Management of cerebral metastasis: An audit of 106 patients newly diagnosed in the year 2003

Date: 25th Feb 2005

Department of Clinical Oncology, Tuen Mun Hospital

Corresponding author: Dr FCS Wong, Dr. KK Yuen, Dr. SK O

Clinical Audit Conference 2005

Reasons for the Project1. Patients with cerebral metastases are usually debilitated. The

prognosis is usually poor. The median survival ranges from few weeks to few months only.

2. Care for this group of patients is a problem both to the medical staff and to their family.

3. Treatment options for patients with cerebral metastases include supportive care (steroid), radiotherapy (whole brain RT, stereotactic radiosurgery), or surgery.

4. The use of steroid should be under supervision as it may be associated with a long list of side effects, esp if it is prescribed for a long duration without objective review.

Objectives

1. To review the daily practice of managing patients who had newly diagnosed cerebral metastases in our department.

2. To audit the side effects of steroid occurred in this group of patients.

3. To generate new management plans for more effective usage of hospital resources, and better patient care after the review, e.g. design of a standard prognostic assessment tool, discharge plan, etc.

1. All patients who were newly diagnosed to have cerebral metastases and received treatment in our department in the year 2003 were included (total 106 patients).

2. We excluded patients with central nervous system (CNS) lymphoma and primary brain tumour as the pathology of their cerebral malignancy

Selection Criteria

1. Data are collected from all the related clinical notes (in-patient record, department out-patient record).

2. Statistical Package for the Social Sciences (SPSS V9.0) is used for statistical analysis.

3. Actuarial survival rates are obtained using the Kaplan-Meier method and compared with the log rank test.

4. Cox's proportional hazards model is used to assess the prognostic importance of various factors: Sex (M), Age (>60), Karnofsky Performance States (KPS<70), Active Extracranial Involvement, No surgical intervention, Primary site of maligancy (Lung).

Data Collection & Standard

Results

A. Patient Characteristics

106 patients with cerebral metastasis, 2003

Gender M:F = 59:47

Age (median, range) 68 (33 – 91)

KPS (median, range) 50 (40 – 90)

EC involvement Yes=87

Primary Site Lung(72)(68%)

(SCLC=8, Unknown=20, NSCLC=44)

Breast (Invasive ductal CA)(10),

Cervix(1)

Colon(2), Rectum(1), Esophagus(1)

Bladder (TCC)(1), Thyroid (large-cell CA)(1),

Renal cell CA(1), Melanoma(4), Unknown (11)

Other CNS site Leptomeningeal (5), Skull base (3), Brainstem (1)

Orbit (4), Cord compression (5)

Symptom Limb weakness (30), Dizziness (20), Confusion (19)

at presentation Convulsion (10), Vomiting (15), Headache (9),

Visual (4), Cranial nerve palsies (4)

Numbness (1), Dysphasia (2)

Incidental (3), Symptom not mentioned (4)

Surgery N=7

RT N=90 (unfit for RT: 10, refused by patients: 6)

(SRS boost: 1)

Steroid N=100

B. Survival and Assessment of Prognosis

Overall survival: median= 62 days (3 – 687)

Univariate analysis Multivariate analysis

Surgical Tx MST=208days

(p=0.0048 p=0.01)

KPS (<70) p<0.0001 p<0.001

Primary site (Lung) p=0.0387 NS

Sex (M) p=0.0466 NS

Age (>60) p=0.15 NS

Extracranial invol p=0.98 NS

Audit (TMH, 2003): survival

C. Patients treated by Supportive Care +/- WBRT

– Prognostic Model

KPS / Age / Sites of invol

Class 1: MST= 7.1mon

(KPS>=70, <65, No extraCNS)

Class 2: MST= 4.2mon

(KPS>=70, >65 or extraCNS)

Class 3: MST= 2.3mon

KPS<70

RTOG Recursive Partitioning Analysis (RPA)(Gaspar et al IJROBP 1997)

Overall survival RTOG (RPA), 1997

(median, range)

