<div><b>Commentary</b></div><div>With a decreasing burden and mortality of infectious diseases in Africa,
the relative importance of non-communicable diseases such as childhood
cancer is increasing. Great progress in childhood cancer care has been
made over the past decades. Various initiatives have increased the
availability of trained staff, drugs, and locally appropriate treatment
guidelines in many low- and middle-income countries (LMIC), including
the Global Initiative for Childhood Cancer (GICC), launched by the WHO
in 2018. The GICC target is to increase survival worldwide to 60% by
2030, with an initial focus on six common and curable (‘index’)
childhood cancer types for which survival is currently over 85- 95% in
high income countries.</div><div>Estimated overall childhood cancer survival in many countries in
sub-Saharan Africa is still below 20% (1, 2). Non-adherence to
treatment, commonly referred to as treatment abandonment, is the most
common cause of treatment failure, with reported proportions between
46% to 89% (3, 4, 5, 6). High quality evidence specific to Africa on
(baseline) survival of children with cancer and sustainable impact of
interventions to increase survival are lacking. There is an urgent need
to close this survival and research gap.</div><div>News that a child has cancer is devastating to any family; the magnitude
of the problem, the length and toxicity of treatment, the repeated
visits to hospital and anxiety about the outcome are overwhelming.
Families discover that even when chemotherapy is free, there are many
out of pocket costs. Travel to and from hospital is costly, daily needs
while in hospital with a child, loss of income if a parent must stop
working and care for the rest of the family drain resources (7).
Providing highly nutritious foods for their child is beyond many
households (8). Even in high income countries where charities and
government subsidies are available, it is estimated that when a child
completes therapy, 1 in 6 families are in debt (9). This financial
burden is particularly difficult for families in low-income settings.
Many live far from the hospital, the mother may be responsible for
several children and run a small-scale business to support the family
and grow the crops that feed her family. It is not surprising that when
a choice has to be made about continuing treatment for one child or
serving the needs of the whole family, that treatment is left
unfinished.</div><div>Thus, treatment abandonment is found to be a common cause of childhood
cancer treatment failure in low-income countries. It is defined as the
failure to complete treatment or interruption of treatment for more than
4 weeks for non-medical reasons (10). Reported causes worldwide include
lack of hope of survival, inadequate counselling, unavailability of
treatment and long travel distances to the hospital (3, 4, 5). A
prospective descriptive study on treatment abandonment in the CANCaRe
Africa network showed that the need to borrow money to reach the
hospital was the only significant predictor of treatment abandonment
(8). In sub-Saharan Africa the overriding cause is inability of the
families to pay for out-of-pocket costs associated with treatment (7, 8,
11). These include costs for diagnosis and treatment, transport between
home and the hospital and food and accommodation while staying at the
hospital.</div><div>Analysis of cost effectiveness is important. The internationally
recognized WHO-CHOICE guidelines are commonly used to define
cost-effectiveness thresholds (12). Interventions that cost less than
three times a country’s per capita income per disability-adjusted life
year (DALY averted are considered cost-effective, while those costing
less than per capita income per DALY averted are considered very
cost-effective. Childhood cancer treatment was found to be very cost
effective in two and cost effective in one out of four centres across
sub-Saharan Africa (13). Evidence from simulations suggest that
interventions to prevent treatment abandonment in sub-Saharan Africa are
likely to be cost-effective (14). Cash incentives have been shown to be
effective to increase adherence on the continent in other areas of
health care such as treatment of TB (15). We also found that 50 USD was
sufficient to cover out-of-pocket costs for 4 weeks of treatment for
50% of all families (8).</div><div>The implementation of cash incentives to primary caregivers of children
with newly diagnosed common and curable cancers was piloted in Malawi in
a prospective study. The intervention consisted of cash incentives for
all transport costs during the whole treatment, on average 200 Euro per
patient (16). Families in Malawi do not have to pay for diagnosis,
treatment or accommodation while staying at the hospital. Treatment
abandonment decreased significantly from 19% (49 of 264) to 7% (10 of
150), p&lt;0.001 (16, 17). The proportion of patients alive and
without evidence of disease at the end of treatment increased from 53%
(139 of 264) to 61% (91 of 150) but was not statistically significant
(p = 0.1). However, we demonstrated a significant increase in the
proportion of patients alive without evidence of disease at the end of
treatment from 38% (57/149) to 53% (44/83) (p = 0.03) in patients with
the most significant decrease in abandonment (Wilms tumour,
retinoblastoma and acute lymphoblastic leukaemia (ALL) (16).</div><div>Data were not prospectively collected to analyse cost-effectiveness
according to established criteria. A rigorous analysis of the
cost-effectiveness would require data on several parameters, including
2-year survival of children who do not abandon therapy, the real-world
cost of treating a child who abandoned therapy, and the real-world cost
of treating a child who did not abandon therapy. Though these data are
not currently available, some parameters have been collected in other
sub-Saharan African jurisdictions.</div><div>We assumed a 2-year survival of children without treatment abandonment
of 30%, a comparable average cost of treating a child with cancer
($2,400 USD) as previously demonstrated in Tanzania, and that the
average cost of treating a child until the point of abandonment is 10%
of the average cost (i.e., $240) (13). Note that these assumptions are
likely to be conservative as evidence and on-the-ground experience
suggests that 2-year survival is higher, average cost of treatment may
be lower, and the average cost of treatment until the point of treatment
may be more than 10% of average treatment cost (16, 18). Conservative
assumptions may in fact underestimate cost-effectiveness.</div><div>Nonetheless, with the assumptions as stated, the decrease in treatment
abandonment seen in the pilot study (19% to7%) would result in an
increase in overall 2-year survival from 24% to 27.9% and an increase
in the average cost of treating a patient of $471 USD (including the
cost of the abandonment intervention itself). Together, this implies
that the incremental cost per life saved would be approximately $121
USD. This is a metric well below the threshold for a very cost-effective
intervention of 629 USD - the per capita Gross Domestic Product (GDP) of
Malawi in that year (19).</div><div>Treatment abandonment is a common and preventable cause of childhood
cancer treatment failure in sub-Saharan Africa. Out-of-pocket costs are
an overriding cause. Evidence suggest that interventions to prevent
treatment abandonment, including cash-incentives for caregivers, are
cost-effective. Collaborative efforts are needed to increase support to
families to enable them to complete the treatment of their child.
