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28-07-2018 | CNS metastases | Article

30. Prognostic Classification Systems for Brain Metastases

Author: Paul W. Sperduto

Publisher: Springer International Publishing

Abstract

Patients with brain metastases are a heterogeneous population. The epidemiology of brain metastases is addressed elsewhere in this textbook. In the past, outcomes were considered uniformly grim for all patients with brain metastases. We now know that outcomes vary widely by diagnosis (type of primary cancer) and diagnosis-specific prognostic factors. This chapter reviews the history of prognostic classifications for patients with brain metastases and the current state of knowledge in this area. Such classification systems are important for two reasons: (1) they facilitate clinical decision-making regarding whether and what treatment is appropriate, and (2) they provide a method for stratification of clinical trials to ensure trials are comparing comparable patients, which is particularly important in such a heterogeneous patient population.

Learning Objectives

  • To understand how prognosis varies by diagnosis.
  • To understand the diagnosis-specific prognostic factors for each of the most common cancers associated with brain metastases.
  • To understand how to calculate the Graded Prognostic Assessment (GPA) for each diagnosis.
  • To understand how the prognosis should influence clinical judgment regarding whether and what treatment is appropriate.

Introduction

Brain metastases are a common and complex conundrum for cancer care. An estimated 300,000 patients are diagnosed each year with brain metastases in the United States [1], and that incidence is growing due to advances in treatment that result in patients living longer and thus at risk for brain metastases [2]. It is a complex problem because of the marked heterogeneity of this patient population: brain metastases may arise from a wide variety of tumor types and subtypes. Furthermore, these patients may have already received a plethora of different treatments for their cancer or may present with brain metastases at the time of initial diagnosis. This heterogeneity has long plagued interpretation of clinical trials involving this patient population because it was essentially impossible to sufficiently stratify studies to verify similar groups of patients were being compared [3]. Interpretation of clinical trials and efforts to estimate prognosis are further complicated by the plethora of possible combinations of currently available treatment options [surgery, stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT) , chemotherapy, targeted drug therapies, and immunotherapies]. Furthermore, four prospective randomized trials have shown WBRT adds no survival benefit over SRS alone in SRS-eligible patients [47], and, on the other end of the prognostic spectrum, in poor prognosis patients, there is evidence that supportive care may be as effective as WBRT [8]. Accordingly, WBRT is used less commonly than in the past.

Classification Systems

These concerns led to efforts to better understand prognosis. The purpose of a prognostic index is to predict outcome before, not after, treatment. It is important to distinguish prognostic from predictive factors. A prognostic factor identifies good vs. bad outcome irrespective of treatment used, whereas a predictive factor identifies good versus bad outcome for a specific treatment. Gaspar et al. published the Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis for brain metastases (Table 30.1) in 1997 [9]. This prognostic index consisted of three classes: I (age < 65, Karnofsky Performance Status (KPS) ≥ 70, controlled primary tumor, no extracranial metastases), II (all patients not in class I or III), and III (KPS < 70) which correlated with median survival of 7.1, 4.2, and 2.3 months, respectively, at that time. Weltman et al. published the Score Index for Radiosurgery (SIR) (Table 30.2) in 2000 [10]. This index used the sum of scores (0–2) for each of five prognostic factors (age, KPS, status of systemic disease, number of brain metastases, and the volume of the largest metastasis). Lorenzoni et al. published the Basic Score for Brain Metastases (BSBM) (Table 30.3) in 2004 [11]. This index is based on the sum of scores (0–1) for three prognostic factors (KPS, control of primary tumor, and extracranial metastases). Sloan-Barnholtz published a nomogram (Fig. 30.1) in an effort to further individualize prognosis [12]. Kondziolka published an interesting survey study in which experts in the field were asked to estimate survival for a series of patients given all relevant clinical parameters. This study showed even experts cannot predict outcomes with certainty for all patients [13]. All prognostic indices have limitations but can provide guidance for clinical decision-making and are essential for stratification of clinical trials so that those trials are comparing comparable patients, thus making the results of those trials worthwhile, relevant, and interpretable.
Table 30.1
Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) for patients with brain metastases
Class
Criteria
Median survival
Class I:
Age < 65 years and
7.1 months
 
