Reasons for abandonment of treatment and strategies to improve follow up

1. Reasons for abandonment of treatment and strategies to improve follow up Prof DC Stefan Stellenbosch University Cape Town

3. 4yr old Orphan 7kg Stunted HIV POSITIVE Marasmic Kwash Leukemia

4. Content of presentation • Some figures • Some definitions • Some photos • Some causes • Some solutions • Delay in diagnosis • Discussion-interaction with Ethiopian doctors • Situation analysis in Ethiopia

5. Abandonment of treatment • What • Where? • When? • Why? • What can be done?

6. WE ARE IN AFRICA! • 70-80% of childhood cancer- curable • 20% of children – “state of art” • 80% developing countries • >200.000 new cases of childhood cancer/yearly

7. How should we help African children with cancer?

8. List of African countries by GDP • GDP= gross domestic product • Ethiopia has the biggest economy in east Africa (GDP) as the Ethiopian economy is also one of the fastest growing in the world. GDP (PPP) of Ethiopia is 61,600 dollars and GDP per capita is 33.920 billion Agriculture accounts for almost 41 per cent of the gross domestic product (GDP), 80% of export, and 80% of the labour force. Ethiopia is Africa’s second biggest maize producer.

11. Some definitions • Abandonment: “the act of giving something up “ • Loss to follow up • Refusal of treatment • Cultural differences • Beliefs

12. How big is the problem? • Africa- a few studies from Morroco • Asia, South America • Same magnitude in the 20th century as in 21st • Rate depends on the type of cancer • Wilms and HD- low 5-10% • Acute leukemias- up to 50% • RS Arora et al PBC 2007; 49:941-946

13. Other factors • Type of cancer • Duration of treatment • Cost of medication/investigations, etc

14. Why abandonment? • Lack of financial resources • Distance from the treating centre • Lack of familial support • Ignorance (lack of education) • Belief (other options)

15. What to do?What worked? • Twinning • Centralized unit • Financial support • Locally adapted protocols • Parents group • Government involvement • Political figure

16. Challenges in management of Childhood cancers Late presentation Treatment protocols need updating Shortages of chemotherapy (Available Vs Optimal drugs) Oncology not a priority in Pediatric Health Care – world wide problem Limited collaboration with regional and international colleagues Lack of manpower – major hurdle HIV associated malignancies , KS, lymphomas Poor follow up of patients (Transport Problems) High cost of treatment Poor data management Courtesy of Dr I. Ticklay

17. Some photographs

19. Bilateral Retinoblastoma 3 yr old Malnourished Extension to the brain

20. 4 months later Radiotherapy Chemotherapy Improved nutrition Had 1 convulsion …Died 3 mo later August 09, after chemo and RT

21. Hodgkins Lymphoma

22. Xeroderma pigmentosa Squamous cell carcinoma

23. When do the patients arrive at hospital Lacor Uganda 84% arrive with late stages of the disease

24. Determinants of delay in diagnosingchildhood cancer DC Stefan A Dippenaar R Uys Femke Siemonsma Stellenbosch University 2009

25. Delay- definition (Cambridge dictionary on line) To make something happen at a later time than originally planned or expected To cause someone or something to be slow or late (I was delayed by traffic.) To not act quickly or immediately (If you delay now, the opportunity might be lost.)

26. Did we miss the opportunity?

27. BACKGROUND Why this study? • Previous research: in Canada, USA, Mexico, Netherlands, Argentina, Switzerland, etc. • No published data in Africa/South Africa • In developing countries diagnosis is said to be made in late stages • Is this true? • Long delays - worse prognosis (Dang et al. 2007 / Haimi et al. 2004) • Early detection can decrease mortality rates (Dang et al. 2007)

28. Developing countries (RSA) Cancer incidence unknown ?lower Cases not reported Underdiagnosis: Ignorance in community Cancer not recognized by health personnel Thus late presentation and late referral

29. Patient vs Physician delay (Dang 2007)

30. Importance of reducing delay in diagnosis • Early detection allows timely treatment and thus prevents advanced/metastatic disease • Childhood cancers: • Short latency • Grow rapidly/very invasive • More responsive to treatment • Difficulties with early detection: • Rarity of the disease • Non-specific symptoms • In Africa: a lot of other life-threatening childhood diseases

31. DELAY – what is delay? “Delay” was used simply to represent a time interval, measured in days, without implying whether the interval exceeded a particular threshold of clinical acceptability, standard expectation or value judgment.

