Palliative Care from the Beginning

james Mark Lazenby
1
, Muhammad Wasif Saif
2
1Yale University School of Nursing and 2Yale Cancer Center; Yale University School of Medicine.
New Haven, CT, USA
Summary
Palliative care ought to be offered at the initiation of treatment for people who are diagnosed with pancreatic cancer, given the poor
relative survival rate and the intractable symptom profile of those who have this life-limiting disease. In this article, we argue that
palliative treatment of people with pancreatic cancer is not found in extending survival, but rather, in promoting quality of life. This
argument is made by reviewing the literature on the state of palliative care in pancreatic cancer and by summarizing key studies
presented at the “2010 ASCO Gastrointestinal Cancers Symposium” held in Orlando, FL, USA on January 22-24, 2010. The studies
discussed here include: i) a study of a random sample of 564 patients with pancreatic cancer that found that the symptom cluster of
fatigue and pain predicted survival (Abstract #265); ii) a retrospective study of 108 patients that identified anticoagulation therapy in
those who developed portal vein thrombosis prolonged survival (Abstract #143); iii) a double-blind randomized control trial of 50
patients with gastrointestinal cancers who were cachexic in which a thalidomide-olanzapine-megasterol acetate combination
attenuated the effects of cancer-anorexia-cachexia syndrome (Abstract #209); iv) a retrospective study on the role of adjuvant
chemoradiation and chemotherapy in the treatment of advanced pancreatic cancer (Abstract #230); and v) the benefit of
chemotherapy in patients with metastatic pancreatic cancer 80-year-old or more (Abstract #232). Based on the results presented at
the meeting, we believe that the discussion of palliative care in the treatment of advanced pancreatic cancer must not conflate the
notion of increased survival with increased quality of life, the latter of which is part and parcel of the goal of palliative care. We
believe that future study on the effect on quality of life of early palliative-care interventions among people with pancreatic cancer is
necessary.
Introduction
While slightly fewer than 1.4% of people alive in the
United States (US) today will face a diagnosis of
pancreatic cancer, its low prevalence belies a poor
relative survival rate: the overall 5-year relative
survival rate for 1999-2005 US Surveillance,
Epidemiology and End Results (SEER) data was 5.5%
[1], though this varies according to stage and location
of the neoplasm within the pancreas [1, 2]. If the
neoplasm is suitable for resection, surgery offers a five-
year survival rate of about 25% [3]. When viewed in
chronological time, the median survival of people with
metastatic pancreatic cancer is three to six months,
while those with locally advanced disease have a
median survival of six to nine months [4, 5].
These unfavorable figures make exigent the World
Health Organization’s (WHO) palliative-care
guidelines that encourage the initiation of palliative
care early in the course of treatment [6]. Palliative care,
following WHO’s definition, is the active total care of
patients’ body, mind, and spirit. By improving quality
of life, palliative care affirms life through alleviating
suffering and relieving pain, without remedying
underlying causes [6]. Given the short survival of those
with advanced pancreatic cancer, ensuring the highest
quality of life possible is one of the foci of palliative-
care interventions with pancreatic cancer patients.
The distressing symptoms people with pancreatic
cancer experience heighten the importance of early
palliative-care intervention. At diagnosis patients often
present with fatigue, loss of appetite, impaired sense of
well-being, and pain [7]. Crippa et al. found that those
with a localized cancer present most commonly with
jaundice, while those with locally advanced or
metastatic disease more likely present with abdominal
pain and weight loss [8]. By initiating palliative care at
Keywords Palliative Care; Pancreatic Neoplasms
Abbreviations CACS: cancer anorexia-cachexia syndrome;
HRQoL: health-related quality of life
Correspondence James Mark Lazenby
Yale University School of Nursing, 100 Church Street South, P.O.
Box 9740, New Haven, CT 06536-0740, USA
Phone: +1-203.737.2324; Fax: +1-203.785.6455
E-mail: mark.lazenby@yale.edu
Document URL http://www.joplink.net/prev/201003/16.html

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the beginning of treatment patients are familiar with
the function of palliative-care providers, which is
important as the disease progresses, for Labori et al.
found that in the last eight weeks of life, these
symptoms intensified [7], and may be accompanied by
cancer anorexia-cachexia syndrome (CACS) [9], a
syndrome that has been identified with a prognosis of
less than 90 days [10].
