Upfront brain radiotherapy improves intracranial progression-free survival but not overall survival in lung adenocarcinoma patients with brain metastases: a retrospective, single-institutional analysis from China

Abstract Aims: There is no consensus on the optimal opportunity of brain radiotherapy (BRT) for the patients with lung adenocarcinoma and brain metastases (BM). In the present study, we performed a retrospective review to investigate the differential benefit of upfront BRT for lung adenocarcinoma patients with BM.Methods: A total of 354 lung adenocarcinoma patients with BM from the Affiliated Cancer Hospital of Shandong University met inclusion criteria for the study. Patients were divided into two groups: upfront BRT and deferred BRT. Intracranial progression-free survival (iPFS) and Overall survival (OS) were measured from the date of brain metastases. Subgroup analyses according to gene mutation status were also performed.Results: For the entire cohort, the median iPFS of upfront BRT and deferred BRT was 16.3 and11.3 months, respectively (p =.001). The median OS of upfront BRT and deferred BRT was 27.6 and 31.5 months, respectively (p =0.813). Subgroup Analyses indicated that upfront BRT yielded a significantly longer iPFS than deferred BRT (p = 0.003) only for patients with no sensitive gene mutation. In all subgroups, the median OS was not significant different for upfront BRT and deferred BRT.Conclusion: This single-institutional retrospective showed that in patients with lung adenocarcinoma and BM, upfront BRT was associated with significantly longer iPFS, but no OS difference between upfront BRT and deferred BRT was observed. Considering the reported neurocognitive toxicities of upfront BRT, deferred BRT might be considered as an acceptable therapeutic option for the treatment of patients with lung adenocarcinoma and BM.

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Upfront brain radiotherapy improves intracranial progression-free survival but not overall survival in lung adenocarcinoma patients with brain metastases: a retrospective, single-institutional analysis from China

10.21203/rs.3.rs-40353/v2 ◽

2020 ◽

Author(s):

Aijun Jiang ◽

Meng Ni ◽

Li Li ◽

Fen Zhao ◽

Yuanhu Yao ◽

...

Keyword(s):

Overall Survival ◽

Retrospective Study ◽

Brain Metastases ◽

Lung Adenocarcinoma ◽

Gene Mutation ◽

Progression Free Survival ◽

Free Survival ◽

Brain Radiotherapy ◽

Significant Difference ◽

Subgroup Analyses

Abstract Aims: The optimal timing of brain radiotherapy (BRT) for lung adenocarcinoma patients with brain metastases (BM) remains controversial. In this retrospective study, we performed a retrospective review to investigate the differential benefit of upfront versus deferred BRT for lung adenocarcinoma patients with BM.Methods: A total of 354 lung adenocarcinoma patients with BM treated in the Affiliated Cancer Hospital of Shandong University met the inclusion criteria for the study. Patients were divided into two groups: upfront BRT and deferred BRT. Intracranial progression-free survival (iPFS) and overall survival (OS) were measured from the date of brain metastases. Subgroup analyses according to gene mutation status were also performed.Results: Among the entire cohort, the median iPFS with upfront BRT (16.3 months) was longer than that with deferred BRT (11.3 months, p=0.001). However, the median OS did not differ significantly between patients who received upfront BRT and deferred BRT (27.6 and 31.5 months, respectively, p=0.813). Subgroup analyses indicated that upfront BRT yielded a significantly longer iPFS than deferred BRT (p=0.003) only for patients without EGFR gene mutation. In all subgroups, the median OS showed no significant difference between upfront BRT and deferred BRT.Conclusion: This single-institutional retrospective study showed that in patients with lung adenocarcinoma and BM, upfront BRT was associated with a significantly longer iPFS but no improvement in OS compared with deferred BRT. Considering the neurocognitive toxicities of BRT previously reported in the literature, deferred BRT might be considered as an acceptable therapeutic option for the treatment of patients with lung adenocarcinoma and BM.

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Stereotactic Radiosurgery for Metastases in Eloquent Central Brain Locations

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.55 ◽

2015 ◽

Vol 42 (5) ◽

pp. 333-337 ◽

Cited By ~ 5

Author(s):

Fred Hsu ◽

Alan Nichol ◽

Roy Ma ◽

Para Kouhestani ◽

Brian Toyota ◽

...