KPS ≥ 70 and
 
 
controlled primary tumor and
 
 
no extracranial metastases
 
Class II:
All patients not in class I or III
4.2 months
Class III:
KPS < 70
2.3 months
KPS Karnofsky Performance Status
Based on data from Ref. [9]
Table 30.2
Score Index for Radiosurgery (SIR)
 
Score
  
 
0
1
2
Age (years)
≥60
51–59
≤50
KPS
≤50
60–70
80–100
Systemic disease
Progressive
Stable
CR or NED
Number of lesions
≥3
2
1
Vol. largest lesion (ml)
>13
5–13
<5
KPS Karnofsky Performance Status, CR complete response, NED no evidence of disease
Median survival (MS) by SIR score: SIR 1–3 (MS 2.91 months), SIR 4–7 (MS 7.00 months), SIR 8–10 (MS 31.38 months)
Based on data from Ref. [10]
Table 30.3
Basic Score for Brain Metastases (BSBM)
 
Score
 
 
0
1
KPS
50–70
80–100
Control of primary tumor
No
Yes
Extracranial metastases
Yes
No
KPS Karnofsky Performance Status
Median survival (MS) by BSBM: BSBM 3 (MS >32 months), BSBM 2 (MS 13.1 months), BSBM 1 (MS 3.3 months), BSBM 0 (MS 1.9 months)
Based on data from Ref. [11]
Our group published the Graded Prognostic Assessment (GPA) in 2008 [14] based on 1960 patients from five randomized Radiation Therapy Oncology Group (RTOG) trials (7916, 8528, 8905, 9104, and 9508). Analysis showed four prognostic factors (age, KPS, extracranial metastases, and number of brain metastases) were significant for survival. Those prognostic factors were weighted in proportion to their regression coefficients and scaled such that patients with the best/worst prognosis would have a GPA of 4.0/0.0, respectively. In 2010, we refined the GPA based on an analysis of a retrospective multi-institutional database of 4259 patients. That study found survival varies by diagnosis and diagnosis-specific prognostic factors [15]. The breast-GPA was then further refined using tumor subtype [16], and a summary report was published [17]. More recently, the GPA indices for lung cancer and melanoma were updated using new data from patients (2186 lung cancer and 823 melanoma patients) diagnosed since 2005 including molecular factors. The lung-molGPA incorporates EGFR and ALK gene status [18, 19], and similarly the melanoma-molGPA incorporates BRAF status [20, 21]. The original melanoma-GPA found only two factors were significant (KPS and the number of brain metastases), whereas in the updated melanoma-molGPA, other clinical factors (age and extracranial metastases) were found to be significant, in addition to BRAF status.
Table 30.4 shows the median survival time for patients with brain metastases by diagnosis-specific GPA. Table 30.5 shows a user-friendly worksheet to facilitate calculation of the Graded Prognostic Assessment by diagnosis and estimate survival for patients with brain metastases. A free online/smartphone application is available at brainmetgpa.​com which further simplifies calculation of the GPA. Table 30.6 shows a multivariate analysis of risk of death and median survival by treatment (excluding drug therapies) and diagnosis. It is important to understand these data are retrospective in nature with the selection bias inherent in all retrospective studies so one should not conclude that one treatment is better than another based on these data. Fig. 30.2 shows Kaplan-Meier curves for survival for six diagnoses by GPA, demonstrating excellent separation between groups.
Table 30.4
Median survival time for patients with brain metastases by diagnosis-specific Graded Prognostic Assessment score
  
