Tumor volume as a predictor of survival and local control in patients with brain metastases treated with Gamma Knife surgery

Object The aim of this study was to examine tumor volume as a prognostic factor for patients with brain metastases treated with Gamma Knife surgery (GKS). Methods Two hundred fifty patients with 1–14 brain metastases who had initially undergone GKS alone at a single institution were retrospectively reviewed. Patients who received upfront whole brain radiation therapy were excluded. Survival times were estimated using the Kaplan-Meier method. Univariate and multivariate analyses using Cox proportional hazard regression models were used to determine if various prognostic factors could predict overall survival, distant brain failure, and local control. Results Median overall survival was 7.1 months and the 1-year local control rate was 91.5%. Median time to distant brain failure was 8.0 months. On univariate analysis an increasing total tumor volume was significantly associated with worse survival (p = 0.031) whereas the number of brain metastases, analyzed as a continuous variable, was not (p = 0.082). After adjusting for age, Karnofsky Performance Scale score, and extracranial disease on multivariate analysis, total tumor volume was found to be a better predictor of overall survival (p = 0.046) than number of brain metastases analyzed as a continuous variable (p = 0.098). A total tumor volume cutoff value of ≥ 2 cm3 (p = 0.008) was a stronger predictor of overall survival than the number of brain metastases (p = 0.098). Larger tumor volume and extracranial disease, but not the number of brain metastases, were predictive of distant brain failure on multivariate analysis. Local tumor control at 1 year was 97% for lesions < 2 cm3 compared with 75% for lesions ≥ 2 cm3 (p < 0.001). Conclusions After adjusting for other factors, a total brain metastasis volume was a strong and independent predictor for overall survival, distant brain failure, and local control, even when considering the number of metastases.

Download Full-text

P14.29 The treatment of melanoma brain metastases with stereotactic radiosurgery concurrently with immune checkpoint inhibition is associated with improved extracranial disease control and overall survival compared to the overall metastatic melanoma cohort - a synergistic effect reaching beyond local control?

Neuro-Oncology ◽

10.1093/neuonc/noab180.150 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii43-ii44

Author(s):

P S Webb ◽

M Zorman ◽

R Watson ◽

M Payne ◽

N Coupe ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Disease Control ◽

Metastatic Melanoma ◽

Local Control ◽

Group Versus ◽

Rank Test ◽

Control Group ◽

Extracranial Disease

Abstract BACKGROUND Melanoma brain metastases (MBM) are an increasingly common referral to the neuro-oncology MDT in the context of lengthening survivorship of metastatic melanoma (MM) patients in the immunotherapy era. Stereotactic radiosurgery (SRS) and immune checkpoint inhibition (ICI) are both effective in the management of MBM and, when combined, 12-month local control rates of >85% and overall survival (OS) >80% have been reported.[4,5] Recent local analysis of patients treated at our tertiary SRS referral centre has revealed even greater outcomes in this patient cohort. This study aimed to compare the outcomes of patients with MBM treated with concurrent SRS and ICI compared to the overall metastatic melanoma cohort, to elucidate whether the addition of SRS to ICI may improve disease control outside of the brain as well as within. MATERIAL AND METHODS A retrospective analysis of our local SRS database and an ARIA ePrescribing database search was performed to identify a cohort of patients treated with concurrent SRS and ICI for MBM, as well as a control cohort of MM patients who received ICI alone, over a 4 year period until February 2020. The primary endpoints were the extracranial progression free survival (PFS) and overall survival (OS) at 12 months. Secondary endpoints were the median PFS (mPFS) and OS (mOS). Kaplan-Meier curves and survival statistics were generated using SPSS v26. RESULTS A total of 34 MBM from 19 patients were identified in the SRS+ICI group and there were 200 patients in the control group. The minimum follow up was 12 months. The median patient age, duration of ICI and use of combination ICI favoured the SRS+ICI group. The number of sites of extracranial disease pre-ICI and overall anti-PD-1 usage was well matched. In the SRS+ICI group, there were no cases of extracranial progression and no deaths within 12 months. In the control group, the 12-month PFS and OS rates were 50.5% and 77.5% respectively. In terms of mPFS, this was not reached (estimated 37.6 months) in the SRS+ICI group, versus 13.4 months in the control group (log rank test, p=0.001). In terms of mOS, this was not reached in the SRS+ICI group, versus 55.8 months in the control group (log rank test, p=0.016). CONCLUSION We demonstrate improved extracranial disease control and survivorship amongst metastatic melanoma patients who develop brain metastases and are treated with concurrent SRS and ICI compared to those who do not. The outcomes of our control cohort are comparable to the 4-year follow up of the CheckMate 067 trial (n=945),[6] which strengthens the validity of the statistical comparisons made in this study. The improved extracranial disease control seen when SRS and ICI are combined in the treatment of MBM questions whether an abscopal effect may be at play, and therefore further accents the utility of SRS in MBM beyond that of local control alone. This could influence management in cases of borderline decisions for SRS.

