Intensive Care Med (2023) 49:345–348
https://doi.org/10.1007/s00134-023-06988-y
WHAT’S NEW IN INTENSIVE CARE
Five new realities in critical care for patients
with cancer
Guillaume Dumas1, Stephen M. Pastores2 and Laveena Munshi3*
© 2023 Crown
Life-threatening complications occur in 5–10% of
patients with cancer requiring admission in an intensive
care unit (ICU). Several factors such as disease-related
or drug-induced complications make this population
unique. In this era of rapid change across oncology, our
understanding of such patients is critical to defining our
clinical approach. In this piece, we highlight five new
realities in cancer care for intensivists.
Serious illness across advanced cancer no longer
means end of life
Historically, ICU admission in patients with advanced
cancer (metastatic solid cancer, high-grade hematologic
malignancies) was associated with poor outcomes [1, 2].
This was driven by (1) poor functional status, (2) guarded
long-term prognosis, or (3) critical illness due to untreat-
able cancer progression. However, the landscape is now
more complex. From an oncological perspective, major
progress has been made in cancer diagnosis, classifica-
tion and treatments. This has allowed a doubling in the
lifespan of many cancer patients. Previously incurable
cancers now have effective life-prolonging therapies lead-
ing to sustained cancer control, such as melanoma or
refractory lymphoma. Intensivists must consider these
new realities to adapt admission policies. In consider-
ing ICU candidacy, there are a few factors unique to
patients with cancer. (1) ICU prognosis is mainly driven
by the patient’s critical care diagnosis and number of fail-
ing organs and not cancer characteristics. If the cause of
critical illness is rapidly reversible (e.g., gastrointestinal
*Correspondence: Laveena.munshi@sinaihealth.ca
3
Interdepartmental Division of Critical Care Medicine, Sinai Health
System/University Health Network, University of Toronto, 18‑206 Mount
Sinai Hospital, 600 University Avenue, Toronto, ON M5G 1X5, Canada
Full author information is available at the end of the article
bleed and catheter-related sepsis) and no conventional
poor prognostic features are present (e.g., significant
frailty), ICU admission should be entertained. This deci-
sion should incorporate the patient’s values, preferences
and expectations of the admission in order to ensure we
are administering goal-concordant care. (2) Conversely,
there are specific cancer-related conditions which carry
a very poor prognosis (e.g., pulmonary-lymphangitic car-
cinomatosis-e-Table-1; Supplemental appendix). Similar
to frailty status, when these conditions are present, irre-
spective of the cause of critical illness, survivability post-
ICU may be guarded, and a palliative approach should
be considered. (3) Finally, for critical illness associated
with more intensive organ support (e.g., invasive venti-
lation) in the setting of advanced cancer, it is critical to
understand the patient’s cancer prognosis, whether life-
sustaining cancer treatments exist and the impact that
critical illness may have on ongoing candidacy. A time-
limited ICU trial (section-4) could be considered in cases
where there is the possibility of ICU survival and return
to cancer treatment following ICU care.
Novel cancer therapies are changing patient
outcomes while creating new diseases
Targeted therapies have revolutionized oncology and are
increasingly used as first-line therapy for certain cancers.
Intensivists must be aware of their mechanisms and tox-
icities (Fig. 1). Depending on drug class, severe toxicities
are not uncommon including pneumonitis and neuro-
toxicity [1]. For some therapies, critical illness may be
expected as part of the treatment course, such as severe
cytokine release syndrome after chimeric antigen recep-
tor-T cell (CAR-T) infusion (15–23%). Most of these
toxicities may be tempered with the administration of
corticosteroids/immunosuppressants [1]. Importantly,
such complications do not necessarily contraindicate
drug rechallenge or alternative classes. In contrast to
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traditional chemotherapy, certain novel therapies may be
offered with organ dysfunctions and some have shown
rapid tumor response, even in critically ill patients. More-
over, by targeting a specific pathway involved in can-
cer pathophysiology, new therapies have demonstrated
greater tolerability compared to chemotherapy. Inten-
sivists should be cognizant about atypical response pat-
terns, like cancer pseudoprogression (defined as an initial
increase in the volume of a cancer lesion in response to
treatment) which can lead to transient locoregional com-
plications and should not be mistaken for treatment fail-
ure [3]. Finally, while the number of new treatments is
increasing, and patients’ trajectories are more complex
(combination of therapies at the same time/over time),
it is likely that new drug-related diseases will manifest as
critical illness and ICUs may be used to diagnose or play
a role in the development of treatment strategies.
We need to take a fresh look at acute respiratory
failure
Since the 1990s, mortality across acute respiratory fail-
ure (ARF) has decreased dramatically. However, invasive
ventilation continues to be associated with high mortal-
ity (50–60%) with a persistent gap between cancer and
non-cancer [4, 5]. There are several opportunities for
further research (1) a greater understanding of the mech-
anisms of ARF in cancer is essential to developing thera-
peutic targets, (2) undetermined ARF remains high and
strategies to improve diagnostic capabilities (infectious
vs. non-infectious) are needed, (3) the identification of
subphenotypes is necessary to advance supportive care
management and lay the groundwork for targeted ARF
therapies. Subphenotypes have been identified within
ARF (e.g. hypo/hyper-inflammatory phenotypes). These
subphenotypes likely have a differential response to treat-
ment. While the ARF community moves this research
program forward, it is essential that immunocompro-
mised/cancer patients are incorporated into this analy-
sis. Historically ARF research grossly divided analyses as
“immunocompromised” vs. non-immunocompromised”;
however, subphenotype identification likely transverses
this historic subdivision. Subphenotype identification
may be the important next step to inform therapeutic
targets in ARF.
