Glioblastoma multiforme (GBM) is the most common and aggressive primary adult brain neoplasm with an age-adjusted incidence rate of 3.22 per 100 000 individuals and a 5-yr survival rate of 6.8%.1 In 2005, Stupp and colleagues proposed maximal safe resection, concomitant temozolomide (TMZ) with radiotherapy, and adjuvant TMZ as the optimal treatment. Implementation of the Stupp protocol in high-income countries (HICs) has resulted in increased survival compared to previous regimens. With little-to-no literature on the management and outcomes of patients with GBM in low- and middle-income countries (LMICs), it is unclear whether the Stupp protocol is being adopted or whether it is, or ever can be, the optimal strategy in LMICs...

1. CORRESPONDENCE
Letter: Is the Stupp Protocol an Expensive and
Unsustainable Standard of Care for
Glioblastoma in Low- and Middle-Income
Country Settings? A Call to Action!
To the Editor:
Glioblastoma multiforme (GBM) is the most common and
aggressive primary adult brain neoplasm with an age-adjusted
incidence rate of 3.22 per 100 000 individuals and a 5-yr survival
rate of 6.8%.1
In 2005, Stupp and colleagues2
proposed maximal
safe resection, concomitant temozolomide (TMZ) with radio-
therapy, and adjuvant TMZ as the optimal treatment. Implemen-
tation of the Stupp protocol in high-income countries (HICs) has
resulted in increased survival compared to previous regimens.3,4
With little-to-no literature on the management and outcomes
of patients with GBM in low- and middle-income countries
(LMICs),5-7
it is unclear whether the Stupp protocol is being
adopted or whether it is, or ever can be, the optimal strategy in
LMICs.
GBM care is marked by high out-of-pocket (OOP) expen-
diture, estimated to be between $333.41 and $17 267.16
per month,8
with TMZ forming the majority of the total
costs of treatment.9
Macready et al (2011)10
demonstrated
that 2.1% of patients filed for bankruptcy within 2.5 yr of
diagnosis. Additional informal costs borne by family caregivers
and supportive healthcare assistants11,12
collaboratively indicate
the financial burden of disease in HICs. LMICs are marked by
poor access to radiotherapy services,13,14
higher OOP expen-
diture (36.6% compared to 13.5% in HICs),15
and reduced
governmental health spending, with 5.4% of their gross domestic
product spent on health services compared to 12.4% in HICs.16
The remarkable costs of concomitant and adjuvant TMZ
therapy7,9,17
inhibit the wider implementation of such an
expensive life-prolonging protocol for patients.
Clinical trials are fundamental to medical innovation. By
allowing us to test novel drug combinations, they are a quality-
assured method for improving patient care.18
Participation in
clinical trials has improved patient survival,19
but given the
financial and logistic burden that is innate to trial development,
there are few LMIC-led trials.20
Additionally, the need of skilled
personnel as well as regulatory bodies for appropriate trial gover-
nance and quality assurance presents another barrier as suggested
by a recent review.21
Notably, only 2.8% of neuro-oncology trials
are led by LMIC institutes.20
With a lack of these trials, there
is less LMIC resource-specific evidence to develop treatment
plans that take into account challenges experienced within a local
context.22
Collectively, these problems present significant barriers in the
optimization of GBM care, particularly in LMICs. But what can
be done to overcome these challenges?
DISEASE MAPPING
Because of the paucity of literature, tumor registries, and
prospectively updated databases on GBMs in LMICs, the current
burden as well as general prognosis is yet to be known.6
With
no knowledge on the current status in respective countries, there
is no scope for informed decision-making, as it relates to tumor
management in these distinct regions. Development of tumor
registries is of utmost importance in order to gauge the burden
of the disease. Lack of electronic medical records and challenges
to follow-up and lack of regular repeat imaging have histori-
cally been a barrier to such reforms.23,24
The development of
regional, hospital-based GBM registries could present a novel
opportunity to initiate such databases, with many free and open
source support systems in setting up and sustaining a registry
already available.25,26
The rapid uptake of Internet connectivity
in LMICs offers a huge opportunity to collect accurate, real-
time epidemiological data in the field using smartphones in
remote regions lacking other forms of infrastructure, opening up
a data-driven approach specific to LMICs.27
Additionally, the
involvement of medical students as an untapped resource may be
pivotal in alleviating some of the workforce barriers in disease-
specific data collection and analysis.28
REGION-SPECIFIC CLINICAL TRIALS
Whilst the Stupp protocol is currently the most optimal
treatment regime for GBM management, there is an undeniable
need for alternative protocols that suit LMIC health systems
better without compromising on outcomes (or do so minimally).
Novel guidelines need to be co-authored by stakeholders in
LMICs who understand the prescriptive need of their respective
resource-limited settings.
For instance, patients dropping out of postoperative radio-
therapy is a widely known phenomenon in LMICs.29,30
In India,
given that tertiary-care oncology centers are far away from most
rural towns, patients have to be either admitted or take residence
locally for the duration of care. In GBM, the need to stay close
for six weeks of radiotherapy necessitates a large cost, and many
poor patients choose not to do so. In such scenarios, there needs
to be exploration through LMIC-driven trials whether accel-
erated, hypofractionated regimens are noninferior to standard
radiotherapy in GBM.
An elegant analogy for this is seen in the global variation in
the diagnostic protocols for gestational diabetes mellitus (GDM).
Although US obstetricians utilize the two-step testing protocol for
diagnosis of diabetes, with a need for fasting and 2 separate visits,
clinicians in India use a single-step testing done in 1 visit without
a need for fasting. The latter recognized that the former strategy,
although having higher accuracy, would preclude testing in several
patients who do not come for follow-up visits and thereby miss
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2. CORRESPONDENCE
out several individuals with GDM given its stringent require-
ments.31-33
CONCLUSION
Collectively, these simple measures outlined above can serve
to ameliorate the current state of GBM in the developing world,
driving informed decision-making to map and improve overall
patient survival.
Funding
This study did not receive any funding or financial support.
Disclosures
The authors have no personal, financial, or institutional interest in any of the
drugs, materials, or devices described in this article.
Gideon Adegboyega, BSc, MBBS(C) ∗‡
Ahmad Ozair, MBBS(C) §
Ulrick Sidney Kanmounye, MD ‡
Soham Bandyopadhyay, BA (Hons), BM, BCh (Oxon) ¶
Babar Vaqas, BM, BCh (Oxon), BSc (Lond), FRCS (SN),
PhD ||#
on behalf of InciSion UK Collaborative
∗
Barts and The London School of Medicine and Dentistry
Queen Mary University of London
London, UK
‡
Research Department
Association of Future African Neurosurgeons
Yaounde, Cameroon
§
Faculty of Medicine
King George’s Medical University
Lucknow, India
¶
Oxford University Global Surgery Group
Nuffield Department of Surgical Sciences
University of Oxford
Oxford, UK
||
Department of Neurosurgery
Queens Hospital
Romford, UK
#
Imperial College London
London, UK
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