DS-GPA
 
Diagnosis
Overall
MST (95% CI)
N
0–1.0
MST (95% CI)
n (%)
1.5–2.0
MST (95% CI)
n (%)
2.5–3.0
MST (95% CI)
n (%)
3.5–4.0
MST (95% CI)
n (%)
p (log-rank)
NSCLC
15.23 (14.17–16.53)
1521
6.90 (5.73–8.70)
337 (22%)
13.67 (11.97–15.33)
664 (44%)
26.47 (23.40–30.63)
455 (30%)
46.77 (36.87–NE)
65 (4%)
<0.001
SCLC
4.90 (4.30–6.20)
281
2.79 (1.83–3.12)
65 (23%)
4.90 (4.04–6.51)
119 (42%)
7.67 (6.27–9.13)
84 (30%)
17.05 (4.70–27.43)
13 (5%)
<0.001
Melanoma
9.80 (9.08–10.59)
823
4.92 (3.67–6.92)
136 (17%)
8.30 (7.34–9.28)
386 (47%)
15.77 (13.12–18.82)
256 (31%)
34.07 (23.61–50.46)
45 (5%)
<0.001
RCC
9.63 (7.66–10.91)
286
3.27 (2.04–5.10)
43 (15%)
7.29 (3.73–10.91)
76 (27%)
11.27 (8.80–14.80)
104 (36%)
14.77 (9.73–19.79)
63 (22%)
<0.001
Breast cancer
13.80 (11.53–15.87)
400
3.35 (3.13–3.78)
23 (6%)
7.70 (5.62–8.74)
104 (26%)
15.07 (12.94–15.87)
140 (35%)
25.30 (23.10–26.51)
133 (33%)
<0.001
GI cancer
5.36 (4.30–6.30)
209
3.13 (2.37–4.57)
76 (36%)
4.40 (3.37–6.53)
65 (31%)
6.87 (4.86–11.63)
50 (24%)
13.54 (9.76–27.12)
18 (9%)
<0.001
Others
6.37 (5.22–7.49)
450
The top row in each cell is the median survival time (MST) in months and its associated 95% CI. The bottom row is the frequency and percentage of patients with the corresponding DS-GPA category for a given diagnosis. Abbreviations: DS-GPA Diagnosis-Specific Graded Prognostic Assessment, NSCLC non-small cell lung cancer (adenocarcinoma), SCLC small cell lung cancer, RCC renal cell carcinoma, GI gastrointestinal, NE not estimable
Based on data from Refs. [17, 19, 21]
Table 30.5
GPA worksheet to estimate survival from brain metastases by diagnosis
Non-small cell/small cell lung cancer
 
GPA scoring criteria
Patient
 
0
0.5
1.0
Score
Age
≥70
<70
n/a
_____
KPS
≤70
80
90–100
_____
ECM
Present
 
Absent
_____
#BM
>4
1–4
n/a
_____
Gene status
EGFR neg/unk
n/a
EGFR pos
 
 
and ALK neg/unk
 
or ALK pos
_____
   
Sum total
_____
Adenocarcinoma MS by GPA: GPA 0–1.0 = 6.9; 1.5–2.0 = 13.7; 2.5–3.0 = 26.5; 3.5–4.0 = 46.8
Non-adenocarcinoma MS by GPA: GPA 0–1.0 = 5.3; 1.5–2.0 = 9.8; 2.5–3.0 = 12.8
Melanoma
    
 
0
0.5
1.0
Score
Age
≥70
<70
n/a
____
KPS
<70
80
90–100
____
ECM
Present
n/a
Absent
____
#BM
>4
2–4
1
____
Gene status
BRAF neg/unk
BRAF pos
n/a
____
   
Sum total =
_______
MS (months) by GPA: GPA 0–1.0 = 4.9; 1.5–2.0 = 8.3; 2.5–3.0 = 15.8; 3.5–4.0 = 34.1
Breast cancer
 
0
0.5
1.0
1.5
2.0
Score
KPS
≤50
60
70–80
90–100
n/a
____
Subtype
Basal
n/a
LumA
HER2
LumB
____
Age
≥60
<60
n/a
n/a
n/a
____
     
Sum total =
_______
Subtype:
Basal, triple negative (ER/PR/HER2-neg)
 
LumA, luminal A (ER/PR-pos, HER2-neg)
 
LumB, luminal B (triple positive, ER/PR/HER2-pos)
 
HER2, HER2-pos, ER/PR-neg
MS (months) by GPA: GPA 0–1.0 = 3.4; 1.5–2.0 = 7.7; 2.5–3.0 = 15.1; 3.5–4.0 = 25.3
Renal cell carcinoma
 
