Nueclear Web Banner
Users Online: 344
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 2  |  Page : 118-122

Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets


1 Department of Medical Oncology, Max Hospital, New Delhi, India
2 Department of Radiation Oncology, Fortis Hospital, Gurugram, Haryana, India
3 Department of Medical Oncology, Manipal Super Specialty Hospital, New Delhi, India
4 Department of Medical Oncology, Mahavir Cancer Sansthan, Patna, Bihar, India
5 Department of Radiation Oncology, Jolly Grant Himalayan Institute, Dehradoon, Uttarakhand, India
6 Department of Radiation Oncology, MAMS, New Delhi, India
7 Department of Radiaton Oncology, Action Balajee Cancer Center, New Delhi, India
8 Department of Oncology, Shalby Cancer and Research Institute, Mumbai, Maharashtra, India
9 Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India

Date of Web Publication11-Apr-2018

Correspondence Address:
Dr. Nitesh Rohatgi
Department of Medical Oncology, Max Hospital, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sajc.sajc_116_18

Rights and Permissions
  Abstract 

Breast cancer is a common cause of brain metastases, with metastases occurring in at least 10–16% of patients. Longer survival of patients with metastatic breast cancer and the use of better imaging techniques are associated with an increased incidence of brain metastases. Current therapies include surgery, whole-brain radiation therapy, stereotactic radiosurgery, chemotherapy and targeted therapies. However, the timing and appropriate use of these therapies is controversial and careful patient selection by using available prognostic tools is extremely important. Expert oncologist discussed on the mode of treatment to extend the OS and improve the quality of life ofHER2-positivebreast cancer patients with Solitary brain metastases. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Keywords: Herceptin, stereotactic radiosurgery, surgery, TDM1, WBCR


How to cite this article:
Rohatgi N, Munshi A, Bajpai P, Singh M, Sahai S, Ahmad M, Singh K, Singh H, Parikh PM, Aggarwal S. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets. South Asian J Cancer 2018;7:118-22

How to cite this URL:
Rohatgi N, Munshi A, Bajpai P, Singh M, Sahai S, Ahmad M, Singh K, Singh H, Parikh PM, Aggarwal S. Practical consensus recommendations on Her2 +ve breast cancer with solitary brain mets. South Asian J Cancer [serial online] 2018 [cited 2018 Apr 20];7:118-22. Available from: http://journal.sajc.org/text.asp?2018/7/2/118/229784


  Introduction Top


Breast cancer is the second-leading cause of central nervous system (CNS) metastases among solid malignancies.[1] The incidence of developing brain metastases (BM) has been reported to range from 10% to 16% among advanced breast cancer patients.[2] Autopsy studies indicate that this figure may underestimate the true incidence since another 10% of BM are human epidermal growth factor receptor 2 (HER2)-positive cancer or triple negative breast cancer (TNBC). TNBC and HER2 positive patients have a higher risk of developing BM than patients with luminal-like disease.[3],[4],[5] Several studies have shown that HER2-positivity is associated with a biological propensity to metastasize to the brain.[6] Previous studies have identified the subgroups of patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer as having an increased risk for the development of brain metastases,[7],[8],[9],[10] with up to half of patients with HER2-positive metastatic breast cancer experiencing brain metastases over time.[5] Tumor subtypes are also an important factor for the median time interval from primary diagnosis to development of brain metastases; a recent large study showed shorter intervals for triple negative and HER2-positive patients, and longer intervals for estrogen receptor (ER) positive tumors.[11]

Brain metastases in breast cancer patients represent a catastrophic event that portends a poor prognosis, with a median survival that ranges from 2 to 25.3 months, despite treatment.[12],[13],[14],[15] Treatment options for patients with breast cancer brain metastases are limited and include surgical resection, whole-brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), chemotherapy and targeted therapy.[13],[16],[17]

An expert group of oncologists met in the update in oncology-X-2017 to discuss on available strategies for patient having HER2 + ve with Solitary Brain Mets Breast cancer.

The update in oncology-X-2017 was organized by Sir Ganga Ram Hospital group to discuss and arrive at a consensus statement to provide community oncologists practical guidelines for challenging common case scenarios in Breast Cancer.[18],[19] The discussion was based on domain expertise of the National as well as international faculty, published evidence and practical experience in real life management of breast cancer patients. Opinion of the present 250 oncologists, which included medical oncologists, radiation oncologists, surgical oncologists, molecular oncologists and radiologists present in the update in oncology-X-2017 was taken into consideration by the expert panel.

