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50     Hope in Terminal Cancer—Han Chong Toh
Commentary


Providing Hope in Terminal Cancer: When is it Appropriate and When is it Not?
Han Chong Toh,1MBBChir (Cambridge), FRCP (Edinburgh), FAMS (Medical Oncology)




                      Abstract
                         Hope is essential in the face of terminal cancer. Generally in Western societies, patients and
                      their families prefer their doctor to engage them in transparent, realistic, authoritative, empathic
                      and open communication about the diagnosis and prognosis of cancer but this topic is not well
                      studied in the Asian context. With the exponential increase in information about cancer and the
                      many permutations in cancer treatment, rational and otherwise, the doctor-patient relationship
                      is even more critical in planning the best treatment strategy and also in rendering both particular
                      and general hope in the patient’s war against cancer. Overall, the majority of drugs tested against
                      cancer have failed to reach the market, and those that have, only provide modest benefits, several
                      major therapeutic breakthroughs notwithstanding. Commoditised medicalisation of the dying
                      process ingrained into the contemporary consciousness can potentially create unrealistic or false
                      hope, therapeutic nihilism and a drain on the resources of both the patient and society. These
                      factors can also detract from the dignity of dying as an acceptable natural process. Hope cannot
                      be confined only to focusing merely on the existential dimension of improving survival through
                      technological intervention. Psychosocial and, where appropriate, spiritual interventions and
                      support also play major roles in relieving suffering and providing hope to the patient. Hope
                      cannot be a victim of misinformation from self-interested external parties, nor be an obsession
                      with just buying promises of extending survival time without sufficient regard for quality of
                      life and achieving a good death.
                                                                                   Ann Acad Med Singapore 2011;40:50-5
                      Key words: Communicating prognosis, Dying well, Therapeutic nihilism



Introduction                                                                    exponential progress in cancer advancement that has
“Hope is the elevating feeling we experience when we see                        significantly impacted on the lives of cancer patients. A
— in the mind’s eye — a path to a better future.”                               once-fatal disease, childhood leukaemia is now curable in
                                                                                over 80% of stricken children. The introduction of platinum
                                  Jerome Groopman, MD
                                                                                chemotherapy has improved cure rates for even advanced
                                    Professor of Medicine                       testicular cancer and the revolution in molecular targeting
                  Harvard Medical School, United States                         therapy has ushered in novel drugs like imatinib (Glivec)
                              From The Anatomy of Hope                          that has induced meaningful remissions in chronic myeloid
                                                                                leukaemia and an uncommon cancer, gastrointestinal
                                                                                stromal tumour (GIST). Inspite of the real advances made
  Hope is a universally valued, central and enduring primal                     in cancer biology, diagnosis and treatment, the latter which
human emotion that has sustained and uplifted humankind                         can cost up to one billion United States (US) dollars to
from the dawn of time. Professor Jerome Groopman proceeds                       bring a single drug to the market,2 many cancer drugs only
to emphasised in his bestselling book that “true hope has                       provide modest incremental benefits for cancer patients3 and
no room for delusion”.1                                                         many more cancer drugs fail to give any real improvements.
  Hope, in the fight against cancer, is oxygen to live on                          Cancer treatment expenditure has escalated dramatically.
meaningfully. Oncologists must respect and actively engage                      In 2005, the total cost of cancer care in the US was $209.9
in the patients’ desire for hope in the face of a disease that                  billion2 and health insurance family coverage premiums
evokes great helplessness, and patients are commonly                            increased by 73% between 2000 and 2005.4 Medical bills
gripped more by a fear of dying than the fear of death itself.                  account for over half of bankruptcy filings in the US.
  Undoubtedly, the last several decades have seen                               Cost-sensitive and cost-benefit decision-making in cancer

1
Department of Medical Oncology, National Cancer Centre, Singapore
Address for Correspondence: Dr Toh Han Chong, Department of Medical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610.
Email: hanchongtoh@gmail.com




                                                                                                                       Annals Academy of Medicine
Hope in Terminal Cancer—Han Chong Toh   51




management is becoming unavoidable.                                  3.     Facilitating coping with the dying
                                                                     4.     Information provision
The Media and Medicine                                               5.     Discussing therapeutic options including second
   The Information Age communicates unparalleled                            opinion
knowledge and empowers patients for making more                      6.     Sharing personal information
informed decisions related to their disease. This can enable
them to arrive at a more realistic sense of hope. Conversely,
the Information Age can also disseminate hype and false            Breaking Bad News
hope. Famously, the 3rd May 1998 issue of The New York                The Hagerty study covered a largely Western population
Times ran a front page story of a mouse study led by the           (Australian) characterised by a safety net healthcare, but
now late Professor Judah Folkman.5 Folkman identified               overall, the above conclusions would have universality
proteins that blocked blood vessels feeding cancers and            to cancer patients worldwide. Clearly, self-determinism
showed dramatic tumour shrinkage in the tumour-bearing             and patient autonomy, then medical paternalism, take on
mice that received the said drugs. In this article by journalist   a broader mantle in the doctor-patient relationship in the
Gina Kolata, Nobel Prize winner James Watson was quoted            modern time. A 1961 study by Oken demonstrated that
as saying that “Judah is going to cure cancer in two years.”5      90% of 219 doctors studied did not tell their patients about
Both drugs failed spectacularly in early phase human clinical      a diagnosis of cancer.7 The study was repeated in 1979,
trials. By the year 2000, cancer had not been cured. Here was      where 97% of physicians surveyed indicated a preference
an example of the power of media spreading unmet hope.             for communicating a diagnosis of cancer to their patients.8
   In 1971, then US President Richard Nixon declared “War          In Singapore, the families of elderly cancer patients with
on Cancer” in his State of the Union address, vowing that          incurable cancer commonly appeal that the patient not be
cancer would be eradicated in the foreseeable future. In           told of his or her diagnosis and/or prognosis. The most often
this new millennium, after 200 billion dollars of public           cited reason is that it would destroy the patient’s feeling of
and private funding support for cancer research, and over          hope. Paradoxically, studies have shown that communicating
1.5 million scientific papers later, those bold promises of         poor prognosis and outcome in the face of terminal cancer do
defeating cancer now seem far too optimistic. In a wired           not extinguish a sense of hope in the patient and may even
flat world, it can be confounding for the lay person to             enhance it.9 I believe that as much as possible, a diagnosis
distinguish accurate medical facts from medical fiction.            of cancer must be conveyed to the stricken individual,
                                                                   regardless of age, social, ethnic or religious backgrounds.
                                                                   The physician need not portray a stark, existential picture
Oncologists and Hope                                               but instead positively frame the situation in more indirect
   Cancer specialists who possess irreplaceable training and       and subtle expressions that would still preserve hope for
experience in cancer management must engender realistic            the patient and their family.10 Still, many oncologists tend
hope by harnessing the most optimal strategy for their cancer      to defer discussions of end-of-life management and hospice
patients. They must stay up-to-date of current knowledge,          decisions until late in the patient’s cancer journey.
objectify the healing process and yet be empathetic patient           In a landmark legal case of Arato versus Avedon,11
advocates. Hagerty et al6 studied cancer patients in their         Miklos Arato was diagnosed with pancreatic cancer which
advanced stages who were asked for the qualities of their          was surgically resected, then followed by chemotherapy
caregivers that best provided hope. Ninety-eight percent           delivered by the oncologist, Dr Avedon. Mr Arato was
of these patients wanted their doctors to be realistic and         cancer-free at that point. Documented evidence showed
still individualise their management, being expert yet             that a general discussion of prognosis did ensue between
collaborative in discussing their care plan. Ninety percent        doctors and Mr Arato. His cancer recurred, and Arato died
of patients felt that if doctors were up-to-date in their          within a year. His family sued the surgeon and oncologists
knowledge of treatment, it created much hope. Eighty-              for not conveying their definition of accurate prognostic
seven percent gained hope if their doctor knew their cancer        information, specifically that 95% of patients with pancreatic
very well, and this assured them their pain would be well          cancer die within 5 years. The oncologist stated in trial that
controlled. Eighty percent of patients felt hopeful if their       the high mortality rate might “deprive the patient of any
doctor had a sense of humour. The study summarises 6               hope of a cure”, and that Mr Arato never asked about his
styles of conveying hope.                                          life expectancy nor directly ask for prognostic information.
   1.    Realism                                                   The surgeon stated that Mr Arato had displayed great
   2.    Emotional support, being open and responsive              anxiety about his cancer, and hence disclosure of prognosis
                                                                   was “medically inappropriate”. In the first instance, a jury



