scholarly journals Outcomes of changing systemic therapy in patients with relapsed breast cancer and 1 to 3 brain metastases

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Omar Alhalabi ◽  
Zaid Soomro ◽  
Ryan Sun ◽  
Elshad Hasanov ◽  
Aya Albittar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Local Treatment ◽  
Progression Free Survival ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Extracranial Disease ◽  
Initiation Of Therapy ◽  
The Impact

AbstractThe development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) following the diagnosis and management of oligometastatic (1–3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52–1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40–1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.

New Era in the Management of Melanoma Brain Metastases

2018 ◽  
pp. 741-750 ◽  
Author(s):  
Hussein A. Tawbi ◽  
Celine Boutros ◽  
David Kok ◽  
Caroline Robert ◽  
Grant McArthur
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Single Agent ◽  
Local Treatment ◽  
New Era ◽  
Therapeutic Modalities ◽  
Melanoma Brain Metastases ◽  
Extracranial Disease ◽  
Induce Response ◽  
The Impact

The remarkable advances in the systemic therapy of metastatic melanoma have now extended the 1-year overall survival rate from 25% to nearing 85%. Systemic treatment in the form of BRAF-targeted therapy and immunotherapy is slowly but surely proving its efficacy in the treatment of metatstatic brain metastases (MBM). Single-agent BRAF inhibitors provide an intracranial response rate of 25% to 40%, whereas the combination of BRAFi/MEKi leads to responses in up to 58%. However, the durability of responses induced by BRAFi/MEKi seems to be even shorter than in extracranial disease. On the other hand, single-agent ipilimumab provides comparable clinical benefit in MBMs as it does in extracranial metastases. Single-agent PD-1 anitbodies induce response rates of approximately 20%, and those responses appear durable. Similarly the combination of CTLA-4+ PD-1 antibodies induces durable responses at an impressive rate of 55% and is safe to administer. Although the local treatment approaches with radiation and surgery remain important and are critically needed in the management of MBM, systemic therapy offers a new dimension that can augment the impact of those therapies and come at a potentially lower cost of neurocognitive impairment. Considerations for combining those modalities are direly needed, in addition to considering novel systemic combinations that target mechanisms specific to MBM. In this report, we will discuss the underlying biology of melanoma brain metastases, the clinical outcomes from recent clinical trials of targeted and immunotherapy, and their impact on clinical practice in the context of existing local therapeutic modalities.

Systemic therapy for patients with breast cancer and one to three brain metastases (BM).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1090-1090
Author(s):  
Zaid A Soomro ◽  
Omar Alhalabi ◽  
Ryan Sun ◽  
Aya Albittar ◽  
Limin Hsu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Brain Metastases ◽  
Survival Time ◽  
Systemic Therapy ◽  
Local Therapy ◽  
Extracranial Disease ◽  
The Impact ◽  
Extracranial Metastases

1090 Background: Despite advances in systemic therapies and improved overall survival of metastatic breast cancer (MBC) patients, the development of brain metastases (BMs) remains a challenging complication that affects quality of life and increases morbidity and mortality. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable systemic disease. Methods: We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) after diagnosis of the initial 1-3 BMs on the patient’s progression-free survival time (PFS), defined as time to death, to a second BMs or to extracranial metastases. All MBC patients with 1 to 3 BMs only (without extracranial disease) treated at our institution between 2002 and 2017 were identified. For each patient, full information on follow-up and administered therapies were mandatory for inclusion. Hazard ratios (HR) were calculated using the Cox proportional hazard model. We also computed the restricted mean survival time (RMST) up to 5 years of follow-up. Results: Among the 2645 patient with BM treated at our institution, 80 were included for analysis. In regards to primary BMs management in patients, 46 of 80 (57%) were treated by radiation therapy, 6 of 80 (7.5%) underwent surgical resection, and 28 of 80 (35%) were managed by a combination of surgery and radiation therapy. All patients had staging imaging documenting lack of extracranial metastases at the time of local therapy of BMs. Following the primary management of BM, we observed that providers changed systemic therapy in 32 of 80 (40%), defined as the CST group. CST included both initiation of therapy in 16 of 80 (20%) and switching of adjuvant therapy in 16 of 80 (20%). Median PFS among CST was 7.7 months vs. 7.2 months among no CST (HR = 0.855, 95% confidence interval (CI) 0.53-1.38, p = 0.52). 5-year RMST for the CST group was 16.6 months vs. 12.8 months in no CST group. The difference of 3.8 months (95% CI 4.3-11.8) was not statistically significant. Conclusions: Patients with 1-3 BMs without extracranial disease had a median PFS close to 7.5 months after local therapy. Consistent with current standard of care of maintaining the same systemic therapy approach upon developing isolated BMs, our findings did not demonstrate a significant difference in PFS between patients who experienced a change in systemic therapy compared to those who did not.

