Access to Treatment for Childhood Cancer

WHO Global Initiative for Children with CancerGetting the job done for 1,000,000 children

Scott Howard, MD, MScConsultant, Management of NCDs, WHO

Professor, University of Tennessee Health Science Center

Secretary General, SIOP (https://siop-online.org/)

CEO, Resonance (www.ResonanceOncology.org)

Trustee, World Child Cancer USA

No child should suffer

Improved survival for acute lymphoblastic leukemia

1

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

0 2 4 6 8 10 12 14 16 18

Years from Diagnosis

93.5%±2.1% XV (n=498) 2000–2007

84.3%±1.7% XIII–XIV (n=465) 1991–1999

80.6%±1.7% XI–XII (n=546) 1984–1991

48.3%±1.7% V–IX (n=828) 1967–1979

21.1%±4.2% I–IV (n=90) 1962–1966

74.1%±2.1% X (n=428) 1979–1983

Pui et al. N Engl J Med 2006;354:166-78

Chemotherapy for acute lymphoblastic leukemia

Drug Year approved in the USA

Mercaptopurine 1953

Methotrexate 1953

Prednisone 1955

Dexamethasone 1958

Cyclophosphamide 1959

Vincristine 1964

Cytarabine 1969

Asparaginase 1978

Daunorubicin 1979

PEG-asparaginase 1994

Imatinib, Dasatinib, Nilotinib, Ponatinib, Clofarabina,

Nelarabine, Rituximab, Blinatumumab, CAR T-cells

High-income

countries

Cu

re

Relapse

Low- and

middle-income

countries

Toxic death

No treatment

Abandonment

Relapse

No diagnosis

Misdiagnosis

Cure

Low- and middle-

income countries

High-income

countries

Treatment failure in childhood cancerPreventable deaths in LMIC

LMICHIC

Cu

re

Cu

re

LMICHIC

Toxic death

Abandonment

Relapse

No diagnosis

Misdiagnosis

Cure

No treatment

Cure

Relapse

Non-relapse

Causes of treatment failure

for children with cancer in

high- versus low- and

middle-income countries

Treatment failure for people with cancer in LMIC

• Bad news

– Numerous causes of preventable treatment failure

for children with cancer in LMIC

– Each cause has several contributing sub-causes

• Good news

– Every cause of preventable treatment failure CAN BE

PREVENTED, even in LMIC

– Published strategies have proven this in many

countries for all of the issues in the following slides

Lack of diagnosis

Contributors Strategies

Lack of awareness by the

patient or family about

cancer symptoms

Community education and

awareness programs

Healthcare providers

unaware of early signs of

cancer

Training of community

health workers and

primary care providers

Lack of diagnostic

capabilities

Equipment and training for

lab, pathology, and

radiology services

Inability to afford a

diagnostic evaluationUniversal health coverage

Cure

Toxic death

Relapse

No diagnosis

Misdiagnosis

Abandonment

No treatment

Zona da

Mata

R.M.R

R.M.R

Recife: 0 km

Olinda: 7 km

Paulista: 19 km

Abreu e Lima: 22 km

Itapissuma: 39 km

Parecer positivos: 5

ZONA DA MATA

Pombos: 72 km Chã Grande: 80 km

Vicência: 81 km Parecer Positivo: 5

Águas Belas: 308km

Angelim: 235 km

Bom Conselho: 276 km

Brejão: 244 km

Caetés: 249 km

Calçado: 200 km

Canhotinho: 194 km

Canhotinho: 194 km

Caruaru: 132km

Gravatá: 79km

Cumaru: 114km

Limoeiro: 76km

Pesqueira: 210km

Bezerros: 116km

Timbauba: 92 km

Capoeira: 252 km

Correntes: 257km

Garanhuns: 228km

Iati: 286 km

Itaiba: 331 km

Jucati: 217 km

Jupi: 207 km

Lagoa do Ouro: 263 km

Lajedo: 192 km

Palmeirinha: 252 km

Paranatama: 247 km

Saloá: 262 km

São João: 240 km

Terezinha: 250 km

Riacho das Almas: 118km

Parecer Positivo: 7

AGRESTE

SERTÃO

Arco Verde: 81 km

Parecer Positivo: 0

Oncologia Pediátrica

Incorrect diagnosis

Contributors Strategies

Insufficient pathology

infrastructure

Public-private partnerships

for training, funding, and

sustainability

Lack of immunohisto-

chemistry, flow cytometry,

and other diagnostics

Implementation of

specialised testing for the

most common cancers

Insufficient numbers of

trained pathologists

Pathology training

programs, telepathology

for remote support

Lack of funding for

specialised testing

Technology innovation,

pooled procurement of

reagentes and services

Cure

Toxic death

Relapse

No diagnosis

Misdiagnosis

Abandonment

No treatment

No treatment and abandonment

Contributors StrategiesLogistical and financial

barriers (travel time or

distance, costs of care,

opportunity costs)

Subsidized transportation,

local housing for out-of-

town patients, subsidized

food, local work program

Miscommunication or

pessimism of healthcare

providers

Consistent messaging,

education of hospital staff

about prognosis

Missed appointments due

to non-logistical factors,

misunderstanding of

treatment

Patient tracking system,

appointment scheduling

and notification system

Health beliefs (curability of

cancer, need for post-

remission therapy)

Patient/family education

Peer/parent support

groups

Cure

Toxic death

Relapse

No diagnosis

Misdiagnosis

Abandonment

No treatment

Causes of treatment failure for children with

cancer by World Bank income group

Time after diagnosis (years)

