1. CHALENGES IN MANAGEMENT OF CANCER IN EMERGING COUNTRIES
Prof. Dr Vladimir Todorovic
Director of Clinic for Oncology and Radiotherapy, Clinical center of Montenegro University of Montenegro

2. Cancer global problem Second cause of death in the world 9 M 2015.
Estimation of increasing of new cases up to 70 % in next two decades (25 M new cases)
70% of death in emerging countries (low middle GDP).
Cancer patients with lower aviability of diagnostic devices and innovative treatments
only 1/3 low GDP countries has pathology
Only 1 of 5 countries has registar with appropriate statistics for planning future steps

3. Different distribution of red areas: all sites* (2012)
Incidence
(per 100,000)
Mortality
(per 100,000)
Data shown is for both sexes.
European Cancer Observatory (EUCAN) factsheet for all sites but non-melanoma skin, 2012, both sexes. Available from: Accessed Mar 9, 2016
*Excluding non-melanoma skin cancers

4. Trends in cancer epidemiology

5. Improving in survival of cancer as an result in improvement of treatment

6. Quality of treatment and the results in survival

8. Lawler M et al. Oncologist 2014;19:217–24

9. Cancer control in Central and Eastern Europe – current situation and recommendations for improvement
Eduard Vrdoljak, Gyorgy Bodoky, Jacek Jassem, Razvan A. Popescu, Jozef Mardiak, Robert Pirker, Tanja Čufer, Semir Bešlija, Alexandru Eniu, Vladimir Todorović, Kateřina Kubáčková, Galia Kurteva, Zorica Tomašević, Agim Sallaku, Snezhana Smichkoska, Žarko Bajić, Branimir I. Šikić

10. All cancers: incidence and mortality
Male
Female
Incidence
Mortality
Median
Median
220 96
CE Europe
271
175
313
129
253 83
Neighbouring
WE countries
Other
WE countries
338
137
262 81
Scandinavian
countries
326
110
263 87
GLOBOCAN 2012 (International Agency for Research on Cancer) online analysis results. Available from: Accessed Jun 19, 2015

11. Facts about CEE: population ≥ 65 years
Highest quartile
Lowest quartile
Median = 15.3%
Population ≥65 years (%)
The World Bank. World Bank Open Data. Available from: Accessed Aug 23, 2015

12. Tobacco smoking Median (%) Median (%) 27 40 29 34 22 28 21 24 Female
World Health Organization. Global Health Observatory Data Repository. Available from: Accessed Aug 23, 2015

13. Population obese: BMI ≥ 30 (age standardised)
Median (%)
CE Europe
23.2
Neighbouring
WE countries
20.1
Other
WE countries
20.2
Nordic
countries
20.6
The World Bank. World Bank Open Data. Available from: Accessed Aug 23, 2015
BMI ≥ 30 (% population)

14. Lung cancer incidence and mortality
Male
Female
Incidence
Mortality
Median
Median 17 13
CE Europe 58 50 39 31 18 14
Neighbouring
WE countries
Other
WE countries 44 38 20 14
Scandinavian
countries 32 26 23 17
GLOBOCAN 2012 (International Agency for Research on Cancer) online analysis results. Available from: Accessed Jun 19, 2015

15. Prostate cancer incidence and mortality
Median 36 12
CE Europe
Neighbouring
WE countries 75 10 91 12
Other
WE countries
Scandinavian
countries
108 18
GLOBOCAN 2012 (International Agency for Research on Cancer) online analysis results. Available from: Accessed Jun 19, 2015

16. SEE region countries….Mediteranean countries AROME
Cancers diagnosed with poorer prognosis (worse cancer type distribution)
Late diagnosis (worse stage distribution)
Lack of true multidisciplinary work
Lack of radiotherapy equipment
Lack of appropriate surgery
Lack of innovative drugs
Lack of proper cancer plans
Lack of primary and secondary cancer prevention
Lack of cancer registries
Lack of financial support and suboptimal spending of limited budgets