January 2011, Vol. 40 No. 1
52    Hope in Terminal Cancer—Han Chong Toh




verdict and the Supreme Court judge ruled in favour of          phase clinical trial efficacy16 offered overseas. The medical
the defendants — that physicians had no obligations under       oncologist emphasised to the patient that none of these
informed consent to disclose statistical life expectancy.       therapies would be curative, and none proven to prolong
The Court of Appeals overruled this decision, in favour of      life. The medical oncologist offered that his average lifespan
the plaintiffs, only for the ruling to be reversed once again   was likely only a few months, although a small number of
by the Supreme Court of California. The Supreme Court           patients could live till one year and beyond. The patient
ruling stated that:                                             was determined to see the birth of his first grandchild in
   “The contexts and clinical settings in which physicians      8 months’ time.
and patient interact and exchange information material to          Advanced pancreatic cancer is one of the most aggressive
therapeutic decisions are so multifarious, the informational    solid tumours with a median survival of about 3 to 6 months.
needs and degree of dependency of individual patients so        The majority of drugs tested against pancreatic cancers,
various, and the professional relationship itself such an       including most chemotherapy drugs and also the newer
intimate and irreducibly judgment-laden one, that we believe    biological agents, have not significantly extended survival
it is unwise to require as a matter of law that a particular    in this disease. The first-line therapeutic decision of either
species of information be disclosed. ”                          gemcitabine alone12 or gemcitabine with oral capecitabine
   The Supreme Court alluded to the importance of sustaining    contributes to not just a modestly better survival but also
hope for cancer patients in explaining its judgement.           improves response rates and clinical benefit by alleviating
                                                                symptoms.13 The oncologist must be able to effectively
                                                                communicate the benefits of treatment in lay language to
A Case of Advanced Pancreatic Cancer                            provide the most accurate information of side effects, cost,
  Mr T is a 62-year-old Chinese male presented with             benefit and overall outcome. For example, gemcitabine
epigastric pain, backache and weight loss. A computed           provides an extra median survival benefit (still significant)
tomography (CT) scan revealed a head of pancreas mass           of about 1 month over the previous standard drug therapy
with surrounding enlarged lymph nodes and an endoscopic         5-fluorouracil.12 If survival data is discussed in this manner,
ultrasound with biopsy of the pancreatic mass confirming an      it seems unimpressive. Using a different, yet equally factual
adenocarcinoma. The surgeon planned towards a Whipple’s         perspective, the oncologist could also explain that stage
procedure, but discovered during surgery that the tumour        IV pancreatic cancer patients treated with gemcitabine,
mass was locally invasive with infiltration of the surrounding   (overall well tolerated) provided a survival rate of 18%
structures, rendering definitive surgery not possible. The       at 1 year whereas those treated with 5-fluorouracil had a
surgeon conveyed this to Mr T in the postoperative period.      1-year survival rate of only 2%.12 This equally accurate
The medical oncologist then explained that his cancer was       statistical statement presents a more hopeful perspective
potentially not curable, and recommended chemotherapy           for a patient and the family. Almost all drug combinations
with either gemcitabine12 alone or gemcitabine with oral        with gemcitabine have failed to improve on these odds,
capecitabine.13 The patient enquired about the combination      except for the addition of oral capecitabine, where in a
of gemcitabine and erlotinib,14 which had also shown            subset of patients, added survival benefit is achievable,13
survival benefits in patients with advanced pancreas cancer.     and with oral erlotinib, where an addition of almost 2 weeks
The medical oncologist expressed that the median survival       is added to median survival.14 Oxaliplatin, 5-fluorouracil
improvement of less than 2 extra weeks with the addition        and irinotecan based combination chemotherapy may be
of erlotinib was not very meaningful and the additional         an alternative first-line treatment instead of gemcitabine. In
cost was high, adding several thousand dollars more per         communicating the benefits of treatments to patients, it is
month to his chemotherapy.15 The patient then asked if          essential to explain terms like ‘progression-free survival’ ,
the chemotherapy would shrink the cancer sufficiently for        ‘overall survival’ and ‘clinical benefit response’. Ultimately,
a complete surgical removal of cancer. The surgeon and          ‘overall survival’ represents the most important endpoint of
medical oncologist explained that while this was possible,      benefit for cancer drug efficacy, with real gains in lifespan.
the opportunity was slim. He responded to a 6-month course      ‘Progression-free survival’ is the time that cancer growth
of chemotherapy with reduction of pain, weight gain and         remains under control as a result of treatment, and this may
some tumour shrinkage, but not enough for complete surgical     or may not translate into real survival time gains (overall
removal. Eventually, his cancer progressed to his liver and     survival).3 In the classical study of gemcitabine (versus
lungs. At this point, second line treatment options offered     5-fluorouracil) in pancreas cancer, clinical benefit response
to him included 5-fluorouracil and oxaliplatin, docetaxel        (measure of improvement in pain, performance status and
or a clinical trial using erlotinib only. He also enquired      weight) in the gemcitabine arm was seen in 23.8% and
about a cancer vaccine called Rexin-G with promising early      in 4.8% in the 5-fluorouracil arm.12 This quality-of-life




