scholarly journals MLTI-03. The relevance of the count of brain metastases for treatment and outcome in NSCLC

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii13-iii13
Author(s):  
David Reinecke ◽  
Stephanie T Jünger ◽  
Martin Kocher ◽  
Maximilian Ruge ◽  
Daniel Ruess ◽  
...  

Abstract Background and Purpose While data reporting the number of brain metastasis as a prognostic factor for patients with NSCLC, we analyzed whether the prognostic importance of the mere count of brain metastasis in a modern, multimodal treatment setting. Patients and Methods We retrospectively analyzed patients treated for BM from non-small lung cancer between 2010 and 2020. Demographics, baseline characteristics, and tumor-associated parameters were retrieved from an electronic database. Prognostic factors for local cerebral control and survival were identified using the log-rank test and Cox regression analysis. Results We included 343 consecutive patients (male n=187, female n=156; median age 61 years). Histological subtypes were adenocarcinoma (n=283), squamous-cell carcinoma (n=42) and neuroendocrine carcinoma (n=18). The median number of BM was one (range 1–20). Single (n = 189), oligo (n=110) and multiple BM (n=44) showed in total a median follow up of 10 months (minimum 1, maximum 142). Treatment comprised surgical resection (n=218) with radiotherapy, stereotactic radiosurgery (n=125) and adjuvant systemic therapy (n=203). The median local cerebral control was 11 months (95%CI 8.5 – 13.5) and the median overall survival was 16 months (95%CI 12.8 – 19.2). The number of BM did not influence local control and overall survival rates (p = 0.234 and p = 0.210, respectively). Controlled systemic disease (HR 0.42; 95% CI 0.2284–0.633; p<0.0001), clinical status (Karnofsky Performance Score > 70; HR 0.41; 95% CI 0.265–0.661; p<0.0001) and adjuvant systemic therapy (HR 0.38; 95% CI 0.279–0.530; p<0.0001) were independent prognostic factors for survival. Conclusions The mere number of brain metastases is not a prognostic factor for survival and local cerebral control in a multimodal treatment setting.

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii35-ii35
Author(s):  
Koichi Mitsuya ◽  
Shoichi Deguchi ◽  
Yoko Nakasu ◽  
Nakamasa Hayashi

Abstract PURPOSE To determine treatment outcome following salvage surgery (SS) for local progression of brain metastasis treated by stereotactic irradiation (STI). METHODS The clinical records of patients who underwent SS of local progression of brain metastases after STI at our institute between October 2002 and July 2019 were retrospectively reviewed. Kaplan-Meier curves were used for the assessment of overall survival (OS). The decision to perform SS was based on findings of magnetic resonance imaging and/or clinical evidence of local progression of the brain metastases and status of systemic disease. Prognostic factors for survival were analyzed; age, sex, primary cancer, RPA classification at surgery, extent of resection, radiotherapy after salvage surgery, and pre-surgical neutrophil-to-lymphocyte ratio (NLR). RESULTS Fifty-four SS of 48 patients were performed. The median age of the patients was 63 years (range 36–79). The median interval from STI to SS was 12 months. The median overall survival was 20.2 months from SS. Primary cancer were lung 34, breast 10, and other 10. Fourteen of 54 lesions (26%) developed local recurrence. Leptomeningeal dissemination occurred after the SS in 3 patients (5.7%). RPA classification (1 vs 3, HR:0.16, 95%CI: 0.03–0.59) (2 vs 3, HR:0.44, 95%CI:0.19–0.97) and primary cancer (breast vs lung, HR:0.21, 95%CI:0.05–0.64) (breast vs others, HR:0.08, 95%CI:0.015–0.32) (lung vs others, HR:0.38, 95%CI:0.16–0.94)) were identified as good prognostic factors of overall survival in multivariate analysis. The optimum NLR threshold value was identified as 3.65 for 1-year survival from SS (AUC0.62, sensitivity:71%). CONCLUSIONS Salvage surgery for local progression of brain metastases after STI in selected cases leads to a meaningful improvement in survival.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 289-289
Author(s):  
İzzet Dogan ◽  
Ayca Iribas ◽  
Nail Paksoy ◽  
Meltem Ekenel ◽  
Sezai Vatansever ◽  
...  