5

100

70

50

10

0

0

Early period

20

30

40

60

80

90

1 2 3 4

St. Jude Total XI

Care-cure gap

Childhood ALL EFS, Recife, Brazil 1980-1989

JAMA 2004, 291: 2471

Improved ALL Outcome in Recife, Brazil

Housing, social work, dentistry, PT/OT

NACC JAMA 2004

Francisco and

Arli Pedrosa

Improved ALL Outcome in Recife, Brazil

Transportation, food, social worker, family

and community education

JAMA 2004, 291

0

2

4

6

8

10

12

14

16

1980's Early 1990's Late 1990's

Recife

St. Jude

Reducing the Care-Cure GapAbandonment

Call-back system for people who miss appointments

• System = software + people + process (Culture of tracking appts)

• 1 social worker per 1000 patient visits

• El Salvador: reduced abandonment (12%➔2%)

El Salvador Abandonment Prevention

0

2

4

6

8

10

12

14

Before After

Patient Tracking to Prevent Abandonment

Toxic death

Contributors Strategies

Infectious diseases

(bacterial, viral, and fungal

infections)

Hand hygiene, nurse

training, Golden Hour QI,

decrease chemotx

intensity, probiotics

Haemorrhage (due to

thrombocytopenia,

coagulopathy, and poor

access to blood products)

Blood bank QI, nurse

training, guest house for

patients living far away

Tumor lysis syndrome,

acute kidney injury

Physician and nurse

training, access to

rasburicase and dialysis

High-dose methotrexate

and other chemotherapy-

specific toxicities

Physician and nurse

training, QI, management

of mucositis, pancreatitis

Cure

Toxic death

Relapse

No diagnosis

Misdiagnosis

Abandonment

No treatment

What can we do about toxic death?

Need research to

know what to do!

Avoidable relapse

Contributors StrategiesProtocols from high-

income countries not

suitable for local

conditions

Deploy locally adapted

protocols, monitor causes

of treatment failure and

adapt

Lack of knowledge about

use of adapted protocols,

suboptimal risk

stratification

Personnel training,

monitoring drugs

prescribed and

administered

Gaps in access to

essential chemotherapy

Mitigate drug shortages:

forecast needs, establish

inventory, measure access

and adherence

Gaps in adherence to

chemotherapy

Information system/patient

tracking

Cure

Toxic death

Relapse

No diagnosis

Misdiagnosis

Abandonment

No treatment

LMICHIC

Toxic death

Abandonment

Relapse

No diagnosis

Misdiagnosis

Cure

No treatment

Cure

Relapse

Non-relapse

Causes of treatment failure

for children with cancer in

high- versus low- and

middle-income countries

Causes of treatment failure and

examples of cause-specific interventions

Cau

ses

of

tre

atm

en

t fa

ilure

CURE AllChildren with Cancer

Access, quality, sustainability

WHO MissionA Healthier Humanity

www.who.int/cancer/childhood-cancer/en/

WHO Global Initiative in Childhood CancerFirst Stakeholder Meeting at WHO Headquarters, Geneva

Avoidable relapse

Contributors StrategiesProtocols from high-

income countries not

suitable for local

conditions

Deploy locally adapted

protocols, monitor causes

of treatment failure and

adapt

Lack of knowledge about

use of adapted protocols,

suboptimal risk

stratification

Personnel training,

monitoring drugs

prescribed and

administered

Gaps in access to

essential

chemotherapy

Mitigate drug shortages:

forecast needs, establish

inventory, measure access

and adherence

Gaps in adherence

to chemotherapyInformation system/patient

tracking

Cure

Toxic death

Relapse

No diagnosis

Misdiagnosis

Abandonment

No treatment

Chemotherapy for acute lymphoblastic leukemia

Drug Year approved in the USA

Mercaptopurine 1953

Methotrexate 1953

Prednisone 1955

Dexamethasone 1958

Cyclophosphamide 1959

Vincristine 1964

Cytarabine 1969

Asparaginase 1978

Daunorubicin 1979

PEG-asparaginase 1994

Imatinib, Dasatinib, Nilotinib, Ponatinib, Clofarabina,

Nelarabine, Rituximab, Blinatumumab, CAR T-cells

Acute Promyelocytic Leukemia98% cure with ATRA + ATO

Nomal life after cureRare cancer

EML update for adults and children 7/9/19

Oral arsenic is safe, well-absorbed, and clinically effective

Oral arsenic is safe, well-absorbed, and clinically effective for APL

Oral arsenic trioxide (ATO) is safe, well-

absorbed, and clinically effective for APL

WHO OneHealth: Forecasting need for drugs

• MedMon

• Essential Medicines List (EML)

• OneHealth suite of tools

– Estimating workforce

– Forecasting needs for drugs and devices

–Costing and resource planning

WHO OneHealth: Forecasting need for drugs

• MedMon

• Essential Medicines List (EML)

• OneHealth suite of tools

– Estimating workforce

– Forecasting needs for drugs and devices

–Costing and resource planning

WHO OneHealth: Forecasting need for drugs

• MedMon

• Essential Medicines List (EML)

• OneHealth suite of tools

– Estimating workforce

– Forecasting needs for drugs and devices

–Costing and resource planning

Call to Action• Most children with cancer can be cured

• Causes of treatment failure in LMIC include non-diagnosis, mis-diagnosis, abandonment, toxic death, and excess relapse

• Each cause is PREVENTABLE with proven, published strategies

• All strategies require high-quality, accessible medications

• All strategies require an information system and continuous quality improvement

• Each cured child brings hope for today and learning for the future

Health and Science for All

Call to Action - Opportunities• WHO collaboration

• NGO collaboration

• Research collaboration (information systems)

• Academic collaboration

• ScottCHoward@outlook.cocm

• Discussion tomorrow: Room 0.7.48

Health and Science for All