                                                                                                     Annals Academy of Medicine
Hope in Terminal Cancer—Han Chong Toh    53




endpoint was a major factor when the Food and Drug Agency         analyses must weigh on decisions to recommend treatments.
(FDA) approved this drug. A single point median survival          By adding erlotinib to gemcitabine, the incremental cost-
may not be an ideal way of expressing real outcome as it          effectiveness ratio is US$410,000 per year of life saved
does not necessarily represent the patient’s own outcome.         or US$7885 per week of life saved. Erlotinib can result in
The late Harvard evolutionary biologist, Professor Steven         more diarrhoea for the patient, and when adjusted for the
Jay Gould, who died of cancer remarked that a median              quality-of-life impact of diarrhoea, the incremental cost-
survival of 8 months for his advanced cancer did not mean         effectiveness ratio increases to US$430,000 (low impact of
he would be dead in 8 months.17 It meant that half of such        diarrhoea) and to US$510,000 (high impact of diarrhoea)
similar patients would still be alive after 8 months. This        per quality-adjusted life year (QALY).15 These numbers
epiphany gave him renewed hope, and indeed he survived            far exceed the acceptable benchmark of cost-effectiveness
well after the median of 8 months. Painting a best case           of US$50,000 to US$100,000 per QALY, questioning
scenario for the patient based on real outcomes analysis is       the significant value of erlotinib added to gemcitabine
an important exercise in giving realistic hope.                   for making a difference in advanced pancreas cancer.
  In Singapore, a discussion with cancer patients and their       Cost has become a critical issue related to hope in cancer
families about hospice care may still be a taboo topic,           treatment. Countries and individuals who are economically
signalling the end of therapeutically-driven hope. In many        challenged do limit their access to best care practices in
societies, the hospice carries a stigma of an institution that    cancer management. Health authorities in countries for
would accelerate the dying process, the end of hope. Atul         which social safety nets exist already consider the cost-
Gawande in his article Letting Go, recounted a 34-year-           benefit of new cancer drug impact at a larger societal and
old non-smoking new mother with advanced lung cancer              population “greater good” level. In such health systems,
who struggled with the dilemma of hospice care when her           drugs with the highest benefit do generally receive strong
conventional treatment options had been exhausted. The            reimbursements and subsidies. In countries like the US
patient was persuaded to the goal of hospice as aiming to         where third party private insurance captures a big market
achieve a good death including freedom from pain, anxiety         in healthcare coverage, overconsumption of healthcare can
and fear, and learning to reconcile the dying process.            occur as a result of moral hazard.2 Individualising cancer
Gawande quoted a study of 4493 Medicare patients with             care and communication with the patient and family must
either terminal cancer or congestive heart failure showed         include financial counselling.
no difference in survival time between the hospice and               Direct revenue gained through prescribing and procedures,
non-hospice patients with breast, prostate and colon cancer,      especially on the background of information asymmetry,
and pancreatic and lung cancer patients who stayed in the         can lead to excessive treatments with possibly marginal or
hospice.18 The will to live on may be related to specific          no gains in clinical outcomes. In this context, the vulnerable
reasons — to see a young baby grow every day, to await            cancer patient may fall prey to therapeutic nihilism, where
the birth of a grandchild, or to attend the graduation of a       the provision of (unrealistic/false) hope is linked to profit
loved one.                                                        for one party over another. When a patient with advanced
  To construct hope in a statistics-and-data-driven health        pancreatic cancer has progressed following first and second
information culture, the physician has to harness the art         lines of conventional chemotherapies, subsequent lines of
of medicine, to process and transmit complex information          treatments render very small real gains for the patient except
to the patient in a clear, coherent, humanistic and positive      for a very small group. In this regard, experimental options
way and initiate sensitive, honest disclosure. At different       outside the limits of evidence-based medicine (since there
milestones of the patient’s cancer journey, the definitions        may be none at this point) may appear as the only hope.
of hope will change, from one where the target is to shrink       The oncologist must offer wise counsel on such alternative
the cancer to potentially extend life, to one which is more       options, not deliver false hope which may incur further
holistic and transformational, including freedom from pain,       financial, physical and emotional burden. The Hippocratic
the contemplation of one’s legacy and possibly seeking            Oath reminds us to, “first do no harm”. In a free market
spiritual answers. The oncologist must encourage and help         healthcare system, it is critical that the trust between doctor
the patient explore and refocus upon these broader scopes         and patient is preserved and not be eroded, a fundamental
of hope. Healthcare professionals and loved ones form an          compact for building real hope.
integral psychosocial pillar to alleviate the “suffering of the      In the context of clinical trials, full disclosure of all
mind” that confronts most cancer patients, which may also         potential risks involved and potential benefits must be
include advance care planning, encouraging integration into       communicated to the patient, dissociated from investigator
support groups and managing financial concerns.                    or institutional self interest. The patient may see such
  In these times of soaring health expenditure, cost-benefit       offerings as “providing hope” where hope would otherwise




January 2011, Vol. 40 No. 1
54    Hope in Terminal Cancer—Han Chong Toh




be extinguished. Personalised medicine by identifying the                                         REFERENCES
right drug target to the right patient phenotype or genotype       1.   Groopman J. The Anatomy of Hope: How people prevail in the face of
is an example of how scientific trial design can potentially             illness. New York: Random House, 2003.

render higher rates of benefit to cancer patients and make          2.   Meropol NJ, Schulman KA. Cost of cancer care: issues and implications.
                                                                        J Clin Oncol 2007;25:180-6.
clinical trials more attractive to patients, than mainly to wish
                                                                   3.   Saltz LB. Progress in cancer care: the hope, the hype, and the gap between
to support a study in hope of making a contribution to the              reality and perception. J Clin Oncol 2008;26:5020-1.
fight against cancer and to bring hope to someone else.19           4.   Kim P. Cost of Cancer Care: the patient perspective. J Clin Oncol
                                                                        2007;25:228-32.