0
1.0
2.0
Score
KPS
<70
70–80
90–100
____
#BM
>3
2–3
1
____
   
Sum total =
_______
MS (months) by GPA: GPA 0–1.0 = 3.3; 1.5–2.0 = 7.3; 2.5–3.0 = 11.3; 3.5–4.0 = 14.8
GI cancers
 
0
1
2
3
4
Score
KPS
<70
70
80
90
100
____
MS (months) by GPA: GPA 0–1.0 = 3.1; 2.0 = 4.4; 3.0 = 6.9; 4.0 = 13.5
Abbreviations: GPA Graded Prognostic Assessment, KPS Karnofsky Performance Status, ECM extracranial metastases, #BM number of brain metastases, ER estrogen receptor, PR progesterone receptor, HER2 human epidermal growth factor receptor 2, MS median survival in months, neg/unk negative or unknown
Based on data from Refs. [17, 19, 21]
Table 30.6
Multivariable analysis of risk of death and median survivala by treatment and diagnosis
  
Treatment
Diagnosis
Statistics
WBRT
SRS
WBRT + SRS
S + SRS
S + WBRT
S + WBRT+SRS
NSCLC
n = 1521
Risk of death (HR)
1.0
1.08
1.20
0.66b
0.78
0.79
95% CI
 
0.92–1.27
0.94–1.54
0.50–0.88
0.58–1.06
0.40–1.58
p-Value
 
0.35
0.15
<0.01
0.11
0.51
Median survivala
13
14
10
32
20
20
n (%)
342 (22%)
767 (50%)
139 (9%)
114 (7%)
76 (5%)
13 (1%)
SCLC
n = 281
Risk of death (HR)
1.0
0.97
0.24b
0.00
0.42b
0.00
95% CI
 
0.41–2.26
0.10–0.59
NA
0.25–0.73
NA
p-Value
 
0.94
0.002
0.99
0.002
0.98
Median survivala
4
7
15
12
15
15
n (%)
229 (81%)
13 (5%)
21 (7%)
1 (0.4%)
16 (6%)
1 (0.4%)
Melanoma
n = 823
Risk of death (HR)
1.0
0.69b
0.62b
0.50b
0.54b
0.70
95% CI
 
0.54–0.89
0.45–0.86
0.36–0.69
0.35–0.84
0.36–1.36
p-Value
 
<0.01
<0.01
<0.01
<0.01
0.29
Median survivala
6
10
9
13
11
11
n (%)
91 (11%)
464 (56%)
73 (9%)
95 (12%)
34 (4%)
12 (1%)
Renal cell
n = 286
Risk of death (HR)
1.0
0.83
0.70
0.87
0.66
0.68
95% CI
 
0.56–1.21
0.43–1.14
0.42–1.83
0.37–1.17
0.09–5.01
p-Value
 
0.33
0.15
0.71
0.16
0.70
Median survivala
5
11
12
13
16
9
n (%)
78 (27%)
131 (46%)
46 (16%)
11 (4%)
18 (6%)
2 (1%)
Breast cancer
n = 400
Risk of death (HR)
1.0
1.07
0.74
0.59
0.72
0.47b
95% CI
 
0.66–1.73
0.47–1.16
0.28–1.23
0.43–1.21
0.23–0.96
p-Value
 
0.80
0.18
0.16
0.72
0.04
Median survivala
7
13
15
24
18
30
n (%)
131 (33%)
115 (29%)
86 (22%)
19 (5%)
28 (7%)
20 (5%)
GI cancer
n = 209
Risk of death (HR)
1.0
0.72
0.69
2.30
0.33b
0.39b
95% CI
 
