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Navigating Diagnostic and Treatment Decisions in Non-Small Cell
Lung Cancer: Expert Commentary on the Multidisciplinary Team
Approach
SANJAY POPAT ,
a,b
NEAL NAVANI,
c
KEITH M. KERR,
d
EGBERT F. SMIT,
e
TIMOTHY J.P. BATCHELOR,
f
PAUL VAN SCHIL,
g
SURESH SENAN,
h
FIONA MCDONALD
a,b
a
Lung Unit, Royal Marsden Hospital, London, United Kingdom;
b
The Institute of Cancer Research, University of London, London, United
Kingdom;
c
Lungs for Living Research Centre, University College London (UCL) Respiratory, UCL and Department of Thoracic Medicine,
University College London Hospitals NHS Foundation Trust, London, United Kingdom;
d
Department of Pathology, Aberdeen University
Medical School and Aberdeen Royal Infirmary, Aberdeen, United Kingdom;
e
Department of Pulmonary Diseases, VU University Medical
Center and Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;
f
Department of Thoracic
Surgery, University Hospitals Bristol and Weston National Health Service Foundation Trust, Bristol, United Kingdom;
g
Department of
Thoracic and Vascular Surgery, Antwerp University Hospital and Antwerp University, Antwerp, Belgium;
h
Department of Radiation
Oncology, Amsterdam University Medical Center, Free University Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands
Disclosures of potential conflicts of interest may be found at the end of this article.
Key Words. Non-small cell lung cancer •Multidisciplinary •Decision making •Lung cancer •Treatment
guidelines
ABSTRACT
Non-small cell lung cancer (NSCLC) accounts for approxi-
mately one in five cancer-related deaths, and management
requires increasingly complex decision making by health
care professionals. Many centers have therefore adopted a
multidisciplinary approach to patient care, using the exper-
tise of various specialists to provide the best evidence-
based, personalized treatment. However, increasingly
complex disease staging, as well as expanded biomarker
testing and multimodality management algorithms with
novel therapeutics, have driven the need for multifaceted,
collaborative decision making to optimally guide the overall
treatment process. To keep up with the rapidly evolving
treatment landscape, national-level guidelines have been
introduced to standardize patient pathways and ensure
prompt diagnosis and treatment. Such strategies depend on
efficient and effective communication between relevant
multidisciplinary team members and have both improved
adherence to treatment guidelines and extended patient
survival. This article highlights the value of a multi-
disciplinary approach to diagnosis and staging, treatment
decision making, and adverse event management in NSCLC.
The Oncologist 2021;26:e306–e315
Implications for Practice: This review highlights the value of a multidisciplinary approach to the diagnosis and staging of
non-small cell lung cancer (NSCLC) and makes practical suggestions as to how multidisciplinary teams (MDTs) can be best
deployed at individual stages of the disease to improve patient outcomes and effectively manage common adverse events.
The authors discuss how a collaborative approach, appropriately leveraging the diverse expertise of NSCLC MDT members
(including specialist radiation and medical oncologists, chest physicians, pathologists, pulmonologists, surgeons, and nursing
staff) can continue to ensure optimal per-patient decision making as treatment options become ever more specialized in
the era of biomarker-driven therapeutic strategies.
Correspondence: Sanjay Popat, Ph.D, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, United Kingdom. Telephone: +44 (0)20
7808 2132; e-mail: sanjay.popat@rmh.nhs.uk. Received June 17, 2020; accepted for publication October 20, 2020; published Online First
on November 21, 2020. http://dx.doi.org/10.1002/onco.13586
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use
and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adapta-
tions are made.
© 2020 The Authors.
The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
The Oncologist 2021;26:e306–e315 www.TheOncologist.com
Lung Cancer
INTRODUCTION
Lung cancer represents a major public health burden. A
majority of cases present as advanced non-small cell lung
cancer (NSCLC) [1, 2], with wide variability in biology, and
tumor burden at presentation, and in prognosis for any
given pathology and stage [3, 4]. Moreover, despite appropri-
ate staging, many patients may be unsuitable for optimal
treatments, necessitating per-patient–level discussions about
suitable treatment modalities to ensure optimal outcomes.