17. Multidisciplinary team working may improve outcomes in CRC
Outcomes before and after the introduction of an MDT for CRC
Cumulative CRC recurrence
Overall survival
P=0.015
P<0.001
Pre-MDT, n=297
MDT, n=298
Ying-jiang Y, et al. Chin Med J 2012;125:172–7

18. Radiotherapy capacity in Europe
+25%
+12%
-50%
Most European countries do not have the quantity or quality of radiotherapy facilities required to provide an adequate service to their populations, while some have more than enough, according to an analysis published in the Lancet Oncology in 2013.
Undercapacity
Overcapacity
+22%
-15%
+20%
-45%
-4%
-21%
+10%
-45%
-20%
+16%
-20%
-8%
+46%
-20%
-46%
-72%
-42%
-64%
-19%
-67%
-9%
-16%
-44%
-9%
Rosenblatt E, et al. Lancet Oncol 2013;14:e79–86

19. CONCORD high-resolution study: geographical variations in radiotherapy administration rates for rectal cancer
Radiotherapy was administered least frequently for rectal cancer in Eastern Europe vs. all other regions shown
Radiotherapy uptake in Dukes A–C rectal cancer
Allemani C, et al. BMJ Open 2013;3:e003055

20. Nationwide primary prevention programmes
Targeted risk factors
Nationwide primary prevention programmes
CEOC study group. Survey of CE Europe countries oncology opinion leaders

21. Nationwide secondary prevention programmes
Population
reached
50%
45%
30%
CEOC study group. Survey of CE Europe countries oncology opinion leaders

22. Health expenditures per capita (currency US$)
Highest quartile
Median = $1,212 US
Lowest quartile
The World Bank. World Bank Open Data. Available from: Accessed Aug 23, 2015

23. Health expenditures as percentage of GDP
Highest quartile
Median = 7.3 %
Lowest quartile
The World Bank. World Bank Open Data. Available from: Accessed Aug 23, 2015

24. Number of oncologists per million inhabitants
Median
CE Europe 28
Neighbouring
WE countries 44
Other
WE countries 25
Scandinavian
countries 28
de Azambuja E, et al. Ann Oncol 2014;25:525–8

25. Salaries Net monthly salary Highest quartile Interquartile range
Lowest quartile
Interquartile range
median = 916 EUR
CEOC study group. Survey of CE Europe countries oncology opinion leaders

26. Correlations of health expenditures per capita and mortality-to-incidence ratio: all cancers/male (n=25)
Overall Spearman’s ρ = -0.90
WE and Scandinavia, ρ = -0.17
CE Europe, ρ = -0.91
United Nations, Department of Economic and Social Affairs PD. World Population Prospects: The 2015 Revision. Available from: Accessed Aug 23, 2015; GLOBOCAN 2012 (International Agency for Research on Cancer) online analysis results. Available from: Accessed Jun 19, 2015

27. Correlations of health expenditures per capita and mortality-to-incidence ratio: all cancers/female (n=25)
Overall Spearman’s ρ = -0.83
WE and Scandinavia, ρ = 0.20
CE Europe, ρ = -0.76
United Nations, Department of Economic and Social Affairs PD. World Population Prospects: The 2015 Revision. Available from: Accessed Aug 23, 2015; GLOBOCAN 2012 (International Agency for Research on Cancer) online analysis results. Available from: Accessed Jun 19, 2015

28. AROME and ESO Scientific and educational cooperation and influence
2015. First joint Consensus conference - access to inovations in cancer control in emerging countries
Inequity in chances for survival od cancer
Significant improvement last years in prevention and treatment of cancer
Reduction of differences between Western and Emerging countries – joint action
States of panelist about inovations in Oncology – prevention, diagnostics, education, treatment and organization of cancer care
Consensus score – priority in inovations