Keyword(s):

Overall Survival ◽

Basal Ganglia ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Whole Brain Radiotherapy ◽

Progression Free Survival ◽

Free Survival ◽

Brain Radiotherapy ◽

Local Progression ◽

Central Brain

AbstractBackground: To examine stereotactic radiosurgery (SRS) following whole brain radiotherapy for metastases in eloquent, central brain locations: brainstem, thalamus, and basal ganglia. Methods: We conducted a retrospective review of patients with metastases in eloquent, central brain locations who were treated with SRS between January 2000 and April 2012. All patients had whole brain radiotherapy. Patients eligible for SRS had one to three brain metastases, metastasis size ≤4 cm, and Karnofsky performance status ≥70. Local progression-free survival and overall survival were calculated using the Kaplan-Meier method. Results: For 24 patients, the median age was 50 years (range, 36-73). Metastases by location were: 11 brainstem, 9 thalamus, and 5 basal ganglia. The median metastasis size was 15 mm (range, 2-33) and the median SRS dose prescription was 15 Gy (range, 12-24). The median local progression-free survival was 13.7 months and median overall survival was 16.4 months. Compared with a cohort of 188 patients with noneloquent brain metastases receiving a median dose of 24 Gy, overall survival of 10.8 months was not significantly different (p=0.16). The only symptomatic complication was grade 2 headache in 8.3%. Asymptomatic adverse radiologic events were radionecrosis in two (8.3%), peritumoural edema in four (16.7%), and hemorrhage in one patient (4.2%). Conclusions: Lower SRS marginal doses do not appear to compromise survival in patients with eloquently located brain metastases compared with higher doses for other brain metastases, with minimal symptomatic complications.

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LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000029 ◽

2021 ◽

pp. 1-9

Author(s):

Ankita Gupta ◽

Budhi Singh Yadav ◽

Nagarjun Ballari ◽

Namrata Das ◽

Ngangom Robert

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Progression Free Survival ◽

Rank Test ◽

Karnofsky Performance Score ◽

Breast Cancer Patients ◽

Free Survival ◽

Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

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Real-world data on management of brain metastases in non-small cell lung cancer, Queen Elizabeth Hospital, Birmingham: a retrospective study on progression free survival, overall survival of different treatment modalities for brain metastases and prevalence of brain metastases in NSCLC receiving immunotherapy

Lung Cancer ◽

10.1016/s0169-5002(20)30142-2 ◽

2020 ◽

Vol 139 ◽

pp. S51

Author(s):

P.J. Teo ◽

Z.M. Oo ◽

G. Pinilla ◽

G. Middleton

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Brain Metastases ◽

Progression Free Survival ◽

Small Cell ◽

Treatment Modalities ◽

Queen Elizabeth Hospital ◽

Small Cell Lung ◽

Real World Data ◽

Free Survival

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A new option in brain-metastases: Hippocampal-sparing whole-brain radiotherapy with simultaneous integrated boost VMAT-IGRT.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13589 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13589-e13589

Author(s):

Alicia Marin ◽

Margarita Martin ◽

Emma Gonzalez ◽

Lisselott Torres ◽

David Hernandez ◽

...

Keyword(s):

Brain Metastases ◽

Whole Brain Radiotherapy ◽

Progression Free Survival ◽

Simultaneous Integrated Boost ◽

Rank Test ◽

Whole Brain ◽

Free Survival ◽

Brain Radiotherapy ◽

Integrated Boost ◽

Hippocampal Sparing

e13589 Background: We report our experience with volumetric modulated arc therapy (VMAT-IGRT) use to plan and deliver whole brain radiotherapy whit a simultaneous integrated boost in patients with brain metastases, using hippocampal sparing. Methods: In this retrospective study 57 patients with brain metastases were treated with radiotherapy VMAT-IGRT were administered in 12 daily fractions of 2.7Gy for a total of 32.4Gy (EBD 40Gy) to whole-brain and simultaneous integrated boost to brain metastases, multiple targets, in 12 fractions to 3.4Gy for a total dose of 40.8Gy (EBD 60Gy). The primary endpoint was intracranial progression-free survival (PFS) and secondary endpoints were preserves neurocognitive function and overall survival (OS). Survival rates were determined by Kaplan-Meier method. Differences between survival curves were analyzed by the log-rank test. Results: From January 2015 to December 2018, 57 patients were enrolled. The median follow-up time was 7 months. PFS6, PFS12 and PFS18 were 91.3%, 70.8% and 70.8% respectively. mOS, OS6, OS12 and OS18 were 10 months (95% IC 4.2-15.7 months), 67.2%, 48.6% and 35.3% respectively. Response rates were as follows: 29RC (50.9%), 21RP (36.8%), 7SD (12.3%) and 0PD (0%). Long progression-free survival patients: PFS > 12, 15 and 18 months for initial diagnosis 70%, 70% and 70% respectively. Conclusions: Whole-brain radiotherapy with simultaneous integrated boost to brain-metastases: VMAT-IGRT is safe and promising and possibly produces survival and tolerance benefits. Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning.