Download Full-text

The Energy Index Does Not Affect Local Control of Brain Metastases Treated by Gamma Knife Stereotactic Radiosurgery

Neurosurgery ◽

10.1227/neu.0000000000000750 ◽

2015 ◽

Vol 77 (1) ◽

pp. 119-125 ◽

Cited By ~ 4

Author(s):

Ashish Jani ◽

Tzlil Rozenblat ◽

Andrew M. Yaeh ◽

Tavish Nanda ◽

Shumaila Saad ◽

...

Keyword(s):

Multivariate Analysis ◽

Brain Metastases ◽

Gamma Knife ◽

Local Control ◽

Tumor Volume ◽

Complete Response ◽

Local Failure ◽

Energy Index ◽

Prescription Dose

Abstract BACKGROUND: The energy index (EI) is a measure of dose homogeneity within a target volume calculated by the integral dose divided by the product of prescription dose and tumor volume. OBJECTIVE: To assess whether a higher EI is associated with greater local control for brain metastases (BMs) treated by Gamma Knife radiosurgery (GKRS). METHODS: We reviewed all patients treated with GKRS for BM at our institution between January 2009 and February 2014. Data on the prescription dose, prescription isodose line, minimum dose, mean dose, integral dose, tumor volume, and EI were collected. Tumor response was assessed by reviewing follow-up brain imaging studies and classified according to the Response Evaluation Criteria in Solid Tumors. Local control per lesion and dosimetric prognostic factors for local control were assessed by univariate and multivariate Cox proportional hazards regression analyses. RESULTS: Of 213 patients treated, 126 had follow-up imaging available with a median follow-up of 6 months. Three hundred seventy-three individual tumors were analyzed. Of these, 133 showed a complete response, 157 showed a partial response, 46 remained stable, and 37 developed local failure. Tumors with EI ≥1.6 mJ.mL−1.Gy−1 showed a higher rate of complete response. Local control rates at 6, 11, and 17 months were 95.4%, 86.5%, and 81.5%, respectively. On univariate analysis, the following factors were associated with higher rates of local failure: prescription doses of 16 and 18 Gy compared with a prescription dose of 20 Gy. The following factors were associated with a greater rate of local control: maximum dose and mean dose. On multivariate analysis, the only statistically significant factor associated with a greater rate of local failure was prescription dose of 16 Gy compared with 20 Gy. CONCLUSION: GKRS for BM results in a high rate of local control with an 11-month rate of 86.5%. A higher EI was not significantly associated with a higher rate of local control on multivariate analysis. Prescription dose was found to be the only significant predictor of local control on multivariate analysis.

Download Full-text

Heterogeneity of HER2 expression in circulating tumor cells of patients with breast cancer brain metastases and impact on brain disease control.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2029 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2029-2029

Author(s):

Douglas Guedes Castro ◽

Antonio Cassio Assis Pellizzon ◽

Alexcia Camila Braun ◽

Michael Jenwei Chen ◽

Maria Leticia Gobo Silva ◽

...

