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Explaining Marginal Benefits to Patients, When "Marginal" Means
Additional but Not Necessarily Small
Thomas J. Smith1,2 and Bruce E. Hillner1,2
Abstract
Patients and their families want us to be realistic, honest, and caring about their prognosis and their
options, even when the news is bad. Most oncologists will tell a patient if he is not curable, but not give
specific survival information unless prompted. As an example, chemotherapy for pancreas cancer improves
survival and does not worsen quality of life, but the impact on lifespan is small. Patients with advanced
pancreas cancer have options that increase their average survival by about 16/100 at 1 year, and by about
9 weeks compared with best supportive care, but almost all patients are dead by 24 months. As an example
of "marginal benefit" ("marginal" is defined here as more than that offered by the alternative care, not
necessarily small or worthless), erlotinib added to gemcitabine compared with gemcitabine alone improves
survival by six additional people at 1 year, and an average of 2 weeks, with no survival tail. In addition, the
additional drug cost alone can be more than $12,000 a month. We use this clinical practice as a way to
describe marginal benefit to patients. Telling patients that they have incurable disease and that treatment is
ineffective is hard. Partly as a result, only about a third of cancer patients are told they are going to die, and
those who are not told live no longer but have worse medical outcomes, such as dying on a ventilator and
less time with hospice. These difficult conversations can be done if the oncologist has the right medical
information, the right script, and some decision aids. Clin Cancer Res; 16(24); 5981–6. Ó2010 AACR.
The majority of medical oncology work is the treatment
of people with metastatic disease. Curable illnesses such as
lymphomas and testicular cancer represent a small percentage of the daily patient load seen in the typical medical
oncology office. There has been an increase in patients
receiving adjuvant treatment, but the majority of our work
is dealing with people who have, at some point, a lifeending illness and who face increasingly small benefits
from noncurative chemotherapy. Our patients tell us that
they want us to be honest, caring, and present, and to give
them the facts about their illness and what can be done
for them.
We were asked how we describe "marginal benefit" to
patients in our own practice. In this case, "marginal" means
additional or incremental. For a Hodgkin lymphoma
patient, the marginal benefit is likely years if not a lifetime.
For a pancreas cancer patient, the marginal benefit may be
Authors' Affiliation: 1Division of Hematology/Oncology; 2Division of Palliative Care and General Internal Medicine, Massey Cancer Center-Virginia
Commonwealth University, Richmond, Virginia
Note: T.J. Smith is Endowed Professor of Palliative Care Research,
Esteemed Professor of Medicine and B.E. Hillner is Eminent University
Scholar, Professor of Medicine.
Corresponding Author: Thomas J. Smith, Division of Hematology/Oncology and Palliative Care, 1101 E. Marshall Street, MCV Box 980230,
Richmond, VA 23298–0230. Phone: 804–828-9723; Fax 804–828-8079;
E-mail: [email protected]
doi: 10.1158/1078-0432.CCR-10-1278
Ó2010 American Association for Cancer Research.
weeks or at best a few months. We review how we can
explain honestly and efficiently the benefits and options of
treatment when the goal is not cure, using chemotherapy
for pancreas cancer with erlotinib and gemcitabine as an
example.
Do Our Patients Want Us to Be Honest with
Them?
For most patients, the answer is an unequivocal yes.
However, not all patients do, and there is no way to find
out what the patient knows or wants to know without
asking directly: "What do you know about your disease?
What do you want to know about your disease and its likely
course?" Nearly all patients and families will ask you to be
honest and direct, even if the news is bad (1). Some
patients and families will be unable to reconcile reality
and hope, and will ask for information without specific
numbers (2), so the only approach must be to ask permission. Some patients will want to negotiate the sharing of
information over time, with nearly all patients wanting
information at the time of diagnosis, but more information
to their caregivers as the terminal illness ensues (3).
Are We Honest with Our Patients? Do They
Believe Us?
Oncologists almost always tell a patient if he or she has a
curable illness. However, they give specific prognosis information only when asked, in one study about 48% of the
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Table 1. The benefits, risks, and costs of treating patients with metastatic pancreas cancer
Therapy
Overall Survival
Clinical Benefit*
Significance
Gemcitabine
versus
5-fluorouracil (29)
Gemcitabine
þ erlotinib versus
gemcitabine
alone (30)
Median 5.65 versus
4.41 months (P ¼ 0.0025).