Rigorous evaluation of impact of such interventions, including an
analysis of cost-effectiveness and other aspects of implementation will
contribute meaningfully to joint and multi-stakeholder advocacy.</div><div><b>Conflict of interest Statement</b> None declared.</div><div>References</div><div>1. Bhakta N, Force LM, Allemani C, Atun R, Bray F, Coleman MP, et al.
Childhood cancer burden: a review of global estimates. Lancet Oncol.
2019;20(1):e42-e53.</div><div>2. Howard SC, Zaidi A, Cao X, Weil O, Bey P, Patte C, et al. The My
Child Matters programme: effect of public-private partnerships on
paediatric cancer care in low-income and middle-income countries. Lancet
Oncol. 2018;19(5):e252-e66.</div><div>3. Slone JS, Chunda-Liyoka C, Perez M, Mutalima N, Newton R, Chintu C,
et al. Pediatric malignancies, treatment outcomes and abandonment of
pediatric cancer treatment in Zambia. PLoS One. 2014;9(2):e89102.</div><div>4. Friedrich P, Lam CG, Itriago E, Perez R, Ribeiro RC, Arora RS.
Magnitude of Treatment Abandonment in Childhood Cancer. PLoS One.
2015;10(9):e0135230.</div><div>5. Njuguna F, Mostert S, Slot A, Langat S, Skiles J, Sitaresmi MN, et
al. Abandonment of childhood cancer treatment in Western Kenya. Arch Dis
Child. 2014;99(7):609-14.</div><div>6. Abuidris DO, Elimam ME, Nugud FM, Elgaili EM, Ahmed ME, Arora RS.
Wilms tumour in Sudan. Pediatr Blood Cancer. 2008;50(6):1135-7.</div><div>7. Israels T, Chirambo C, Caron H, de Kraker J, Molyneux E, Reis R. The
guardians’ perspective on paediatric cancer treatment in Malawi and
factors affecting adherence. Pediatr Blood Cancer. 2008;51(5):639-42.</div><div>8. Chagaluka G, Afungchwi GM, Landman L, Njuguna F, Hesseling P,
Tchintseme F, et al. Treatment abandonment: A report from the
collaborative African network for childhood cancer care and
research-CANCaRe Africa. Pediatr Blood Cancer. 2021;68(12):e29367.</div><div>9. [Available from:
https://www.forbes.com/sites/lizfrazierpeck/.</div><div>10. Mostert S, Arora RS, Arreola M, Bagai P, Friedrich P, Gupta S, et
al. Abandonment of treatment for childhood cancer: position statement of
a SIOP PODC Working Group. Lancet Oncol. 2011;12(8):719-20.</div><div>11. Atwiine B, Busingye I, Kyarisiima R, Baluku E, Mbabazi R, Bamwine B,
et al. ”Money was the problem”: Caregivers’ self-reported reasons for
abandoning their children’s cancer treatment in southwest Uganda.
Pediatr Blood Cancer. 2021;68(11):e29311.</div><div>12. Bertram MY, Lauer JA, Stenberg K, Edejer TTT. Methods for the
Economic Evaluation of Health Care Interventions for Priority Setting in
the Health System: An Update From WHO CHOICE. Int J Health Policy Manag.
2021;10(11):673-7.</div><div>13. Githang’a J, Brown B, Chitsike I, Schroeder K, Chekwenda-Makore N,
Majahasi F, et al. The cost-effectiveness of treating childhood cancer
in 4 centers across sub-Saharan Africa. Cancer. 2021;127(5):787-93.</div><div>14. Ward ZJ, Yeh JM, Bhakta N, Frazier AL, Girardi F, Atun R. Global
childhood cancer survival estimates and priority-setting: a
simulation-based analysis. Lancet Oncol. 2019;20(7):972-83.</div><div>15. Richterman A, Steer-Massaro J, Jarolimova J, Luong Nguyen LB,
Werdenberg J, Ivers LC. Cash interventions to improve clinical outcomes
for pulmonary tuberculosis: systematic review and meta-analysis. Bull
World Health Organ. 2018;96(7):471-83.</div><div>16. Chakumatha E, Khofi H, Landman L, Weijers J, Bailey S, Chagaluka G,
et al. Towards zero percent treatment abandonment of patients with
common and curable childhood cancer types in Blantyre, Malawi. Pediatr
Blood Cancer. 2022;69(12):e29899.</div><div>17. Chakumatha E, Weijers J, Banda K, Bailey S, Molyneux E, Chagaluka G,
et al. Outcome at the end of treatment of patients with common and
curable childhood cancer types in Blantyre, Malawi. Pediatr Blood
Cancer. 2020;67(7):e28322.</div><div>18. Bhakta N, Martiniuk AL, Gupta S, Howard SC. The cost effectiveness
of treating paediatric cancer in low-income and middle-income countries:
a case-study approach using acute lymphocytic leukaemia in Brazil and
Burkitt lymphoma in Malawi. Arch Dis Child. 2013;98(2):155-60.</div><div>19. : Worldbank; [Available from:
https://data.worldbank.org/indicator/NY.GDP.PCAP.CD?locations=MW.</div>