29. General recommendations access to innovations in oncologyCS
Y(%)
N(%)
A(%) 1.
Innovation in cancer care better solutions - impact epidemiology, treatment strategies and at least improve cancer survival and/or QoL of cancer patients. 94 3 2.
Access to innovations fundamental right for patients
100 3.
In countries with limited resources, the first innovative prevention and early diagnosis 95 5 4.
Education of the population primary and secondary prevention 97 5.
Increasing significantly the price of tobacco 86 6 8 6.
Mammography screening impact with sufficient participation and follow-up 7.
Colorectal screening impact with sufficient participation 8.
Cervical cancer screening impact with sufficient participate 9.
HPV vaccination importanthealth project that might impact cancer mortality 83 7 10
10.
Prostate cancer screening (PSA) is important public health project 48 22 52 26
11.
Education and primary prevention - melanoma mortality and/or QoL treatmen
12.
The applicability of an innovation in cancer care must be evaluated by national oncology board including healthcare professional, patients and healthcare authorities (payers)
13.
Education of healthcare professional on cancer, contribute

30. General recommendations access to innovations in oncologyCS
Y(%)
N(%)
A(%)
14.
Surgical oncologists must receive education on general oncology. 91 3 6
15.
Education and specialization of gynaecologic oncologic surgeons influence the survival o operated patients.
100
16.
Education of onco- pathologists is mandatory.
17.
Investments means in onco-paediatrics with participation to international clinical research programs is considered high priority. 83 14
18.
Education in onco-geriatrics must be part of the oncologists’ education. 89 11
19.
Multidisciplinary decision, tumor boards must be mandatory for treatment strategy decisions allowing better and earlier access to innovations.
20.
For metastatic disease, access to palliative medicine and supportive care is a high priority with QoL and survival impact.
89.5 21
21.
For metastatic bony disease, access to bone antiresorptive treatments (bisphosphonates or rank ligand inhibitors) is a priority.
81.5 63 37
22.
An expert centre for molecular diagnostic with quality control insurance is request for a population of 3 million inhabitants. 94
23.
One PET-CT facility per a population of 0,6 to 1 million inhabitants is a standard for cancer care. 82 84 8
24.
For countries with limited resources, concerning radiotherapy, minimal requirements are a number of machines in accordance with AIEA guidelines and must include: CT simulator (in RT or radiology department); 3D treatment planning system; linear accelerator with multi-leaf collimation and on-line electronic port vision; QA/QC program and dosimetry equipment and create at least one centre of excellence.
25.
For countries with limited resources, concerning chemotherapy, minimal requirements are: access to WHO list of anticancer drugs, education on Medical Oncology specialist and education on Oncology Pharmacists. 85 15

31. GIT malignancies Colorectal carcinoma Gastric carcinomaCS
H(%)
M(%)
L(%)
Colorectal carcinoma
For adjuvant colorectal cancers, access to oxaliplatinum and capecitabine is a priority 93 86 6 8
For metastatic colorectal , access to RAS mutation status is a priority with treatment impact. 78 64 28
For metastatic colorectal cancers, access to RAF mutation status is a priority with treatment strategy impact. 42 14 56 30
For RAS wild type metastatic colorectal cancers, access to anti-EGFR treatment is a priority with survival
73.5 47 53
For metastatic colorectal cancers, access to antiangiogenic drug is a priority with survival and/or QoL impact. 66 38 15
Gastric carcinoma
For high risk non-metastatic gastric cancers, access to adjuvant chemotherapy is a priority with survival and/or QoL impact.
94.5 89 11
For high risk non-metastatic gastric cancers, access to adjuvant radiotherapy usually in combination with chemotherapy is a priority with survival and/or QoL impact. 60 41 21
For metastatic gastric cancers, access to HER2 testing is a priority with treatment strategy impact
75.5 61 29
For HER2 positive metastatic gastric cancers, access to trastuzumab is a priority with survival and/or QoL impact.
80.5 67 27
For metastatic gastric cancers, access to taxanes is a priority with survival and/or QoL impact. 81 62
Pancreatic cancer
For metastatic pancreatic cancers, access to gemcitabine is a priority with survival and/or QoL impact.
For metastatic pancreatic cancers, access to erlotinib is low priority without clinically relevant survival and quality of life impact.
14.5 3 23 74