1 year 18% versus 2%
Median 6.2 versus 5.9
months (P ¼ 0.038).
1 year 23% versus 17%
23.8% versus 4.8%
(P ¼ 0.0022)
The average person will gain
9 weeks of life.
No difference in
quality of life. Side effects
especially rash and diarrhea
more common in erlotinib arm.
The average person will gain
2 additional weeks. The
marginal CER of erlotinib was
$7,885 per week of life saved
and $410,000 to $498,379
per year of life saved.
*Improvement in pain, performance status, or weight without a deterioration in any other factor (31).
time, and do not routinely give patients an estimated
survival time (4).
Patients may believe that the goal of the treatment is to
cure the cancer, when the actual goal is palliative. Even if the
oncologist tells them, some patients will choose not to
believe the information, or interpret it as not applying to
them. In two studies separated by 15 years, one third of
palliative radiation oncology patients believed they were
being treated for cure, when they had been told they had
incurable disease (5, 6). In our most recent study, 58% of
patients with incurable breast, colorectal, lung, or hormonerefractory prostate cancer thought they could be cured. This
number only decreased to about 33% when they were given
specific printed information with their own chance of cure
(7). The situation is likely similar to that in the intensive care
unit, where patients and their surrogates are twice as optimistic as their intensive care unit doctors, even when given
real survival numbers. Confidence in the ability of doctors
to predict prognosis, alternative belief systems, and lack of
trust in doctors all play a major role in not accepting the
medical facts (8). This suspension of belief may be different
from denial, in that our cancer patients will often make
plans for death but not want to dwell on it.
What Are the Medical and Economic Facts
about Pancreas Cancer Chemotherapy?
Metastatic pancreas cancer remains an incurable disease
with the majority of patients dead at 12 months. The
landmark trial that showed an improvement in overall
survival and clinical benefit has provided a model for
relative, albeit limited, success in treating this cancer
(Table 1). To date, no therapy has been proven substantially more effective or less toxic than infusional gemcitabine (9). There has not been a change in population
survival with pancreas cancer as seen in breast and colorectal cancer. In fact, recent analyses of Medicare patients
with pancreas cancer who did not use hospice versus those
who used hospice (and no chemotherapy at the end of life)
showed that those who used hospice actually lived longer:
210 versus 189 days, P ¼ 0.0102 (10). Reasonable expla-
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nations include that n-th line chemotherapy and complications actually hastened death, or that the physical and
spiritual comfort of hospice prolongs life.
Table 1 summarizes the findings from another landmark
study in which erlotinib was added to gemcitabine in a
large randomized clinical trial of 569 patients. Compared
with gemcitabine alone, survival was improved but only by
2 weeks for the average person, with no improvement in
response, cure rate, or a prolonged "tail" of survival.
This marginal or incremental benefit may be viewed by
some as being too small (another meaning of "marginal")
to be important. There is no consensus for a lower limit or
threshold beyond which chemotherapy should not be
given; the American Society of Clinical Oncology (ASCO)
technology assessment panel could not define a lower
limit, but stated that some proven benefit must be demonstrable for a treatment to be recommended (11).
In addition, the high cost of the erlotinib increases the
marginal or incremental cost effectiveness ratio (CER),
estimated at $410,000 (12) to $500,000 (13) per life year
gained. These CER numbers are several times higher than
the accepted U.S. norm for medical interventions (14); this
is due primarily to the cost of the erlotinib ($4,153 for
1
30 days of 100 mg tablets). The drug cost would have to be
reduced by 80% to fit accepted CERs. Of course, the patient
might have to pay all or none of that amount, depending
on their insurance, but the cost to other members of the
health care plan and society would remain exceedingly
high for a small benefit.
With Whom, Where, When, and How Can We
Have These Conversations?
Every visit offers an opportunity to have these conversations. Oncologists often say they are too busy to have these
conversations, but during the time course of treatment,
each clinic visit is a potential. We suspect that oncologists
who use the time excuse, similar to those who use it about
1
Available from: http://www.drugstore.com/. Accessed July 18, 2010.
Clinical Cancer Research
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Explaining Marginal Benefits
"do not resuscitate" (DNR) discussions that take 6 (15) or
10 (16) minutes, are protecting themselves from the difficult emotional exposure of sharing sad and bad news (17).
