Hem/oncs toe ‘line in the sand’ between quest for cure, overly aggressive end-of-life care

Patients with hematologic malignancies are significantly more likely than those with solid tumors to receive chemotherapy or spend time in the hospital during their final month of life.

Further, more than half of hematologic oncologists report they wait too long to conduct end-of-life conversations with patients.

Although alarming, hem/oncs say the statistics are misleading because of the stark differences between patients with blood cancers and those with solid tumors.

“With the vast majority of solid tumors, once they’re metastatic, [there is] a very clear line in the sand that those patients are not going to be cured,” Anna C. Beck, MD, associate professor of medical oncology at University of Utah School of Medicine, as well as director of supportive oncology and survivorship and an investigator at Huntsman Cancer Institute, told HemOnc Today. “Hematologic malignancies are a very different creature.”

Photo courtesy of Huntsman Cancer Institute.

Because blood cancers can present in indolent forms that cause few — if any — symptoms, they sometimes are considered chronic illnesses. Even advanced lymphomas and leukemias may be curable.

“Even with very poor performance status and multisystem organ failure, oncologists can still cure patients who can go on and live a fairly normal life,” Beck said. “Drawing that line in the sand ... is not quite as clear.”

HemOnc Today spoke with hematologic oncologists about the quality metrics under which they operate, whether end-of-life care for patients with hematologic malignancies may be too aggressive, the challenges clinicians face when they conduct end-of-life conversations with these patients, and the appropriate timing of palliative care.

’Important gap in care’

A study by David Hui, MD, MSc, and colleagues — published in 2014 in Cancer — showed patients with advanced hematologic malignancies were 29% more likely than those with advanced solid tumors to receive chemotherapy in the last 30 days of life. Individuals with blood cancers also were 31% more likely to be admitted to an ICU during that time, 29% more likely to die in acute care facilities and 26% less likely to have palliative care consultations.

“This study highlights an important gap in care for patients with hematologic malignancies,” Hui, assistant professor in the department of palliative care and rehabilitation medicine at The University of Texas MD Anderson Cancer Center, told HemOnc Today when the study was published. “Clinical practice guidelines for hematologic malignancies should include guidance to limit aggressive cancer treatments at the end of life and encourage early referral to palliative care.”

A year later, Hui and colleagues surveyed 120 hematologic oncologists and 120 solid tumor oncologists at their institution about end-of-life care. When presented a case vignette about a 60-year-old man with advanced incurable cancer and an expected survival of 1 month, hematologic oncologists were much more likely than solid tumor specialists to say they would offer treatment to the patient.

Hematologic oncologists also were more likely to feel a sense of failure when they were unable to alter the course of disease (46% vs. 31%; P = .04) and more comfortable prescribing treatment to patients with an ECOG performance status of 4 (OR = 2.77; P = .002).

The different trajectories of each disease influence these decisions, according to Samuel M. Silver, MD, PhD, professor in the department of internal medicine and director of the Cancer Center Network at University of Michigan Cancer Center, former chair of the National Comprehensive Cancer Network’s board of directors, and HemOnc Today’s section editor for health policy and value of care.

“When a patient comes in with stage IV metastatic non–small cell lung cancer or metastatic pancreatic cancer, they have a limited lifespan,” Silver told HemOnc Today. “Options for treatment certainly are growing, but oncologists immediately think of the limited lifespan and how one can best have optimal comfort for that patient for the remainder of their lives.

“In hematologic oncology, the first thing we think of for a patient with stage IV large B-cell lymphoma or aggressive Hodgkin lymphoma is the curative potential for those patients,” he added. “The mindset is very different.”

End-of-life conversations

The different mindset hem/oncs and solid tumor oncologists have may explain the differences in timing of end-of-life conversations for these patients.

In their survey, Hui and colleagues also determined hematologic oncologists are less comfortable than solid tumor specialists discussing death and dying with patients (72% vs. 88%; P = .007).

Oreofe Odejide, MD, MPH, instructor in medicine at Harvard Medical School and member of the division of population sciences at Dana-Farber Cancer Institute, surveyed 349 U.S.–based hematologic oncologists about the timing of end-of-life conversations. More than half (56%) of respondents reported having end-of-life discussions “too late.”