Keyword(s):

Breast Cancer ◽

Multivariate Analysis ◽

Brain Metastases ◽

Disease Control ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Her2 Expression ◽

Brain Failure ◽

Breast Cancer Brain Metastases ◽

Distant Brain Failure

2029 Background: The HER2 expression switching in circulating tumor cells (CTC) of breast cancer is dynamic and may have prognostic and predictive clinical implications. This study aims to analyse the association between expression of HER2 in CTC of patients with breast cancer brain metastases (BCBM) and brain disease control. Methods: Exploratory analysis of a prospective assessment (NCT02941536) of CTC before (CTC1) and 4–5 weeks after (CTC2) stereotactic radiotherapy/radiosurgery (SRT). CTC were isolated and quantified by a method of isolation by size of tumors and analyzed by immunocytochemistry to evaluate the expression of HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, and overall survival (OS) were estimated by Kaplan-Meier estimator. Log-rank tests were applied in order to compare the survival curves. For multivariate analysis of prognostic factors that affected DBFFS and OS, the Cox proportional model was adjusted. Results: The median age at SRT was 54 (34-70), the diagnosis-specific graded prognostic assessment (DS-GPA) was 1–2 in 17.5% and 2.5–4 in 82.5% and the primary immunophenotype (PIP) was HER2-enriched in 51%, luminal B (LB) in 31% and triple negative (TN) in 18% of the total of 39 patients. CTC were detected in all 39 patients before SRT and the median CTC1 was 2 CTC/mL. After SRT, CTC were detected in 34 of 35 patients (4 deaths between CTC1 and CTC2) and the median CTC2 was 2.33 CTC/mL. HER2 was expressed in CTC1 and/or CTC2 in 9 patients, of which only 2 patients had PIP HER2-enriched. After a median follow-up of 16.6 months, there were 15 patients with distant brain failure and 16 deaths. The median DBFFS and OS were 15.3 and 19.5 months, respectively. Median DBFFS was 7 months in patients with PIP TN and was not reached in PIP LB and HER2-enriched (p = 0.036); 14 months in patients with DS-GPA 1-2 and 7 months with DS-GPA 2.5-4 (p = 0.017); 10 months in patients without HER2 expressed in CTC and not reached in patients with HER2 expressed in CTC (p = 0.012). Median OS was 4.8 months in patients with PIP TN and was not reached in PIP LB and HER2-enriched (p = 0.0026); 19.54 months in patients with DS-GPA 1-2 and 7.6 months with DS-GPA 2.5-4 (p = 0.00088); 17 months in patients without HER2 expressed in CTC and not reached in patients with HER2 expressed in CTC (p = 0.104). On multivariate analysis, DBFFS was superior in patients with PIP HER2-enriched (HR 0.128, 95% CI 0.025–0.534; p = 0.013) and OS was superior in patients with PIP HER2-enriched (HR 0.073, 95% CI 0.018-0.288; p < 0.0001) and LB (HR 0.224, 95% CI 0.062–0.816; p = 0.023). The status of expression of HER2 in CTC was not included in Cox model for DBFFS due to lack of events in patients with HER2 expressed in CTC. Conclusions: The expression of HER2 in CTC was associated with a longer DBFFS and the switching of HER2 expression between PIP and CTC may have impact on prognosis and treatment selection of BCBM.

Download Full-text

RADT-09. TYPE AND TIMING OF SYSTEMIC THERAPY USE PREDICT SURVIVAL IN PATIENTS WITH BRAIN METASTASES TREATED WITH RADIATION THERAPY

Neuro-Oncology ◽

10.1093/neuonc/noaa215.763 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii183-ii183

Author(s):

Kevin Fan ◽

Nafisha Lalani ◽

Nathalie Levasseur ◽

Andra Krauze ◽

Lovedeep Gondara ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Systemic Therapy ◽