Clinical impact of the Mexican healthcare system "Seguro Popular" on breast cancer survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6569-6569
Author(s):  
Luis Antonio Cancel ◽  
Carlos Eduardo Salazar-Mejía ◽  
Francisco Emilio Vera Badillo ◽  
Juan Francisco Gonzalez Guerrero ◽  
Jackeline Grace Lara-Campos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Universal Access ◽  
Clinical Stage ◽  
Progression Free Survival ◽  
Formal Sector ◽  
Her2 Positive ◽  
Seguro Popular ◽  
Significant Difference ◽  
The Impact

6569 Background: Breast cancer (BC) is one of the leading issues in public health in low and middle-income countries. In Mexico, access to healthcare is fragmented according to the patient´s employment and not by its needs; IMSS and ISSTE (Social Security) provide access to prepaid medicine to those under the formal sector of the economy, leaving up to 50 million Mexicans without access to a prepaid scheme. In 2003, the Seguro Popular (SP) was created in order to bring universal access to prepaid medicine in Mexico, and in 2007 expanded its coverage for BC. Methods: Retrospective and comparative study. The primary endpoint was to determine the impact on survival of SP on BC. Records were obtained from the electronic database of the Hospital Universitario “Dr. José Eleuterio González”. We included patients with invasive BC stage I-IV. Patients with any other kind of healthcare schemes other than SP, patients who underwent treatment outside our institution, and those with a follow up no greater than 3 months were excluded. 104 patients from the period prior the implementation of the SP (2000-2007) met the criteria for evaluation; thereafter we randomly selected a second cohort with the same size from the period after the implementation of the SP (2008-2013). Results: Median age at diagnosis was 48 and 51 years, respectively, for the periods before and after the implementation of SP. Distribution by clinical stage (Non-SP vs SP): CS I, 4.8 vs 10%, CS II, 31 vs 44%, CS III, 52 vs 38%, and CS IV, 10 vs 6.7%. Molecular subtypes distribution (Non-SP vs SP): Luminal, 61 vs 62%, HER2 Positive (IHC+++/FISH+) 17 vs 22%, TNBC, 21 vs 18%, unknown 6.7 vs 5.7%. Regarding survival, we observed a statistically significant difference on progression-free survival and overall survival favoring the SP cohort; PFS at 5 years, 54 vs 81% (p = < 0.0001) and OS at 5-year, 72 vs 86% (p = 0.01). Conclusions: We present evidence that the Mexican healthcare scheme SP, created to bring medical access to those patients without prepaid health protection, provides a significant clinical benefit on survival (PFS and OS) in women with breast cancer.

Effect of type and timing of systemic therapy on risk of radiation necrosis in patients with HER2+ breast cancer brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14002-e14002
Author(s):  
Christine Park ◽  
Evan Buckley ◽  
Amanda E.D. Van Swearingen ◽  
Will Giles ◽  
James Emmett Herndon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Radiation Necrosis ◽  
Treatment Modalities ◽  
Conformity Index ◽  
Her2 Breast Cancer ◽  
Breast Cancer Brain Metastasis ◽  
The Impact ◽  
Systemic Therapies

e14002 Background: It is estimated that 30% of patients with metastatic human epidermal growth factor receptor 2-positive (HER2+) breast cancer will develop brain metastases. Current standard of care options for HER2+ breast cancer brain metastasis (BCBrM) includes radiation therapy (stereotactic radiosurgery [SRS] or whole brain radiation), brain permeable systemic therapies, and in select cases, neurosurgical resection. A multimodal approach combining these different treatment modalities has improved the overall survival and functional outcomes of patients with BCBrM. Some HER2-directed systemic therapies, however, may increase the risk of radiation necrosis (RN), a longer-term consequence of SRS. This study explores the impact of timing and type of systemic therapies on the development of RN in patients treated with SRS for HER2+ BCBrM. Methods: This was a single-institution, retrospective study including patients ≥18 years of age with HER2+ BCBrM who received SRS between 2013 and 2018 at Duke University with at least 12-month post-SRS follow-up. Presence of RN was determined at one-year post-SRS. Demographics, radiotherapy parameters (total dose, fractions, clinical target volume [CTV], gross tumor volume [GTV], conformity index [CI], volume receiving 12 gray [V12Gy]), and timing (during [within 4 weeks of SRS] vs. not during SRS) and type of systemic therapy (HER2-directed therapy, mitosis inhibitors, DNA synthesis inhibitors, others) were evaluated. Results: Among 46 patients with HER2+ BCBrM who received SRS, 28 (60.9%) developed RN and 18 (39.1%) did not. Age at time of SRS did not differ between those who developed RN and those who did not (mean 53.3 vs 50.4 years, respectively). There was a higher percentage of African Americans in the RN group (28.6% vs 11.1%, p = 0.3). There were no significant differences between the measured radiotherapy parameters—including dose, fraction, CTV, GTV, CI, V12Gy—between the two groups (all p > 0.05). Receipt of any type of systemic therapy during SRS did not differ between patients who did or did not develop RN (60.7% vs 55.6%, p = 0.97). However, patients who developed RN more commonly received more than one line of HER2-directed therapy independent of SRS timing compared to those who did not develop RN (75.0% vs 44.4%, p = 0.08). In fact, a significantly higher proportion of those who developed RN received more than one line of HER2-directed therapy during SRS compared to those did not develop RN (35.7% vs 5.6%, p<0.05). Conclusions: Patients with HER2 BCBrM who receive multiple lines of HER2-directed therapy during SRS for BCBrM may be at higher risk of RN. This data supports a practice of holding HER2-directed therapy during SRS if medically acceptable. Further investigation of next generation HER2-directed therapies in a larger cohort of patients should be investigated to help guide best practice to minimize RN.