Further, 59% reported that “uncertainty about prognosis” is sometimes, often or always a barrier to high-quality end-of-life care.

The lack of distinction between curative and end-of-life phases for many hematologic cancers — even among those with advanced-stage disease — likely contributes to delayed initiation of end-of-life discussions, Odejide said.

However, in a series of focus groups she and colleagues conducted, hematologic oncologists identified “clinical signposts” — such as relapsed or refractory disease — “that may indicate that the end of life is near,” Odejide told HemOnc Today.

“Leveraging these signposts as triggers to initiate or readdress discussions about end-of-life preferences could potentially improve the timeliness of such discussions,” she said.

When Mikkael A. Sekeres, MD, MS, director of the leukemia program at Cleveland Clinic’s Taussig Cancer Institute, meets with patients and their families for the first time, he does not feel comfortable raising end-of-life issues. He believes those initial conversations already are emotionally charged, and patients often take away only snippets of the conversation.

“Over time, and after getting to know the patient,” Sekeres told HemOnc Today, “I am perfectly comfortable raising these issues and predicating it on, ‘This is not a signal to you that you are about to die. I’m bringing this issue up because you’re doing so well and I’d rather you think about these important issues while you’re feeling well than at times when you’re not feeling well.’”

Sekeres, who treats patients with leukemia or myelodysplastic syndrome, described the timing of end-of-life discussions as “tricky.”

“We usually do not have an epiphany and realize that everything we are doing is futile,” Sekeres said. “It’s iterative. Often, we’ll try one therapy in a patient that may work for a while and then stop working. Then, we’ll try another that may work and again stop working. ...

“Sometimes it takes a seminal event, like being admitted to the hospital with a bad infection, for patients and their families to come to terms with the fact the end of life is approaching,” Sekeres added. “A person may then recognize that he or she does not want to ever see the inside of a hospital again and, therefore, wants to refocus on palliative care as opposed to aggressive interventional care.”

Benefits of palliative care

In November, a panel of palliative care specialists updated ASCO’s guidelines for the treatment of patients with advanced cancers, suggesting palliative consultation should occur within 8 weeks of diagnosis. These guidelines applied to patients with solid tumors and hematologic malignancies, and did not distinguish between the two.

Areej R. El-Jawahri, MD, director of the bone marrow transplant survivorship program at Massachusetts General Hospital Cancer Center, said she believes palliative care can begin even sooner, and that it can be particularly beneficial to patients who undergo intensive therapies and stem cell transplantation.

“I have watched patients with blood cancers experience substantial physical and psychological symptoms during their treatment,” El-Jawahri told HemOnc Today. “Many clinicians believed that these symptoms are just a natural part of the transplant process and are not modifiable. Palliative care has expertise in complex symptom management and can provide an extra layer of support to help patients and caregivers undergo such intensive therapy.”

El-Jawahri and colleagues conducted a study, published in November in JAMA, that showed hematopoietic stem cell transplant recipients who underwent a palliative intervention experienced less depression, lower anxiety, lower symptom burden and better quality of life than those who received standard treatment.

Hematologic oncologists should direct their approach to palliative care based on many factors, including need for pain management, according to T. Declan Walsh, MD, MSC, who helped create the nation’s first palliative care program at Cleveland Clinic in 1987 and now serves as chair of the department of supportive oncology at Levine Cancer Institute.

“We know pain control is a really big issue for patients with multiple myeloma because they nearly all will develop significant pain during their illness, whereas pain is less frequent in some other hematologic malignancies,” Walsh said. “There’s differences in both prevalence in symptoms as well as severity, so the posture of approaching supportive care needs to be different in a hematological setting.”

However, one tenet appears clear.

“Most reasonable people looking at the data would conclude that the addition of palliative and supportive care services is good, and the earlier the better,” Walsh said.

Still, the importance of initiating palliative care early in the disease course for patients with hematologic malignancies may not be as readily accepted as it is for patients with solid tumors due to a difference in symptomatology. When initiated later in the disease course, palliative care often can be confused with end-of-life care.

“Much of the focus on symptom management in advanced cancer has focused on lung or colon cancers, and there has been much less attention paid to the common problems that people with hematologic malignancies may experience,” Walsh said. “They may have a different symptom burden, but that does not mean it’s proven that they do not need palliative care until late in the illness.”