0.40–1.28
0.39–1.22
0.43–12.4
0.19–0.56
0.17–0.90
p-Value
 
0.26
0.21
0.33
<0.001
0.03
Median survivala
3
7
7
9
10
8
n (%)
95 (45%)
35 (17%)
35 (17%)
2 (1%)
34 (16%)
8 (4%)
Diagnoses: NSCLC non-small cell lung cancer (adenocarcinoma), SCLC small cell lung cancer, GI gastrointestinal
Treatments: S surgery, WBRT whole-brain radiation therapy, SRS stereotactic radiosurgery
Statistics: Risk of death: hazard ratio (HR) normalized to patients treated with whole-brain radiation therapy alone (HR = 1.0) and calculated by multivariable Cox regression, adjusted for DS-GPA and stratified by institution
Based on data from Refs. [17, 19, 21]
aMedian survival in months based on one-sample Kaplan-Meier method
bStatistically significantly better than WBRT alone; 95% confidence interval
The diagnosis-specific GPA indices presented here hold several implications for clinical management and research involving patients with brain metastases:
1.
There is marked heterogeneity in outcomes for patients with brain metastases, and these outcomes vary not only by diagnosis but also by diagnosis-specific prognostic factors, as detailed herein. Because of this heterogeneity, we should not treat all patients with brain metastases the same way; treatment should be individualized, and the past philosophy of fatalistic futility should be abandoned.
 
2.
On the other hand, as shown in Table 30.4, if a patient has a GPA of 0–1.0, regardless of diagnosis, their expected survival is poor. For these patients, supportive care, as suggested by the QUARTZ trial [8], may be the best option.
 
3.
For patients with GPA scores above 1.0, the median survival time (Table 30.4) varies more by diagnosis, and more aggressive treatment strategies may be appropriate, but these retrospective data do not provide a basis for assuming that longer survival is a consequence of more aggressive treatment. Indeed, the survival by treatment data shown in Table 30.6 is certainly fraught with selection bias and should not be blindly applied or expected. Nonetheless, these data reflect patterns of care for patients with brain metastases.
 
4.
Performance status is prognostic in every diagnosis. Clinicians should take the time to accurately assess and document their patients’ performance status.
 
5.
Table 30.5 shows the number of brain metastases is a significant prognostic factor for lung cancer, melanoma, and renal cell carcinoma, but not for breast or gastrointestinal cancers. Patients should not be denied treatment because of the number of brain metastases.
 
6.
Extracranial metastases are only prognostic in lung cancer and melanoma but not in breast cancer, renal cell carcinoma, or gastrointestinal cancers. The implication here is that those patients with non-lung, non-melanoma malignancies should not be denied aggressive treatment for their brain metastases because they have extracranial metastases.
 
7.
Age is strongly prognostic in lung cancer and weakly prognostic in breast cancer and melanoma but not prognostic in renal cell carcinoma or gastrointestinal cancers. Thus, age should not be used as a rationale to withhold aggressive treatment for non-lung malignancies.
 
8.
Because lung cancer and brain metastases from lung cancer are so common, those patients have masked our understanding of the distinct course for patients with non-lung malignancies and brain metastases, as demonstrated by points 5, 6, and 7.
 
9.
Tumor subtype in breast cancer is of paramount importance and prognostic significance, but it is not as prognostic as the breast-GPA index .
 
10.
A disproportionate number of patients with gastrointestinal cancers present with GPA of 0–1.0. Whether this is due to lack of screening MRI in these patients versus other biological reasons remains unclear, but the finding should serve as a reminder that brain metastases are not uncommon in GI cancer patients. Ongoing research will better elucidate prognosis for these patients, and the GI-GPA will be updated accordingly.
 