Conclusion                                                         5.   Kolata G. Hope in the lab: a special report – a cautious awe greets drugs
                                                                        that eradicate tumors in mice. The New York Times, 3 May 1998.
   Hope over disease and death cannot be synonymous                6.   Hagerty RG, Butow PN, Ellis PM, Lobb EA, Pendlebury SC, Leighl N,
solely with cancer control and gain in physical survival                et al. Communicating with realism and hope: incurable cancer patients'
time.20 Providing psychosocial,21 lifestyle,22 as well as               views on the disclosure of prognosis. J Clin Oncol 2005;23:1278-88.
spiritual23 interventions have proven to improve survival          7.   Oken D. What to tell cancer patients. A study of medical attitudes. JAMA
in cancer patients.                                                     1961;175:1120-8.
                                                                   8.   Oken D. The doctor's job — an update. Psychosom Med 1978;40:449-61.
   The burden of communication and care of cancer patients
                                                                   9.   Mack JW, Wolfe J, Cook EF, Grier HE, Cleary PD, Weeks JC. Hope and
assumes a new dimension with the now multiple channels of               prognostic disclosure. J Clin Oncol 2007;25:5636-42.
access via telephone, emails, short text messaging and social      10. Baile WF, Buckman R, Lenzi R, Glober G, Beale EA, Kudelka AP.
networking sites like Facebook.24 In the face of patients going        SPIKES — A six-step protocol for delivering bad news: application to
through the emotional cycle of shock, anger, denial, and loss,         the patient with cancer. Oncologist 2000;5:302-11.
the physician has to be careful that the distinct demarcation      11. Annas GJ. Informed consent, cancer, and truth in prognosis. N Engl J
of the doctor-patient relationship does not get blurred, nor the       Med 1994;330:223-5.
relationship become casually over-familiar, over-demanding         12. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML,
                                                                       Modiano MR, et al. Improvements in survival and clinical benefit with
on the time and energy of the doctor. Professional burnout             gemcitabine as first-line therapy for patients with advanced pancreas
is a real concern and psychiatric morbidity and emotional              cancer: a randomized trial. J Clin Oncol 1997;15:2403-13.
exhaustion are especially frequent amongst oncologists.25          13. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, et
Still, the physician must professionally be available to the           al. Phase III randomized comparison of gemcitabine versus gemcitabine
patient and their families and be arbiters of both particular          plus capecitabine in patients with advanced pancreatic cancer. J Clin
                                                                       Oncol 2009;27:5513-8.
hope (systematised project to achieve tangible gains
                                                                   14. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al.
in hope) and general hope (absolute trust in the future                Erlotinib plus gemcitabine compared with gemcitabine alone in patients
with no predetermined goals).26 Ivan Illich criticises the             with advanced pancreatic cancer: a phase III trial of the National Cancer
medicalisation of the dying process, in that it devalues and           Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25:1960-6.
dehumanises suffering and dying which should ideally be            15. Miksad RA, Schnipper L, Goldstein M. Does a statistically significant
accepted as meaningful processes of life. The concept of “a            survival benefit of erlotinib plus gemcitabine for advanced pancreatic
                                                                       cancer translate into clinical significance and value? J Clin Oncol
good death” may be marred by potentially futile treatments             2007;25:4506-7.
that represent an unnecessarily aggressive war against the         16. Bruckner H, Chawla SP, Chua CS, Quoin DV, Fernandez L, Marylou
inevitable, which should instead be edified in its natural              A, et al. Phase I and II studies of intravenous Rexin-G as monotherapy
dignity.27 The late Dame Cecily Saunders introduced the                for stage IVb gemcitabine-resistant pancreatic cancer. J Clin Oncol
concept of ‘total pain’ to describe the complex combination            2010;28:7s (suppl; abstr 4149).
of physical, emotional and spiritual pain in patients with         17. Gould SJ. The median isn’t the message. Ceylon Med J 2004;49:139-40
terminal illness.28 Multidisciplinary palliative care aiming       18. Gawande A. Letting Go. What should medicine do when it can’t save
                                                                       your life? The New Yorker, August, 2010.
at achieving a good death must strive towards a pain-free
                                                                   19. Schilsky RL. Personalized medicine in oncology: the future is now. Nat
and symptom-free journey, confronting and reconciling                  Rev Drug Discov 2010;9:363-6.
the dying process, addressing emotional and spiritual
                                                                   20. Penson RT, Gu F, Harris S, Thiel MM, Lawton N, Fuller AF Jr, et al.
distress, attaining closure and closeness with loved ones,             Hope. Oncologist 2007;12:1105-13.
and settling unresolved matters, thus providing hope where         21. Sherman KA, Heard G, Cavanagh KL. Psychological effects and mediators
a technology-centric battle against physical life-limiting             of a group multi-component program for breast cancer survivors. J Behav
disease offers little further mileage.                                 Med 2010. Epub 26 May 2010.
                                                                   22. Morey MC, Snyder DC, Sloane R, Cohen HJ, Peterson B, Hartman TJ, et
“Hope is definitely not the same thing as optimism. It is
                                                                       al. Effects of home-based diet and exercise on functional outcomes among
not the conviction that something will turn out well, but              older, overweight long-term cancer survivors: RENEW: a randomized
the certainty that something makes sense, regardless of                controlled trial. JAMA 2009;301:1883-91.
how it turns out. ”                                                23. Balboni TA, Paulk ME, Balboni MJ, Phelps AC, Loggers ET, Wright
                                                                       AA, et al. Provision of spiritual care to patients with advanced cancer:
                                                 Vaclav Havel



                                                                                                                  Annals Academy of Medicine
Hope in Terminal Cancer—Han Chong Toh             55




    associations with medical care and quality of life near death. J Clin Oncol   26. Daneault S, Dion D, Sicotte C, Yelle L, Mongeau S, Lussier V, et al.
    2010;28:445-52.                                                                   Hope and noncurative chemotherapies: which affects the other? J Clin
24. Chin JJ. Medical professionalism in the internet age. Ann Acad Med                Oncol 2010;28:2310-3.
    Singapore 2010;39:345-3.                                                      27. Clark D. Between hope and acceptance: the medicalisation of dying.
25. Taylor C, Graham J, Potts HW, Richards MA, Ramirez AJ. Changes in                 BMJ 2002;905:905-7.
    mental health of UK hospital consultants since the mid-1990s. Lancet          28. Grant L, Murray SA, Sheikh A. Spiritual dimensions of dying in pluralist
    2005;366:742-4.                                                                   societies. BMJ 2010;341:c4859.