Performance Status ◽

Population Based ◽

The Novel ◽

Brain Radiotherapy ◽

Prognostic Assessment ◽

Baseline Variable ◽

Extracranial Disease

Abstract PURPOSE We aimed to investigate whether systemic therapy (ST) use around the time of brain radiotherapy (RT) predicts overall survival for patients with brain metastases (BM). We also aimed to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) in a population-based cohort. METHODS We used provincial RT and pharmacy databases to retrospectively review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016. We used a randomly selected subset with complete baseline data to develop a multivariate analysis (MVA)-based nomogram including ST use to predict survival after RT and to validate the DS-GPA. RESULTS In our 3095-patient cohort, the median overall survival (OS) of the 999 recipients of ST after RT was 5.0 months (CI 4.1-6.0) longer than the OS of the 2096 non-recipients of ST after RT (p< 0.0001): targeted therapy (HR 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55) and cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79). The OS of patients who discontinued ST after RT was 0.9 months (CI 0.3-1.4) shorter than the OS of those who did not receive ST before nor after RT (p< 0.0001). A MVA in the 200-patient subset demonstrated that the traditional baseline variables: cancer diagnosis, age, performance status, presence of extracranial disease, and number of BMs predicted survival, as did the novel variables: ST use before RT and ST use after RT. The MVA-based nomogram had a bootstrap-corrected Harrell’s Concordance Index of 0.70. In the 179 patients within this subset with DS-GPA-compatible diagnoses, the DS-GPA overestimated OS by 6.3 months (CI 5.3- 9.8) (p= 0.0006). CONCLUSIONS The type and timing of ST use around RT predict survival for patients with BMs. A novel baseline variable “ST planned after RT” should be prospectively collected to validate these findings in other cohorts.

Download Full-text

Association of tumor volume and outcomes in T3 larynx cancer with organ preservation approach.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18044 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18044-e18044

Author(s):

Nauman Malik ◽

Nicolin Hainc ◽

Gia Gill ◽

Steven Nakoneshny ◽

Paul Kerr ◽

...

Keyword(s):

Overall Survival ◽

Cohort Study ◽

Local Control ◽

Systemic Therapy ◽

Retrospective Cohort Study ◽

Organ Preservation ◽

Retrospective Cohort ◽

Tumor Volume ◽

Local Failure ◽

Larynx Cancer

e18044 Background: Organ preservation approaches to treatment of locally advanced larynx cancers are widely used and consist of radiotherapy (RT) with or without concurrent systemic therapy (CRT). Analyses of the National Cancer Database point to decreasing survival as CRT became widely adopted in place of total laryngectomy (TL). Tumor volume in T3 laryngeal tumors has been postulated as one variable to explain this finding, with higher volume associated with lower local control based on small sample size studies largely in pre-intensity modulated radiotherapy (IMRT) era, and low volume T3 tumors being associated with improved local control with CRT. We sought to validate these findings in a contemporary cohort of T3 larynx patients treated with IMRT. Methods: This was a national, multicentre retrospective cohort study of patients diagnosed with American Joint Committee on Cancer (AJCC) T3 N0-3 M0 glottic and supraglottic cancers who underwent curative intent IMRT with or without systemic treatment from 2002-2018. Tumor volumes were calculated using a validated standardized approach by a Neuroradiologist. Primary predictor was tumor volume, primary outcome was local control (LC), and secondary outcomes included overall survival (OS), as well as late grade 3+ toxicities. Kaplan Meier estimates and log-rank tests were used for survival analyses, with Cox proportional hazards used for univariable analyses. Results: 246 patients met inclusion criteria, 147 glottic and 99 supraglottic cancers. At baseline, glottic patients were more likely to be male (p < 0.01), have a fixed vocal cord (p < 0.01), not have pre-epiglottic space invasion ( < 0.01), be cN0 (p < 0.01), and have lower grade tumors (p < 0.01). Mean tumor volumes for glottic and supraglottic tumors were 5.0 (4.2-5.8) cc and 13.0 (10.3–15.6) cc respectively. Univariable analysis showed systemic therapy was associated with improved local failure (HR 0.49, 95%CI 0.24 – 0.99, p = 0.05). Within the glottic cohort, tumor volume was not associated with local failure (HR 1.09, 95%CI 0.71 – 1.67, p = 0.38), however having a local failure event was associated with increased feeding tube dependence (HR 2.52, 95%CI 1.05 – 6.02, p = 0.04). Median local failure free survival in the overall cohort was 28.5 months, with median OS 23.2 months. There was a trend towards improved local control in the supraglottic cohort compared to glottic patients (log-rank p = 0.08), but the supraglottic cohort had significantly worse overall survival (log-rank p = 0.02). Conclusions: In this retrospective cohort study, there were baseline and outcome differences between patients with T3 glottic and supraglottic larynx cancer, with worse overall survival in supraglottic patients. Tumor volume was not associated with local control in the glottic cohort. These findings are pending further validation in a larger cohort and will be analyzed separately for supraglottic tumors.