The NSCLC treatment landscape has been evolving rap-
idly over the past decade, with targeted therapies [5] and
immune checkpoint inhibitors (alongside advanced radiation
techniques) joining traditional chemotherapy (CTx), radiation
therapy (RTx), and surgery as key components of disease
management. Treatment recommendations are therefore
highly dependent on patients’tumor and biomarker charac-
teristics, alongside stage and physiology [3, 6, 7]. Therefore,
a sound understanding of current therapy data is important
and can be used alongside all relevant patient data and local
and regional guidelines to make the appropriate diagnostic
and therapeutic decisions throughout treatment, especially
where scientific data may be lacking.
Although many treatment recommendations can be
protocolized, multifaceted treatment options have driven
the need for a multidisciplinary team (MDT) to manage the
full spectrum of the patient treatment journey, especially
for the increasing burden of complex cases that may not
neatly fit into standard diagnostic/treatment algorithms.
Moreover, MDT working is increasingly recognized as a stan-
dard for high-quality cancer care [8]. Lung cancer-specific
MDTs therefore require insight from a diverse group of spe-
cialists, including pulmonologists, thoracic surgeons, radi-
ologists, medical oncologists, pathologists, radiation
oncologists, nuclear medicine specialists, palliative care
specialists, and specialist nurses (Fig. 1) [9–11]. In specific
instances, this core group will also require the expertise
of other specialists, including immunologists, dermatologists,
gastroenterologists, endocrinologists, neurologists, cardiolo-
gists, nephrologists, and molecular biologists [12].
The need for a multidisciplinary approach is particularly
evident for patients with stage III NSCLC. Some studies sug-
gest that the benefits of MDTs are most notable in patients
with more advanced (stage III or IV) NSCLC, but we argue
for MDT involvement for patients with early-stage tumors
as well [2, 13], for example in maximizing radical treatment
options among patients with borderline operable disease
due to comorbidities, or in those with multifocal lung
changes [14, 15]. Indeed, survival rates of patients with
NSCLC are positively correlated with use of active treat-
ment [16], and deployment of MDTs is linked to a higher
probability of patients receiving active treatment [17].
Thus, MDT-led decision making might expand the pool of
patients who may benefit from standard of care (SoC) cura-
tive therapy and potentially improve recruitment to clinical
trials.
However, the benefits of MDT-led decision making must
be weighed against the significant associated cost (£415
[$550 or €486] for every new patient discussed), particularly
for cases where interspecialty input is not required and deci-
sion making can be performed per-protocol [18].
In this review, we highlight the value of a multi-
disciplinary approach to diagnosis, staging, treatment deci-
sion making, and adverse event management in NSCLC.
MDTs: IMPACT AND BENEFIT OF JOINT DECISION MAKING
A wider and more standardized implementation of MDTs
could help to address a number of decision-based factors
that can influence patient outcomes, including differences
in local guidelines and procedures or the type of treating
center and referral route.
The use of MDTs is considered in several national and
international guidelines that are designed to ensure rapid
diagnosis, staging, and decision making and the provision of
radical treatment whenever possible. For example, the
National Optimal Lung Cancer Pathway developed by the
U.K.’s National Health Service requires a case be discussed
by the MDT within 3 weeks of initial triage and any addi-
tional investigations performed within the following week
[19]. Similarly, the Dutch Association of Physicians for Pul-
monary Diseases and Tuberculosis recommend a multi-
disciplinary approach to reduce diagnostic and therapeutic
delays, with targets stipulating that 80% of patients should
have a complete diagnosis within 3 weeks of presentation;
of these, 80% should start treatment within 2 weeks of
diagnosis [20]. Furthermore, regional guidelines in the
U.S. (National Comprehensive Cancer Network), Europe
(European Society for Medical Oncology [ESMO]), and Asia
(ESMO guidelines adapted and endorsed by a collective of
six Asian countries as the Pan-Asian Guidelines Adaptation
[PAGA]) stress the particular importance of MDT collabora-
tive decision making when a biopsy (and therefore histolog-
ical confirmation) is impossible during diagnostic evaluation
and in disease settings with multiple treatment options
(e.g., borderline resectable disease, synchronous oligometastatic
disease), which require case-by-case evaluation [3, 21–24].