289 Background: The study aimed to evaluate the outcomes and prognostic factors in patients with brain metastatic renal cell carcinoma (bmRCC). Methods: The data of 322 patients with renal cell carcinoma, between 2012 and 2020, were retrospectively reviewed. The clinicopathological features and treatments of the patients with bmRCC were recorded. Overall survival (OS) and prognostic factors were evaluated with Kaplan-Meier analysis and Cox-regression analysis. Results: Forty (12.4%) of the patients had bmRCC. The median follow-up period was 7.3 months (range, 0.2-55.5). The male/female ratio was 2.3, and the median age at diagnosis was 62 years (range, 25-84). Seventeen (42.5%) of the patients were de-novo metastatic, and nine (22.5%) of the patients had brain metastases at presentation. The most common extracranial metastatic sites of the disease were lung (72.5%), bone (47.5%), lymph node (27.5%), and liver (12.5%). Twenty-four (60%) patients previously had received various therapies (tyrosine kinase inhibitor, checkpoint inhibitors, or palliative radiotherapy). After brain metastases developed, 92% of the patients received brain radiotherapy (whole-brain radiotherapy or stereotactic radiosurgery), and twenty-five (62.5%) patients received different therapies. Nine patient received sunitinib, nine patient pazopanib, five patient nivolumab, and two patient axitinib. A total of 32 (80%) patients died during the study period. The median OS was 8.8 months (range, 2.9-14.6) for all patients with bmRCC. Six months- and one-years overall survival ratios were 60% and 40%, respectively. In univariate analysis, the number of brain metastasis (p = 0.352), the localization of brain metastasis (p = 0.790), the longest size of brain metastasis (p = 0.454), the number of extracranial metastatic sites (p = 0.812), de-novo metastatic disease (p = 0.177), primary tumor localization (left or right) (p = 0.903), and tumor grade (p = 0.093) were not statistically significant factors on OS. However, age (p = 0.02), a history of nephrectomy (p < 0.001), receiving brain radiotherapy (p = 0.005), and type of treatment (p = 0.044) was statistically significant. Only, the effect of brain radiotherapy on OS (p = 0.011) was confirmed in multivariate analysis. Conclusions: The prognostic data of patients with bmRCC is limited. In this study, we observed that the prognosis of patients with bmRCC was poor. Despite a small number of patients, we detected that the effect of tyrosine kinase inhibitors and nivolumab was comparable, and receiving brain radiotherapy was a prognostic factor for OS.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii183-ii183
Author(s):  
Kevin Fan ◽  
Nafisha Lalani ◽  
Nathalie Levasseur ◽  
Andra Krauze ◽  
Lovedeep Gondara ◽  
...  

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&lt; 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&lt; 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.


Author(s):  
Yukinori Okada ◽  
Mariko Kobayashi ◽  
Mio Shinozaki ◽  
Tatsuyuki Abe ◽  
Naoki Nakamura

Abstract Aim: To identify prognostic factors and investigate patient survival after whole-brain radiotherapy (WBRT) for initial brain metastases arising from non-small cell lung cancer (NSCLC). Methods: Patients diagnosed with NSCLC between 1 January 2010 and 30 September 2019, and who received WBRT upon first developing a brain metastasis, were investigated. Overall survival was determined as related to age, sex, duration between initial examination and brain metastasis detection, stage at the first examination, presence of metastases outside the brain, blood analysis findings, brain metastasis symptoms, radiotherapy dose and completion, imaging findings, therapeutic course of chemotherapy and/or radiation therapy, histological type, and gene mutation status. Results: Thirty-one consecutive patients (20 men and 11 women) with a mean age of 63·8 years and median survival of 129 days were included. Multivariate analysis with stepwise testing was performed to investigate differences in survival according to gene mutation status, lactate dehydrogenase (LDH) level, irradiation dose, WBRT completion and Stage status. Of these, a statistically significant difference in survival was observed in patients with gene mutation status (hazard ratio: 0·31, 95% CI: 0·11–0·86, p = 0·025), LDH levels <230 vs. ≥230 IU/L (hazard ratio: 4·08, 95% CI: 1·45–11·5, p < 0·01) received 30 Gy, 30 Gy/10 fractions to 35 Gy/14 fractions, and 37·5 Gy/15 fractions (hazard ratio: 0·26, 95% CI: 0·09–0·71, p < 0·01), and stage IV versus non-stage IV (hazard ratio: 0·13, 95 CI:0·02–0·64, p < 0·01) Findings: Gene mutation, LDH, radiation dose and Stage are prognostic factors for patients with initial brain metastases who are treated with WBRT.


2021 ◽  
pp. ijgc-2021-002906
Author(s):  
Eva Meixner ◽  
Tanja Eichkorn ◽  
Sinem Erdem ◽  
Laila König ◽  
Kristin Lang ◽  
...  

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for radiosurgery in women with primary pelvic gynecologic malignancies metastatic to the brain. The aim of the present study is to evaluate the feasibility, safety, outcomes, and impact of established prognostic scores.MethodsWe retrospectively identified 52 patients treated with radiotherapy for brain metastases between 2008 and 2021. Stereotactic radiosurgery was utilized in 31 patients for an overall number of 75 lesions; the remaining 21 patients received whole-brain radiotherapy. Kaplan-Meier survival analysis and the log-rank test were used to calculate and compare survival curves and univariate and multivariate Cox regression to assess the influence of cofactors on recurrence, local control, and prognosis.ResultsWith a median follow-up of 10.7 months, overall survival rates post radiosurgery were 65.3%, 51.3%, and 27.7% for 1, 2, and 5 years, respectively, which were significantly higher than post whole-brain radiotherapy (p=0.049). Five local failures (6.7%) were detected, resulting in 1 and 2 year local cerebral control rates of 97.4% and 94.0%, respectively. Univariate factors for prediction of superior overall survival were high performance status (p=0.030) and application of three prognostic scores, especially the Recursive Partitioning Analysis score (p=0.028). Uni- and multivariate analysis revealed that extracranial progression prior to radiosurgery was significant for inferior overall survival (p<0.0001). Radionecrosis was diagnosed in five women (16%); long-term neurotoxicity was significantly worse after whole-brain radiotherapy compared with radiosurgery (p=0.023).ConclusionStereotactic radiosurgery for brain metastases from pelvic gynecologic malignancies appears to be safe and well tolerated, achieving promising local cerebral control. Prognostic scores were shown to be transferable and radiosurgery should be recommended as primary intracranial treatment, especially in women with no prior extracranial progression and Recursive Partitioning Analysis class I.