In addition to traditional palliative measures of
managing pain and symptoms, surgery and endoscopy
may in some instances play a role in palliation. While
Crippa et al. found that surgery can favorably affect
quality of life [8], Neiveen van Dijkum et al. found that
quality of life decreased after surgery, though it
returned to baseline after three months [11]. If life
expectancy is short, surgery may not, then, offer
palliative benefits. Unequivocal, however, are proven
palliative outcomes of endoscopy for placing metal
stents for biliary or duodenal obstruction [7, 8, 12, 13,
14], as well as transhepatic portography for portal vein
thrombosis [15, 16].
On the other hand, the literature does not suggest a
clear palliative role for chemoradiation and
chemotherapy alone. Crippa et al., who followed
health-related quality of life (HRQoL) scores in
patients who underwent chemoradiation and
chemotherapy alone for treatment of pancreatic cancer,
found that chemoradiation did not change HRQoL
scores, but the HRQoL scores of those who received
chemotherapy alone significantly decreased, a decrease
perhaps explained by chemotherapy preferentially
performed in patients with metastatic disease [8].
Recent literature on the role of chemotherapy in the
treatment of advanced pancreatic cancer focuses on
whether it results in significant survival benefit [17].
Little, however, has addressed the role of
chemotherapy alone in the palliation of symptoms and
improvement of HRQoL in advanced pancreatic
cancer. Indeed, one review article made the logical
category mistake of conflating prolonged survival
through treatment with chemotherapeutic agents as
having in and of itself a palliative effect [18].
Prolonged survival is not necessary and sufficient to
claim palliative benefits such as improved HRQoL.
That there is a need to provide palliative care to
patients with pancreatic cancer, thereby positively
affecting their HRQoL, is uncontestable. To the end of
reporting on the state of palliative care in pancreatic
cancer, we review the data presented at the 2010
ASCO Gastrointestinal Cancers Symposium held on
January 22 through 24 in Orlando, Florida, USA.
Highlights on Issues in Palliative Care in the
Treatment of Pancreatic Cancer
Often a difficulty in determining whether to cease
treatment for prolonged survival and to put all efforts
into palliative care - or, if the patient is within six
months of dying, hospice care - is complicated by not
having clear and reliable prognostic indicators.
However, Gupta et al. identified fatigue and pain at
initial presentation as independent predictors of
survival. In their study, Gupta et al. randomly sampled
564 pancreatic cancer patients treated between January
2001 and December 2009. Newly diagnosed
participants were 324; 240 participants had no prior
treatment history. Males accounted for 333
participants, and females 231. Mean age at presentation
was 56.6 years. At presentation, 345 had metastatic
disease. Median overall survival of participants was 7.5
months, with a range from 6.7 to 8.3 months.
Researchers assessed participants’ symptoms at
presentation with the European Organisation for
Research and Treatment of Cancer Quality of Life
Questionnaire-C 30 (EORTC QLQ-C30); assessed
were fatigue, pain, nausea/vomiting, dyspnea,
insomnia, appetite loss, constipation, and diarrhea.
Multivariate analysis found that, independent of age at
presentation, gender, stage at diagnosis, and prior
treatment history, fatigue (P=0.02) and pain (P=0.01)
significantly predicted survival. Gupta et al. concluded
that identifying the symptom cluster of fatigue and pain
may aid decision-making vis-à-vis symptom
management [19].