Early initiation of palliative care services can help patients with hematologic malignancies understand the unpredictable trajectory of their disease, Beck said.

“A lot of what we do as palliative care doctors is based on communication,” Beck said. “We provide a safe place for patients and caregivers to talk about the things that worry or frighten them or that bring their life meaning, and helping them treasure and protect that as they go forward in their care.”

Beck recommended using the American Academy of Hospice and Palliative Medicine 10-step Measuring What Matters guideline.

Recommendations include providing patients with a comprehensive assessment — physical, psychological, social, spiritual and functional — soon after admission; assessing pain, dyspnea, nausea and constipation during admission and introducing pain management options; discussing emotional and spiritual concerns; and providing life-sustaining options.

Early palliative care consultations can prevent patients near the end of life from feeling like they personally failed to get better.

“What sticks with me most is when patients do not have a safe space to ask, ‘Am I really dying? Is it not really working?’” Beck said. “When we are called in the last few days of life to get involved, patients often have a pervasive sense of failure, and they feel like they have disappointed their providers and their family. If we were involved from the beginning and could work with those patients on different sorts of ‘what-if’ situations, it might be easier to support them and their caregivers when things do not turn out well.”

‘What would you do?’

One of the most intensely debated issues among hematologic oncologists is whether their curative approach may be too aggressive for their patients, many of whom report high symptom burdens following stem cell transplantation.

It is hard to define what care is too aggressive, Sekeres said.

“If I have a patient who says to me, ‘I will do anything to extend my life, even if that means spending most of my remaining days in the hospital,’ that opens the door for a variety of therapies that anyone would consider aggressive,” he said.

“If, on the other hand, a patient says to me, ‘You know what? I never want to see the inside of a hospital again,’ then I have a different armamentarium I can offer to that patient as an outpatient that has a much lower likelihood of causing harm and subsequent hospitalization.”

The most appropriate level of care may be different for each patient.

Because patients with AML or myelodysplastic syndrome are typically aged 65 to 75 years at diagnosis, initial consultations can include their partner and children. During those conversations, Sekeres — who is 47 and has three school-age children — often determines the aggressiveness of treatments he will provide.

“It is really hard for those of us in health care and not yet in our upper 60s or 70s to look back across a life and determine what the next best step is,” Sekeres said. “I try to be clear about this. Often, somebody in the room will bring it up. We’ll be talking about some aggressive therapies and my patients will say to me, ‘What would you do?’

“My response to them is, ‘I’m at an age when I still have young children and our job as parents is to escort those children into adulthood. I would do anything under the sun to make sure I realize that goal of bringing my kids into adulthood.’ Somebody in their late 60s, 70s or 80s, for the most part, that job is done, and their goal may be completely different.”

Walsh agreed, saying his own life experiences as a 69-year-old oncologist play a crucial role in the conversations he has with and treatments he offers patients.

“You’ll find that physicians, as they age in their practice, sometimes will have personal or family experiences with illness that change them and change their perspectives on end-of-life care,” Walsh said. “We’re all influenced by these life events and experiences.”

Defining ‘too much, too late’

Within the clinical community, opinions vary about the extent of treatment hematologic oncologists should provide patients in their final weeks of life.

Odejide and colleagues received completed surveys from 349 hematologic oncologists who were asked whether they deemed standard measures as “acceptable” or “not acceptable” indicators of good quality end-of-life care.

Results — published last year in Journal of Clinical Oncology — showed 80% of respondents said they agreed chemotherapy should not be administered within the last 14 days of life. However, when asked about hematology-specific measures, only 58.7% agreed avoidance of red cell transfusions within the last 7 days of life was an acceptable indicator of good quality end-of-life care, and only 59.9% said the same about platelet transfusions.

Sekeres — who considers blood and platelet transfusions palliative — said he often opts for the nonaggressive hydroxyurea, a pill that can lower white blood cell count and alleviate many of the flu-like symptoms associated with leukemia.

“Our patients’ quality of life suffers when they are profoundly anemic or when they have extremely low platelet counts and are at risk for bleeding,” he said. “My patients have told me they fear pain or bleeding to death most at the end of life. If we are not meeting our patients’ needs with respect to blood products, we are not providing adequate palliative care and we are not working to maximize their quality of life.”