2020 ◽  
Vol 37 (5) ◽  
pp. 390-400
Author(s):  
Yusuke Yamamoto ◽  
Teiichi Sugiura ◽  
Yukiyasu Okamura ◽  
Takaaki Ito ◽  
Ryo Ashida ◽  
...  

Background: Selecting patients who will benefit from resection among those with advanced gallbladder cancer (GBCa) having poor prognostic factors is difficult. Methods: One hundred twenty-one patients who underwent resection for stage II–IV GBCa and 19 unresected patients (unresectable group) were enrolled. The clinical impact of carbohydrate antigen 19-9 (CA19-9) and advanced surgical procedures for GBCa was evaluated. Results: The optimal CA19-9 cutoff value (based on the greatest difference in overall survival) was 250 U/mL. CA19-9 ≥250 U/mL was found to be an independent prognostic factor. Patients with CA19-9 <250 U/mL who developed jaundice (median survival time [MST], 49.1 months) or who required major hepatectomy (MST, 21.5 months) or pancreatoduodenectomy (PD; MST, 50.3 months) had a better prognosis than those with CA19-9 ≥250 U/mL who developed jaundice (MST, 16.1 months; p = 0.061) or who required major hepatectomy (MST, 9.2 months; p = 0.066) or PD (MST, 8.6 months; p = 0.025); their prognosis was comparable to that of the unresectable group (jaundice: p = 0.145, major hepatectomy: p = 0.292, PD: p = 0.756). Conclusions: Even if GBCa patients develop jaundice or require major hepatectomy, or combined PD, resection can be considered for those with CA19-9 <250 U/mL. However, surgical indication should be carefully determined in patients with CA19-9 ≥250 U/mL.


2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
Koichi Mitsuya ◽  
Shoichi Deguchi ◽  
Nakamasa Hayashi ◽  
Hideyuki Harada ◽  
Yoko Nakasu

Abstract BACKGROUND Stereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. Just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. METHODS We evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Prognostic factors for survival were analyzed. RESULTS Fifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 64 years. The median diameter of the enhanced lesions was 35 mm (range 19–58 mm). The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1–2 (RPA 1 vs. 3, HR: 0.13), (RPA 2 vs 3, HR: 0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. CONCLUSION We insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi56-vi56
Author(s):  
Soumya Sagar ◽  
Adam Lauko ◽  
Addison Barnett ◽  
Wei (Auston) Wei ◽  
Samuel Chao ◽  
...  

Abstract BACKGROUND Melanoma is the third most common malignancy that results in brain metastasis and is associated with a median overall survival (OS) of approximately 9 months. In recent years, management of melanoma brain metastases (MBM) by surgery and radiation [stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT)] has been bolstered by targeted therapy and immune checkpoint inhibitors (ICI). METHODS 351 patients, treated for MBM at our tertiary care center from 2000–2018, were grouped into: received chemotherapy, ICI, or targeted therapy. 34% of patients treated with ICI had received other systemic therapies as well as part of their management. OS was calculated from the date of diagnosis of the brain metastases. The Kaplan Meier analysis was utilized to determine median OS and difference in OS was determined by utilizing the Cox proportional hazard model. RESULTS The median survival after the diagnosis of brain metastasis was 10.4, 11.96, and 7.06 months in patients who received ICI, chemotherapy and targeted therapy respectively. A multivariate model was developed including the type of systemic therapy, presence of extracranial metastases, age, KPS and number of intracranial lesions. 114 patients underwent SRS alone, 56 underwent SRS and WBRT, 43 underwent SRS and surgical removal, 28 had surgical removal, SRS and WBRT, and 78 had no intracranial therapy. Compared to patients who received chemotherapy, patients who received immunotherapy had a hazard ratio, HR = 0.628 (confidence interval = 0.396 – 0.994, p-value = 0.047). Presence of EC metastases (HR= 1.25, p-value < .001), lower KPS (HR = .97, p-value < .0001) and multiple brain lesions (HR = 1.117, p-value < .0001) were associated with significantly worse OS. CONCLUSIONS Addition of ICI significantly improves the OS in MBM compared to chemotherapy. Lower performance status, multiple brain metastases, and EC metastases are associated with poor OS.


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