Palliative Therapy for the
“Incurable” Patient
Sonali M. Smith, MD
Associate Professor, Section of Hematology/Oncology
Director, Lymphoma Program
The University of Chicago
Leading Sites of Cancer Cases
and Death
Lymphoma Vital Statistics
Total
Cases
Male Female
Total
Deaths
Male Female
USA
75,190
40,880
34,310
20,620
10,510
10,110
EU
52,440
28,043
24,397
25,906
13,285
12,261
8375
4471
3904
4212
2225
1987
Germany
10,179
5203
4976
5260
2501
2759
Italy
10,825
5906
4919
4675
2390
2285
8307
4515
3792
4507
2380
2127
France
UK
www.seer.cancer.gov; cancer
mondial website
What is an “incurable” lymphoma?
• Newly diagnosed: double hit
• All indolent lymphomas and CLL
• Relapsed/refractory aggressive
lymphomas in the elderly
• Multiply relapsed and/or refractory disease
in the young
• Mantle cell lymphoma
• Most T-cell lymphomas
What is an incurable lymphoma?
• 41 yo woman with MYC+BCL2+ B-cell lymphoma
unclassifiable (BCLU)Biology
who progresses through DAEPOCH-R with a large breast mass
• 78 yo man with MCL since 2005 s/p R-HyperCVAD,
Cumulative
bortezomib, BR,
temsirolimus,toxicity
DHAP who has persistent
cytopenias due to marrow involvement
• 92 yo man with DLBCL
who relapses
Advanced
age 8 months after RCHOP (with dose reductions)
• 67 yo woman with FL since 2008 who has no symptoms
but with radiographicHistology
progression after 2 prior lines of
therapy
MYC pos DLBCL: BCCA analysis
•Patients with MYC pos
DLBCL had inferior PFS and
OS
66%
PFS
31%
•Even when excluding BCL2
pos cases, MYC was an
adverse prognostic factor
•2 of 12 (17%) of patients with
MYC pos DLBCL had CNS
recurrence compared to 4 of
123 (3%) of MYC neg DLBCL
72%
OS
33%
Savage Blood 2009
“Double hit lymphomas”: BCL2 worsens
prognosis of MYC pos lymphomas
Prognostic factors for survival
Age > 60 yrs
PS > 1
High IPI
BM pos
BCL2 protein pos
R-CHOP
Johnson Blood 2009
FL is an incurable lymphoma
•Goals of therapy change
over time
•Selection of any
treatment must reflect
short- and long-term
goals
•Can be difficult to
identify when patient
should move to palliative
care
Swenson WT et al. J Clin Oncol. 2005;23:5019-5026.
FL has multiple disease states…
Treatment
naive
Sensitive
Resistant
Low tumor burden
High tumor burden
1st
2nd
or
Relapse
Low tumor burden
High tumor burden
Multiply
relapsed/refractory
…with different treatment goals
Age and prognosis
IPI
Age
PS
LDH
>1 EN site
stage
FLIPI-1
Age
LN sites >4
LDH
Stage
Hgb
FLIPI-2
Age
B2M
BM +
LN>6cm
Hgb
MIPI
Age
PS
LDH
WBC
(Ki67)
PIT
Age
PS
LDH
BM +
The recurrent identification of age as an
adverse prognostic factor implies that
elderly patients are less “curable” overall
New agents challenge our definition of
“incurable” and “untreatable”: HL example
Median
survival
<8 months
after relapse
OS and PFS after
ASCT in r/r HL
Brentuximab vedotin
Med survival
22 months
Younes JCO 2012; Lavoie Blood 2005
When does the change to
palliative approach occur?
Living with
cancer
•
•
•
•
•
Dying with
cancer
Loss of marrow reserve
Worsening comorbidities due to disease
Irreversible toxicity due to treatment
Change in performance status
Patient/family request
Domains of palliative care
Domain
Anxiety
Depression
Anorexia
Pain control
Nausea/vomiting
Diarrhea
Constipation
Emotional aspects of palliative care
and impact on treatment goals
Anxiety
Generalized
anxiety disorder
• A state of feeling
apprehension,
uncertainty or fear
• May lead to some
level of dysfunction
• A state of excessive
anxiety or worry
lasting ≥ 6 months
• Impacting day-to-day
activities
1. Up to 25% of cancer patients
experience anxiety
2. Many develop PTSD
3. Barrier to improving the overall
cancer experience
Panic attacks
• Sudden onset of intense
terror, apprehension,
fearfulness, terror or
felling of impending
doom
• Usually occurring with
symptoms (Shortness of
breath, palpitations,
Chest discomfort, Sense
of choking, Fear of going
crazy or losing control
• Lasts15 – 30 minutes
Anorexia
Cachexia – wasting syndrome
•
•
•
•
 Lean tissue
 Performance status
Altered resting energy expenditure
 Appetite
Impact
•
•
•
•
•
≥ 5% weight loss and poor prognosis
Trend toward lower chemotherapy response rates
Anorexia and poor prognosis
 QOL, function
Affects caregivers
MacDonald N, et al. J Am Coll Surg, 2003.
Dewys WD, et al. Am J Med, 1980.
Loprinzi CL, et al. JCO, 1994.
Timing of palliative care initiation
• Generally done too late
– 60% of cancer pts hospitalized in last month of life
– 25% of US cancer pts die in the hospital
– Median length of time between hospice referral and death is 33
days
• Not clearly documented
– Fragmented health care systems
• Need better tools to recognize when patients have 6 months (not
days, weeks) to live before making palliative care the dominant
aspect of pt care
– Only 32% of physicians accurately predicted shortened life
expectancy
– Consistently overestimated survival
Timing of shift to palliative care
is important
• Timely recognition of poor prognosis led to
– less ‘aggressive’ end‐of‐life care
– earlier hospice referrals
– improved anxiety, less depression, and improved
quality of life compared
• Disconnect between patient desire and physician goals
– Occasionally, disconnect between patient perceptions
and reality
Delayed recognition leads to increased
suffering and increased socioeconomic burden
Model
of
palliative
care
REVIEWS
Focus of care
Traditional oncological care
(curative, life-prolonging, palliative)
Palliative care
Hospice
Diagnosis
Symptom
burden
6-month prognosis
Bereavement
Death
incl
tion
trea
thes
of c
par
to e
fina
the
of d
give
and
Time
Def
Figure 1 | Model of palliative care for patients with cancer. The prominence of
As d
hospice care may vary depending on the country. Permission obtained from
that
Thieme Publishers © Campbell, T. C. & Roenn, J. H. Semin. Intervent. Radiol. 24,
Rocque,
G.
B.
&
Cleary,
J.
F.
Nat.
375–381 (2007), and adapted with permission from Emanuel, L. L., Ferris, F. D.,
lies
Rev.
Clin.
Oncol.
10,
80–89
(2013)
von Gunten, C. F. & Von Roenn, J. H. EPEC-O: Education in Palliative and End-of-Life
illn
Important tools when approaching
pts with palliative intent
•
•
•
•
Symptom control is key
Steroids
Radiation
Multidisciplinary approach
Palliative care in the “incurable”
patient: take-home points
• Death from lymphoma is an important and still common occurrence
• Many lymphomas are inherently or progressively incurable as
defined by
– Biology
– Advanced age
– Cumulative toxicities
– Histology
• Important to recognize when the goal of treatment is palliative
– Symptom management is critical
– Particularly challenging in indolent NHL
– Need to discuss with patient/family
– Need to clearly document the goals of treatment