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IL-11RA is a Prognostic Biomarker and Correlated with Immune Infiltration in Lung Adenocarcinoma

10.21203/rs.3.rs-673757/v1 ◽

2021 ◽

Author(s):

Aitao Nai ◽

SHOAIB BASHIR ◽

Ling Jin ◽

Zirui He ◽

Shuwen Zeng ◽

...

Keyword(s):

Overall Survival ◽

Lung Adenocarcinoma ◽

Cox Regression ◽

Progression Free Survival ◽

Clinicopathological Parameters ◽

Free Survival ◽

Cox Regression Analysis ◽

Immune Infiltration ◽

Potential Biomarker

Abstract Background: Interleukin-11 receptor subunit alpha (IL-11RA) contributes to multiple biological processes in various tumors. However, the role of IL-11RA in Lung adenocarcinoma (LUAD) is still undetermined. The study aims to explore the role of IL-11RA in LUAD via an integrated bioinformatics analysis. Methods: TIMER, GEPIA, TCGA and HPA databases analysis were used to detect IL-11RA expression. UALCAN database was used to analysis the correlation between IL-11RA expression and clinicopathological parameters of LUAD. Kaplan-Meier Plotter, TCGA and GEO databases were used to analysis overall survival (OS) and progression-free survival (PFS) of the LUAD patients. Univariate Cox regression analysis was used to assess the prognostic value of IL-11RA in different clinical characteristics. GSEA, and TIMER were used to investigate the relationship between IL-11RA and immune infiltration.Results: The expression of IL-11RA was down-regulated in LUAD tissues. Furthermore, IL-11RA expression was closely associated with clinical stage, lymph node stage and smoking habits. The patients with lower IL-11RA expression had poorer overall survival (OS) and progression-free survival (PFS). Lower IL-11RA expression was significantly associated with its hypermethylation, and the hypermethylation of CpG site at cg14609668 and cg21504624 was obviously correlated with poorer OS. Then, we found that IL-11RA may play an important role in LUAD progression and immune regulations. Notably, High expression of IL-11RA may suppress the progression of LUAD through inhibiting cell proliferation and immune cell infiltration, especially in B cells, CD4+ T cells, and Dendritic Cell. Conclusions: Decreased IL-11RA expression correlates with poor prognosis and immune infiltration in LUAD. Our work highlights IL-11RA might be a potential biomarker for prognosis and provide a new therapeutic target for LUAD patients.

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Impact of different timing of radiation therapy in patients with brain metastases from epidermal growth factor receptor-mutant non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20667 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20667-e20667

Author(s):

Xiaozhen Ying ◽

Shuiyun Han ◽

Chenxue Jiang ◽

Xiaojiang Sun ◽

Yaping Xu ◽

...

Keyword(s):

Brain Metastases ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Small Cell Lung ◽

Concurrent Treatment ◽

Free Survival ◽

Brain Radiotherapy ◽

Epidermal Growth ◽

Egfr Mutant ◽

Egfr Tki

e20667 Background: To perform a retrospective analysis of patients with brain metastases (BM) from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) to evaluate the preferred treatment timing of EGFR-tyrosine kinase inhibitors (TKIs) in this population. Methods: Of 94 initial or recurrent patients diagnosed BM from EGFR-mutant NSCLC between Jan 1, 2012, and Jun 31, 2016, 30 received upfront brain RT followed by EGFR-TKI, 39 EGFR-TKI combined with concurrent brain RT, and 25 upfront EGFR-TKI then brain RT. Disease-specific-graded prognostic assessment was similar among all 3 groups. The primary endpoint was overall survival (OS), and the second endpoint was intracranial progression-free survival. Results: Although the median OS was not significantly different among the upfront RT, concurrent treatment, and upfront EGFR-TKI groups (29.0 vs 24.0 vs 17.0 months; P = 0.186), however, it was longer in the upfront RT group compared with the upfront EGFR-TKI group (P = 0.035). On subgroup analysis, the exon 19 deletions patients had longer OS than the exon 21 mutations patients in upfront EGFR-TKI group (23.0 vs 15.0 months; P = 0.048), but the upfront RT (34.0 vs 23.0 months; P = 0.186) and the concurrent treatment groups (24.0 vs 13.0 months; P = 0.827) did not. According to multivariate COX analysis, KPS (≥ 70) and intracranial metastasis alone was associated with a longer OS. The median intracranial progression-free survival was significantly improved in patients receiving upfront RT compared with those receiving concurrent treatment or upfront EGFR-TKI (not reached vs 40.0 vs 9.0 months; P = 0.003). Conclusions: The present study suggests that the use of upfront brain radiotherapy, and the deferral of EGFR-TKI may result in superior OS in patients with brain metastases from EGFR-mutant NSCLC. Also, upfront brain radiotherapy management could significantly reduce the risk of intracranial progression. A prospective, multi-institutional, randomized trial of upfront EGFR-TKI then RT versus upfront RT followed by EGFR-TKI is urgently needed, especially based on different subgroup population.