Decision making, and thus patient outcomes, can also
vary according to the type of treatment center providing
patient care. A retrospective study of the U.S. National Can-
cer Database identified a clear disparity in the survival of
patients with NSCLC between academic and community
centers, a gap that widened significantly over time [25]. The
investigators reasoned that academic centers improved
their adaptability to the introduction of novel treatment
methods (e.g., tyrosine kinase inhibitors) dependent on
molecular analysis or histology, which contributed to the
widening of this gap in patient survival. Academic centers
likely have earlier experience of novel treatments through
participation in clinical trials. It is also likely that academic
centers have a greater variety of specialists and thus may
be better equipped to implement effective MDT-led deci-
sion making, especially for patients with borderline radi-
cally treatable disease, a previously observed phenomenon
[26]. The U.K. National Lung Cancer Audit identified that,
even after adjustment for case-mix factors, patients were
more likely to undergo surgical resection if first seen with
an MDT based in thoracic surgical centers, probably
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Popat, Navani, Kerr et al. e307
because of surgical peer review of decision making [26,
27]. However, one must also consider other factors that
contribute to differences in outcomes between academic
and community centers, including patient selection
(e.g., better performing patients are able to travel to aca-
demic centers), better and faster diagnostics [28], and
potential enrollment into clinical trials.
Regardless of where patients ultimately receive their
treatment, initial referral route can lead to treatment
decision disparities. Approximately 50% of patients with
lung cancer in the U.K. were referred by their general practi-
tioner (GP), whereas 32% of patients were diagnosed follow-
ing emergency presentation [29]. Those referred by GPs
were approximately five times more likely to undergo
tumor resection (with or without adjuvant and/or neo-
adjuvant therapy) than patients with emergency presenta-
tion [30]. Indeed, emergency patients tend to be “more
unwell”with poorer performance status, resulting in
Figure 1. Key members of the lung cancer MDT, highlighting specialist and supra-regional/national MDTs contributing to patient
care and their potential composition.
Abbreviation: MDT, multidisciplinary team.
© 2020 The Authors.
The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
Decision Making in NSCLC: The MDT Approache308
increased mortality rates compared with electively referred
patients [31, 32]; this suggests referral route alone is
unlikely to account for differences in treatment decisions.
However, such inconsistencies could be reduced through
standardized application of an MDT at the point where a
patient enters care for their suspected NSCLC, regardless of
referral route. Additionally, MDT case review can serve to
highlight patients suitable for clinical trials, enabling sys-
tematic screening and tracking of new patients and maxi-
mizing recruitment.
Regional bodies have also endeavored to address this
variability in decision making. In 2013, a European Expert
Group convened to develop a “best practice”guide for
diagnosis. The key outcome was a need for standardized
procedures (e.g., biopsy size and quality, pathologist involve-
ment, molecular testing and reporting of test results, and
administrative procedures) [33]. Similar statements and rec-
ommendations from the British Thoracic Society and the
European Respiratory Society further support the role of a
multidisciplinary approach to patient care [10, 34]. In the fol-
lowing section, we aim to build and expand on these frame-
works by discussing the major considerations for an MDT in
the treatment of patients with NSCLC, based on stage of
disease.
MDT TREATMENT CHOICES
Recommended treatments (per guidelines) at each stage of
NSCLC are summarized in Table 1. We discuss these recom-
mendations focusing on areas of controversy requiring MDT
discussion and consensus, as well as possible additional
specialist MDT input, below. At every stage, individual
patient decisions should be considered and the MDT should
endeavor to identify patients’suitability for clinical trial
enrollment [35].
Stage I NSCLC: Surgery Versus SBRT
Stage I disease is ideally treated with surgical resection,
preferentially video-assisted thoracoscopic surgery lobec-
tomy; the best outcomes are associated with an R0 resec-
tion [4, 36–39]. Despite this, surgery rates have fallen in
Europe and the U.S. in recent years (but not in England and
Wales) [40, 41]. Where MDTs are currently employed in
surgical decision making, two possible explanations for this
decline arise: an MDT might conclude that surgery is clini-
cally inappropriate based on patient characteristics (such as
comorbidities) and recommend other treatments [15];
alternatively, patients who are borderline unfit or unwilling
to undergo surgery may choose a less invasive treatment
option.
Stereotactic body RTx (SBRT) may be considered in
patients unfit for, or who decline, surgery and has been
associated with increased overall survival (OS) for RTx and
surgical patients alike [40]. Thus, the suitability of individual
patients for SBRT should be discussed among members of
the MDT and particularly with a thoracic surgeon [42].
Moreover, a specialist advanced radiotherapy MDT may be
consulted for complex situations (e.g., very mobile tumors
in proximity to the left hemidiaphragm or the heart, or
when coexistent interstitial lung disease is present), where
a catheter-based ablative approach may be more appropri-
ate. Shared decision making with patients should be per-
formed in all cases to ensure the patient understands the
risks, side effects, and alternative treatments available [43].