The expert group was chaired by Dr. Kishore Singh and Dr. Harpreet Singh whereas the discussions were moderated by Dr. NiteshRohtagi and Dr. Anusheel Munshi. The core expert group consisted Dr. Peyush Bajpai, Dr. Manisha Singh, Dr. Siddarth Sahai, and Dr. Stephen C Malamud. Consensus answers were used as the basis of formulating the consensus statement providing community oncologists with ready-to-use practical recommendations.

As part of the background work, the best existing evidence was compiled and provided to the expert group panel members for review in preparation of the expert group meeting.[20],[21],[22] The national and international experts invited to this meeting were also provided the data on the voting by the audience delegates from the update in oncology-X-2017. Members of the panel were also allowed to share their personal experiences, make comments and record dissent while voting for the consensus statements. A total of six broad question categories were part of the expert group discussions [Table 1].
Table 1: Question categories addressed by the update in oncology-X-2017

Click here to view


In the past, even after treatment by whole-brain radiotherapy (WBRT), the median survival of patients with breast cancer brain metastases (BCBM) was poor, ranging from 3 to 6 months.[23]

After the introduction of effective anti-HER2 therapy, survival after diagnosis of BM among HER2-positive patients has been significantly improved compared with that among patients with HER2-negative disease, mainly due to the improvement of extracranial disease control.[24],[25] Several retrospective studies have reported that the median OS after diagnosis of BM is around 2 years for HER2-positive patients.[24],[25],[26],[27] Meanwhile, with the OS significantly prolonged, the proportion of people dying of cerebral progression has been increasing.

A retrospective study reported that up to 50% of HER2-positive patients died of cerebral progression,[28] which makes BM among HER2-positive patients a critical issue. To improve management, the American Society of Clinical Oncology (ASCO) published a guideline focusing on this issue in 2014.[29]


  Treatment Approach Top


As mentioned above, treatment approach includes symptomatic treatment, surgical excision of solitary metastasis, stereotactic radiosurgery (SRS) for small (< 3 cm) lesions not amenable to surgery, whole-brain radiotherapy (WBRT) and chemotherapy [Table 2], [Table 3], [Table 4], [Table 5], [Table 6].[30]
Table 2: Question 1 (I)- What is the next line of action?

Click here to view
Table 3: Question 1 (II)- Patient undergoes surgery, what is the next line of action?

Click here to view
Table 4: Question 1 (III) - Patient undergoes complete resection followed by stereotactic radiosurgery then what next should be done?

Click here to view
Table 5: Question 2 (I)- Patient is given T-DM1 for 9 months, then she develops five lesions (total) in both cerebral hemispheres and cerebellum. What next?

Click here to view
Table 6: Question 2 (II) - Stereotactic radiosurgery done, What next?

Click here to view



  Surgery Top


In order to achieve long-lasting control, surgical resection is a standard treatment for patients with a favorable prognosis and a solitary lesion, especially a large lesion (over 3-4 cm). There were several randomized control trials conducted to define the role of surgical resection in solitary BM, and they demonstrated a significant survival benefit for patients receiving surgical resection.[31],[32],[33],[34] Surgical resection is also used for immediate mass effect relief in patients with limited BM (2e4 lesions) who have a large lesion causing neurologic symptoms; however, the effect of surgery on survival of these patients with limited BM is still unknown. Since there is a high recurrence rate after surgical resection,[35] postoperative radiation is usually recommended to improve local control.


  Stereotactic Radiosurgery Top


Stereotactic radiosurgery (SRS) is a radiationtherapy technique using multiple intersecting beams to deliver a highly conformal and high dose of radiation to a target volume. The aim is to produce an ablative effect with minimal damage to surrounding normal tissues. SRS is usually delivered in a single fraction, but it can also be delivered in 5 or more fractions [fractionated stereotactic radiotherapy (FSRT)]. For local control of BM, SRS can be used as a therapy alone or a boost after whole brain radiotherapy (WBRT).