32. Lung cancer CS
H(%)
M(%)
L(%)
Lung Cancers that might benefit from local treatment, access to PET CT is a priority with treatment strategy impact
77.5 58 39 2
Access to treatment without predictive factors in metastatic lung cancers
For metastatic lung cancers, access to taxanes is a priority with survival and/or QoL impact 93 86 14
For metastatic lung cancers, access to gemcitabine is a priority with survival and/or QoL impact.
86.5 76 21 3
For metastatic lung cancers, access to pemetrexed is a prioritywith survival and/or QoL impact.
59.5 31 57 11
For metastatic non-squamous lung cancers, access to anti-angiogenic drugs is a priority with survival and/or QoL impact.
45.5 16 53 29
For metastatic lung cancers, access to immune check-point drugs is a priority with survival and/or QoL impact 46 23
Access to targeted treatments with biologic predictors of efficacy in metastatic lung cancers
For metastatic lung cancers, access to EGFR mutation status is a priority with treatment strategy impact 84 71 26
For EGFR mutated metastatic lung cancers, access to EGFR-TKI is a priority with survival and/orQoL impact. 87 74
For metastatic lung cancers, access to ALK rearrangement status is a priority with treatment strategy impact. 68 47 42
For ALK rearranged metastatic lung cancers, access to ALK-TKI is a priority with survival and/or QoL impact.
74.5 33 9
For metastatic lung cancers, access to MEK mutation status is a priority with treatment strategy impact. 28 5 49

33. Breast cancer CS Non-metastatic breast cancer Metastatic brast cancer
H(%)
M(%)
L(%)
Non-metastatic breast cancer
For patient with personal and/or familial history suggesting a genetic risk of breast cancers, access to BRCA mutation status is a priority with treatment strategy impact. 74 52 44 4
For adjuvant breast cancers, access to taxanes and anthracyclines is a priority with survival and/or QoL impact. 97 3
For HER2 positive adjuvant breast cancers, access to trastuzumab is a priority with survival and/or QoL impact.
For hormone receptor positive adjuvant breast cancers, access to aromatase inhibitors is a priority with survival and/or QoL impact. 92 84 46
For non-menopaused hormone receptor positive adjuvant breast cancers, access to LHRH agonists is a priority but not consensually considered as a high priority. 72 55 34 11
Metastatic brast cancer
For HER2 positive metastatic breast cancers, access to pertuzumab is a priority with survival and/or QoL impact.
78.5 63 31 6
For HER2 positive metastatic breast cancers, access to T-DM1 is a priority with survival and/or QoL impact. 49 14 70 16
For HER2 positive metastatic breast cancers, access to lapatinib is a priority with survival and/or QoL impact. 56 28 17
For HR positive metastatic breast cancers, access to both aromatase inhibitors (steroidal and non-steroidal) is a priority 88 76 24
For HR positive mBC, access to fulvestrant is a priority with survival and/or QoL impact 66 42 48 10
For HR positive mBC, access to everolimus is a priority with survival and/or QoL impact.
35.5 37
For HR positive mBC, access palbociclib is a priority with survival and/or QoL impact 30 15
For mBC, access to capecitabine is a priority with survival and/or QoL impact.
83.5 73 21
For mBC, access to vinorelbine is a priority with survival and/or QoL impact.
62.5 39 47
For mBC, access to bevacizumab is a priority with survival and/or QoL impact.
23.5 57

