scholarly journals Impact of New Systemic Treatment and Radiotherapy in Melanoma Patients with Leptomeningeal Metastases

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2635
Author(s):  
Pauline Tétu ◽  
Lila Sirven-Villaros ◽  
Stefania Cuzzubbo ◽  
Renata Ursu ◽  
Barouyr Baroudjian ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Systemic Treatment ◽  
Elevated Serum ◽  
Serum Lactate Dehydrogenase ◽  
Leptomeningeal Disease ◽  
Melanoma Patients ◽  
Systemic Therapies

Importance: Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies. Objective: To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment. Design: Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival. Setting: Monocentric, retrospective, real-life cohort of patients with LM from melanoma. Participants: All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM. Exposure: Impact of new systemic therapies and radiotherapy. Results: Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM “confirmed” or “probable” after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09–1.90, p < 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25–6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response. Conclusion: Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.

Overall survival benefits of advances in NSCLC systemic treatments: Younger versus older adults.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 93-93
Author(s):  
Bonnie Leung ◽  
Aria Shokoohi ◽  
Zamzam Salam Al-Hashami ◽  
Sara Moore ◽  
Alexandra Pender ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Targeted Therapy ◽  
Systemic Therapy ◽  
Advanced Nsclc ◽  
Systemic Treatment ◽  
Age Groups ◽  
Stage Iv ◽  
Novel Therapeutics ◽  
Systemic Treatments

93 Background: Historically, there has been limited systemic therapy options for older adults with cancer attributed to underlying frailty, co-morbidities, poor functional status, and limited social supports. In the past decade, treatment for advanced NSCLC has changed with increasing availability of novel therapeutics associated with improved tolerability and efficacy, such as targeted therapy and immunotherapy. The study goal is to compare the difference in overall survival (OS) between younger adults and older adults with the introduction of novel therapeutic options. Methods: All patients with stage IV NSCLC referred to BC Cancer in 2009, 2011, 2015 and 2017 were included in the study. One-year time points were chosen based on molecular testing implementation and provincial formulary listing: baseline (2009), EGFR testing (2011), ALK testing (2015) and immunotherapy listing (2017). Age was categorized as younger (< 70 years) and older (≥70 years) adults. Baseline demographics, simplified comorbidity score (SCS ≥9 associated with poor prognosis), disease characteristics, and systemic therapy details (agent, duration, line of therapy) were collected retrospectively. Univariate analysis using X2 and Fisher’s exact tests were used to compare age groups. OS was calculated using the Kaplan-Meier method and compared using the log-rank test. Results: 3325 patients with stage IV NSCLC were identified. Baseline characteristics for patients < 70 y; female 51%, non-squamous 62%, ECOG ≥2 50%, SCS ≥9 29% vs patients ≥70 y; female 49%, non-squamous 57%, ECOG ≥2 61%, SCS ≥9 58%. In the four time cohorts 2009/2011/2015/2017, systemic treatment was delivered to < 70 y 44/53/51/52 % vs ≥70 y 23/25/28/30 %. Median OS with BSC for < 70 y 3.1/2.8/2.8/2.5 m vs ≥70 y 3.8/3.3/3.4/3.1 m (p = 0.10). Median OS with systemic treatment for < 70 y 9.0/10.9/13.9/15.5 m (p < 0.001) vs ≥70 y 11.4/11.7/13.9/14.9 m (p < 0.001). Median OS by type of treatment BSC/chemotherapy only/targeted therapy/immunotherapy; < 70 y 2.8/8.9/21.4/20.2 m vs ≥70 y 3.1/10.1/21.5/20.1 m (p < 0.001). Conclusions: In this real-world retrospective review of patients with advanced NSCLC, there was an increased uptake of systemic therapy for both age groups with the introduction of novel therapeutics. Although there was a smaller proportion of older adults who received systemic therapy, those who received treatment had comparable OS to their young counterpart. The benefit of systemic therapy in both age groups was seen across the different types of treatments. This suggests with careful assessment and selection of appropriate candidates, older adults with advanced NSCLC should receive equitable access to systemic therapy.

scholarly journals Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Achiraya Teyateeti ◽  
Paul D Brown ◽  
Anita Mahajan ◽  
Nadia N Laack ◽  
Bruce E Pollock
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Median Overall Survival ◽  
Recursive Partitioning ◽  
Leptomeningeal Disease ◽  
Resection Cavity ◽  
Whole Brain Radiation ◽  
Class 1 ◽  
Outcome Comparison ◽  
Brain Radiation

Abstract Background To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity. Methods Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed. Results Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively. Conclusions Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

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

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&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.

scholarly journals CMET-23. IMPACT OF SYSTEMIC THERAPY IN MELANOMA BRAIN METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi56-vi56
Author(s):  
Soumya Sagar ◽  
Adam Lauko ◽  
Addison Barnett ◽  
Wei (Auston) Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Performance Status ◽  
Tertiary Care ◽  
P Value ◽  
Surgical Removal

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.