In addition, the role of pathological mediastinal/hilar stag-
ing may warrant MDT discussion contingent on positron
emission tomography–computed tomography (CT) findings
to exclude occult involvement [44]. Finally, in a real-world
analysis, only 54% of patients with stage I disease under-
went resection and 24% received no active treatment, rep-
resenting a major opportunity for MDT decision making to
improve patient survival [45]. Many patients with stage I
NSCLC have background pulmonary nodules, with manage-
ment requiring rigorous systematic evaluation [46]. Many
countries have reorganized MDT functioning to develop a
specialist pulmonary nodule MDT, where imaging can be
reviewed according to guidelines with dedicated radiolo-
gists to allow quantification.
Stage II NSCLC: Surgery Versus SBRT Versus
Chemoradiotherapy
Similar to stage I, where surgery with lobectomy remains
the gold standard where possible, the possibility of lymph
node involvement necessitates that increased importance
is given to preoperative mediastinal staging [47–49]. This
is especially relevant in patients with borderline fitness for
a radical approach, and, for patients undergoing surgery,
review of the postoperative pathology report is valuable.
MDT review is important in confirming the “R”status of
the tumor [35], establishing that a complete resection has
been performed [50], and to review the pathological nodal
stations (harvested and involved) alongside margins.
Therefore, MDT review of resection cases, with pathol-
ogy reports and preoperative staging alongside surgical
review, remains the cornerstone to confirming complete re-
section and decision making regarding appropriate adjuvant
therapy, allowing adequate discussion on patient selection
for adjuvant CTx [23, 47].
A number of trials are also evaluating the potential role
of (neo)adjuvant immunotherapy in early-stage NSCLC, with
MDT discussion critical to ensuring eligible patients are
enrolled [35].
Stage III NSCLC: Multimodal Therapy of
Chemoradiotherapy and Surgery Versus
Chemoradiotherapy with Durvalumab
Stage III NSCLC is a highly heterogeneous disease classifica-
tion treated with curative-intent multimodality therapy
[36, 51]. However, as almost equal heterogeneity exists in
decision making around diagnostic, staging, and therapeutic
choices [3, 4, 52], close MDT working is essential. Again,
MDT consensus around mediastinal staging is essential to
planning the optimal approach [49, 53], particularly regard-
ing operability and establishing RTx target volumes [54].
A tumor should be deemed unresectable based on eval-
uation within an MDT that includes an experienced thoracic
surgeon [24]. For cases of borderline resectable tumors,
MDT discussion involving the relevant specialists (including
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Popat, Navani, Kerr et al. e309
Table 1. Treatment guideline recommendations by tumor stage and areas of controversy for MDT discussion
NSCLC tumor
stage Usual treatment recommendation
Areas for discussion in which MDT
review may benefit
Areas in which additional MDTs
may input into care
I Surgery, ideally lobectomy by VATS
SBRT for medically comorbid
patients
SBRT as either an alternative or
preferred option
Role of catheter ablation vs. SBRT,
especially if comorbidities such as
fibrotic lung disease
Enrollment into clinical trials
Management of endolumenal
disease
Consideration of patient’s wishes
Input from regional advanced
radiotherapy MDT
Input from specialist pulmonary
nodule management MDT
Input from regional specialist MDT
II Surgery, ideally lobectomy by VATS Accurate mediastinal staging
SBRT as an alternative or preferred
option if node negative
Role of catheter ablation vs. SBRT,
especially if comorbidities such as
fibrotic lung disease
Review of resection quality and
decision making on role of adjuvant
chemotherapy
Staging, diagnosis and treatment of
medically comorbid patients,
especially those with poor lung
reserve
Enrollment into clinical trials
Consideration of patient’s wishes
Input from regional advanced
radiotherapy MDT
Input from specialist pulmonary
nodule management MDT
III Multimodality therapy with/
without surgery, radiotherapy, or
durvalumab
Accurate mediastinal staging
Agreed multimodality approach
Diagnostic specimen PD-L1 status
Management of borderline
resectable patients
Staging, diagnosis, and treatment
of medically comorbid patients,
especially those with poor lung
reserve
Systemic therapy; e.g.,
immunotherapy adverse event
management
Enrollment into clinical trials
Consideration of patient’s wishes
Input from regional multimodality
therapy MDT
IV Systemic therapy Pathological sampling to maximize
yield for biomarker evaluation
Management of synchronous or
metachronous oligometastastic
disease
Management of oligoconsolidation
or oligoprogression
Evaluation of sites to rebiopsy on
acquired resistance to systemic
therapy
Systemic therapy e.g.