January 2011, Vol. 40 No. 1

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Providing Hope in Terminal Cancer: When Communication is Key

  • 1. 50 Hope in Terminal Cancer—Han Chong Toh Commentary Providing Hope in Terminal Cancer: When is it Appropriate and When is it Not? Han Chong Toh,1MBBChir (Cambridge), FRCP (Edinburgh), FAMS (Medical Oncology) Abstract Hope is essential in the face of terminal cancer. Generally in Western societies, patients and their families prefer their doctor to engage them in transparent, realistic, authoritative, empathic and open communication about the diagnosis and prognosis of cancer but this topic is not well studied in the Asian context. With the exponential increase in information about cancer and the many permutations in cancer treatment, rational and otherwise, the doctor-patient relationship is even more critical in planning the best treatment strategy and also in rendering both particular and general hope in the patient’s war against cancer. Overall, the majority of drugs tested against cancer have failed to reach the market, and those that have, only provide modest benefits, several major therapeutic breakthroughs notwithstanding. Commoditised medicalisation of the dying process ingrained into the contemporary consciousness can potentially create unrealistic or false hope, therapeutic nihilism and a drain on the resources of both the patient and society. These factors can also detract from the dignity of dying as an acceptable natural process. Hope cannot be confined only to focusing merely on the existential dimension of improving survival through technological intervention. Psychosocial and, where appropriate, spiritual interventions and support also play major roles in relieving suffering and providing hope to the patient. Hope cannot be a victim of misinformation from self-interested external parties, nor be an obsession with just buying promises of extending survival time without sufficient regard for quality of life and achieving a good death. Ann Acad Med Singapore 2011;40:50-5 Key words: Communicating prognosis, Dying well, Therapeutic nihilism Introduction exponential progress in cancer advancement that has “Hope is the elevating feeling we experience when we see significantly impacted on the lives of cancer patients. A — in the mind’s eye — a path to a better future.” once-fatal disease, childhood leukaemia is now curable in over 80% of stricken children. The introduction of platinum Jerome Groopman, MD chemotherapy has improved cure rates for even advanced Professor of Medicine testicular cancer and the revolution in molecular targeting Harvard Medical School, United States therapy has ushered in novel drugs like imatinib (Glivec) From The Anatomy of Hope that has induced meaningful remissions in chronic myeloid leukaemia and an uncommon cancer, gastrointestinal stromal tumour (GIST). Inspite of the real advances made Hope is a universally valued, central and enduring primal in cancer biology, diagnosis and treatment, the latter which human emotion that has sustained and uplifted humankind can cost up to one billion United States (US) dollars to from the dawn of time. Professor Jerome Groopman proceeds bring a single drug to the market,2 many cancer drugs only to emphasised in his bestselling book that “true hope has provide modest incremental benefits for cancer patients3 and no room for delusion”.1 many more cancer drugs fail to give any real improvements. Hope, in the fight against cancer, is oxygen to live on Cancer treatment expenditure has escalated dramatically. meaningfully. Oncologists must respect and actively engage In 2005, the total cost of cancer care in the US was $209.9 in the patients’ desire for hope in the face of a disease that billion2 and health insurance family coverage premiums evokes great helplessness, and patients are commonly increased by 73% between 2000 and 2005.4 Medical bills gripped more by a fear of dying than the fear of death itself. account for over half of bankruptcy filings in the US. Undoubtedly, the last several decades have seen Cost-sensitive and cost-benefit decision-making in cancer 1 Department of Medical Oncology, National Cancer Centre, Singapore Address for Correspondence: Dr Toh Han Chong, Department of Medical Oncology, National Cancer Centre, 11 Hospital Drive, Singapore 169610. Email: hanchongtoh@gmail.com Annals Academy of Medicine
  • 2. Hope in Terminal Cancer—Han Chong Toh 51 management is becoming unavoidable. 3. Facilitating coping with the dying 4. Information provision The Media and Medicine 5. Discussing therapeutic options including second The Information Age communicates unparalleled opinion knowledge and empowers patients for making more 6. Sharing personal information informed decisions related to their disease. This can enable them to arrive at a more realistic sense of hope. Conversely, the Information Age can also disseminate hype and false Breaking Bad News hope. Famously, the 3rd May 1998 issue of The New York The Hagerty study covered a largely Western population Times ran a front page story of a mouse study led by the (Australian) characterised by a safety net healthcare, but now late Professor Judah Folkman.5 Folkman identified overall, the above conclusions would have universality proteins that blocked blood vessels feeding cancers and to cancer patients worldwide. Clearly, self-determinism showed dramatic tumour shrinkage in the tumour-bearing and patient autonomy, then medical paternalism, take on mice that received the said drugs. In this article by journalist a broader mantle in the doctor-patient relationship in the Gina Kolata, Nobel Prize winner James Watson was quoted modern time. A 1961 study by Oken demonstrated that as saying that “Judah is going to cure cancer in two years.”5 90% of 219 doctors studied did not tell their patients about Both drugs failed spectacularly in early phase human clinical a diagnosis of cancer.7 The study was repeated in 1979, trials. By the year 2000, cancer had not been cured. Here was where 97% of physicians surveyed indicated a preference an example of the power of media spreading unmet hope. for communicating a diagnosis of cancer to their patients.8 In 1971, then US President Richard Nixon declared “War In Singapore, the families of elderly cancer patients with on Cancer” in his State of the Union address, vowing that incurable cancer commonly appeal that the patient not be cancer would be eradicated in the foreseeable future. In told of his or her diagnosis and/or prognosis. The most often this new millennium, after 200 billion dollars of public cited reason is that it would destroy the patient’s feeling of and private funding support for cancer research, and over hope. Paradoxically, studies have shown that communicating 1.5 million scientific papers later, those bold promises of poor prognosis and outcome in the face of terminal cancer do defeating cancer now seem far too optimistic. In a wired not extinguish a sense of hope in the patient and may even flat world, it can be confounding for the lay person to enhance it.9 I believe that as much as possible, a diagnosis distinguish