Because of the nature of hematologic malignancies, red blood transfusions may be necessary for patients to have enough stamina to continue other treatments, Beck said.

“But I don’t know that patients would necessarily agree with undergoing treatments that allow them to live a few days to a few weeks longer at end of life but keep them in the hospital,” she said.

A study by Wright and colleagues, published in 2014 in BMJ, showed use of palliative chemotherapy 4 months before death was associated with higher rates of CPR and mechanical ventilation in the last week of life, along with late hospice referrals. However, there was no discernible difference in survival rates among patients who received palliative chemotherapy and those who did not.

Patients who received palliative chemotherapy also were more likely to die in intensive care and less likely to die in their preferred setting.

The reason for this disparity is because hematologic oncologists sometimes “can pull a rabbit out of a hat,” Beck said.

“They can take somebody who is very critically ill and bring them back to life again with effective therapy,” she said. “Unfortunately, it doesn’t work the majority of time.”

Although Silver said he respects studies on end-of-life care, he suggested many hematologic oncologists will opt for a curative stance over a palliative one.

“When one is talking about a bone marrow transplant for a patient with acute leukemia, very likely they will have received chemotherapy in the last 2 weeks of care because it may be their initial chemotherapy,” Silver said. “Or, they may have gone to the ICU because the hope is that they are experiencing a side effect of the therapy as opposed to the disease, and you are just trying to get them over that so you can continue in your curative modality.”

Because the metrics often used to define quality end-of-life care are developed by ASCO and pertain to all types of cancers, they may not be ideal for hematologic malignancies.

“Most of the ASCO guidelines really pertain to solid tumors, and even the needs of patients with follicular lymphoma and someone with acute leukemia are very different, so a single set of guidelines is not going to help,” Silver said. “We do not have good quality metrics in hematology to monitor care for our patients. We are still trying to figure that out.”

The goal of every oncologist is to find a way to either place or keep their patients in remission, Silver said.

How long they go about doing that, Beck said, can depend on the palliative consultations conducted weeks or months earlier.

“We see patients whose goal, first and foremost, is to make sure they get every single treatment that has a chance of helping them,” Beck said. “If that is their goal, we can help them protect and preserve that.

“But maybe their goal is to receive every kind of treatment that has a reasonable chance of helping them, but without keeping them from spending time at home or having meaningful interactions with family and friends, or without being a financial burden to their families,” she added. “All of those things that people care about at end of life get brushed aside when we are trying to do aggressive therapy with a life-saving intent.”

Granting patients’ wishes

Ultimately, experts with whom HemOnc Today spoke said the best way to provide quality care at the end of life to patients with hematologic malignancies is to listen to their goals.

“Patients may have other hopes besides getting every single treatment,” Beck said. “As treatments tend to wear them down, their disease becomes a more prominent factor and the treatments have less effect, patients value things like being at home with their family and spending what time and energy they have left devoted to the things that matter most to them.”

Caregivers also play a role in striking the proper balance in treatments, Beck said.

Sometimes caregivers may encourage patients to undergo more treatment at the end of life.

“Patients are under this pressure, and they are exhausted and may not want more treatments because they are not making them feel better or, more importantly, they are not allowing them to recover the kind of life they want to live,” Beck said. “But the caregivers keep encouraging them to fight. Everybody, including the physicians, start losing track of what it is they are fighting for. Are they fighting for days of life? That’s generally not what patients want.”

In these instances, if caregivers are part of the conversation, physicians can emphasize that they have done everything they can, Beck said.

Because patients with hematologic malignancies are prone to many infections, it is a challenge to reduce hospitalization in the final 30 days of life, especially if patients have stated a desire to undergo every possible treatment that could keep them alive, Walsh said.

“Some of the desire to be in the hospital is coming from patients and their families, and we have to respect that,” Walsh said. “I’m a big believer in looking after patients in the community, but we need to be careful we don’t throw out the baby with the bath water.”

Further, a patient’s preferred treatment plan at the time of diagnosis may evolve over time.