Compliance With Consensus Recommendations for Systemic Therapy Is Associated With Improved Survival of Women With Node-Negative Breast Cancer

2004 ◽  
Vol 22 (18) ◽  
pp. 3685-3693 ◽  
Author(s):  
Nicole Hébert-Croteau ◽  
Jacques Brisson ◽  
Jean Latreille ◽  
Michèle Rivard ◽  
Nadia Abdelaziz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Systemic Therapy ◽  
Administrative Databases ◽  
Minimal Risk ◽  
Node Negative ◽  
Consensus Recommendations ◽  
Hazard Ratios ◽  
Node Negative Breast Cancer ◽  
The Impact

Purpose The impact of consensus recommendations for systemic therapy on outcome of disease is unclear. We evaluated if compliance with guidelines for systemic adjuvant treatment is associated with improved survival of women with node-negative breast cancer. Patients and Methods The study population included women diagnosed with invasive node-negative breast cancer in Québec, Canada, in 1988 to 1989, 1991 to 1992, and 1993 to 1994. Information was collected by chart review, linkage with administrative databases, and queries to attending physicians. Guidelines from the 1992 St Gallen conference were used as standard of care. Survival was estimated by Kaplan-Meier and Cox proportional hazards analyses. Results Among 1,541 women, 358 died before December 1999. Median follow-up was 6.8 years. Seven-year event-free and overall survivals were 66% and 81%, respectively. Survival was 88%, 84%, and 74% in women at minimal, moderate, or high risk of recurrence. Virtually all women at minimal risk were treated according to the consensus (98.4% of 370). In comparison, adjusted hazard ratios of death were 1.0 (95% CI, 0.6 to 1.7) and 2.3 (95% CI, 1.3 to 4.0) among women at moderate risk treated according to the consensus or not, respectively. Among women at high risk, adjusted hazard ratios of death were 2.0 (95% CI, 1.4 to 2.8) and 2.7 (95% CI, 1.9 to 3.9), respectively. Both risk category (P < .0005) and compliance with guidelines (P < .0005) were independent significant predictors of survival. Conclusion Treatment according to consensus recommendations is associated with improved survival of women with breast cancer in the community. Promoting the adoption of guidelines for treatment is an effective strategy for disease control.

Recursive Partitioning Analysis of Systemic Therapy after Radiotherapy in Patients with Brain Metastases

2021 ◽  
pp. 1-6
Author(s):  
Carsten Nieder ◽  
Astrid Dalhaug ◽  
Ellinor Haukland
Keyword(s):  
Brain Metastases ◽  
Systemic Therapy ◽  
Group Performance ◽  
Recursive Partitioning ◽  
Local Treatment ◽  
Eastern Cooperative Oncology Group ◽  
Recursive Partitioning Analysis ◽  
Endocrine Treatment ◽  
Brain Irradiation ◽  
Extracranial Disease