immunotherapy adverse event
management
Pleural effusion management
Enrollment into clinical trials
Consideration of patient’s wishes
Input from GTAB to advise systemic
therapy
Input from regional neuroscience
MDT on management of untreated
or treated (reactive) CNS
metastases
Input from supra-regional MDT to
advise on treatments for patients
with rare genomic variants
Immunotoxicity MDT to advise on
toxicity identification and
management
Input from regional advanced
radiotherapy MDT
Abbreviations: CNS, central nervous system; GTAB, genomic tumor advisory board; NSCLC, non-small cell lung cancer; MDT, multidisciplinary
team; PD-L1, programmed cell death ligand-1; SBRT, stereotactic body radiotherapy; VATS, video-assisted thoracoscopic surgery.
© 2020 The Authors.
The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
Decision Making in NSCLC: The MDT Approache310
at least one surgeon) is vital in the optimal management of
patients as there is no defined “best approach”; this is
reflected in recommendations across multiple national and
international guidelines [3, 21, 24]. The increasing preva-
lence of multimodality treatment for stage III NSCLC
emphasizes the need for continuous and regular feedback
between MDT members to ensure guideline compliance
and the local audit of outcomes.
Based on results from the PACIFIC trial, which showed
that treatment with durvalumab after concurrent CTx and
RTx significantly increased progression-free survival (strati-
fied hazard ratio [HR], 0.52; 95% confidence interval [CI],
0.42–0.65; p< .0001; median, 16.8 vs. 5.6 months) and OS
(stratified HR, 0.68; 99.73% CI, 0.47–0.997; p= .0025;
median not reached vs. 28.7 months) in patients with stage
III, unresectable NSCLC [55–61], durvalumab following
chemoradiotherapy (CRTx) was rapidly established as the
SoC for this population. However, the European approval of
durvalumab for unresectable stage III NSCLC limits use to
tumors with programmed cell death ligand-1 (PD-L1)
expression on ≥1% of tumor cells [7]. This stipulation was
based on an exploratory subgroup analysis in PACIFIC
requested by the European Medicines Agency, where eva-
luable PD-L1 expression data were only available for 66% of
patients [60]. This caveat makes accurate testing for PD-L1
expression in patients with stage III disease particularly cru-
cial in European centers; however, testing-related difficul-
ties may emerge, requiring MDT assessment of the stage III
patient treatment paradigm. Tissue samples retrieved must
have adequate tumor content (quality and quantity) to per-
mit a full subtype diagnosis and genotyping as appropriate,
as well as PD-L1 immunohistochemical testing. Tissue avail-
ability will, in turn, depend on MDT discussion to ensure
appropriate sampling while respecting patient safety and
need for diagnosis, as post-CRTx biopsy sampling is not
feasible.
Tumor samples are used for both core diagnosis and
biomarker testing, and the MDT typically needs rapid
results. Therefore, the choice of which tests to order should
be made based on local expertise and protocols, need, cost,
and tissue availability [62, 63]. To enable accurate assess-
ment of potential benefit, PD-L1 expression results should
be communicated as a percentage of evaluable tumor cells
expressing PD-L1, rather than simply “high”or “low”[7].
Given that the majority of patients with stage III NSCLC
undergo endobronchial ultrasound mediastinal staging, it is
imperative that these samples are deemed locally suitable
for PD-L1 testing, as previously validated in the BLUEPRINT2
study, to avoid patients undergoing an additional biopsy for
predictive biomarker testing [64].
In addition to ongoing trials, there is emerging evidence
to suggest that the use of immunotherapy in a neoadjuvant
capacity prior to surgery could potentially improve out-
comes [65]. In an exploratory trial of patients with stage IIIA
resectable NSCLC treated with platinum-based CTx plus
nivolumab before undergoing surgery (n=13), the overall
response rate was approximately 85%, with 9 patients (69.2%)
achieving complete pathological response (95% CI, 38.6–90.9%)
[66]. The SAKK 16/14 trial demonstrated a 1-year event-free sur-
vival rate of 73.3% with CTx and durvalumab, followed by
surgery and 12 months of postoperative durvalumab, in patients
with resectable stage IIIA NSCLC [67]. The TOP 1501 trial fea-
tures patients with stage IB, II, or IIIA NSCLC being treated with
neoadjuvant pembrolizumab monotherapy, followed by postop-
erative CTx and pembrolizumab [7]. Thus, in this highly hetero-
geneous disease group, clinical trial enrollment is critical for
progression toward greater treatment consensus.
