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

USA EU France Germany Italy UK Total 75,190 52,440 8375 10,179 10,825 8307

Cases

Male 40,880 Female 34,310 28,043 4471 5203 5906 4515 24,397 3904 4976 4919 3792 Total 20,620

Deaths

Male 10,510 Female 10,110 25,906 4212 5260 4675 4507 13,285 2225 2501 2390 2380 12,261 1987 2759 2285 2127 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 EPOCH-R with a large breast mass • 78 yo man with MCL since 2005 s/p R-HyperCVAD, cytopenias due to marrow involvement CHOP (with dose reductions) • 67 yo woman with FL since 2008 who has no symptoms therapy

MYC pos DLBCL: BCCA analysis

•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

PFS OS 66% 31% 72% 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

1 st or 2 nd 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 Brentuximab vedotin OS and PFS after ASCT in r/r HL 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 • A state of feeling apprehension, uncertainty or fear • May lead to some level of dysfunction Generalized anxiety disorder • 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

Traditional oncological care (curative, life-prolonging, palliative) including watching for adverse effects, mana ging medica tions, and deciding when to call the doctor to administer treatments.

45 Half of caregivers report that they provide these services without training, which can lead to a lack of confidence in their ability to provide the support, particu larly the valuable emotional support.

45 In addition Palliative care Hospice Bereavement to emotional stress, caregivers can experience substantial financial burden. In a large survey of informal caregivers, the economic burden at the end of life (within 6 months of death) was US$14,234, which included the cost of care giver lost earnings, relocation costs, out-of-pocket costs, Diagnosis Symptom burden 6-month prognosis Death and costs of acquiring additional home support.

46 Time Figure 1 | Model of palliative care for patients with cancer. The prominence of Defining palliat ive and hospice care hospice care may vary depending on the country. Permission obtained from As defined by the WHO, palliative care is “an approach Thieme Publishers von © Campbell, T. C. & Roenn, J. H. Gunten, C. F. & Von Roenn, J. H.

Semin. Intervent. Radiol.

Rocque, G. B. & Cleary, J. F.

Rev. Clin. Oncol. Car e—Oncology

(The EPEC Project, Chicago, 2005).

10, 80 24,

Nat.

that improves the quality of life of patients and their fami lies facing the problems associated with a life- threatening illness, through the prevention and impeccable assess ment and treatment of pain and other problems, physi cal, psychosocial, and spiritual ”.

47 Palliative care can be resuscitation preferences —which is transferrable across care settings.

37 By 2014, Massachusetts institutions that care for patients with life-limiting illness will be delivered to patients with a variety of life-threatening diseases, although early recommendations —including those published by the WHO —were focused on patients required to systematically identify patients and provide access to hospice or palliative care.

38 Other states, such as with cancer. All patients with advanced-stage, non curable cancer are potentially eligible for palliative care Oregon, West Virginia, New York, and Wisconsin, also have similar systems in place in many communities.

39,40 Further programmes are being developed throughout the world to address end-of-life planning in this patient population, such as the Advanced Medical Directive Act in Singapore and development of a National Framework for Advanced Care Directives in Australia.

41,42 Further limitations of end-of-life planning are the lack of physician time and an emphasis on the ‘technical’ aspects of patient care. During a follow-up clinic visit — often only 15 –20 min in length—an onco logist may be addressing tests results, adverse effects of chemo therapy, and plans for future treatment, leaving little time for disease- related symptom management and advanced care planning. Direct observation of communi cation during care of patients with a terminal cancer diagnosis demon strated that physicians focus more on the techni cal, medical issues than emotional and quality-of-life concerns.

31 In patients receiving chemotherapy, 64% of conversations focused on the medical and/or technical issues and 23% of the conversations addressed health related quality-of-life and symptom complaints.

43 Physicians perceive sensitive discussions to be more time intensive; therefore, emotional, spiritual and existen tial aspects, important components of palliative care, often go unaddressed.

31 This lack of discussion has an impact on caregivers, who can experience suffer ing while provi ding support, which is a concern of many patients. In a comparison of the perception of care givers ’ assessments of symptoms with the perception of the patients them selves, caregivers often view the symptoms as worse or more burdensome than do patients.

44 These caregivers, often family or friends, are also often called to assist with additional duties beyond activities of daily living. Caregivers report a range of tasks that they undertake, regardless of their life expectancy. The role of a pallia tive care team varies through the course of a patient ’s illness, increasing during symptom flairs and as a patient approaches death (Figure 1).

48 The palliative care skills emphasized by the American Academy of Hospice and Palliative Medicine are described in Box 1.

49 The pallia tive care team addresses the concerns of patients, families, and caregivers. This team provides support to both the patient and the family, including bereavement support after the patient ’s death.

Confusion can exist among both patients and provi ders about the difference between hospice and palliative care, particularly in the US medical system. In the USA, hospice care is one of the major providers of pallia tive care, and has historically been the main provider of end-of-life care for patients with cancer; however, hospice care is defined independently from palliative care owing to its place in the Hospice Medicare Benefit. Hospice care, as defined by the USA ’s National Hospice and Palliative Care Organization, is a “model for quality, compassionate care for people facing a life-limiting illness or injury. Hospice care involves a team-oriented approach to expert medical care, pain management, and emotional and spiritual support expressly tailored to the patient ’s needs and wishes”.

50 Hospice services in the USA are focused on caring for the patient, rather than curing a disease. Hospice services can be delivered in the home, in nursing homes, in hospitals, and in free-standing inpatient hospice agencies.

50 Use of hospice-based care has shown benefits in terms of quality of care, as well as patient and family satisfaction.

50 Despite the benefits derived from hospice services, referral to a hospice is often delayed. At major US cancer centres, the length of time between referral of patients with cancer to a hospice and death is 1 –2 months. A 82 | FEBRUARY 2013 | VOLUME 10 www.nature.com/ nrclinonc © 2013 Macmillan Publishers Limited. All rights reserved

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