Adjuvant systemic therapy in elderly patients with breast cancer: A Brazilian single center experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20711-e20711
Author(s):  
G. Ismael ◽  
A. L. Coradazzi ◽  
C. A. Beato ◽  
P. Milhomem ◽  
J. Oliveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Elderly Patients ◽  
Systemic Therapy ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
Adjuvant Systemic Therapy ◽  
Free Survival ◽  
Adjuvant Systemic Treatment ◽  
Disease Free

e20711 Background: Breast cancer is the leading cause of cancer in women in Brazil and in the western world. Despite the high incidence of breast cancer in elderly women, there is no solid information regarding the real impact of the adjuvant systemic therapy in this population, considering the underrepresentation of patients with 65 years of age or older in cancer-treatment trials. Moreover, elderly patients may face some difficulties to receive adequate adjuvant systemic treatment in the routine clinical practice. Methods: Two hundred fifty eight patients with 65 years of age or older at the time of diagnosis of operable breast cancer and treated in our Institution from February 2000 to December 2005 were retrospectively studied. Clinical and pathological data were recorded as well as the type of adjuvant systemic therapy: hormonal therapy (HT), chemotherapy (CT) or both. We evaluated the disease free survival and overall survival and compared the results between the group of patients treated with HT only and the group of patients treated with both HT and CT. Results: Ninety five (37.5%) patients were stage I, 150 (58.1%) were stage II and 6 (2.3%) were stage III, while 5 (1.9%) patients were diagnosed with DCIS. Ductal carcinoma was the most frequent histological type (81%) and grade II were reported in the majority of patients (47.3%). Mostly of patients were hormonal sensible (74.4% were ER+ and 64% were PR+) and HER 2 negative (81.8%). One hundred seventy eight (69%) patients received any kind of adjuvant HT while 91 (35.3%) received any kind of adjuvant CT. There was no statistical difference between patients treated with HT when compared with the group of patients treat with HT and CT, regarding disease free survival and overall survival. However, a higher rate of high risk patients were observed in the group treated with both HT and CT. Conclusions: Despite the age, a considerable part of this elderly breast cancer patient's population has received adjuvant systemic treatment. Benefits from HT and/or CT may be considered in this group of patients. No significant financial relationships to disclose.

Brain metastases in patients treated with targeted therapy for metastatic renal cell carcinoma (mRCC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 326-326
Author(s):  
H. Alharbi ◽  
T. K. Choueiri ◽  
C. K. Kollmannsberger ◽  
S. North ◽  
M. J. MacKenzie ◽  
...  
Keyword(s):  
Overall Survival ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Treatment Time ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Local Treatment ◽  
Multivariable Analysis ◽  
First Line ◽  
The Brain

326 Background: Patients with brain metastases from advanced RCC treated in the targeted therapy era are not well characterized. Methods: Data from patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium from 6 centers. Results: One hundred six out of 705 (15%) patients with mRCC had brain metastases. Forty-seven patients had brain metastases at the start of first-line anti-VEGF therapy and the rest developed metastases during follow-up. Of the patients with brain metastases, 6%, 68%, and 26% were in the favorable, intermediate and poor prognosis groups, respectively, per the Heng et al JCO 2009 criteria. Ninety percent had cerebral metastases, 17% had cerebellar metastases, 40% had a Karnofsky performance status (KPS) <80%, and 81% had symptoms of brain metastases. The median largest size and number of brain metastases was 1.8 cm (range 0.2–6.6) and 1 (range 1–20), respectively. Patients were treated with first-line sunitinib (n=77), sorafenib (n=23), bevacizumab (n=5), and temsirolimus (n=1). Local disease treatment included whole brain radiotherapy (81%), stereotactic radiosurgery (25%), and neurosurgery (25%). The brain metastases of 59 patients were evaluable and based on the local treatment and/or targeted therapy achieved 7 (12%) complete responses, 23 (39%) partial responses, 14 (24%) patients with stable disease, and 15 (25%) patients with progressive disease in the brain metastases. Patients with more than 4 brain metastases vs. those with no more than 4 have an overall survival time from diagnosis of brain metastasis of 3.9 vs. 15.4 months (p=0.0051). Previous nephrectomy, sarcomatoid, and non-clear cell histology are not associated with development of brain metastases. On multivariable analysis, KPS<80% (p=0.0139), diagnosis to treatment with targeted therapy <1 year (p=0.0012), and higher number of brain metastases (p=0.0311) were associated with worse survival from diagnosis of brain metastases. Conclusions: In patients with brain metastases from RCC, KPS at start of therapy, diagnosis to treatment time and number of brain metastases may be prognostic factors for overall survival. [Table: see text]

scholarly journals THER-07. DEVELOPMENT OF A NEW MOLECULAR PREDICTOR FOR RISK OF BRAIN METASTASES AND EFFICACY OF TARGETED THERAPY IN MELANOMA

