the study support the use of linac-SRS for patients with brainstem metastases. We advocate 14 to 16 Gy, given the high local control rate and low complication rate with this dose.

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

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03564-z ◽

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.

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P14.120 Phase II study of weekly carboplatin in pretreated adult malignant gliomas

Neuro-Oncology ◽

10.1093/neuonc/noz126.355 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii97-iii97

Author(s):

V Villani ◽

A Pace ◽

A Vidiri ◽

A Tanzilli ◽

F Sperati ◽

...

Keyword(s):

Malignant Glioma ◽

Phase Ii ◽

Clinical Benefit ◽

Phase Ii Study ◽

Karnofsky Performance Status ◽

Performance Status ◽

Single Agent ◽

Malignant Gliomas ◽

Recurrent Malignant Glioma ◽

Eligibility Criteria

Abstract BACKGROUND Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas MATERIAL AND METHODS This was a single arm, Phase II study. Eligibility criteria included progressive or recurrent malignant glioma after radiotherapy and chemotherapy-based treatments and Karnofsky Performance Status (KPS) > 60. RESULTS Thirty-two patients (median age: 43.5 y) were enrolled to receive weekly carboplatin monotherapy in intravenous mode of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival (PFS) was 2.3 months while overall survival (OS) was 5.5 months. Patients achieving clinical benefit exhibited a longer PFS (4.6 vs 1.5 months; p>0.001) and OS (7.9 vs 3.2 months; p=0.041) compared to those not achieving clinical benefit. CONCLUSION Our findings show that single agent, weekly, intravenous carboplatin may have a role in the treatment patients with recurrent malignant glioma

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Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2

Journal of Clinical Oncology ◽

10.1200/jco.18.00089 ◽

2019 ◽

Vol 37 (3) ◽

pp. 230-238 ◽

Cited By ~ 25

Author(s):

Teresa Macarulla ◽

Roberto Pazo-Cid ◽

Carmen Guillén-Ponce ◽

Rafael López ◽

Ruth Vera ◽

...

Keyword(s):

Phase I ◽

Pancreatic Ductal Adenocarcinoma ◽

Phase Ii ◽

Karnofsky Performance Status ◽

Performance Status ◽

Ductal Adenocarcinoma ◽

Tolerability Profile ◽

Ecog Performance Status ◽

Actuarial Survival ◽

Number Of Patients

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

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

Neurosurgery ◽

10.1093/neuros/nyx346 ◽

2017 ◽

Vol 83 (1) ◽

pp. 128-136 ◽

Cited By ~ 2

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.

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Mature Results of a Prospective Trial of Rituximab in Patients (Pt) with Post Transplant Lymphoproliferative Disorder (PTLD) Unresponsive or Ineligible for Reduced Immunosuppression (RIS).

Blood ◽

10.1182/blood.v108.11.2755.2755 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2755-2755

Author(s):

Jeff P. Sharman ◽

Donald E. Tsai ◽

Clare J. Twist ◽

Steven M. Horwitz ◽

Carol D. Jones ◽

...

Keyword(s):

Site Response ◽

Karnofsky Performance Status ◽

Performance Status ◽

Univariate Analysis ◽

Prospective Trial ◽

Large Cell ◽

Cytotoxic Therapy ◽

Free Survival ◽

Co Morbidity ◽

The Impact

Abstract Background: PTLDs are typically B-cell neoplasms occurring as uncommon but serious complications of reduced T-cell immune surveillance associated with organ transplantation. RIS benefits only a subset of PTLD patients and cytotoxic therapy may be poorly tolerated. Therefore, in October 1998 we initiated a prospective study of rituximab in patients who failed or were unable to receive RIS and now report mature results. Methods: Patients with CD20+ PTLD were eligible if they had failed to completely respond to RIS or RIS was contraindicated and had Karnofsky performance status >60, age 3–70 years (y), measurable disease, and no change in immunosuppression for at least 2 weeks and no cytotoxic therapy within 4 weeks. Rituximab was given as 375 mg/m2 weekly x 4 with disease evaluation at 1, 3, 6, 9, 12 and 18 months. Response data, survival curves, and the impact of clinical and pathological factors were evaluated. Results: 24 of 26 enrolled pt were eligible and evaluable. Median age was 42y with 5 <17 y, 18 were male, and 14 progressed on RIS. Median time to PTLD from transplant was 47 months (m) (8 <24 m). 17/22 were EBV+, 17 were large cell or Burkitt histology, and 10 PTLD occurred in the allograft site. Response rate was 63% (46 %CR, 17% PR) and CRs were durable (1/11 progressed). With median follow-up of 65 m (range 44–82), outcomes at 5 y are: overall survival 48%, freedom from progression 41% and failure-free survival 21%. 7 pt died without progression, yielding 5 y cause-specific survival of 69%. Nine of 13 pt with disease progression were successfully salvaged with second-line therapy. In univariate analysis PTLD characteristics did not significantly correlate with outcome but 2/2 Burkitt pt quickly progressed. Conclusions: Rituximab provided effective, durable treatment for ~40% of pt failing RIS in this series of mainly late PTLD and a majority of pt progressing after rituximab could be treated successfully. However, overall and failure-free survival reflect significant co-morbidity in this population.

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

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.487 ◽

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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