32. Literature: Aspects of delay • Age at onset of symptoms • Older patients have longer delays • Type of tumor • Longer delay for brain tumors, Hodgkin • Gender • Gender has no significant influence

33. Literature: Aspects of delay cont. • Ethnicity • Ethnicity did not influence delay • Level of education of parents/guardians • Financial means

34. Literature: Aspects of Physician Delay • Availability of advanced medical services • Knowledge and recognition of the disease by healthcare providers • Availability of diagnostic tests • Age at onset of symptoms • Ethnicity

35. Methodology • Study population: patients (0-15yrs), included in the tumor registry of Tygerberg Hospital (diagnosed between 2000-2009, and one patient diagnosed in 1997) • Prospective component: • Questionnaire • Informed consent • Retrospective component • Medical charts • Waiver of informed consent • Data-entry: Epidata 3.1 • Analysis: Statistica 8.0 • Research approved by The Health Research Ethics Committee of the Stellenbosch University.

36. Questionnaire Data collected through questionnaire: • Personal information • Ethnicity • Level of education of parent • Type of tumor • Dates (onset of symptoms, first visit to healthcare and diagnosis) • First symptoms • Information about medical research done after first visit • Alternative diagnosis and treatment

37. Results • Female:Male ratio = 1:1,37 • Gender did not have a significant influence on the total diagnosis delay (Mann-Whitney U, p=0.73), patient delay (Mann-Whitney U, p=0.29) or physician delay (Mann-Whitney U, p=0.32) • Mean age at the start of the symptoms = 5,9yrs • Age at onset of the symptoms - slight influence There is a trend of increased total diagnosis delay (Spearman, r=0.13 p=0.08) and increased patient delay (Spearman, r=0.15 p=0.07) with increased age. Trend for a positive correlation > not significant on the 5% level.

38. Results • Ethnicity: • Coloured = 77 (med. patient delay: 5 days) • Black = 18 (med. patient delay: 6 days) • White = 8 (med. patient delay: 6 days) • Ethnicity - no significant effect on any of the delays • Level of education of the parents: available of 68 patients: • No education = 1 • Primary level = 16 • Secondary level = 43 • Higher than secondary level = 8 • Level of education - no significant effect on any of the delays

39. Results: Tumor Type

40. Results • Type of tumor - no significant effect on any of the delays • Type of tumor - significant relationship with misdiagnosis • Blastoma - 21 (60%) correctly diagnosis (most often correctly diagnosed) • Other tumor categories - more than 50% misdiagnosed • Sarcoma - 18 (81%) misdiagnosed (most often misdiagnosed)

41. Results

42. Results • Medical research: (information available of 111 patients) • Testing done after first visit - 66 (59%) • No testing done after first visit - 45 (41%) • Testing done: • Lab work (36 patients) • X-rays (17 patients) • CT-scan (14 patients) • Ultrasound (8 patients) • Mantoux test (4 patients) • MRI scan (1 patient) • Median physician delays: • Testing done: 16.5 days • No testing done: 25.5 days • Trend of positive correlation between testing being done and shorter physician delays noticeable (Mann-Whitney U, P=0,08)

43. Results • First diagnosis: • Correctly (first diagnosis tumor) - 66 (34%) • Misdiagnosed at first - 112 (58%) • No information available - 16 (8%) • Common misdiagnosis and treatments:

44. Results • Health care provider delay- 112 patients • Eventual diagnosis: • Made/thought of by same doctor/clinic/nurse - 52 (46%) of the 112 misdiagnosed at first • Most common reasons: • treatment first diagnosis failed (N=20; 38%) • symptoms changed (N=12; 23%) • further testing done (N=10; 19%) • symptoms got worse (N=5; 9%) • Ended up at another doctor/clinic/nurse before diagnosis was made/thought of- 38 (46%) of 112 • Most common ways to end up with another: • looked for another doctor themselves (N=18; 47%) • decided to go to the hospital (N=11; 29%) • referred, but the first doctor didn’t think of diagnosis (N=6; 16%) • No information available - 22 (20%)

45. Results • Patient delay longer than 7 days - 47 patients • Reasons for patient delay >7 days: (information available of 26 patients) • Symptoms did not seem very important/not very sick (N=17) • Financial means unavailable (N=3) • Parents/guardians did not notice the symptoms (N=2) • Symptoms were intermittent (N=2) • Thought symptoms were caused by existing condition (N=2) • Reasons to seek help eventually (information available of 20 patients) • Symptoms got worse (N=17) • Symptoms changed (N=3)

46. Discussion • Delay mainly consisted out of physician delay • Outliers - long delays usually caused by physician delay (same result as in the review of Dang-Tan et al.)

48. Conclusion The median total diagnosis delay - 34 days The median patient delay - 5 days The median physician delay - 20 days This data is comparable with data found in the literature No specific causative factors were detected influencing the diagnostic delay

50. CHILDHOOD CANCER IN AFRICA- STILL MANY QUESTIONS, FEW ANSWERS