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i12-i12
Author(s):  
Howard Colman ◽  
Ken Boucher ◽  
Chris Stehn ◽  
David Kircher ◽  
Sheri Holmen
Keyword(s):  
Targeted Therapy ◽  
Brain Metastases ◽  
Predictive Power ◽  
Data Set ◽  
Multiple Gene ◽  
Methods Development ◽  
Melanoma Patients ◽  
Therapeutic Prevention ◽  
Screening Trial ◽  
Molecular Predictor

Abstract Despite therapeutic advances in the treatment of melanoma, development of brain metastases (BM) continues to be a major manifestation of treatment failure. The ability to identify those patients who are at highest risk of developing brain metastases is limited with current methods. Development of sensitive and specific biomarkers to predict which stage II-III melanoma patients are at highest risk of BM would enable initiation of prospective clinical trials focused on both intensive surveillance and therapeutic prevention. To accomplish this goal, we embarked on an effort to optimize a combined molecular/clinical/pathologic predictor of BM risk. We firstanalyzed multiple gene expression datasets including TCGA (n = 437) and an independent series from Australia (n = 183) and identified a list of 60 consensus genes that is robustly predictive of development of melanoma BM (p &lt; 0.05; FDR 5%). Next, we performed a similar analysis of association of miRNAs and melanoma BM risk which identified a set of miRNAs with significant predictive power. An optimized combined set of mRNA and miRNA markers was a better predictor of BM risk than either mRNA or miRNA list alone when applied to the TCGA data set. The combined predictor was most sensitive in separating patients with no metastases from those with either BM or systemic metastases. Current efforts are focused on optimizing miRNA and mRNA separation of patients specifically with BM from those with other mets, and with integrating the expression classifier with other clinical and pathologic predictive factors including: age, stage, thickness, location, histology, ulceration, gender. The sensitivity and specificity of the resulting clinical/molecular predictor will be validated in an independent retrospective cohort, and subsequently implemented in a prospective BM screening trial to determine real-world utility of this approach in preparation for prospective BM adjuvant/chemoprevention trials utilizing both immunotherapy and targeted therapy approaches.

Presence of genetic aberrations in patients with brain metastases from non-small cell lung cancer (NSCLC) and clinical outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20604-e20604 ◽  
Author(s):  
Robert H. Press ◽  
Xinyan Zhang ◽  
Richard John Cassidy ◽  
Matthew Jeffrey Ferris ◽  
Jim Zhong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Brain Metastases ◽  
Clinical Outcomes ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Genetic Alterations ◽  
Kras Mutations ◽  
Brain Radiotherapy ◽  
Systemic Therapies

e20604 Background: Historically, survival in patients (pts) with NSCLC brain metastases (BM) is poor, however, improved systemic therapies are now available including targeted therapies and immunotherapy. We sought to evaluate the prevalence of genetic alterations in pts with BM from non-squamous (NS) lung cancer, and to determine clinical outcomes in the modern era. Methods: With IRB approval, pts with BM from NS-NSCLC from 1/2010-1/2016 with genetic testing were captured and retrospectively reviewed. Snapshot genotyping was performed prior to 1/2014, after which Next Generation Sequencing was utilized, along with FISH lung cancer panel. Genes examined included: EGFR, ALK, RET, ROS1, TP53, KRAS, NRAS, MET, PTEN, BRAF, FBXW7, MAP2K1, APC, PIK3CA, CTNNB1, and SMAD4. Univariable and multivariable analysis (MVA) were utilized to assess factors associated with overall survival (OS). Results: 92 pts were included. Median number of BM was 4 (range 1-45). Median age was 64 (32-90 years). 59.8% were male. 38% received targeted therapy, 11% received immunotherapy, and 70% received conventional chemotherapy. 52.2% and 47.8% received whole brain radiotherapy and stereotactic radiosurgery, respectively. Median OS from first brain radiotherapy (RT) was 10.7 months (0.1-56.4). EGFR mutation, ALK fusion, ROS1 rearrangement, and RET rearrangement occurred in 27.5%, 5.2%, 1.7%, and 0% of pts. EGFR L858 and EGFR T790 mutations occurred in 19.2% and 2.7% of all pts. TP53, KRAS, and NRAS mutations occurred in 63.9%, 28.8% and 7% of pts. All other mutations had an incidence of less than 3%. On MVA, targeted therapy (HR 0.43 95% CI 0.22-0.86), immunotherapy (HR 0.04 95% CI 0.01-0.3), surgical resection (HR 0.38 95% CI 0.18-0.81), and ECOG performance status (0.23 95% CI 0.1-0.54) were associated with improved OS. No specific genetic aberration, RT modality, or number of BM was associated with OS. Conclusions: In pts with BM from NS-NSCLC, the most common molecular aberrations include TP53, EGFR, and KRAS mutations. Treatment with brain RT and modern systemic therapies yields a median survival greater than ten months. The use of targeted therapy or immunotherapy was associated with increased OS.

Sign in / Sign up

Export Citation Format

Share Document