In a retrospective study of medical records, Price et al.
determined the frequency and the natural history of
portal vein thrombosis and venous thromboembolism
in 108 patients with pancreatic cancer, and the effect of
portal vein thrombosis on survival [20]. They also
analyzed whether ten potential risk factors (age,
gender, stage, primary tumor size, progression, venous
thromboembolism development, prior surgery, prior
radiation, and use of erythropoiesis-stimulating agents
or transfusion support) for portal vein thrombosis had
any prognostic significance. Portal vein thrombosis
occurred in 30% (n=32) of all patients, including in
21% of patients who had had resection, 33% of patients
with locally advanced pancreatic cancer, and 36% of
patients with metastatic disease. From diagnosis,
average time to development of portal vein thrombosis
was 9.1 months, ranging from an average of 6.3
months for patients with metastatic disease, 12.1
months for patients who had had resection, to 15.8
months for patients with locally advanced pancreatic
cancer. The average time to death from the
development of portal vein thrombosis was 4.1 months:
in patients with metastatic disease it was 2.2 months,
4.9 months in patients who had had resection, and 6.1
months in patient with locally advanced disease. On
bivariate analysis, the ten potential risk factors did not
predict portal vein thrombosis. However, Price et al.
found that of the 32 patients who developed portal vein
thrombosis, 8 had received therapeutic anticoagulation;
the survival of these 8 was 4.2 months longer than
those who did not receive anticoagulation (6.6 months
versus 2.4 months, respectively) [20]. So though no
potential risk factors were identified, Price et al. did
find that development of portal vein thrombosis was
associated with less than six months to live, an
important prognostic tool when considering initiation
of hospice care, and that therapeutic anticoagulation
may benefit pancreatic cancer patients [20].

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Sanchetee, located in “a resource poor area” where at
presentation 90% of the patients with pancreatic cancer
have advanced disease for whom palliative care is the
only treatment option, assessed in a single-center,
double-blind study whether thalidomide or thalidomide
with olanziapine and megastrol acetate were safe and
effective treatments of the late symptom of CACS [21].
Fifty patients with GI cancers who had lost 10% of the
body weight were included in the study. Sixteen
patients were randomized to thalidomide 100 mg daily;
and 17 patients to thalidomide 100 mg, olanzipine 5
mg, and megestrol acetate 80 mg daily. They were
evaluated at four weeks. Twelve patients were
randomized to a thalidomide only group, and eight to a
control group; they were evaluated at eight weeks. At
four weeks, patients in the thalidomide-olanzipine-
megestrol group had gained 0.37 kg in weight and 1.0
cmin arm muscle mass, compared with a loss of 2.21
kg of weight (absolute difference -2.59 kg; P=0.005)
and 4.6 cmin arm muscle mass (absolute difference -
5.6 cm3; P=0.002) in the thalidomide only group. At
eight weeks, patients in the thalidomide-olanzipine-
megestrol group had lost 0.06 kg in weight and 0.5 cm3
in arm muscle mass, while patients in the thalidomide
only group lost 3.62 kg in weight (absolute difference -
3.57; P=0.034) and 8.4 cm(absolute difference -7.9
cm3; P=0.014). Improvement in physical functioning
positively correlated with weight gain (P=0.001).
Sanchetee concluded that the thalidomide-olanzapine-
megestrol acetate combination attenuated weight loss
and loss of lean body mass in patients with GI cancers
who experienced CACS [21].
Two studies presented at the 2010 ASCO
Gastrointestinal Cancers Symposium dealt with the
vexing question of the roles of chemoradiation and
chemotherapy in the treatment of advanced pancreatic
cancer: Subbiah et al. [22] and Aldoss et al. [23].
Subbiah et al. retrospectively analyzed medical records
from the Veterans Affairs Central Cancer Registry
database of 742 patients who had resection for early-
stage pancreatic cancer between the years 1995 and
2007[22]. Fifty-seven percent of patients had no
adjuvant therapy, 11% had adjuvant chemotherapy,
28% had chemoradiation, and 4% had adjuvant
radiation. Median overall survival in the adjuvant
chemotherapy group was 1.36 years, and in the
adjuvant chemoradiation group was 1.54 years. In the
adjuvant chemotherapy group, 63%, 19%, and 13%
survived one, three, and five years, compared with
72%, 28%, and 19% in the adjuvant chemoradiation
group, respectively. Multivariate analysis associated
decreased survival with advanced age, number of
positive lymph nodes, and poorly differentiated tumors
(P=0.0001). Race, gender, smoking history, and
number of examined lymph nodes were not associated
with survival [22].