A critical, but often overlooked, part of the discussion is
the "framing effect," in which people come to different
decisions on the basis of how information is presented or
framed (18). For example, presenting the results as "a 10%
chance of survival" versus a "90% chance of dying" could
well be associated with differences in decision making.
Most practitioners and patients prefer to first consider
the potential benefits of treatment before discussing the
potential harms. In addition, when a choice of two strategies is available, our experience shows that the default is to
estimate the largest potential benefit even if it may not be
the most likely outcome.
The simplest way to ask is the most direct (19): "Is the
treatment giving you enough benefit that you want to
continue?" Clinicians often wonder how much information should be given or can be given about the choice of
chemotherapy. Studies in multiple countries have consistently shown that patients want to know the truth, but they
may have a different perspective than their caregivers. They
are far more likely to want treatments with small potential
benefit (or even no proven benefit) than their families or
their health care providers (20).
We provide a format for the discussion as shown in the
Appendix. We developed this format for a randomized trial
of insurance types (21) in patients with advanced lung
cancer and have found it useful for discussing benefits and
risks in an open, honest way. These questions have recently
been incorporated into ASCO Decision Making Tools (22)
for patients with non–small cell lung cancer and are available to the public on the ASCO website for first- through
fourth-line chemotherapy (23). These decision tools are
designed for the patient to use with the oncology treatment
team.
In this case, we present the known facts fairly and
objectively so that patients have several options. In our
experience, most patients will opt for chemotherapy, and
some good responses will occur. However, at the same
time, we have offered a realistic discussion about prognosis
and survival such that patients can "Hope for the best, but
plan for the worst."
When Should Chemotherapy Be Stopped, or Not
Offered?
Using non–small cell lung cancer as an example, the
National Comprehensive Cancer Center Network guidelines (24) suggests that chemotherapy not be given, and
supportive care considered, when the patient no longer has
"good" performance status [usually described as Eastern
Cooperative Oncology Group (ECOG) 0, 1, and possibly 2]
or has progressed on two treatments. As oncologists, we are
concerned that nononcologists may recommend hospice
too early; there is ample evidence to suggest that secondline chemotherapy improves survival and gives clinical
benefit to lung cancer patients with good performance
www.aacrjournals.org
status (25). However, that cannot be said for n-th line
chemotherapy, or for patients with poor performance
status; in those cases, it is time to stop and have the difficult
conversation.
Should We Hold out Hope of a "Survival Tail"?
The possibility of a survival tail is very real for patients
with resectable cancer. However, for patients with known
metastatic disease, our suggested guidance is "It is unlikely
that one exists." In the case of pancreas cancer, there is a
minimal survival tail and all the patients on both the
landmark trials above died by 24 months. In truthfulness,
if we point out that some patients will live a lot longer than
6 months, we should also point out that an equal number
will live less than 6 months. Robinson and colleagues
found that if the oncologist made just positive statements,
such as "Well, it could be a lot longer than those 6
months. . .," then patients had an unrealistic view of their
prognosis. If the oncologist made just one negative, but
truthful, statement, such as ". . .but it could be less than 6
months, so we should plan for that, too," patients had a
much more realistic viewpoint of their prognosis (26). If
patients do not know the prognosis, they cannot plan.
What Time Frame Should Be Used?
For pancreas cancer, the time frames of discussion
should be from "a few months to one year for most
people." The shorter time interval provides a much more
realistic anchor of what can be expected from the therapy
under consideration.
Remember, Survival Is Just One Indicator of
Benefit
Should the impact of therapy on cancer symptoms be
different than when discussing survival? Benefits in terms
of pain and other symptom management may be underappreciated by nononcologists. The critical point is making
the distinction about marginal benefit(s) in treating the
cancer, while making the quality of life as rich as possible
and minimizing treatment-induced symptoms. Our
impression is that because so much of the typical oncologist-patient interaction is about controlling the cancer,
that "inactive" therapy is too often associated with abandonment and not being willing or available to deal with
changing symptoms.
Why Should We Have These Conversations?
