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.

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.

Validation of Adjuvant!Online on Slovenian collective of early breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11532-e11532
Author(s):  
M. Ravnik ◽  
A. Sadikov ◽  
N. Snoj ◽  
P. Nussdorfer ◽  
T. Cufer
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Systemic Therapy ◽  
First Generation ◽  
Local Therapy ◽  
Adjuvant Systemic Therapy ◽  
Breast Cancer Patients ◽  
Small Group Size ◽  
Positive Effect

e11532 Background: Adjuvant!Online is a very useful tool for prognosis assessment of early breast cancer (EBC) patients. In the validation study, made on mostly untreated (45%) Canadian EBC patients, Adjuvant!Online proved to be a very reliable prognostic tool. The aim of our study was to validate Adjuvant!Online on EBC patients mainly treated with some kind of adjuvant systemic therapy. Methods: 753 EBC patients diagnosed and treated at the Institute of Oncology Ljubljana, Slovenia, with at least 10-year follow-up were included into the study. All patients received radical local therapy. Adjuvant chemotherapy (ChT) was either CMF or anthracycline-based schema and hormonal therapy (HT) was mainly tamoxifen. Adjuvant!Online 8.0 individual prediction of OS was calculated (with default value of “minor problems” as comorbidity for all patients). The average prediction over all patients was compared to the observed 10-year OS. Results: The predicted and observed 10-year OS of the whole group were 65.5% and 61.5%, respectively. The differences between predicted and observed OS did not differ substantially in the subgroups of patients stratified according to the classical prognostic factors, however, a large difference was found when stratifying by adjuvant systemic therapy. The puzzling difference in patients without systemic therapy (ST) can be both due to small group size and due to special selection of these patients (comorbidity). Conclusions: According to our observation, Adjuvant!Online is a reliable tool for prognosis assessment in EBC patients treated with HT, but it seems to overestimate prognosis in patients treated with ChT, alone or in combination with HT. This is evident even for our collective of EBC patients mainly treated with the first generation ChT - CMF or anthracyclines. Apparently, both Adjuvant!Online and Overview overestimate the positive effect of ChT, disregarding the biologic characteristics of the tumors and inherent effect of HT in HR+ patients. [Table: see text] No significant financial relationships to disclose.

Outcome at 8 Years After Breast-Conserving Surgery and Radiation Therapy for Invasive Breast Cancer: Influence of Margin Status and Systemic Therapy on Local Recurrence

2000 ◽  
Vol 18 (8) ◽  
pp. 1668-1675 ◽  
Author(s):  
Catherine C. Park ◽  
Michihide Mitsumori ◽  
Asa Nixon ◽  
Abram Recht ◽  
James Connolly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Logistic Regression ◽  
Radiation Therapy ◽  
Local Recurrence ◽  
Systemic Therapy ◽  
Surgical Margin ◽  
Breast Conserving Surgery ◽  
Margin Status ◽  
Positive Margins

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.

Survival of breast cancer patients receiving adjunctive psychosocial support therapy: a 10-year follow-up study.

1993 ◽  
Vol 11 (1) ◽  
pp. 66-69 ◽  
Author(s):  
G A Gellert ◽  
R M Maxwell ◽  
B S Siegel
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Survival Time ◽  
Cancer Diagnosis ◽  
Psychosocial Support ◽  
Support Program ◽  
Breast Cancer Patients ◽  
Nonsignificant Difference ◽  
The Impact

PURPOSE The impact of an adjunctive psychosocial support program on length of survival with breast cancer was evaluated in a retrospective cohort study. The duration of observation of survival was extended 10 years beyond a previous study of the same cohort of patients. PATIENTS AND METHODS One hundred two nonparticipants were individually matched to 34 participants on major prognostic factors. Both groups were monitored from the date of cancer diagnosis (1971 through 1980) until March 1991. The support program consisted of weekly cancer peer support and family therapy, individual counseling, and use of positive mental imagery. Survival analysis controlled for the effects of other major prognostic factors in the outcome of breast cancer. RESULTS The mean +/- SD survival time from date of cancer diagnosis to last date of follow-up was 96.0 +/- 53.2 months in the participant group compared with 85.1 +/- 63.4 months in the nonparticipant group, a nonsignificant difference (P = .1). Median survival was 84.0 months for participants (95% confidence interval [CI], 59 to 133) and 66.0 months for nonparticipants (95% CI, 48 to 105). A second analysis restricted nonparticipants to those who had a survival time > or = that of the matched case at time of entry into the support program. Survival increased to a mean of 101.1 months (median, 105.0; 95% CI, 71 to 132) for nonparticipants and remained unchanged for participants, also a statistically nonsignificant difference (P = .9). CONCLUSION While the program may have beneficial effects on quality of life, this study does not indicate a significant favorable impact on survival with breast cancer or that the program is serving as a social locus for the gathering of exceptional survivors.