accurate medical facts from medical fiction. of cancer must be conveyed to the stricken individual, regardless of age, social, ethnic or religious backgrounds. The physician need not portray a stark, existential picture Oncologists and Hope but instead positively frame the situation in more indirect Cancer specialists who possess irreplaceable training and and subtle expressions that would still preserve hope for experience in cancer management must engender realistic the patient and their family.10 Still, many oncologists tend hope by harnessing the most optimal strategy for their cancer to defer discussions of end-of-life management and hospice patients. They must stay up-to-date of current knowledge, decisions until late in the patient’s cancer journey. objectify the healing process and yet be empathetic patient In a landmark legal case of Arato versus Avedon,11 advocates. Hagerty et al6 studied cancer patients in their Miklos Arato was diagnosed with pancreatic cancer which advanced stages who were asked for the qualities of their was surgically resected, then followed by chemotherapy caregivers that best provided hope. Ninety-eight percent delivered by the oncologist, Dr Avedon. Mr Arato was of these patients wanted their doctors to be realistic and cancer-free at that point. Documented evidence showed still individualise their management, being expert yet that a general discussion of prognosis did ensue between collaborative in discussing their care plan. Ninety percent doctors and Mr Arato. His cancer recurred, and Arato died of patients felt that if doctors were up-to-date in their within a year. His family sued the surgeon and oncologists knowledge of treatment, it created much hope. Eighty- for not conveying their definition of accurate prognostic seven percent gained hope if their doctor knew their cancer information, specifically that 95% of patients with pancreatic very well, and this assured them their pain would be well cancer die within 5 years. The oncologist stated in trial that controlled. Eighty percent of patients felt hopeful if their the high mortality rate might “deprive the patient of any doctor had a sense of humour. The study summarises 6 hope of a cure”, and that Mr Arato never asked about his styles of conveying hope. life expectancy nor directly ask for prognostic information. 1. Realism The surgeon stated that Mr Arato had displayed great 2. Emotional support, being open and responsive anxiety about his cancer, and hence disclosure of prognosis was “medically inappropriate”. In the first instance, a jury January 2011, Vol. 40 No. 1
  • 3. 52 Hope in Terminal Cancer—Han Chong Toh verdict and the Supreme Court judge ruled in favour of phase clinical trial efficacy16 offered overseas. The medical the defendants — that physicians had no obligations under oncologist emphasised to the patient that none of these informed consent to disclose statistical life expectancy. therapies would be curative, and none proven to prolong The Court of Appeals overruled this decision, in favour of life. The medical oncologist offered that his average lifespan the plaintiffs, only for the ruling to be reversed once again was likely only a few months, although a small number of by the Supreme Court of California. The Supreme Court patients could live till one year and beyond. The patient ruling stated that: was determined to see the birth of his first grandchild in “The contexts and clinical settings in which physicians 8 months’ time. and patient interact and exchange information material to Advanced pancreatic cancer is one of the most aggressive therapeutic decisions are so multifarious, the informational solid tumours with a median survival of about 3 to 6 months. needs and degree of dependency of individual patients so The majority of drugs tested against pancreatic cancers, various, and the professional relationship itself such an including most chemotherapy drugs and also the newer intimate and irreducibly judgment-laden one, that we believe biological agents, have not significantly extended survival it is unwise to require as a matter of law that a particular in this disease. The first-line therapeutic decision of either species of information be disclosed. ” gemcitabine alone12 or gemcitabine with oral capecitabine The Supreme Court alluded to the importance of sustaining contributes to not just a modestly better survival but also hope for cancer patients in explaining its judgement. improves response rates and clinical benefit by alleviating symptoms.13 The oncologist must be able to effectively communicate the benefits of treatment in lay language to A Case of Advanced Pancreatic Cancer provide the most accurate information of side effects, cost, Mr T is a 62-year-old Chinese male presented with benefit and overall outcome. For example, gemcitabine epigastric pain, backache and weight loss. A computed provides an extra median survival benefit (still significant) tomography (CT) scan revealed a head of pancreas mass of about 1 month over the previous standard drug therapy with surrounding enlarged lymph nodes and an endoscopic 5-fluorouracil.12 If survival data is discussed in this manner, ultrasound with biopsy of the pancreatic mass confirming an it seems unimpressive. Using a different, yet equally factual adenocarcinoma. The surgeon planned towards a Whipple’s perspective, the oncologist could also explain that stage procedure, but discovered during surgery that the tumour IV pancreatic cancer patients treated with gemcitabine, mass was locally invasive with infiltration of the surrounding (overall well tolerated) provided a survival rate of 18% structures, rendering definitive surgery not possible. The at 1 year whereas those treated with 5-fluorouracil had a surgeon conveyed this to Mr T in the postoperative period. 1-year survival rate of only 2%.12 This equally accurate The medical oncologist then explained that his cancer was statistical statement presents a more hopeful perspective potentially not curable, and recommended chemotherapy for a patient and the family. Almost all drug combinations with either gemcitabine12 alone or gemcitabine with oral with gemcitabine have failed to improve on these odds, capecitabine.13 The patient enquired about the combination except for the addition of oral capecitabine, where in a of gemcitabine and erlotinib,14 which had also shown subset of patients, added survival benefit is achievable,13 survival benefits in patients with advanced pancreas cancer. and with oral erlotinib, where an addition of almost 2 weeks The medical oncologist expressed that the median survival is added to median survival.14 Oxaliplatin, 5-fluorouracil improvement of less than 2 extra weeks with the addition and irinotecan based combination chemotherapy may be of erlotinib was not very meaningful and the additional an alternative first-line treatment instead of gemcitabine. In cost was high, adding several thousand dollars more per communicating the benefits of treatments to patients, it is month to his chemotherapy.15 The patient then asked if essential to explain terms like ‘progression-free survival’ , the chemotherapy