11.
Clinicians may use the worksheet in Table 30.5 to calculate their patient’s GPA score and estimate survival.
 
12.
The GPA may be used for purposes of stratification in clinical trials dealing with patients with brain metastases.
 

Case Study

A 36-year-old [22] white female marathon runner presented in August 2005 with a right neck mass. Fine needle aspiration initially confirmed a malignancy, later confirmed as a malignant melanoma by excisional biopsy of a posterior scalp lesion on 9-15-05. This malignant melanoma was histopathologically staged as Clark’s Level IV, Breslow depth at least 6 mm, with angiolymphatic invasion, and positive deep and peripheral margins. Brain MRI for initial radiologic staging on September 27, 2005, showed multiple scalp lesions but no evidence of parenchymal brain metastases. PET scan September 27, 2005, showed hypermetabolic activity only in the left neck. On October 11, 2005, she underwent a left modified radical neck dissection and wide local excision of the scalp lesion. Pathology confirmed metastatic melanoma in 3 of 28 lymph nodes with extension into the adjacent soft tissues in two areas. Pathology from the scalp excision showed a maximum tumor depth of 1.9 cm, and the deep margin remained positive. She underwent two additional scalp excisions, and the deep margin remained positive. Her stage was T4bN2bM0, stage IIIC. She received 64 Gy radiation therapy to the left neck and scalp, completed 1-20-06. She then received three cycles of cisplatinum, interferon, and vinblastine followed by interleukin-2, completed in March 2006. She did well without evidence of recurrence until November 2006 when she underwent a debridement of necrotic tissue in the scalp lesion. PET scan on December 05, 2006, showed a 0.7 cm hypermetabolic nodule in the retroperitoneum consistent with metastatic recurrence. Brain MRI on December 06, 2006, showed three brain metastases (2.5 cm right caudate, 1.1 cm left parieto-occipital, and 0.7 cm left posterior frontal) (Fig. 30.3a), which were not present on the prior scan of June 22, 2006.
Whole-brain radiation therapy was not given (and has not been given) due to the prior scalp radiation. She underwent SRS (Gamma Knife) on December 13, 2006, to all three lesions: right caudate, 20 Gy to a volume of 8.4 cc (Fig. 30.3b); left posterior frontal, 24 Gy to a volume of 0.47 cc (Fig. 30.3c); and left parieto-occipital, 24 Gy to a volume of 1.6 cc (Fig. 30.3d). She underwent SABR to the pelvic soft tissue metastasis (25 Gy in five fractions over 2 weeks, completed on February 23, 2007). Between March and June 2007, she received four cycles of carboplatin, paclitaxel, and temozolomide treatment. In September 2007, she developed headaches, nausea, vomiting, and confusion. MRI on September 26, 2007, showed a marked increase in enhancement and edema in the right frontal lobe consistent with radiation necrosis (Fig. 30.3e). Due to increased headaches and possible radiation necrosis, the temozolomide was discontinued. She has received no treatment since September 2007. The edema was treated with steroids, which were gradually tapered off over 4 months. Brain MRI on May 23, 2008, showed improvement with central necrosis of the previously solid-appearing lesion (Fig. 30.3f). Brain MRI on October 23, 2008, showed further resolution of the enhancement/necrosis with minimal residual enhancement (Fig. 30.3g). Serial imaging since that time has shown no evidence of recurrent tumor or necrosis.
She remains clinically and radiographically free of disease 11 years after the diagnosis of multiple brain metastases and more than 10 years after completion of treatment. Brain MRI on August 02, 2017, showed no change in the minimal residual enhancement/scar tissue (Fig. 30.3h), and PET scan on August 02, 2017, showed no evidence of disease. She has remained asymptomatic for over a decade and continues to run marathons, as recently as October 14, 2017. In November 2017, she completed the FACT-Brain questionnaire, a patient-reported QOL tool to reassess brain cognition. Her FACT-BR score was perfect (200 on a scale of 200), 11 years after diagnosis of her brain metastases. Notably, this patient never underwent craniotomy or whole-brain radiation therapy and thus avoided the related long-term neurocognitive toxicity of these interventions.
To fully appreciate this patient’s remarkable outcome, it is appropriate to review how her outcome compares to the best available evidence of survival for melanoma patients with brain metastases. We recently updated and published the melanoma-molGPA [7] based on a multi-institutional retrospective study of 483 melanoma patients with brain metastases diagnosed between January 01, 2006, and December 31, 2015. Notably, the patient presented here was diagnosed in 2006, so she is a contemporary of the patients in the melanoma-molGPA update study. The study showed five prognostic factors significant for survival. Table 30.5 shows a worksheet with which to calculate the melanoma-molGPA. To further simplify calculation of the melanoma-molGPA, a free user-friendly app is available at brainmetgpa.​com. Overall median survival has improved from 6 to 10 months since the 1980s, and the median survival by melanoma-molGPA groups for GPA of 0–1.0, 1.5–2.0, 2.5–3.0, and 3.5–4.0 was 4.9, 8.3, 15.8, and 34.1 months, respectively. The patient presented here had a melanoma-GPA of 3.0 on a 4.0 scale on both the original and updated GPA index, correlating with an estimated survival of 8.8 and 15.8 months, respectively. This patient is disease-free and asymptomatic with a perfect FACT-Brain QOL score 11 years after the diagnosis of multiple brain metastases. Clearly, prognostic indices are imperfect but nonetheless provide our best estimate of survival for these patients.