We have recently outlined all the good reasons why
doctors should have these discussions with their patients
who have incurable diseases (27). Briefly, giving honest
information is the right ethical, medical, and legal course
for patients who want the information. It may keep some
patients from receiving treatment that has minimal if any
chance of benefit yet substantial harms, and may convince
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some patients to try chemotherapy when it is known to be
helpful. As noted above, it may help patients enroll in
hospice rather than do n-th line chemotherapy, a strategy
that is associated with better survival in several common
cancers.
Such conversations will likely increase referrals to hospice, and save money for society. At present, only 37% of
U.S. cancer patients could recall their doctor ever telling
them they could die of their disease, and only 11% of
doctors told their patients about impending death, even
when it was imminent. This situation may account for the
20% of U.S. patients receiving chemotherapy in the 14 days
before they die. Of note, when the University of Michigan
instituted the Quality Oncology Practice Initiative that
emphasizes feedback to practices and individuals, the number of solid tumor patients receiving chemotherapy within
14 days of their death fell from more than 50 to 20% (28).
Conclusions
Treatment interventions (usually chemotherapy) in the
setting of metastatic cancer with a poor prognosis must be
as realistic as possible in the presentation of benefits and
harms. Practitioners need to be aware of the impact of how
they frame decisions (survival or responses versus death or
progression) and discuss the potential harms of therapy as
well. For some cancers, there is evidence that people who
continue treatment and avoid hospice do not live as long.
For many patients, continuing chemotherapy when activities of daily living are compromised is a mistake that
directs limited time and energy to an unwinnable battle
against the cancer, when time and energy should be directed at life transition planning. For patients wishing to
consider additional treatment when the benefits are small,
decision aids with graphic representation of anticipated
benefits and trade-offs should be encouraged.
Appendix: Decision Aid for a Patient with
Metastatic Pancreas Cancer
What is my chance of being alive at 1 year if I take
chemotherapy, or do best supportive care such as
hospice?
The numbers shown are what happens to the average
person with this disease in this situation. Half the patients
will do better than this, and half will do worse. The numbers
given for the chance of cure are very accurate. The numbers
are given to help you with your own decision making.
If you are having symptoms because of the cancer that
limit your daily activities, the chances of being alive at 1
year are less than that described above.
Without chemotherapy, about 2 of 100 people would be
alive at one year. With chemotherapy, about 18 of 100
people would be alive at one year. The following table gives
some estimates from a recent trial of chemotherapy with
gemcitabine versus best supportive care, or hospice-type
care. The chance of being alive at 1 year was higher with
chemotherapy.
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Clin Cancer Res; 16(24) December 15, 2010
Alive at 1 year
Chemotherapy
Dead at 1 year
18
82
Best supportive
2
care, or hospice
98
0%
20% 40% 60% 80% 100%
Chance of being alive at 1 year
© 2010 American Association for Cancer Research
How long will I live if I do or don’t take
chemotherapy?
The average person with pancreas cancer treated with
chemotherapy lived about 5.7 months, or 24 weeks.
The average person who did not receive chemotherapy
lived 4.4 months, or 18 weeks. All patients died within
19 months.
How long people lived, in months.
Best supportive
care, or hospice
4.41
Chemotherapy
5.65
0
3
6
Months
9
12
© 2010 American Association for Cancer Research
What if I take erlotinib (tarceva) in addition to
gemcitabine chemotherapy?
A large trial done in Canada showed that about 6 more
people of 100 would be alive at 1 year if they took erlotinib
pills along with gemcitabine chemotherapy.
Alive at 1 year
Gemcitabine
17
Gemcitabine +
erlotinib
23
0%
Dead at 1 year
83
77
20% 40% 60% 80% 100%
Chance of being alive at 1 year
© 2010 American Association for Cancer Research
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Explaining Marginal Benefits
People who got erlotinib lived 2 weeks longer, on average. All patients had died by 22 months after start of
treatment.
How long people lived, in months.
Gemcitabine
alone
5.9
Gemcitabine +
erlotinib
6.2
0
3
6
Months
9
12
© 2010 American Association for Cancer Research
What is the chance of my being cured by
chemotherapy?
In this setting, there is no chance of cure, and all patients
are dead within 24 months. The goal may change to
controlling the disease and any symptoms for as long as
possible. You may want to talk with your doctor about your
own chances and goals of therapy.
What are the most common side effects?
The most common side effects will vary with the type of
treatment given.
Some of the most common ones include the following:
Fatigue.