would shrink the cancer sufficiently for ‘overall survival’ and ‘clinical benefit response’. Ultimately, a complete surgical removal of cancer. The surgeon and ‘overall survival’ represents the most important endpoint of medical oncologist explained that while this was possible, benefit for cancer drug efficacy, with real gains in lifespan. the opportunity was slim. He responded to a 6-month course ‘Progression-free survival’ is the time that cancer growth of chemotherapy with reduction of pain, weight gain and remains under control as a result of treatment, and this may some tumour shrinkage, but not enough for complete surgical or may not translate into real survival time gains (overall removal. Eventually, his cancer progressed to his liver and survival).3 In the classical study of gemcitabine (versus lungs. At this point, second line treatment options offered 5-fluorouracil) in pancreas cancer, clinical benefit response to him included 5-fluorouracil and oxaliplatin, docetaxel (measure of improvement in pain, performance status and or a clinical trial using erlotinib only. He also enquired weight) in the gemcitabine arm was seen in 23.8% and about a cancer vaccine called Rexin-G with promising early in 4.8% in the 5-fluorouracil arm.12 This quality-of-life Annals Academy of Medicine
  • 4. Hope in Terminal Cancer—Han Chong Toh 53 endpoint was a major factor when the Food and Drug Agency analyses must weigh on decisions to recommend treatments. (FDA) approved this drug. A single point median survival By adding erlotinib to gemcitabine, the incremental cost- may not be an ideal way of expressing real outcome as it effectiveness ratio is US$410,000 per year of life saved does not necessarily represent the patient’s own outcome. or US$7885 per week of life saved. Erlotinib can result in The late Harvard evolutionary biologist, Professor Steven more diarrhoea for the patient, and when adjusted for the Jay Gould, who died of cancer remarked that a median quality-of-life impact of diarrhoea, the incremental cost- survival of 8 months for his advanced cancer did not mean effectiveness ratio increases to US$430,000 (low impact of he would be dead in 8 months.17 It meant that half of such diarrhoea) and to US$510,000 (high impact of diarrhoea) similar patients would still be alive after 8 months. This per quality-adjusted life year (QALY).15 These numbers epiphany gave him renewed hope, and indeed he survived far exceed the acceptable benchmark of cost-effectiveness well after the median of 8 months. Painting a best case of US$50,000 to US$100,000 per QALY, questioning scenario for the patient based on real outcomes analysis is the significant value of erlotinib added to gemcitabine an important exercise in giving realistic hope. for making a difference in advanced pancreas cancer. In Singapore, a discussion with cancer patients and their Cost has become a critical issue related to hope in cancer families about hospice care may still be a taboo topic, treatment. Countries and individuals who are economically signalling the end of therapeutically-driven hope. In many challenged do limit their access to best care practices in societies, the hospice carries a stigma of an institution that cancer management. Health authorities in countries for would accelerate the dying process, the end of hope. Atul which social safety nets exist already consider the cost- Gawande in his article Letting Go, recounted a 34-year- benefit of new cancer drug impact at a larger societal and old non-smoking new mother with advanced lung cancer population “greater good” level. In such health systems, who struggled with the dilemma of hospice care when her drugs with the highest benefit do generally receive strong conventional treatment options had been exhausted. The reimbursements and subsidies. In countries like the US patient was persuaded to the goal of hospice as aiming to where third party private insurance captures a big market achieve a good death including freedom from pain, anxiety in healthcare coverage, overconsumption of healthcare can and fear, and learning to reconcile the dying process. occur as a result of moral hazard.2 Individualising cancer Gawande quoted a study of 4493 Medicare patients with care and communication with the patient and family must either terminal cancer or congestive heart failure showed include financial counselling. no difference in survival time between the hospice and Direct revenue gained through prescribing and procedures, non-hospice patients with breast, prostate and colon cancer, especially on the background of information asymmetry, and pancreatic and lung cancer patients who stayed in the can lead to excessive treatments with possibly marginal or hospice.18 The will to live on may be related to specific no gains in clinical outcomes. In this context, the vulnerable reasons — to see a young baby grow every day, to await cancer patient may fall prey to therapeutic nihilism, where the birth of a grandchild, or to attend the graduation of a the provision of (unrealistic/false) hope is linked to profit loved one. for one party over another. When a patient with advanced To construct hope in a statistics-and-data-driven health pancreatic cancer has progressed following first and second information culture, the physician has to harness the art lines of conventional chemotherapies, subsequent lines of of medicine, to process and transmit complex information treatments render very small real gains for the patient except to the patient in a clear, coherent, humanistic and positive for a very small group. In this regard, experimental options way and initiate sensitive, honest disclosure. At different outside the limits of evidence-based medicine (since there milestones of the patient’s cancer journey, the definitions may be none at this point) may appear as the only hope. of hope will change, from one where the target is to shrink The oncologist must offer wise counsel on such alternative the cancer to potentially extend life, to one which is more options, not deliver false hope which may incur further holistic and transformational, including freedom from pain, financial, physical and emotional burden. The Hippocratic the contemplation of one’s legacy and possibly seeking Oath reminds us to, “first do no harm”. In a free market spiritual answers. The oncologist must encourage and help healthcare system, it is critical that the trust between doctor the patient explore and refocus upon these broader scopes and patient is preserved and not be eroded, a fundamental of hope. Healthcare professionals and loved ones form an compact for building real hope. integral psychosocial pillar to alleviate the “suffering of the In the context of clinical trials, full disclosure of all mind” that confronts most cancer patients, which may also potential risks involved and potential benefits must be include advance care planning, encouraging integration into communicated to the patient, dissociated from investigator support groups and managing financial concerns. or institutional self interest. The patient may see such In these times of soaring health expenditure, cost-benefit offerings as “providing hope” where hope would otherwise January 2011, Vol. 40 No. 1