Additional MDT review may be required for patients
with stage III NSCLC, particularly around surgical and RTx
assessments and especially the delivery of trimodality ther-
apy (CTx-RTx-surgery), where MDT and center expertise is
consistently identified as a critical factor in decision making.
Hence, such patients may need to be discussed at a regional
specialist MDT with expertise in such complex therapy, par-
ticularly for borderline patients, such as those requiring
large radiation volumes.
Patient preference is a key part of any treatment deci-
sion making process in stage III NSCLC: patients may decline
surgery, fail to adhere to treatment schedules, or be intoler-
ant of treatment-adverse events. Patient feedback about
their experiences with MDTs has highlighted a desire for
transparency. If resection is not an option, then an explana-
tion of why that is the case may make patients more likely
to adhere to the alternative [68]. Likewise, if a multimodality
treatment regimen is recommended it is prudent for the
entire treatment plan to be explained as early as possible to
prepare patients and carers.
Stage IV NSCLC: Role of Local Treatment and
Pathological Oversight
Stage IV disease is incurable for the vast majority of
patients. Thus, whether any additional survival benefit can
be gained in a systemically disseminated disease by opti-
mally treating local sites is hotly debated. ESMO guidelines
suggest that the use of local ablative therapies should be
based on the extent of tumor metastasis [23]; there is limited
evidence that patients with synchronous oligometastatic disease
(featuring only 1–5metastasesinupto3organs)mayexperi-
ence long-term disease-free survival following systemic therapy
and SBRT or surgery [69]. It is highly recommended that these
cases should be discussed extensively within the MDT because
evidence for local consolidation is inconclusive and clinical deci-
sion making will ultimately depend on specific patient character-
istics. Whether for synchronous/metachronous oligometastatic
disease or oligoprogressive disease on long-term systemic ther-
apy, ESMO/PAGA treatment guidelines emphasize the impor-
tance of identifying such patients through MDT discussion and
enrolling them in clinical trials (to establish an evidence base for
the use of local ablative therapies in this disease setting) [22,
23]. Notably, results from a recent phase II trial demonstrated
OS benefit with local radical consolidative therapy (definitive
RTx and/or surgical intervention) versus maintenance treatment
and observation (41.2 months vs. 17.0 months, respectively: HR,
0.46; 95% CI, 0.21–0.99; p= .048) [70]. However, as the sample
size was relatively small (25 vs. 24 patients in the local con-
solidative therapy vs. maintenance and observation arms,
respectively) and the degree of benefit derived appeared to
vary according to disease variables (number of metastases,
mutation status), further investigationiswarrantedinthisarea
to definitively adjudicate the optimal treatment approach.
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Popat, Navani, Kerr et al. e311
MDT discussion regarding these patients should therefore
heavily focus on the assessment of patient suitability for
ablative therapies and, ideally, clinical trial enrollment.
Although genotyping to identify driver gene alterations
and PD-L1 testing of tumors are now standard in stage IV
NSCLC, performing genotyping procedures is often challeng-
ing [71]. The emergence of multiple molecularly targeted
therapies for advanced NSCLC over the past 15 years rein-
forces the critical need for a pathologist (and potentially a
molecular biologist, as required) on the MDT to facilitate
optimal sample-handling for successful and informative
molecular analyses, minimize tissue wastage and optimize
sample flows (as molecular laboratories may not be
colocated with diagnostic centers or pathology laborato-
ries), and minimize delays to result publication. Moreover,
given that the current World Health Organization classifica-
tion of thoracic malignancies now includes recommenda-
tions on small biopsies, the presence of a pathologist is
critical in ensuring the appropriate histological subtype has
been identified to aid prior predictive utility of genotyping
[72]. As genotyping technologies progress, the identification
of rare and indeterminate genetic variants is increasing,
particularly in patients with oncogene-addicted disease
whose tumors may undergo genotyping at multiple stages
during acquired systemic therapy resistance. Here, MDT
decision making can be critical, not only to identifying
lesions suitable for rebiopsy to identify drug resistance
mechanisms but also via genomic tumor advisory boards
(GTABs) that can review the data underpinning a genetic
variant and give appropriate advice on actionability. Finally,
for patients with central nervous system (CNS) involvement,
the optimal treatment strategy will require discussion with
neuroscience specialists, alongside those from pathology or
molecular diagnostics, to best decide the role of stereotatic
radiosurgery upfront versus on demand at relapse, with
optimal systemic therapy using a CNS-penetrant drug.
