Discussion
We report the first longitudinal assessment of HRQoL using PROs in SSA
among pediatric cancer patients. We used the Chichewa Pediatric
PROMIS-25 to serially measure HRQoL among pediatric lymphoma patients in
Malawi. Our experience highlights important disparities in pediatric
cancer care experiences and suggests incorporating assessments of HRQoL
via PROs in SSA is feasible, generates clinically meaningful data to
inform supportive care interventions, and may provide prognostic
information.
Our cohort presented with overwhelmingly advanced disease, exemplified
by late stage at diagnosis, high LDH, and poor performance status, which
is common across SSA.2,36 We have previously
demonstrated that HRQoL at diagnosis is poorer among Malawian patients
than the PROMIS reference population and similar pediatric oncology
populations in the United States, likely reflecting more advanced
disease.32 In HICs, children with cancer are
frequently diagnosed early in their disease course with no/minimal
symptom burden and have preserved HRQoL.17,37 In
contrast, our patients reported poor HRQoL and extremely high pain
intensity, with 32/75 (43%) of patients reporting a maximum 10/10 pain
score at diagnosis. Pain medication is available in Malawi, but the
extreme pain burden among our patients suggests their pain may not have
been identified or adequately managed prior to referral and/or
diagnosis. Efforts to educate providers on appropriate pain management
in children and ensure reliable medication access, as well as outreach
to facilitate early cancer diagnosis and referral are
priorities.1,38–40
Patients reported significantly improved HRQoL during active treatment
that far exceeded (>12 points) the MID thresholds of 2-3
points, with the exception of peer relationships which improved by 3.3
points. These improvements likely reflect reduced tumor burden and
improved symptom management during active treatment. HRQoL continued to
improve after treatment completion and through follow-up. In contrast,
children with cancer in HICs have no/ minimal symptom burden at
diagnosis, and report decreased HRQoL during cancer treatment due to
therapy-related adverse effects, which then improves following treatment
completion.17,37
One unique observation was that peer relationships were strong
throughout all timepoints. Patients in our cohort often receive
treatment in an open pediatric ward and are able to develop strong
friendships with other children undergoing similar experiences.
Additionally, they remain socially connected in their home villages,
where they live in close proximity with their neighbors, family, and
friends, and continue to attend school during their treatment course.
The preservation of peer relationships throughout cancer treatment in
Malawi is likely common in other LMICs but is not observed among
pediatric cancer patients in HIC. In HIC, children with cancer are
typically treated in private rooms and with infection control
restrictions, thus experiencing significant decreases in social HRQoL
with poor peer relationship scores during
treatment.17,18,20,41,42
We are sad to report that mortality in our cohort was high. Most of our
patients died (37/75, 49%) or were LTFU (8/75, 11%), an indication of
unverifiable death in our setting.43 One-year overall
survival was 47% (95% CI [37-59%]), which is consistent with
historical and published survival rates for Burkitt lymphoma across SSA,
and is significantly worse than reported survival rates of
>90% in HIC.2,22,43–47 Given the high
mortality and the challenges associated with cancer treatment in
resource-poor health systems, appropriate risk stratification of
patients is critical in SSA, where administering aggressive treatment to
optimize survival must be weighed against toxicity risks for vulnerable
children. Poor LPS has consistently been identified as a risk factor for
mortality in research from both LMICs and
HICs.2,22,45,46,48 Further, emerging data from HICs
suggest PROs offer superior assessment of performance status when
compared to traditional physician-reported measures.49We observed significantly increased mortality risk and worse survival in
our cohort among patients with physician-reported LPS ≤ 70 and
patient-reported Pain Intensity of 10 at diagnosis. Patient-reported
poor Mobility domain scores < 40 also increased risk of
mortality and worse overall survival, but this trend was not statically
significant. Further evaluation of the potential prognostic utility of
Pediatric PROMIS-25 in a larger patient cohort with adequate power is
necessary to understand how PROs can assist with treatment risk
stratification in SSA.
PROs are especially important in SSA, where providers are often
over-worked, healthcare infrastructure/access is limited, and shared
decision making between patients and providers is not the norm.
Assessments of HRQoL via PROMIS can assist providers in quickly
identifying and prioritizing patients for referral to ancillary,
multidisciplinary providers, such as physiotherapists and
palliative/supportive care specialists. Further, PROMIS measures mental
wellbeing, which is often overlooked in pediatric oncology despite being
a significant problem, and can screen patients for anxiety and
depression to facilitate referrals for psychosocial
support.50 In addition to generating clinically
meaningful data, Pediatric PROMIS-25 surveys were feasible to administer
at clinical visits while patients were receiving chemotherapy infusions
or waiting to be seen by the provider.
Study strengths include prospective design, longitudinal data
collection, and use of the first rigorously validated Bantu-language
pediatric PRO instrument to assess HRQoL among pediatric cancer patients
in SSA. Our data are limited by high mortality, which is comparable to
other pediatric lymphoma studies across SSA, and LTFU, which is low
compared to other studies in the region.2,22,44,51,52This may have introduced survivorship bias in observed HRQoL
improvements during active treatment and follow-up. However, among the
17 patients who completed surveys at all three timepoints, we observed
substantial improvements across all HRQoL domains, except for two
patients with relapsed disease. An additional limitation is the use of
parent-proxy reporting for some children (35/140, 25%), as parents tend
to report worse HRQoL than children self-report.35However, our sensitivity analysis without parent proxy-reported surveys
showed that HRQoL mean domain scores did not significantly differ.
Finally, raw PROMIS-25 scores were transposed to T-scores based on the
Pediatric PROMIS reference population of children in the United States.
As PROMIS is increasingly translated and incorporated into care
throughout the world, region-specific reference populations will
facilitate better interpretation of patient HRQoL scores. In our future
work, we are developing voice-enabled tablet-based software to
administer PROMIS-25 surveys without an intermediary to allow for a
truly patient-reported measure in our low-literacy patient population.