Summary

Patients with brain metastases are a heterogeneous population and outcomes vary widely by diagnosis and diagnosis-specific prognostic factors. Because of this heterogeneity and the plethora of available treatment options, it is difficult to estimate survival. These problems have complicated clinical decision-making as well as interpretation of clinical trials. The Graded Prognostic Assessment (GPA) is a diagnosis-specific prognostic index which has been updated to reflect the current treatment era by incorporating diagnosis-specific prognostic factors including molecular factors such as tumor subtype and gene status. The GPA is useful for clinical decision-making as physicians determine whether and what treatment is appropriate for these patients. It can also be useful to stratify clinical trials to ensure those trials are comparing comparable patients, which is especially important in such a heterogeneous patient population. Without accurate stratification, the results of clinical trials are uninterpretable and a waste of resources.

Self-Assessment Questions

1.
According to the updated Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for lung cancer (lung-molGPA), the significant prognostic factors for patients with lung cancer and brain metastases are which of the following?
A.
Age, KPS, number of brain metastases
 
B.
Age, KPS, presence of extracranial metastases
 
C.
Age, KPS, EGFR status, presence of extracranial metastases
 
D.
Age, KPS, EGFR and ALK status, presence of extracranial metastases, number of brain metastases
 
 
2.
According to the updated Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for breast cancer (breast-GPA), the significant prognostic factors for patients with breast cancer and brain metastases are which of the following?
A.
Age, KPS, number of brain metastases
 
B.
Age, KPS, presence of extracranial metastases
 
C.
Age, KPS, estrogen, and progesterone receptor status
 
D.
Age, KPS, tumor subtype
 
 
3.
According to the updated Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for melanoma (melanoma-molGPA), the significant prognostic factors for patients with melanoma and brain metastases are which of the following?
A.
Age, KPS, BRAF status, number of brain metastases
 
B.
Age, KPS, presence of extracranial metastases, number of brain metastases
 
C.
Age, KPS, BRAF status, presence of extracranial metastases
 
D.
Age, KPS, BRAF status, presence of extracranial metastases, number of brain metastases
 
 
4.
The two prognostic indices, the Radiation Therapy Oncology Group Recursive Partitioning Analysis (RTOG RPA) and the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with brain metastases differ in which of the following ways?
A.
Both consider control of the primary tumor.
 
B.
They use the same factors but the DS-GPA is based on larger, more current data.
 
C.
The DS-GPA considers the molecular profile of the tumor.
 
D.
The estimated survival for the best prognostic group for each index is about the same.
 
 
5.
What is the GPA and estimated survival for a 69-year-old patient with ALK-positive lung adenocarcinoma, KPS 90, no extracranial metastases, and four brain metastases?
A.
GPA 4.0, estimated survival 47 months
 
B.
GPA 3.0, estimated survival 26.5 months
 
C.
GPA 2.0, estimated survival 13.7 months
 
D.
GPA 3.5, estimated survival 12 months
 
 

Answers

1.
D
 
2.
D
 
3.
D
 
4.
C
 
5.
A
 

Acknowledgments

This work has been a collaborative multi-institutional effort. The faculty and residents of the following institutions have selflessly contributed time and energy to one or more of the studies on the Graded Prognostic Assessment: MD Anderson; Memorial Sloan Kettering Cancer Center; Mayo Clinic; University of California, San Francisco; Massachusetts General Hospital; Dana-Farber Cancer Institute; Duke University; Yale University; University of Colorado Denver; Cleveland Clinic; University of Wisconsin-Madison; McGill University; Centre Hospitalier de l’ Université de Montreal; University of Maryland; University of Alabama at Birmingham; and the University of Minnesota. This work would not have been possible without the tireless work of these dedicated colleagues. Special recognition is appropriate for Ryan Shanley who has provided his statistical wisdom for nearly a decade.
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