THE ROLE OF THE MDT IN ADVERSE EVENT MANAGEMENT
Adverse events (AEs) are an unavoidable consequence of all
known cancer treatments [3]. Specialist lung cancer nurses
and palliative care specialists play a crucial role in monitor-
ing AEs, coordinating the involvement of physicians outside
of the core MDT, and (together with nutritionists) facilitat-
ing optimal preparation of patients for, and support during,
treatment [11, 73, 74].
CTx is associated with side effects that can seriously
affect quality of life (and potentially decrease adherence),
ranging from anemia, nausea and vomiting to hemoptysis,
and severe neutropenia [75, 76]. One AE associated with
CRTx (and immunotherapy) that is of particular interest for
the MDT is pneumonitis [77]. Considering the differential
diagnoses of infection, progression, immune-related-, or pos-
tradical radiation-induced pneumonitis, MDT input, from
radiologists, radiation oncologists, pulmonologists, and medi-
cal oncologists, can be instrumental in confirming the diagno-
sis through image interpretation and review of radiation
treatment volumes. Given a need for early intervention,
additional investigations, such as an early investigative bron-
choscopy (with differential cell count on lavage) to exclude
an immune-related pneumonitis or cardiology involvement
to exclude cardiac failure or myocarditis, may be indicated
[78, 79]. Similarly, a surprisingly high rate of pneumocystis
pneumonia occurs in patients after radical radiotherapy or
while on long-term steroids [80] for other immune-related
adverse events, presenting with a subacute pneumonitis pic-
ture; in this situation, MDT review can be crucial to ensuring
optimal management.
As immune checkpoint inhibitors are implemented into
wider routine practice, specialist MDTs can be considered
to review immune-mediated AEs alongside potential drug
benefits (immunotoxicity MDTs). As indications broaden and
combination immunomodulatory therapies are delivered, this
may be particularly important in regions with initially limited
immune checkpoint inhibitor experience. Immunotoxicity
MDTs would aim to share knowledge regarding service deliv-
ery, AE management, and patient selection, alongside mortal-
ity review, and ensure robust organizational phamacovigilance.
Such immunotoxicity MDTs may be composed of oncologists
from different tumor types and with expertise in both sys-
temic therapy and RTx (alongside other relevant specialists,
e.g., pulmonary physicians, endocrinologists, gastroenterolo-
gists, critical care physicians, pharmacists, nurses) and may
become increasingly important as novel methods of immuno-
modulation (e.g. cell therapies) are more widely implemented.
MDT ORGANIZATION AND ROLE
Although it is now clearly recognized that MDT working is a
key quality measure [8], the associated time spent and
financial cost may be limiting. Different solutions for MDT
working may be considered to streamline this process, con-
tingent on the health care system. For example, patients
who fitintoapredefined MDT staging and treatment path-
way(e.g., staging,diagnosis,andsurgeryforstageI–II NSCLC
without comorbidity) may be efficiently managed by a local
MDT, whereas patients with borderline indications (e.g., stage
I NSCLC with poor lung function or comorbidities) or requiring
MDT discussion (e.g., radically treatable stage III NSCLC) may
be considered for a supra-regional MDT, where there may be
additional experience afforded by the cumulative volume of
complex cases. As CT screening becomes more widely
implemented, a dedicated MDT should discuss manage-
ment of detected nodules above certain sizes [8]. Supra-
regional or even national MDTs could be considered for
rare defined conditions, to leverage a greater volume of
experience. For example, the French nationwide RYTHMIC
network, dedicated to the management of thymic epithelial
tumors, ensures coverage by 14 regional expert centers,
aiming to disseminate the highest standards for diagnosis
and treatment and promote collaborative research [81].
The twice-monthly virtual RYTHMIC MDT meetings feature
a minimum of three expert teams discussing the manage-
ment of patients according to network guidelines, with
patient details prospectively collected in a database. Simi-
larly in the U.K., with the implementation of whole genome
sequencing, supra-regional GTABs review somatic and
germline patient data and directly feedback to local MDTs
or treating physicians [82]. Although traditionally recog-
nized as important for patients with metastatic NSCLC, as
© 2020 The Authors.