WBRT, or an adjuvant treatment preoperatively or postoperatively.[36] Different technologies are presently available for delivering stereotactic radiosurgery, however there exists no evidence of superiority of one over the other.[37],[38],[39],[40],[41],[42],[43] The essentials for a good SRS program remain robust immobilisation, tight margins to the tumour volume, excellent quality assurance and on board CT imaging before treatment delivery [43],[44],[45],[46],[47]

Traditionally SRS has been used in patients with 1-3 brain metastasis (either alone or after whole brain radiotherapy). However recent evidence suggests that SRS alone can be used in patients with even upto 10 metastasis.[48]


  Postoperative and Preoperative Radiation Therapy Top


Because of the high recurrence rate after surgical resection,[35],[47] postoperative radiation is usually recommended as a boost for intracranial control. Adjuvant WBRT is the standard treatment in the postoperative setting, although focal radiotherapy (SRS/SRT) to the lesion bed with margin is also an emerging option.[49] Multiple studies have demonstrated that postoperative WBRT can significantly reduce the risk of local recurrence, distant brain recurrence, and neurologic causes of death, but has no benefit for OS.[35],[47] Because of potential toxicity associated with WBRT, clinicians have used postoperative SRS to defer WBRT and to improve intracranial control. Because of the size limitation of SRS, FSRT has been used for large surgical cavities over 3 cm and has a similar control rate as SRS.[50]


  Whole-Brain Radiation Therapy Top


One of the most important treatments available for brain metastases is WBRT, particularly in the setting of multiple brain lesions. This approach has two main goals—the control of macroscopic metastases, and the eradication of microscopic seeding of the brain. The majority of patients are given conventional WBRT, a total dose of 30 Gy in 10 fractions with daily fractions of 3–4 Gy.[51]

The benefit of WBRT after surgical resection has been demonstrated in a prospective trial that randomized 95 patients who had single brain metastases to WBRT or observation.[51] The study showed that patients in the WBRT group had fewer recurrences both at the operative site (10 vs. 46%, P < 0.001) and at other sites in the brain (14 vs. 37%, P < 0.01), however overall survival was not increased. Controversy exists about the role of WBRT versus focal SRS/SRT in patients with few (≤4) brain metastases.[52],[53] Associated toxicities with WBRT included worse neurocognitive outcomes and quality of life.[54],[55] Also, there is paucity of data directly comparing hippocampal sparing WBRT techniques with focal SRS treatments. Withholding WBRT can result in risk of progressive disease in the brain, which in turn could also negatively impact cognition – factors that need to be considered in the decision making process.[56],[57]


  Targeted Therapy for Her2-Positive Breast Cancer Brain Metastases Top


Unlike estrogen and progesterone status, expression of HER2 has been reported to be highly concordant between the primary and brain metastatic tumors,[58] which makes targeted therapy possible for treating patients with HER2-positive BCBM. Although the OS of patients with HER2-positive breast cancer has improved substantially in the trastuzumab (T-DM1) era,[3],[4],[5] the incidence of BM among these patients has been increasing in recent years. One of main reasons for this is that the blood brain barrier (BBB) makes the CNS a perfect sanctuary for tumor cells. The BBB is a barrier that selectively chooses molecules to enter the CNS. It consists of endothelial cells, a basement membrane, and astrocyte foot processes. The permeability of the BBB decreases 100-fold as the molecular weight of the drug increases from 200 Da to 450 Da.[59] As a large molecule (145,531 Da), trastuzumab cannot penetrate the intact BBB, but multiple factors can disrupt the BBB, including metastatic tumors, surgery, and radiotherapy, which then allows limited amounts of large molecular agents to penetrate the CNS. Because the incidence of BM is higher in patients with HER-2 positive tumors, a specific interest in this subset exists.

Standard systemic treatment of HER-2 positive disease typically includes trastuzumab, (T-DM1) which has been shown to cross a disrupted BBB in some patients (albeit in limited amounts)[60] and is associated with both longer time to the development of BM and survival after a diagnosis of BCBM.[61]


  Conclusion Top


For patients with HER2-positive breast cancer with Solitary brain metastases, consideration should be given to treat with combination of surgery, radiotherapy, chemotherapy and anti HER2 treatments is at present the best way to extend the OS and improve the quality of life of patients.

Current care involves radiotherapy, either SRS or WBRT, and/or surgery and depends on the number, size, and site of metastases, as well as overall systemic disease control and a patient's performance status. Systemic chemotherapeutic approaches are gaining traction and are increasingly efficacious options that are being used earlier in the course of the illness. Early vigorous treatment can enhance a patient's functional status and prolong CNS disease control and survival. The output of this discussion is to provide the best and effective treatment options for patients with HER2-positive breast cancer with solitary brain metastases.



Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Weil RJ, Palmieri DC, Bronder JL, Stark AM, Steeg PS. Breast cancer metastasis to the central nervous system. Am J Pathol 2005;167:913-20.  Back to cited text no. 1
[PUBMED]    
2.
Lin NU. Breast cancer brain metastases: New directions in systemic therapy. Ecancermedicalscience 2013;7:307.  Back to cited text no. 2
    
3.
Lin NU, Winer EP. Brain metastases: The HER2 paradigm. Clin Cancer Res 2007;13:1648-55.  Back to cited text no. 3
    
4.
Pestalozzi BC, Holmes E, de Azambuja E, Metzger-Filho O, Hogge L, Scullion M, et al. CNS relapses in patients with HER2-positive early breast cancer who have and have not received adjuvant trastuzumab: A retrospective substudy of the HERA trial (BIG 1-01). Lancet Oncol 2013;14:244-8.  Back to cited text no. 4
    
5.
Aversa C, Rossi V, Geuna E, Martinello R, Milani A, Redana S, et al. Metastatic breast cancer subtypes and central nervous system metastases. Breast 2014;23:623-8.  Back to cited text no. 5
    
6.
Pestalozzi BC, Zahrieh D, Price KN, Holmberg SB, Lindtner J, Collins J, et al. Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the international breast cancer study group (IBCSG). Ann Oncol 2006;17:935-44.  Back to cited text no. 6
    
7.
Gabos Z, Sinha R, Hanson J, Chauhan N, Hugh J, Mackey JR, et al. Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. J Clin Oncol 2006;24:5658-63.  Back to cited text no. 7
    
8.
Tham YL, Sexton K, Kramer R, Hilsenbeck S, Elledge R. Primary breast cancer phenotypes associated with propensity for central nervous system metastases. Cancer 2006;107:696-704.  Back to cited text no. 8
    
9.
Pestalozzi BC, Zahrieh D, Price KN, Holmberg SB, Lindtner J, Collins J, et al. Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the international breast cancer study group (IBCSG). Ann Oncol 2006;17:935-44.  Back to cited text no. 9
    
10.
Nam BH, Kim SY, Han HS, Kwon Y, Lee KS, Kim TH, et al. Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res 2008;10:R20.  Back to cited text no. 10
    
11.
Sperduto PW, Kased N, Roberge D, Chao ST, Shanley R, Luo X, et al. The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer. J Neurooncol 2013;112:467-72.  Back to cited text no. 11
    
12.
Leone JP, Lee AV, Brufsky AM. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy. Cancer Med 2015;4:989-94.  Back to cited text no. 12
    
13.
Lee SS, Ahn JH, Kim MK, Sym SJ, Gong G, Ahn SD, et al. Brain metastases in breast cancer: Prognostic factors and management. Breast Cancer Res Treat 2008;111:523-30.  Back to cited text no. 13
    
14.
Ogawa K, Yoshii Y, Nishimaki T, Tamaki N, Miyaguni T, Tsuchida Y, et al. Treatment and prognosis of brain metastases from breast cancer. J Neurooncol 2008;86:231-8.  Back to cited text no. 14
    
15.
Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Effect of tumor subtype on survival and the graded prognostic assessment for patients with breast cancer and brain metastases. Int J Radiat Oncol Biol Phys 2012;82:2111-7.  Back to cited text no. 15
    
16.
Gil-Gil MJ, Martinez-Garcia M, Sierra A, Conesa G, Del Barco S, González-Jimenez S, et al. Breast cancer brain metastases: A review of the literature and a current multidisciplinary management guideline. Clin Transl Oncol 2014;16:436-46.  Back to cited text no. 16
    
17.
Niwi ska A, Pogoda K, Murawska M, Niwi ski P. Factors influencing survival in patients with breast cancer and single or solitary brain metastasis. Eur J Surg Oncol 2011;37:635-42.  Back to cited text no. 17
    
18.
National Cancer Registry Programme, Indian Council of Medical Research. Leading sites of cancer. In: Consolidated Report of Population Based Cancer Registries 2001 2004, Incidence and Distribution of Cancer. Bangalore: Coordinating Unit, National Cancer Registry Programme (ICMR); 2006. p. 8 30.  Back to cited text no. 18
    
19.
Badwe RA, Gangawal S, Mitra I, Desai PB. Clinico pathological featuresand prognosis of breast cancer in different religious communities in India. Indian J Cancer 1990;27:220 8.  Back to cited text no. 19
    
20.
Altekruse SF, Kosary CL, Krapcho M, editors. SEER Cancer Statistics Review. ???: National Cancer Institute; 1975 2007.  Back to cited text no. 20
    