Characterization of treatments and disease course for women with breast cancer brain metastases: Five-year retrospective single institution experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13055-e13055
Author(s):  
Sonya Chew ◽  
Hailey Kathryn Carroll ◽  
Waseem Mohammed Zaid Darwish ◽  
Michaela Jane Higgins ◽  
John McCaffrey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Median Time ◽  
De Novo ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Disease Course ◽  
First Line ◽  
Time To Death ◽  
Extracranial Disease

e13055 Background: Up to 30% of patients (pts) with breast cancer (BC) will develop brain metastases (BM) during the course of their disease. BM can have a devastating effect on independence and quality of life. The incidence of BM and overall survival (OS) differs according to BC subtype. We sought to characterise disease course, treatments and outcomes for our patient cohort with BM over the last 5 years. Methods: We extracted clinicopathological data using electronic records from Jan 2015 to Dec 2020 on BC subtype, time to BM development, type and number of therapies given for BM, and OS from BM diagnosis. Results were generated using SPSS Statistics v27. Results: We identified 99 pts. Median age was 49 (Interquartile range (IQR) 41 to 57). Of the BC subtypes; 41 (41.4%) were hormone receptor (HR)+/HER2-; 28 (28.2%) HR+/HER2+; 15 (15.2%) HR-/HER2+ and 15 (15.2%) were HR-/HER2-. 20% presented with de novo MBC (of which 4 had BM at presentation) and 80% had relapsed MBC. At first presentation with MBC (relapsed and de novo) 74% of pts had no brain metastases, 18% had BM with extracranial disease and 8% had BM only with no extracranial disease (5 had HER2+, 2 had HR-/HER2- and 1 had HR+/HER2-). HR-/HER2- pts had the highest incidence (40%) of presentation of BM at MBC diagnosis. Median time to BM development was 17 months (HR+/Her2-), 11 months (HR+/HER2+), 12 months (HR-/HER2+) and 3 months (HR-/HER2-). Almost half (46%) of pts had systemic treatment after developing BM. HR+Her2+ pts received the most treatment lines post BM development with a median of 2 lines (range 1-6). Almost 70% of pts (n=68) received local therapy for brain metastases with a median of 1 line of treatment (IQR 1-2). Whole brain radiotherapy (WBRT) (n=48, 70%) was the most frequently used modality followed by surgery (n=15, 23%) and stereotactic body radiotherapy (SBRT) (n=5, 7%). Patients with HER2+ BM had the highest incidence of receiving SBRT or surgery in the first line (33%). In pts who received WBRT alone (n=40) the median time to death post WBRT was 2.6 months, while in those who received surgery or SBRT (n=20) the median time to death was 15.5 months. Median OS from BM diagnosis was 4 months (HR+/HER2-), 10 months (HR+/HER2+), 8 months (HR-/HER2+), and 2 months (HR-/HER2-). For the 15 pts with HER2+ BC given TDM-1 after BM development 60% had a progression free survival of 1 year. 3 pts received palbociclib after BM in the first line and all died within 3 months. Conclusions: OS from BM diagnosis in our cohort is similar to international figures, with HR-/HER2- pts having the worst prognosis. Although our cohort is small, OS was >1 year for 60% of HER2+ pts who received TDM1 after BM development which is encouraging for antibody drug conjugates and CNS activity. OS was poor at less than 3 months for pts who received WBRT indicating higher burden of disease in the CNS and highlights an important question about whether it has a role in this setting.

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.

Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

2021 ◽  
Author(s):  
Michael A Vogelbaum ◽  
Paul D Brown ◽  
Hans Messersmith ◽  
Priscilla K Brastianos ◽  
Stuart Burri ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Local Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Whole Brain Radiation ◽  
Brain Radiation

Abstract Purpose To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors. Methods ASCO convened an Expert Panel and conducted a systematic review of the literature. Results Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base. Recommendations Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non–small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status &lt; 70 with no systemic therapy options do not derive benefit from radiation therapy. Additional information is available at www.asco.org/neurooncology-guidelines.

scholarly journals Oncological safety of immediate rectus abdominis myocutaneous breast reconstruction in patients with locally advanced disease (stage IIb and III)

2013 ◽  
Vol 02 (04) ◽  
pp. 239-242
Author(s):  
Mushtaq Mir ◽  
Muddassir Shahdhar ◽  
Khurshid Ganaie ◽  
Quibtiya Syed
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Breast Reconstruction ◽  
Systemic Therapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Immediate Breast Reconstruction ◽  
Rectus Abdominis ◽  
Reconstructed Breast

Abstract Background: The management of locally advanced (Stage IIb and III) breast cancer is challenging. It often includes multimodal treatment with systemic therapy and/or radiation therapy and surgery. Immediate breast reconstruction has not traditionally been performed in these patients. We review the results of immediate rectus abdominis musculo-cutaneous (TRAM/VRAM) flap in 60 patients treated for Stage IIb and III breast cancer. Materials and Methods: Data were collected prospectively on 60 patients diagnosed with Stage IIb (32 patients) and Stage III (28 patients) breast cancer between May 2008 and May 2012. All patients had mastectomy and immediate rectus abdominis myocutaneous reconstruction (TRAM in 40 patients and VRAM in 20 patients). All patients received primary systemic therapy, and all patients received postoperative radiotherapy to the operative site. Results: Mean age was 40.13 (range 28-53) years, mean hospital stay was 8.86 days and mean follow-up for the group was 28 months. Neither of them developed local disease recurrence in the operative site till the last follow-up. Eight (13.3%) patients had some delay in chemo-radiation therapy due to flap-related complications. Flap-related complications were present in eight patients (partial flap failure in four and superficial skin necrosis in four). There was no adverse effect of chemo-radiation therapy on reconstructed breast. Conclusion: Immediate TRAM/VRAM breast reconstruction for locally advanced breast cancer is not associated with a significant delay in adjuvant therapy or an increased risk of local relapse. Radiation therapy can be delivered to the reconstructed breast when indicated without difficulty. Breast reconstruction facilitates surgical resection of locally advanced breast cancer with primary closure and should be considered if the patient desires immediate breast reconstruction.

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