<b><i>Purpose:</i></b> The purpose of this study was to identify factors associated with the initiation or continuation of systemic treatment after brain irradiation. The outcome of interest was a utilization rate of at least 75%, given that active extracranial disease is common in patients with brain metastases. If left untreated, extracranial disease limits survival, regardless of successful local treatment of the brain metastases. In this context, systemic therapy has been shown to improve survival, e.g., after whole-brain radiotherapy. <b><i>Patients and Methods:</i></b> The study included 185 patients with active extracranial disease, 60% of whom received systemic therapy. <b><i>Results:</i></b> Survival from the start of brain irradiation was longest in patients who received additional immune checkpoint inhibitors, endocrine treatment, or anti-HER-2 drugs. After uni- and multivariate analyses, Eastern Cooperative Oncology Group performance status (PS) was selected as the first prediction criterion in the recursive partitioning analysis (RPA) decision tree analysis. RPA was successful for patients with PS 0–1, but patients with PS 2 had lower treatment utilization rates (maximum 60–70%, with a disease-dependent impact of age and LabBM score [blood test results]). The highest utilization rates were observed in (1) patients with PS 0 and (2) those with breast cancer, small-cell lung cancer, or lung adenocarcinoma with PS 1. <b><i>Conclusions:</i></b> These results inform the multidisciplinary discussion and treatment planning for the common scenario of simultaneous intra- and extracranial metastases.

scholarly journals Systemic treatment of HER2-positive breast cancer patients with brain metastases: current status and exploratory case study in a Portuguese cohort

2021 ◽  
Vol 18 (1) ◽  
pp. 1-14
Author(s):  
Paulo Luz ◽  
Elsa Campoa ◽  
Rita Gameiro ◽  
Marta Vaz ◽  
Isabel Fernandes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Systemic Treatment ◽  
Local Treatment ◽  
Current Status ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
The Impact

Over the last years, the incidence of brain metastases in HER2 breast cancer patients has increased. Surgery and radiotherapy are the current standard local therapies. Nevertheless, it is unclear which and when systemic treatment should be applied in addition to local treatment. This work aims to present an updated review of current systemic treatment options for patients with HER2+ metastatic breast cancer with brain metastases and to present a case study of clinical cases that occurred in a Portuguese population. The methodology of this work included a literature search in PubMed for the impact of HER2-targeting agents, such as pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, neratinib, trastuzumab deruxtecan, and tucatinib in the treatment of patients with HER2+ breast cancer with brain metastases. Then, a cohort of Portuguese patients with HER2+ breast cancer (n=44) was analyzed. In this exploratory study, considering a follow-up of 23.9 months, three patients (6.8%) developed brain metastases despite having shown a complete pathological response. The role of systemic treatment for patients with HER2 breast cancer with brain metastases has rapidly evolved following recent successes in phase II and III clinical trials. The biggest challenge is how to integrate systemic and local treatment in the management of these patients.

Intensified local treatment and systemic therapy significantly increase time to progression and survival in patients with brain metastases from advanced breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10536-10536
Author(s):  
R. Bartsch ◽  
S. Muschitz ◽  
C. Wenzel ◽  
K. Roessler ◽  
K. Dieckmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Advanced Breast Cancer ◽  
Systemic Therapy ◽  
Systemic Treatment ◽  
Local Treatment ◽  
Advanced Breast ◽  
Cytotoxic Agents ◽  
Time To Progression ◽  
Metastatic Sites

10536 Background: Brain metastases (BM) have evolved from a rare to a frequently encountered event in advanced breast cancer (ABC) due to advances in palliative systemic treatment. Especially since the introduction of trastuzumab, different groups reported an increased incidence of BM. In this study, we retrospectively tried to establish factors predicting a prolonged survival in those patients (P). Methods: All P treated at our centre from 1994 to 2004 with whole brain radiotherapy for BM from ABC were included. Cerebral time to progression (cTTP) and overall survival (OS) were calculated using the Kaplan-Meier product limit method. A multivariate analysis (Cox regression) was performed to explore which factors are able to influence significantly cTTP and OS (metastatic sites [visceral versus non-visceral], Karnofsky performance score [KPS], age, intensified local treatment [boost irradiation, neuro-surgical resection], further palliative systemic treatment). Results: Overall 174 P, median age 51 years (y), range 27–76 y, were included. Median cTTP was 3 months (m), range 1–33+ m (95% CI 4.67–7.37). Median OS was 7 m, range 1–44 m (95% CI 5.08– 8.92). Factors significantly influencing cTTP were KPS (p = 0.0024), intensified local treatment (p < 0.0001), and palliative systemic treatment (P = 0.0003). Factors significantly influencing OS were intensified local treatment (p = 0.004), metastatic sites (p = 0.008), KPS (p = 0.006), and palliative systemic treatment (p < 0.001). Conclusion: As shown by the significant influence of metastatic sites, some P die from their advanced systemic disease situation before they would experience cerebral progression, in part explaining the influence of systemic treatment. In other individuals however, intensified local treatment and systemic treatment appear to influence both cTTP and OS significantly, implicating a direct influence of systemic therapy on BM. This might result from an impaired blood brain barrier around metastatic sites, making sufficient tissue concentrations of cytotoxic agents possible. No significant financial relationships to disclose.

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