Nausea and/or vomiting, which is usually controllable.
Alopecia (hair loss), which is usually minor.
Neutropenia (low white blood cell count) and infection
requiring antibiotics.
Anemia (low red blood cell counts) that may require blood
transfusions.
If erlotinib is added to gemcitabine, there is more chance
for diarrhea, 56% compared with 41%. For the erlotinib
patients 72% had some rash, but it was severe in only 6%.
Quality of life was the same in both groups, except for the
diarrhea.
Are there other issues that I should address at this
time?
Because this is such a serious illness, and nearly all
people die within 2 years, many people use this time to
address a life review. That would include what they have
learned during life that they want to share with their
families, and planning for events in the future like birthdays or weddings.
Some people address spiritual issues.
Some people address financial issues like a will.
Some people address advance directives (living wills).
For instance, if you could not speak for yourself, who
would you want to make decisions about your care? If
your heart stopped beating, or you stopped breathing,
because of the cancer worsening, would you want to have
resuscitation [cardiopulmonary resuscitation (CPR)], or be
allowed to die naturally without resuscitation?
Some people use this time to discuss with their loved
ones how they would like to spend the rest of their life. For
instance, how and where do you want to spend your last
days? Do you want to have hospice involved?
These are all difficult issues, but important to discuss
with your family and your health care professionals.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Grant Support
GO8 LM0095259 from the National Library of Medicine.
Received 07/26/2010; revised 09/08/2010; accepted 09/29/2010;
published online 12/15/2010.
References
1.
2.
3.
4.
5.
6.
Kirk P, Kirk I, Kristjanson LJ. What do patients receiving palliative care
for cancer and their families want to be told? A Canadian and
Australian qualitative study. BMJ 2004;328:1343.
Innes S, Payne S. Advanced cancer patients’ prognostic information
preferences: a review. Palliat Med 2009;23:29–39.
Parker SM, Clayton JM, Hancock K, et al. A systematic review of
prognostic/end-of-life communication with adults in the advanced
stages of a life-limiting illness: patient/caregiver preferences for the
content, style, and timing of information. J Pain Symptom Manage
2007;34:81–93.
Daugherty CK, Hlubocky FJ. What are terminally ill cancer patients
told about their expected deaths? A study of cancer physicians’ selfreports of prognosis disclosure. J Clin Oncol 2008;26:5988–93Epub
2008 Nov 24.
Mackillop WJ, Stewart WE, Ginsburg AD, Stewart SS. Cancer
patients’ perceptions of their disease and its treatment. Br J Cancer
1988;58:355–8.
Chow E, Andersson L, Wong R, et al. Patients with advanced cancer:
A survey of the understanding of their illness and expectations from
palliative radiotherapy for symptomatic metastases. Clin Oncol (R Coll
Radiol) 2001;13:204–8.
www.aacrjournals.org
7.
8.
9.
10.
11.
12.
13.
Smith TJ, Dow LA, Virago E, Lyckholm LJ, Khatcheressian J. A pilot
trial of decision aids for patients with metastatic advanced cancer. J
Clin Oncol 2010;28:15s(suppl; abstr 9108).
Lee Char SJ, Evans LR, Malvar GL, White DB. A randomized trial of
two methods to disclose prognosis to surrogate decision makers in
ICUsintensive care units. Am J Respir Crit Care Med 2010;182:
905–9.
Ryan DP, Goldberg RM. Chemotherapy for advanced exocrine panc 2010UpToDate, Inc. All rights reserved.
creatic cancer. *
Connor SR, Pyenson B, Fitch K, Spence C, Iwasaki K. Comparing
hospice and nonhospice patient survival among patients who die
within a three-year window. J Pain Symptom Manage 2007;33:238–
46. PubMed doi:10.1016/j.jpainsymman.2006.10.010
American Society of Clinical Oncology Outcomes Working Group.
Outcomes of cancer treatment for technology assessment and cancer
treatment guidelines. J Clin Oncol 1996;14:671–9.
Grubbs SS, Grusenmeyer PA, Petrelli NJ, Gralla RJ. Is it cost effective
to add erlotinib to gemcitabine in advanced pancreatic cancer? J Clin
Oncol 2006;24:313s.