  • 5. 54 Hope in Terminal Cancer—Han Chong Toh be extinguished. Personalised medicine by identifying the REFERENCES right drug target to the right patient phenotype or genotype 1. Groopman J. The Anatomy of Hope: How people prevail in the face of is an example of how scientific trial design can potentially illness. New York: Random House, 2003. render higher rates of benefit to cancer patients and make 2. Meropol NJ, Schulman KA. Cost of cancer care: issues and implications. J Clin Oncol 2007;25:180-6. clinical trials more attractive to patients, than mainly to wish 3. Saltz LB. Progress in cancer care: the hope, the hype, and the gap between to support a study in hope of making a contribution to the reality and perception. J Clin Oncol 2008;26:5020-1. fight against cancer and to bring hope to someone else.19 4. Kim P. Cost of Cancer Care: the patient perspective. J Clin Oncol 2007;25:228-32. Conclusion 5. Kolata G. Hope in the lab: a special report – a cautious awe greets drugs that eradicate tumors in mice. The New York Times, 3 May 1998. Hope over disease and death cannot be synonymous 6. Hagerty RG, Butow PN, Ellis PM, Lobb EA, Pendlebury SC, Leighl N, solely with cancer control and gain in physical survival et al. Communicating with realism and hope: incurable cancer patients' time.20 Providing psychosocial,21 lifestyle,22 as well as views on the disclosure of prognosis. J Clin Oncol 2005;23:1278-88. spiritual23 interventions have proven to improve survival 7. Oken D. What to tell cancer patients. A study of medical attitudes. JAMA in cancer patients. 1961;175:1120-8. 8. Oken D. The doctor's job — an update. Psychosom Med 1978;40:449-61. The burden of communication and care of cancer patients 9. Mack JW, Wolfe J, Cook EF, Grier HE, Cleary PD, Weeks JC. Hope and assumes a new dimension with the now multiple channels of prognostic disclosure. J Clin Oncol 2007;25:5636-42. access via telephone, emails, short text messaging and social 10. Baile WF, Buckman R, Lenzi R, Glober G, Beale EA, Kudelka AP. networking sites like Facebook.24 In the face of patients going SPIKES — A six-step protocol for delivering bad news: application to through the emotional cycle of shock, anger, denial, and loss, the patient with cancer. Oncologist 2000;5:302-11. the physician has to be careful that the distinct demarcation 11. Annas GJ. Informed consent, cancer, and truth in prognosis. N Engl J of the doctor-patient relationship does not get blurred, nor the Med 1994;330:223-5. relationship become casually over-familiar, over-demanding 12. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with on the time and energy of the doctor. Professional burnout gemcitabine as first-line therapy for patients with advanced pancreas is a real concern and psychiatric morbidity and emotional cancer: a randomized trial. J Clin Oncol 1997;15:2403-13. exhaustion are especially frequent amongst oncologists.25 13. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, et Still, the physician must professionally be available to the al. Phase III randomized comparison of gemcitabine versus gemcitabine patient and their families and be arbiters of both particular plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009;27:5513-8. hope (systematised project to achieve tangible gains 14. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. in hope) and general hope (absolute trust in the future Erlotinib plus gemcitabine compared with gemcitabine alone in patients with no predetermined goals).26 Ivan Illich criticises the with advanced pancreatic cancer: a phase III trial of the National Cancer medicalisation of the dying process, in that it devalues and Institute of Canada Clinical Trials Group. J Clin Oncol 2007;25:1960-6. dehumanises suffering and dying which should ideally be 15. Miksad RA, Schnipper L, Goldstein M. Does a statistically significant accepted as meaningful processes of life. The concept of “a survival benefit of erlotinib plus gemcitabine for advanced pancreatic cancer translate into clinical significance and value? J Clin Oncol good death” may be marred by potentially futile treatments 2007;25:4506-7. that represent an unnecessarily aggressive war against the 16. Bruckner H, Chawla SP, Chua CS, Quoin DV, Fernandez L, Marylou inevitable, which should instead be edified in its natural A, et al. Phase I and II studies of intravenous Rexin-G as monotherapy dignity.27 The late Dame Cecily Saunders introduced the for stage IVb gemcitabine-resistant pancreatic cancer. J Clin Oncol concept of ‘total pain’ to describe the complex combination 2010;28:7s (suppl; abstr 4149). of physical, emotional and spiritual pain in patients with 17. Gould SJ. The median isn’t the message. Ceylon Med J 2004;49:139-40 terminal illness.28 Multidisciplinary palliative care aiming 18. Gawande A. Letting Go. What should medicine do when it can’t save your life? The New Yorker, August, 2010. at achieving a good death must strive towards a pain-free 19. Schilsky RL. Personalized medicine in oncology: the future is now. Nat and symptom-free journey, confronting and reconciling Rev Drug Discov 2010;9:363-6. the dying process, addressing emotional and spiritual 20. Penson RT, Gu F, Harris S, Thiel MM, Lawton N, Fuller AF Jr, et al. distress, attaining closure and closeness with loved ones, Hope. Oncologist 2007;12:1105-13. and settling unresolved matters, thus providing hope where 21. Sherman KA, Heard G, Cavanagh KL. Psychological effects and mediators a technology-centric battle against physical life-limiting of a group multi-component program for breast cancer survivors. J Behav disease offers little further mileage. Med 2010. Epub 26 May 2010. 22. Morey MC, Snyder DC, Sloane R, Cohen HJ, Peterson B, Hartman TJ, et “Hope is definitely not the same thing as optimism. It is al. Effects of home-based diet and exercise on functional outcomes among not the conviction that something will turn out well, but older, overweight long-term cancer survivors: RENEW: a randomized the certainty that something makes sense, regardless of controlled trial. JAMA 2009;301:1883-91. how it turns out. ” 23. Balboni TA, Paulk ME, Balboni MJ, Phelps AC, Loggers ET, Wright AA, et al. Provision of spiritual care to patients with advanced cancer: Vaclav Havel Annals Academy of Medicine
  • 6. Hope in Terminal Cancer—Han Chong Toh 55 associations with medical care and quality of life near death. J Clin Oncol 26. Daneault S, Dion D, Sicotte C, Yelle L, Mongeau S, Lussier V, et al. 2010;28:445-52. Hope and noncurative chemotherapies: which affects the other? J Clin 24. Chin JJ. Medical professionalism in the internet age. Ann Acad Med Oncol 2010;28:2310-3. Singapore 2010;39:345-3. 27. Clark D. Between hope and acceptance: the medicalisation of dying. 25. Taylor C, Graham J, Potts HW, Richards MA, Ramirez AJ. Changes in BMJ 2002;905:905-7. mental health of UK hospital consultants since the mid-1990s. Lancet 28. Grant L, Murray SA, Sheikh A. Spiritual dimensions of dying in pluralist 2005;366:742-4. societies. BMJ 2010;341:c4859. January 2011, Vol. 40 No. 1