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NCOG-01. STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES AT THE GUY’S CANCER CENTER, LONDON: AN AUDIT FOR THE FIRST 17 MONTHS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.540 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii129-ii129

Author(s):

Kallol Bhadra ◽

Omar Al-Salihi ◽

Sheila Hassan ◽

Angela Swampillai ◽

Kirsty Blythe ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Primary Tumour ◽

Progression Free Survival ◽

Cancer Center ◽

Free Survival ◽

Randomized Control ◽

Visceral Disease

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) commenced at Guy’s Cancer Hospital in August 2017. We report our first seventeen months’ data (August 2017 to December 2018) for brain metastases SRS. METHOD Patients referred via Neuro Oncology MDT were assessed for suitability for SRS via clinical review and 1mm-slice MRI. Treatment was planned on Eclipse v15.6 and delivered using Truebeam STx Linac(FFF) and Align RT v5.1 for matching. Dose prescription, according to departmental protocol, was set at 100% isodose, ranging from 18Gy to 25Gy, with fractionation varying from single to five fractions depending on factors including size, volume and locations. Post-treatment, patients were discharged back to their primary treating team for 3-monthly MRI. RESULTS Between Aug-17 to Dec-18, 70 patients with brain metastases were treated with a total of 122 lesions. Mean age was 66 years (range 37-93) and Median follow-up 9 months. Primary tumour sites mainly included lung 34(48.5%), breast 16(22.8%) and melanoma 17(24.3%). Brain-only metastases, including small volume primary with brain metastases were found in 85.4% cases, whilst visceral disease with brain metastases were found in 14.5% patients. Out of 122 lesions, the majority were treated in the primary setting; 95(77.8%) vs 27(22.1%) in the adjuvant setting. At 9-months follow up, local failure rate was in 26(21.3%) sites and 17 new sites in distant brain appeared. 31(44.2%) patients received no systemic therapy after SRS, whilst immunotherapy was received by 14(20%), with the remaining receiving hormones or chemotherapy. Median Overall Survival was 9.2 months (95% CI: 4.5-13.8) and Median progression-free survival was 5.9 months (95% CI: 7.0-10.4). CONCLUSION Overall Survival results were encouraging with initial auditing proving SRS as effective approach. Local control rates correlate well with randomized control trials results for SRS in brain metastases.

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Metastasiertes nicht kleinzelliges Lungenkarzinom: Operation vor zielgerichteter Therapie mit EGFR-TKI

Karger Kompass Pneumologie ◽

10.1159/000516436 ◽

2021 ◽

pp. 1-2

Author(s):

Tobias Rachow ◽

Susanne M. Lang

Keyword(s):

Overall Survival ◽

Lung Adenocarcinoma ◽

Tumor Resection ◽

Progression Free Survival ◽

Kleinzelliges Lungenkarzinom ◽

Free Survival ◽

Resection Group ◽

Metastatic Burden ◽

The Impact ◽

Egfr Tki

Objectives: The characteristics and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in advanced EGFR-mutant lung adenocarcinoma patients with primary tumor resection (PTR) is not yet clear. Methods: We enrolled advanced EGFR-mutant lung adenocarcinoma patients with EGFR-TKI as first-line therapy to access the impact of PTR on the outcomes. Results: A total of 466 patients were enrolled with 76 patients (16.3%) undergoing PTR; 59 patients recurred after curative surgery, while 17 patients underwent surgery as diagnostic purposes. PTR patients displayed a better performance status, a lower metastatic burden, and much less measurable diseases (30.3 vs. 97.4%, p < 0.001). PTR patients experienced a significantly longer progression-free survival (25.1 [95% CI 16.6–33.7] vs. 9.4 [95% CI 8.4–10.4] months; aHR 0.40 [95% CI 0.30–0.54], p < 0.001) and overall survival (56.8 [95% CI 36.3–77.2] vs. 31.8 [95% CI 28.2–35.4] months; aHR 0.57 [95% CI 0.39–0.84], p = 0.004). Survival advantage was still observed while comparing PTR patients with the better performance and lower metastatic burden subgroup found within the non-resection group. Moreover, the progression-free survival and overall survival of 11 patients who were found having pleural metastases during surgery and underwent PTR plus pleural biopsy, were also longer than those with pure N0–1/M1a-malignant pleural effusion disease in the non-resection group (n = 19) (p < 0.001 and p = 0.002, respectively). Conclusion: PTR was associated with significantly better outcomes in advanced lung adenocarcinoma patients treated with EGFR-TKI. Further studies are needed to evaluate the biological role of PTR among these patients.

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