21.
National Cancer Registry Program. Ten Year Consolidated Report of the Hospital Based Cancer Registries, 1984–1993, An Assessment of the Burden and Care of Cancer Patients. New Delhi: Indian Council of Medical Research; 2001.  Back to cited text no. 21
    
22.
Agarwal G, Pradeep PV, Aggarwal V, Yip CH, Cheung PS. Spectrum of breast cancer in Asian women. World J Surg 2007;31:1031-40.  Back to cited text no. 22
    
23.
Mahmoud-Ahmed AS, Suh JH, Lee SY, Crownover RL, Barnett GH. Results of whole brain radiotherapy in patients with brain metastases from breast cancer: A retrospective study. Int J Radiat Oncol Biol Phys 2002;54:810-7.  Back to cited text no. 23
    
24.
Kirsch DG, Ledezma CJ, Mathews CS, Bhan AK, Ancukiewicz M, Hochberg FH, et al. Survival after brain metastases from breast cancer in the trastuzumab era. J Clin Oncol 2005;23:2114-6.  Back to cited text no. 24
    
25.
Park YH, Park MJ, Ji SH, Yi SY, Lim DH, Nam DH, et al. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer 2009;100:894-900.  Back to cited text no. 25
    
26.
Gori S, Rimondini S, De Angelis V, Colozza M, Bisagni G, Moretti G, et al. Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: Incidence, survival, and risk factors. Oncologist 2007;12:766-73.  Back to cited text no. 26
    
27.
Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, et al. Summary report on the graded prognostic assessment: An accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 2012;30:419-25.  Back to cited text no. 27
    
28.
Bendell JC, Domchek SM, Burstein HJ, Harris L, Younger J, Kuter I, et al. Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma. Cancer 2003;97:2972-7.  Back to cited text no. 28
    
29.
Ramakrishna N, Temin S, Chandarlapaty S, Crews JR, Davidson NE, Esteva FJ, et al. Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2-positive breast cancer and brain metastases: American society of clinical oncology clinical practice guideline. J Clin Oncol 2014;32:2100-8.  Back to cited text no. 29
    
30.
Rorive A, Collignon J, Martin M, André C, Jerusalem G, Coucke P, et al. Breast cancer and brain metastases. Rev Med Liege 2011;66:299-305.  Back to cited text no. 30
    
31.
Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494-500.  Back to cited text no. 31
    
32.
Noordijk EM, Vecht CJ, Haaxma-Reiche H, Padberg GW, Voormolen JH, Hoekstra FH, et al. The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age. Int J Radiat Oncol Biol Phys 1994;29:711-7.  Back to cited text no. 32
    
33.
Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996;78:1470-6.  Back to cited text no. 33
    
34.
Tabouret E, Metellus P, Gonçalves A, Esterni B, Charaffe-Jauffret E, Viens P, et al. Assessment of prognostic scores in brain metastases from breast cancer. Neuro Oncol 2014;16:421-8.  Back to cited text no. 34
    
35.
Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: A randomized trial. JAMA 1998;280:1485-9.  Back to cited text no. 35
    
36.
Badiyan SN, Regine WF, Mehta M. Stereotactic radiosurgery for treatment of brain metastases. J Oncol Pract 2016;12:703-12. Coffey RJ, Lunsford LD. Stereotactic radiosurgery using the 201 cobalt-60 source gamma knife. Neurosurg Clin N Am 1990;1:933-54.  Back to cited text no. 36
    
37.
Coffey RJ, Lunsford LD. Stereotactic radiosurgery using the 201 cobalt-60 source gamma knife. Neurosurg Clin N Am 1990;1:933-54.  Back to cited text no. 37
    
38.
Mack A, Czempiel H, Kreiner HJ, Dürr G, Wowra B. Quality assurance in stereotactic space. A system test for verifying the accuracy of aim in radiosurgery. Med Phys 2002;29:561-8.  Back to cited text no. 38
    
39.
Adler JR Jr., Chang SD, Murphy MJ, Doty J, Geis P, Hancock SL, et al. The cyberknife: A frameless robotic system for radiosurgery. Stereotact Funct Neurosurg 1997;69:124-8.  Back to cited text no. 39
    
40.
Chang SD, Main W, Martin DP, Gibbs IC, Heilbrun MP. An analysis of the accuracy of the cyberKnife: A robotic frameless stereotactic radiosurgical system. Neurosurgery 2003;52:140-6.  Back to cited text no. 40
    