(See figure on next page.)
Fig. 1 Overview of new and traditional cancer therapies (upper panel) and nomenclature of newly available cancer drugs (lower panel). CRS
cytokine release syndrome, GI gastrointestinal tract complications, HypoT hypothyroidism, LV left ventricle, PAH pulmonary hypertension, Pu pro‑
teinuria. Braf-MEK v-raf murine sarcoma viral oncogene homolog B1 (part of MAP kinase pathway), BiTE bispecific T cell engager, BCR-Abl chimeric
gene of BCR and ABL (Philadelphia-chromosome), CAR​ chimeric antigen receptor, CTLA4 cytotoxic T-lymphocyte-associated protein 4, EGFR epi‑
dermal growth factor receptor, ICB immune checkpoint inhibitor, IL interleukin, mTor mechanistic target of rapamycin, NK natural killer, PD-1/PD-L1
programmed death-1 (ligand), VEGF vascular endothelial growth factor
Goals of care and the time‑limited trial
Effective communication between the ICU and oncology
teams is essential to ensuring appropriate escalation and
limitations are offered. Great variations in clinical prac-
tices likely exist according to geographical areas, physi-
cian beliefs, and cancer subtypes. Given the absence of
reliable severity of illness scores in predicting outcomes
of patients with cancer, the decision of ICU admission
should be made on an individual basis. This decision
must consider patients’ values/preferences, prognosis of
the critical care condition, and the expected long-term
cancer outcome (with and without ongoing cancer treat-
ment eligibility). The decision for ICU admission is often
straightforward for a patient receiving curative treatment.
However, the literature lacks clarity on admission policies
in the era of new cancer drugs for patients with advanced
cancer. Novel treatments like CAR-T cell infusion imply
a high risk of critical illness and ICU admission may be
considered part of the pathway of care. On the other
hand, across patients treated with other targeted thera-
pies, there are uncertainties about patients’ trajectories
and how ICU admission could impact their future treat-
ment eligibility. Given this, an “ICU time-limited trial”
(TLT) [6] has been proposed in the early 2000s to inte-
grate such uncertainties in decision-making. This admis-
sion policy can be defined as an agreement between all
stakeholders (i.e., patient, family, oncologist, and inten-
sivist) on the types of advanced organ support for a lim-
ited period to assess the plausibility of recovery. For this
to be successful, meticulous collaboration between criti-
cal care and oncology is essential to best inform the util-
ity of ICU trials. Currently, the optimal number of days of
a TLT is poorly defined (mostly ranged from 5 to 7 days
for solid tumors but possibly up to 14 days for hemato-
logic malignancies) [7]. The number of failed organs may
modify the duration. The implementation of high-quality
palliative within ICU should also be pursued. Further
research is needed to define the TLT across different can-
cer subtypes and causes of ICU admission.
It is time to look beyond the ICU
ICU mortality has decreased from 80 to 90% in historic
reports to 30–50% [5, 8]. However, this encouraging pro-
gress is usually balanced against the more disappointing
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Fig. 1 (See legend on previous page.)

348
reported long-term survival rates (> 3 months) ranging
from 25 to 55% with frequent and persistent declines
in quality of life (QoL) following ICU discharge [1, 3, 9,
10]. To date, only a few studies have focused on long-
term survival after ICU discharge in cancer patients [2,
8, 11–13]. We must shift our focus to defining the impact
of critical illness on cancer care, and long-term can-
cer prognosis post-ICU in addition to patient-centered
outcomes such as functional, cognitive and symptom
burden post-ICU. This shift aligns with the critical care
community’s effort to characterize the burden of illness
post-ICU. There is a complex interplay between criti-
cal care and oncology that cannot be extrapolated from
non-cancer patients. Additional considerations include
eligibility for life-sustaining or curative cancer treatments
following recovery from critical illness. It is imperative
that we understand (pre-ICU) (1) cancer treatments
available, (2) whether those have been administered, and
(3) how critical illness recovery impacts candidacy for
ongoing treatment. We need to appraise determinants of
return-to-treatment after ICU (functional status, disease
progression, persistent organ dysfunction, and patient
preferences) to guide clinician and patient decisions. This
is necessary to inform future research of potential thera-
pies to optimize these factors in the future.
Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1007/​s00134-​023-​06988-y.
Author details
1 systematic review with meta-analysis on individual data. Intensive Care
Service de Médecine Intensive‑Réanimation, CHU Grenoble-Alpes, Université
Grenoble-Alpes, INSERM, U1042‑HP2 Grenoble, France. 2 Critical Care Center,
Department of Anesthesiology and Critical Care Medicine, Memorial Sloan
Kettering Cancer Center, New York, NY, USA. 3 Interdepartmental Division
of Critical Care Medicine, Sinai Health System/University Health Network,
University of Toronto, 18‑206 Mount Sinai Hospital, 600 University Avenue,
Toronto, ON M5G 1X5, Canada.
Declarations
Conflicts of interest
No conflicts to declare.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in pub‑
lished maps and institutional affiliations.
Received: 26 September 2022 Accepted: 16 January 2023
Published: 9 February 2023
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