The research question Aldoss et al. asked was whether
chemotherapy played a palliative role for metastatic
pancreatic cancer in the Veterans Affairs population
aged 80 and above [23]. To answer the question, they
retrospectively reviewed medical records from the
Veterans Affairs Central Cancer Registry of all cases
of metastatic pancreatic cancer from 1995 to 2005 in
the age 80 and over population. Of the 440 eligible
patients, 12% received chemotherapy alone, 2%
received radiotherapy alone, 1% received
chemoradiation therapy, and 2% underwent surgery.
Aldoss et al. found that patients who received
chemotherapy survived 4.9 months, whereas those who
received no therapy (83%) survived 1.7 months; this
difference in survival was significant (P<0.0001).
Thirteen percent of patients who received
chemotherapy survived one year, while 3% of patients
who received no therapy survived one year. Current
smoking was significantly associated with a decrease in
median overall survival compared to past or never
smoking status (P=0.001). However, tumor grade, race,
or gender was not significantly associated with overall
survival [23].
Discussion
Aldoss et al. entitled their paper “Benefit of
chemotherapy in very elderly patients … with
metastatic” pancreatic cancer [23]. In the body of the
abstract of their paper, they state that their interest lay
in the palliative role of chemotherapy. The conclusions
they draw, however, focus solely on survival benefit.
While they do acknowledge in their concluding
remarks that “increased survival with chemotherapy
could have been at the cost of excessive toxicity … and
poor quality of life,” they still imply that increased
survival is a benefit [23]. This is the philosophical
mistake of question-begging, that is, the mistake in
which the conclusion is contained in the premise: for
by “benefit” they seem to mean increased survival, and
by “benefit” they seem to imply “palliative”. But
HRQoL must be studied to determine whether the 3.2
months of survival gained by the administration of
chemotherapy was, as they noted, associated with
unbearable toxicity and untenably poor HRQoL. Until
the effect of therapies on the cancer are evaluated in
the context of the therapies’ effects on the whole
patient - body, mind, and spirit - then one cannot imply
that increased overall survival is a palliative benefit.
While increased survival through therapies is not to be
begrudged in pancreatic cancer, a cancer type that is
associated with poor survival rates, future research into
whether care that does not aim at life-prolonging
treatment but rather improvement of HRQoL is itself
associated with increased survival rates must be
undertaken. Subbiah et al. [22] make the same
conceptual mistake. More tellingly, however, Subbiah
et al. have no novel finding: their finding that
decreased survival is associated with increased age,
number of positive nodes, and poorly differentiated
tumors is so commonplace a statement that it borders
on being hackneyed.
Important and interesting, however, is the finding by
Sanchetee that CACS can be ameliorated by the
combination of thalidomide, olanziapine and megastrol

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acetate [21]. CACS affects not only pancreatic cancer
patients who live in poorly resourced areas, but
pancreatic cancer patients worldwide, rich or poor.
Sanchetee’s study, though its strength lies in that it is a
double-blind randomized control trial, needs to be
replicated, and what is meant by saying that the
thalidomide-olanziapine-megastrol acetate combination
is well tolerated needs to be explicated; but
Sanchetee’s finding is important to the aims of
palliative care, for by reducing the effects of CACS,
HRQoL is indeed increased. Likewise, the finding by
Price et al. [20] that anticoagulation therapy can reduce
the incidence of portal vein thrombosis in the
pancreatic cancer population merits further study; for
the practice of palliative care among patients with
pancreatic cancer needs safe and effective
anticoagulation strategies to address portal vein
thrombosis. Finally, Gupta et al. identify the cluster of
pain and fatigue as a predictor of survival [19], a
finding that can be a useful prognostic indicator,
especially when making the decision to change the goal
of care from life-prolonging to enhancing the quality of
life.
In pancreatic cancer, with poor relative survival rates,
palliative care, with its attention to improving HRQoL,
needs to be initiated at the onset of treatment. Future
research needs to understand the effect of early
palliative care interventions not only on HRQoL but
also on survival.
Conflict of interest Authors report no conflict of
interest
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