The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.
Decision Making in NSCLC: The MDT Approache312
indications broaden and sequencing technologies identify
rare variants with increasing frequency, GTABs may become
increasingly important for radically treated NSCLC. Finally,
an additional MDT of importance for lung cancer patients
would be a neuroscience MDT, as implemented at a regional
level in England. Here, patient cases with CNS involvement
can be evaluated to determine metastatic involvement
(or potential for radionecrosis in treated patients) and decide
an appropriate treatment plan. Moreover, as the complexity
of treatment decision making increases, we also recognize the
role of information technology–based assistance; for example,
GTABs employ such tools to identify trials suitable for patient
genotype, a concept that can be broadly expanded for rare
diseases or supra-regional MDTs. As diagnostic and treatment
indications continue to increase at a pace for thoracic malig-
nancies, in parallel to regional changes in health care service
delivery, there will inevitably be ongoing change to each
nation’s requirement for local or supra-regional MDT work-
ing. The limited availability of clinician time and financial
resources, and the relative scarcity and consequent value of
academic clinicians, will remain major obstacles to wider
implementation.
CONCLUSION
With the treatment landscape in NSCLC continuously evolv-
ing because of the integration of new treatments such as
SBRT and immune checkpoint inhibitors into routine care,
the broad expertise of an MDT is required to design the
most effective treatment plan and thereby attain maximal
clinical benefit. The effectiveness of MDTs in improving
patient outcomes requires further study.
ACKNOWLEDGMENTS
Medical writing support, which was in accordance with Good
Publication Practice guidelines, was provided by James King,
B.Sc., and James Holland, Ph.D., of Cirrus Communications
(Macclesfield, U.K.), an Ashfield company, and was funded by
AstraZeneca.
Neal Navani is supported by a Medical Research Council
/National Institute for Health Research (NIHR) Clinical Aca-
demic Research Partnership (MR/T02481X/1). The work was
partly undertaken at University College London Hospitals/
University College London and the Institute for Cancer
Research/the Royal Marsden Hospital, which received a pro-
portion of funding from the Department of Health’sNIHR
Biomedical Research Centre’s funding scheme.
AUTHOR CONTRIBUTIONS
Conception/design: Sanjay Popat, Neal Navani, Keith M. Kerr, Egbert F. Smit,
Timothy J.P. Batchelor, Paul Van Schil, Suresh Senan, Fiona McDonald
Manuscript writing: Sanjay Popat, Neal Navani, Keith M. Kerr, Egbert F. Smit,
Timothy J.P. Batchelor, Paul Van Schil, Suresh Senan, Fiona McDonald
Final approval of manuscript: Sanjay Popat, Neal Navani, Keith M. Kerr,
Egbert F. Smit, Timothy J.P. Batchelor, Paul Van Schil, Suresh Senan, Fiona
McDonald
DISCLOSURES
Sanjay Popat: Bristol Myers Squibb, Roche, Takeda, AstraZeneca,
Pfizer, Merck Sharpe & Dohme, EMD Serono, Guardant Health,
Abbvie, Boehringer Ingelheim, OncLive, Medscape (Other-Personal
fees); Neal Navani: Hitachi, Pentax, Cook and AstraZeneca (Other-
Educational grants, Other-Fees-institution); Keith M. Kerr: Abbvie,
Archer Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim,
Celgene, Eli Lilly & Co, Merck Serono, Merck Sharpe & Dohme,
Novartis, Pfizer, Roche, Ventana, Medscape, PER, Prime Oncology,
Springer (Other-Fees for consultancy and/or lecturing); Egbert
F. Smit: AstraZeneca (Advisory board); Timothy J.P. Batchelor:
Medtronic, Johnson & Johnson, AstraZeneca (Other-Fees); Paul
Van Schil: National Cancer Institute external expert (France),
AstraZeneca, Merck Sharpe & Dohme (Institutional fees); Suresh
Senan: AstraZeneca, Merck, Celgene, Eli Lilly & Co (C/A),
AstraZeneca, ViewRay Inc., Varian (RF); Fiona McDonald: Accuray,
AstraZeneca (C/A), AstraZeneca, Elekta (Other-Fees).
(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert
testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/
inventor/patent holder; (SAB) Scientific advisory board
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