Class 1: MST= 7.1mon 4.1 mon (3 – 5.5) 7.1mon

(KPS>=70, <65, (n=4)

No extraCNS)

Class 2: MST= 4.2mon 5.1 mon (0.4-22.9) 4.2mon

(KPS>=70,

>65 or extraCNS)

Class 3: MST= 2.3mon 1.2 mon (0.1-13.9) 2.3mon

KPS<70 (p<0.0001)(Logrank)

Prognostic Model (1)

2nd Workshop on Palliative RT & Symptom Control:

(1.KPS: <70 2. Active extracranial disease 3. Age: >60)

Overall survival(median, range)

Group I: all 3 factors 30 days (3 – 244)

Group II: any 2 78 days (4 – 418)

Group III: 0 – any 1 144 days (3 – 687)

(p<0.0001) (Logrank)

Prognostic Model (2): UK model, 2001

Overall Survival (UKPF)

0102030405060708090

100

0 100 200 300 400 500 600 700

Time (Days)

Su

rviv

al R

ates

(%

)

Group 1

Group 2

Group 3

(P<0.0001)

D. Clinical course ofGroup 1, 2 & 3 patients

No objective response to treatment & died during their 1st hospital stay

Next Planned FU (week)(range)

Need of early readmission before planned follow-up

Group I (n=38)(all 3 factors)

(MST 30 days)

20/38 (53%) 3.5 (2 – 4) 8/14 (57.1%)

Group II (n=44)any 2 factors

(MST 78 days)

6/44 (14%) 4 (1 – 8) 14/31 (45.2%)

Group III (n=17)(0 – 1 factor)

(MST 144 days)

2/17 (12%) 2 (1 - 5) 4/12 (33.3%)

E. Steroid-related toxicities

Candidiasis 20 (21.5%)

Chest infection 6 (6.5%)

UTI 5 (5.4%)

HZV 3 (3.2%)

GIB 5 (5.4%)

Impaired glucose profile 3 (3.2%)

Proximal myopathy 5* (5.4%)

Cushinghoid 2* (2.2%)

N.B. *Patients were maintained on steroid for more than two months.

Steroid ToxicityLiterature

29.7%-34%

2%-6%

24%-60%

• Every effort should be taken to identify patients who are candidates for surgery, as patients who had been treated by surgery had a significantly better survival.

• Patients who had undergone surgery should be treated differently, and multi-disciplinary approaches (e.g.neurosurgical team) are important

Evaluation (1)

• The 3 factors-model can predict the clinical outcomes well

• The prognosis of group one patients is very poor. The median survival time is very short (30 days). More than half (53%) will die during their hospital stay. For patients who became stable and were then discharged, >50% developed early deterioration (e.g. A&E admission) before next planned follow-up.

• The care for this group of patients is very demanding. A good supporting team is required if we want to further reduce their total length of stay at our acute beds. High re-admission rate through A&E may be encountered, if long follow-up gap is given (e.g. 4weeks FU).

Evaluation (2): nonsurgical group

• The median survival time for group 2 and group 3 is 78 days and 144 days, respectively.

• These two groups of patients are more likely to encounter the side effects of steroid, especially if steroid is prescribed for a long time without under regular review.

• Guidelines on use of steroid are needed

Evaluation (3)

• Team work with neurosurgeons

• For patients who are medically unfit for surgery, we are now trying new radiotherapy technique (e.g. stereotactic radiosurgery)

Implementation of Change & Impact of the project: candidates for surgery

• A team called Integrated Patient Care Pathwary (IPCP) has been set up in October 2004. It emphases the importance of multi-disciplinary approaches for this group of patients. Working protocol has been written for managing this group of patients, including guidelines on use of steroid, based on the findings of this audit.

• The 3-factors model will be used to assess our patients. A shorter FU gap (e.g. FU 1-2 wks) will be arranged, in order to pick up deterioration earlier.

• An 2nd audit will be performed later to assess the effectiveness of new measures (length of hospital stay, readmission rate through A&E, incidence of side effects of steroid, etc.)

Implementation of Change & Impact of the project: nonsurgical

Thank you