34. Skin cancer Basocellular carcinoma Melanoma CS 96 4 17 6 22 72 47 21
H(%)
M(%)
L(%)
Melanoma
In high risk melanoma without clinical node positivity, SLNB is the standard procedure 96 4
For non-metastatic melanoma, access to RAF mutation status is a priority with treatment strategy impact. 17 6 22 72
In high risk non-metastatic melanoma, access to interferon alpha is a priority with survival and/or QoL impact. 47 21 52 28
For metastatic melanoma, access to RAF mutation status is a priority with treatment strategy impact
92.5 85 15
For RAF mutated metastatic melanoma, access to BRAF inhibitors is a priority with survival and/or QoL impact
93.5 87 13
For metastatic melanoma, access to MEK inhibitors is a priority with survival and/or QoL impact. 55 31 48
For metastatic melanoma, access to immune check-points treatments(ipilimumab)is a priority with survival and/or QoL impact. 61 37
For metastatic melanoma, access to DTIC is a priority with survival and/or QoL impact.
73.5 58 12
For metastatic melanoma, access to temozolomide is a priority with survival and/or QoL impact.
45.5 23 45 32
Basocellular carcinoma
First standard of treatment to be considered is loco regional treatment (surgery and/or radiotherapy)
100
Previously treated with (or non-eligible for) loco regional treatments, access to hedgehog inhibitors is a priority with survival and/or QoL impact.
71.5 18
Mixed basal cell carcinoma and squamous cell cancer histology type, previously treated with (or non-eligible for) loco regional treatments, access to hedgehog inhibitors is a priority with survival and/or QoL impact. 36

35. 2 nd AROME-ESO JOINT
CONSENSUS CONFERENCE: ACCESS TO CANCER CARE INNOVATIONS IN EMERGING COUNTRIES
Gligorov (France), Todorovic (Montenegro), Aapro (Switzerland) Pavlidis (Greece) 7th of October 2017, Budva, Montenegro

36. 2. AROME ESO Concensus Conference October 2017. Budva , Montenegro
Initiation of anticancer treatment – only tumor board (MDT)
86 CS
Explain to the patient the optimal way of treatment even if not reimbursed
97 CS
Generics and biosimilars only by regulation of EMEA FDA
88 CS
Clinical trials in developing countrries
93 CS
Younger doctors – education in referent centers abroad
100 CS
Brain drain – loss of investment
ESMO examination- part of education
100 CS
90 CS

37. 2. AROME ESO Concensus Conference October 2017. Budva , Montenegro
Colorectal antiangiogenetic agents
63 % + 33 % CS
Anti EGFR
75 % + 22 % CS
-NSCLC antiagiogenic drugs
18 % + 68 % CS
ALK inhibitors
73 % + 21 % CS
Renal antiangiogenic
82 % CS
Second line
52 % % CS
-Cervical bevacizumab
48 % + 44 % CS
Ovarian III+ bevacizumab
Ovarian BRCA mutation + PARP
HN cetuximab + RT
cetuximab metastatic
73 % + 26 % CS
79 % +20 % CS
70 % + 29 % CS
55 % + 40 % CS

38. 2. AROME ESO concensus conference October 2017. Budva Montenegro
Adjuvant pertuzumab - high risk
% CS
Her 2 + metastatic TDM1
% CS
- HR+ metast. everolimus
% CS
- HR + metast. Inhibitori CDK 4/6
CS…….
HR+ metastatic fulvestrant CS
- Metastatic soft tissue pazopanib
CS…….

40. WHO 2016.

41. Investment in primary and secondary prevention programmes
What should be done ? Together….. Initiatives…AROME, SEEROG, SEE Regional Network ….2018.
Investment in primary and secondary prevention programmes
Multidisciplinary boards – better outcomes
Cancer registres
Population education – better understand the problem of cancer
National cancer plans - action
Investment in cancer diagnostics
Investment in surgery – crucial and with great pharmacoeconomics ratio
Investment in radiation oncology – every EUR invested will be amplified by 6 times
Investment in systemic, innovative drugs

42. Messages Bridges science : clinic
patients : guidelines - optimal treatment
Whats priorities ? Consensuss score
Access to inovations – lowering the gep and inequity
4. AROME COURSE
3. AROME ESO CONSENSUS CONFERENCE
October Herceg Novi, Montenegro
More than 200 oncologist from Mediteran
incorporate Project of SEE REGIONAL NETWORK