Download Full-text

Tumor volume shrinkage during stereotactic body radiotherapy is related to better prognoses in patients with stage I non-small-cell lung cancer

Journal of Radiation Research ◽

10.1093/jrr/rraa040 ◽

2020 ◽

Vol 61 (5) ◽

pp. 740-746

Author(s):

Nam Vu ◽

Hiroshi Onishi ◽

Masahide Saito ◽

Kengo Kuriyama ◽

Takafumi Komiyama ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Local Control ◽

Cell Lung Cancer ◽

Tumor Volume ◽

Small Cell ◽

Stage I ◽

Small Cell Lung ◽

Volume Changes

Abstract The purpose of the study was to investigate the association between tumor volume changes during stereotactic body radiation therapy (SBRT) and prognoses in stage I non-small-cell lung cancer (NSCLC). This retrospective review included stage I NSCLC patients in whom SBRT was performed at a total dose of 48.0–50.5 Gy in four or five fractions. The tumor volumes observed on computed tomography (CT) simulation and on the CT performed at the last treatment session using a CT-on-rails system were measured and compared. Then, the tumor volume changes during the SBRT period were measured and assessed for their association with prognoses (overall survival, local control, lymph node metastases and distant metastases). A total of 98 patients with a mean age of 78.6 years were enrolled in the study. The T-stage was T1a in 42%, T1b in 32% and T2a in 26% of the cases. The gross tumor volume (GTV) shrank and increased ≥10% in 23 (23.5%) and 36 (36.7%) of the cases, respectively. The 5-year local control and overall survival rates in the groups with a tumor shrinkage of ≥10% vs the group with a shrinkage of <10% were 94.7 vs 70.8% and 85.4 vs 47.6%, respectively; these differences were significant, with a P-value < 0.05. During a short SBRT period, the tumor shrank or enlarged in a small number of cases. A decrease of ≥10% in the GTV during SBRT was significantly related to better overall survival and local control.

Download Full-text

Correlation of V12 to the Number of Lesions, Total Tumor Volume and Dose Prescription in Multiple Brain Metastases Stereotactic Radiosurgery Treatment

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2019.06.2475 ◽

2019 ◽

Vol 105 (1) ◽

pp. E793-E794

Author(s):

R. He ◽

M.R. Kanakamedala ◽

W.N. Duggar ◽

C.C. Yang ◽

S. Vijayakumar

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Tumor Volume ◽

Total Tumor Volume ◽

Multiple Brain Metastases

Download Full-text

Comparison of Total Tumor Volume, Size and Number of Colorectal Liver Metastases in Prediction of Survival in Patients after Liver Resection

Polish Journal of Surgery ◽

10.1515/pjs-2015-0019 ◽

2015 ◽

Vol 87 (2) ◽

Author(s):

Wacław Hołówko ◽

Michał Grąt ◽

Karolina Maria Wronka ◽

Jan Stypułkowski ◽

Rafał Roszkowski ◽

...