41.
Yu C, Main W, Taylor D, Kuduvalli G, Apuzzo ML, Adler JR Jr., et al. An anthropomorphic phantom study of the accuracy of cyberknife spinal radiosurgery. Neurosurgery 2004;55:1138-49.  Back to cited text no. 41
    
42.
Yu C, Jozsef G, Apuzzo ML, Petrovich Z. Dosimetric comparison of cyberKnife with other radiosurgical modalities for an ellipsoidal target. Neurosurgery 2003;53:1155-62.  Back to cited text no. 42
    
43.
Collins SP, Coppa ND, Zhang Y, Collins BT, McRae DA, Jean WC, et al. CyberKnife radiosurgery in the treatment of complex skull base tumors: Analysis of treatment planning parameters. Radiat Oncol 2006;1:46.  Back to cited text no. 43
    
44.
Flickinger JC, Lunsford LD, Wu A, Maitz AH, Kalend AM. Treatment planning for gamma knife radiosurgery with multiple isocenters. Int J Radiat Oncol Biol Phys 1990;18:1495-501.  Back to cited text no. 44
    
45.
Leith JT, Cook S, Chougule P, Calabresi P, Wahlberg L, Lindquist C, et al. Intrinsic and extrinsic characteristics of human tumors relevant to radiosurgery: Comparative cellular radiosensitivity and hypoxic percentages. Acta Neurochir Suppl 1994;62:18-27.  Back to cited text no. 45
    
46.
Wowra B, Muacevic A, Tonn JC. Quality of radiosurgery for single brain metastases with respect to treatment technology: A matched-pair analysis. J Neurooncol 2009;94:69-77.  Back to cited text no. 46
    
47.
Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: Results of the EORTC 22952-26001 study. J Clin Oncol 2011;29:134-41.  Back to cited text no. 47
    
48.
Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): A multi-institutional prospective observational study. Lancet Oncol 2014;15:387-95.  Back to cited text no. 48
    
49.
Tsao MN, Rades D, Wirth A, Lo SS, Danielson BL, Gaspar LE, et al. Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American society for radiation oncology evidence-based guideline. Pract Radiat Oncol 2012;2:210-25.  Back to cited text no. 49
    
50.
Minniti G, Esposito V, Clarke E, Scaringi C, Lanzetta G, Salvati M, et al. Multidose stereotactic radiosurgery (9 gy × 3) of the postoperative resection cavity for treatment of large brain metastases. Int J Radiat Oncol Biol Phys 2013;86:623-9.  Back to cited text no. 50
    
51.
Kaal EC, Niël CG, Vecht CJ. Therapeutic management of brain metastasis. Lancet Neurol 2005;4:289-98.  Back to cited text no. 51
    
52.
Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs. stereotactic radiosurgery alone for treatment of brain metastases: A randomized controlled trial. JAMA 2006;295:2483-91.  Back to cited text no. 52
    
53.
Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: Results of the EORTC 22952-26001 study. J Clin Oncol 2011;29:134-41.  Back to cited text no. 53
    
54.
Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: A randomised controlled trial. Lancet Oncol 2009;10:1037-44.  Back to cited text no. 54
    
55.
Soffietti R, Kocher M, Abacioglu UM, Villa S, Fauchon F, Baumert BG, et al. A European organisation for research and treatment of cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: Quality-of-life results. J Clin Oncol 2013;31:65-72.  Back to cited text no. 55
    
56.
Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol 2007;25:1260-6.  Back to cited text no. 56
    
57.
Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 2007;68:1388-95.  Back to cited text no. 57
    
58.
Shen Q, Sahin AA, Hess KR, Suki D, Aldape KD, Sawaya R, et al. Breast cancer with brain metastases: Clinicopathologic features, survival, and paired biomarker analysis. Oncologist 2015;20:466-73.  Back to cited text no. 58
    
59.
Koo T, Kim IA. Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: From biology to treatment. Radiat Oncol J 2016;34:1-9.  Back to cited text no. 59
    
60.
Dijkers EC, Oude Munnink TH, Kosterink JG, Brouwers AH, Jager PL, de Jong JR, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther 2010;87:586-92.  Back to cited text no. 60
    
61.
Park YH, Park MJ, Ji SH, Yi SY, Lim DH, Nam DH, et al. Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients. Br J Cancer 2009;100:894-900.  Back to cited text no. 61
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Treatment Approach
Surgery
Stereotactic Rad...
Postoperative an...
Whole-Brain Radi...
Targeted Therapy...
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed15    
    Printed0    
    Emailed0    
    PDF Downloaded15    
    Comments [Add]    

Recommend this journal