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
www.seer.cancer.gov; cancer mondial website
Cases Deaths
Total Male Female Total 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
France 8375 4471 3904 4212 2225 1987
Germany 10,179 5203 4976 5260 2501 2759
Italy 10,825 5906 4919 4675 2390 2285
UK 8307 4515 3792 4507 2380 2127
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) who progresses through DA-EPOCH-R with a large breast mass
• 78 yo man with MCL since 2005 s/p R-HyperCVAD, bortezomib, BR, temsirolimus, DHAP who has persistent cytopenias due to marrow involvement
• 92 yo man with DLBCL who relapses 8 months after R-CHOP (with dose reductions)
• 67 yo woman with FL since 2008 who has no symptoms but with radiographic progression after 2 prior lines of therapy
Biology
Cumulative toxicity
Advanced age
Histology
MYC pos DLBCL: BCCA analysis
66%
31%PFS
OS72%
33%
• Patients with MYC pos DLBCL had inferior PFS and OS
• 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
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
1st or 2nd Relapse
Multiply relapsed/refractory
Low tumor burden
High tumor burden
Low tumor burden
High tumor burden
Sensitive
Resistant
…with different treatment goals
Age and prognosis
IPIAge PS
LDH>1 EN site
stage
FLIPI-1Age
LN sites >4LDH
StageHgb
FLIPI-2Age B2MBM +
LN>6cmHgb
MIPIAge PS
LDHWBC(Ki67)
PITAge PS
LDHBM +
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
OS and PFS after ASCT in r/r HL
Younes JCO 2012; Lavoie Blood 2005
Median survival
<8 months after relapse
Med survival 22 months
Brentuximab vedotin
When does the change to palliative approach occur?
• Loss of marrow reserve• Worsening comorbidities due to disease• Irreversible toxicity due to treatment• Change in performance status• Patient/family request
Living with cancer
Dying with cancer
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
• 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
Generalized anxiety disorder
• 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
Panic attacks
1. Up to 25% of cancer patients experience anxiety
2. Many develop PTSD3. Barrier to improving the overall
cancer experience
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
Rocque, G. B. & Cleary, J. F. Nat. Rev. Clin. Oncol. 10, 80–89 (2013)
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