Keyword(s):

Overall Survival ◽

Liver Resection ◽

Liver Metastases ◽

Predictive Value ◽

Colorectal Liver Metastases ◽

Tumor Volume ◽

Univariate Analysis ◽

Total Tumor Volume ◽

Right Hemihepatectomy ◽

Volume Size

AbstractLiver is the most common location of the colorectal cancer metastases occurrence. Liver resection is the only curative method of treatment. Unfortunately it is feasible only in 25% of patients with colorectal liver metastases, often because of the extensiveness of the disease.The aim of the study was to evaluate the predictive value of total tumor volume, size and number of colorectal liver metastases in patients treated with right hemihepatectomy.Material and methods. A retrospective analysis was performed in a group of 135 patients with colorectal liver metastases, who were treated with right hemihepatectomy. Total tumor volume was estimated based on the formula (4/3)πr3. Moreover, the study included an analysis of data on the number and size of tumors, radicality of the resection, time between primary tumor resection and liver resection, pre-operative blood serum concentration of carcinoembryonal antigen (CEA) and carcinoma antigen Ca19-9. The predictive value of the factors was evaluated by applying a Cox proportional hazards model and the area under the ROC curve.Results. The univariate analysis has shown the predictive value of size of the largest tumor (p=0.033; HR=1.065 per each cm) on the overall survival, however no predictive value of number of tumors (p=0.997; HR=1.000) and total tumor volume (p=0.212; HR=1.002) was observed. The multivariate analysis did not confirm the predictive value of the size of the largest tumor (p=0.141; HR=1.056). In the analysis of ROC curves, AUROC for the total tumor volume, the size of the largest tumor and the number of tumors were 0.629, 0.608, 0.520, respectively.Conclusions. Total tumor volume, size and number of liver metastases are not independent risk factors for the worse overall survival of patients with colorectal liver metastases treated with liver resection, therefore increased values of these factors should not be a contraindication for surgical treatment

Download Full-text

31. RADIATION NECROSIS IN STEREOTACTIC RADIOSURGERY AND CHECKPOINTS INHIBITORS FOR BRAIN METASTASES FROM LUNG ADENOCARCINOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.019 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii5-ii5

Author(s):

James Jurica ◽

Shraddha Dalwadi ◽

David Baskin ◽

Eric Bernicker ◽

Brian Butler ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Brain Metastases ◽

Lung Adenocarcinoma ◽

Stereotactic Radiosurgery ◽

Median Survival ◽

Radiation Necrosis ◽

Concomitant Treatment ◽

Prognostic Assessment ◽

Graded Prognostic Assessment

Abstract PURPOSE Treatment with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is increasingly common for brain metastases (BM) from lung adenocarcinoma. Rates of radiation necrosis (RN) with SRS in the setting of ICIs is an ongoing area of research. We investigated rates of RN in patients with BM from lung adenocarcinoma treated with SRS with or without concurrent ICIs. METHODS We identified 39 patients at a single institution who underwent SRS treatment for BM from lung adenocarcinoma. Of these, 19 (49%) received SRS without ICIs and 20 (51%) patients received ICIs within a month of SRS. The rate of RN, defined by MRI features and histology when available, was compared between each group using multivariate analysis. Kaplan Meier survival estimates were calculated based on overall survival and compared to median survival predicted by the graded prognostic assessment. RESULTS Overall survival for all patients from diagnosis of brain metastases was 16.6 months (range 3.6–45.9) and median survival predicted by the graded prognostic assessment was 13.7 months (range 6.9–26.5). In total 11 (28%) patients developed MRI and/or histologic evidence for RN during the follow-up period; 5 of 20 (25%) from the SRS with ICI group and 6 of 19 (31%) from the SRS without ICI group. In multivariate analysis, ICI treatment had no significant impact on rates of RN between groups (OR 0.72 [95% CI: 0.17–2.93]; p=0.65) while bevacizumab treatment was associated with a decreased RN risk (OR 0.88 [95% CI: 0.43–0.99]; p=0.02). CONCLUSION Retrospective analysis of patients with BM from lung adenocarcinoma treated with SRS suggested that administration of ICIs does not increase risk for development of RN. Further, concomitant treatment with bevacizumab may decrease risk of RN. These findings suggest that patients with BM from lung adenocarcinoma can be treated with combination therapy without increased risk of neurologic toxicity.

Download Full-text