Miksad RA, Schnipper L, Goldstein M. Does a statistically significant
survival benefit of erlotinib plus gemcitabine for advanced pancreatic
Clin Cancer Res; 16(24) December 15, 2010
Downloaded from clincancerres.aacrjournals.org on June 18, 2017. © 2010 American Association for Cancer Research.
5985
CCR FOCUS
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
5986
cancer translate into clinical significance and value? J Clin Oncol
2007;25:4506–7.
Hillner BE, Smith TJ. Efficacy does not necessarily translate to cost
effectiveness: a case study in the challenges associated with 21stcentury cancer drug pricing. J Clin Oncol 2009;27:2111–3
Smith TJ, Desch CE, Hackney MH, Shaw JE. How long does it take to
get a "do not resuscitate" order? J Palliat Care 1997;13:5–8.
Tulsky JA, Chesney MA, Lo B. How do medical residents discuss
resuscitation with patients? J Gen Intern Med 1995;10:436–42
Fallowfield L, Jenkins V. Communicating sad, bad, and difficult news
in medicine. Lancet 2004;363:312–9.
Moxey A, O’Connell D, McGettigan P, Henry D. Describing treatment
effects to patients: how they are expressed makes a difference. J Gen
Intern Med 2003;18:948–59.
Harrington SE, Smith TJ. The role of chemotherapy at the end of life:
"When is enough, enough? JAMA 2008;299:2667–78.
Matsuyama R, Reddy SN, Smith TJ. Why do patients choose chemotherapy near the end of life? A review of the perspective of those
facing death from cancer. J Clin Oncol 2006;24:3490–6.
Swisher KN, Ulmer DL, Carpenter W, et al. Patient indemnification as a
way to involve patients in economic decision-making about their care:
barriers in the current system. Proc ASCO 1996: 939a.
Azzoli CG, Baker S, Jr, Temin S, et al. American Society of Clinical
Oncology Clinical Practice Guideline Update on Chemotherapy for
Stage IV Non-Small-Cell Lung Cancer. J Clin Oncol 2009;27:
6251–66.
American Society of Clinical Oncology. Alexandria (VA): American
Society of Clinical Oncology. Available from: http://www.asco.org/
ASCO/Downloads/Cancer%20Policy%20and%20Clinical%20Affairs/
Clin Cancer Res; 16(24) December 15, 2010
24.
25.
26.
27.
28.
29.
30.
31.
Clinical%20Affairs%20(derivative%20products)/NSCLC/NSCLC%
20ALL%20Decision%20Aids%2011.12.09.pdf
National Comprehensive Cancer Network (NCCN). Fort Washington
(PA): National Comprehensive Cancer Network (NCCN) guidelines.
available online at Available from:http://www.nccn.org/professionals/
physician_gls/f_guidelines.asp. (Accessed July 18, 2010).
Lilenbaum RC. Back Second-line therapy for patients with previously
treated advanced non-small cell lung cancer. Available from: www.
uptodate.com. Up to Date, 2010.
Robinson TM, Alexander SC, Hays M, et al. Patient-oncologist communication in advanced cancer: predictors of patient perception of
prognosis. Support Care Cancer 2008;16:1049–57. PubMed
doi:10.1007/s00520-007-0372-2
Swetz KM, Smith TJ. Palliative chemotherapy: when is it worth it and
when is it not? The Cancer Journal 2010;16:467–72.
Blayney DW, McNiff K, Hanauer D, Miela G, Markstrom D, Neuss M.
Implementation of the Quality Oncology Practice Initiative at a university comprehensive cancer center. J Clin Oncol 2009;27:3802–7.
Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival
and clinical benefit with gemcitabine as first-line therapy for patients
with advanced pancreas cancer: a randomized trial. J Clin Oncol
1997;15:2403–13.
Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine
compared with gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of
Canada Clinical trials group. J Clin Oncol 2007;25:1960–6.
Rothenberg ML, Moore MJ, Cripps MC, et al. A phase II trial of
gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann
Oncol 1996;7:347–53.
Clinical Cancer Research
Downloaded from clincancerres.aacrjournals.org on June 18, 2017. © 2010 American Association for Cancer Research.
Explaining Marginal Benefits to Patients, When ''Marginal'' Means
Additional but Not Necessarily Small
Thomas J. Smith and Bruce E. Hillner
Clin Cancer Res 2010;16:5981-5986.
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