“It’s imperative to be clear on the patients’ wants and needs repeatedly,” Sekeres said. “Those change very frequently, and a form signed 2 years ago may not be relevant anymore. A form signed 2 weeks ago may not be relevant anymore. The same is true with goals of care, particularly for hematologic malignancies, because they can change how a person feels very quickly.

“We all know it’s the wrong thing to treat somebody in the last 30 days, and [it’s] the wrong thing to hospitalize them,” Sekeres added. “But in real time, that is really hard to recognize. Often, it’s when that decision to remove therapy is made that somebody dies.” – by Chuck Gormley

Click here to read the , “Is hospitalization within the final 30 days of life appropriate for patients with hematologic malignancies?”

References:

El-Jawahri A, et al. JAMA. 2016;doi:10.1001/jama.2016.16786.

Ferrell BR, et al. J Clin Oncol. 2017;doi:10.1200/JCO.2016.70.1474.

Hui D, et al. Ann Oncol. 2015:26:1440-6. doi: 10.1093/annonc/mdv028.

Hui D, et al. Cancer. 2014;doi:10.1002/cncr.28614.

Measuring what matters. American Academy of Hospice and Palliative Medicine. Available at aahpm.org/uploads/education/AAHPM15_MWM_Handout_Nonclinical_FINAL.pdf. Accessed on Jan. 11, 2017.

Odejide OO, et al. JAMA Intern Med. 2015;doi:10.1001/jamainternmed.2015.6599.

Odejide OO, et al. J Clin Oncol. 2016;doi:10.1200/JCO.2016.67.8177.

Wright AA, et al. BMJ. 2014;doi:10.1136/bmj.g1219.

For more information:

Anna C. Beck, MD, can be reached at anna.beck@hci.utah.edu.

Oreofe O. Odejide, MD, MPH, can be reached at oreofe_odejide@dfci.harvard.edu.

Mikkael A. Sekeres, MD, MS, can be reached at sekerem@ccf.org.

Samuel M. Silver, MD, PhD, can be reached at msilver@med.umich.edu.

Areej R. El-Jawahri, MD, can be reached at ael-jawahri@partners.org.

Declan Walsh, MD, MSC, can be reached at declan.walsh@carolinashealthcare.org.

Disclosure: Beck, El-Jawahri, Odejide, Sekeres, Silver and Walsh report no relevant financial disclosures.

 

Hospice vs. hospital care at end of life

The fact that many hospice programs do not accept patients undergoing palliative chemotherapy, radiation or blood transfusions makes it difficult for patients with hematologic malignancies to spend their final days in the comfort of their homes.

“Blood transfusions and platelet transfusions can’t be performed in the home,” Mikkael A. Sekeres, MD, MS, director of the leukemia program at Cleveland Clinic’s Taussig Cancer Institute, said. “There are some palliative care or hospice organizations that are sensitive to those facts and allow for patients who come to clinics to receive a blood or platelet transfusion. What we don’t want to place our patients into is essentially a Faustian bargain, where they have to decide between palliative care or their fear of bleeding to death.”

As a palliative care specialist, Christopher Jones, MD, HMDC, FAAHPM, assistant professor of clinical medicine at Perelman School of Medicine at University of Pennsylvania, said it is difficult for many families, even with home hospice support, to provide the care patients may require in their final days.

“Taking home a loved one who is bleeding or at high risk for exsanguination is risky, even with a high-quality hospice program offering support,” Jones said. “For many of these patients, dying in a [medical] facility offers the highest likelihood of comfort, dignity and peace for the patient and family. Skilled nursing facilities vary tremendously in their skills caring for dying patients and that care is, sometimes, suboptimal.”

Transition to a hospice facility to receive care in a more homelike environment may provide the best emotional care for patients with a short life expectancy, for whom blood product transfusions are no longer providing symptomatic benefit.

“Medical and emotional support by hospice clinicians, social workers and chaplains, along with the formal bereavement care hospice provides, often help families accept that their loved one’s time is short and decrease posttraumatic stress disorder in some surviving family members,” Jones said. “When energy is focused on making good memories instead of propping up lab values, incredible benefits can be seen for patients and their families.” – by Chuck Gormley

For more information:

Christopher Jones, MD, HMDC, FAAHPM, can be reached at christopher.jones2@uphs.upenn.edu.

Disclosure: Jones and Sekeres report no relevant financial disclosures