8-A842A-2018-Multiple-00021-Chapter 29-ROUND1

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Section II Techniques, Modalities, and Modifiers in Radiation Oncology

Chapter 28 Radiation Oncology in the Developing World

Timothy P. Hanna

in many LMCs, with 47% of all cases of gastric cancer in the world occurring in China alone (Fig. 28.2). 3 Kaposi’s sarcoma is a common cancer in Sub-Saharan Africa because of the AIDS epidemic, 7 and esophageal cancer has the highest incidence rates worldwide in regions of Asia and Africa. 3 Oral cancer has a high incidence in South Asia, particularly among men. 3 Among nine common modifiable risk factors for cancer, tobacco smoking is associated with the largest proportion of attributable risk. 8 In the developing world, an estimated 49% of men and 8% of women were current smokers in 1995. 9 With large populations and high tobacco use in China and India, tobacco is an extremely important risk factor for cancer in Asia. 10 In general, many LMCs have demonstrated increased tobacco use during the past three decades. National consump- tion continues to rise in many countries, and in others, a peak occurred in the 1980s and 1990s. 11 History has shown a 30- to

One of the greatest challenges facing the international radia- tion oncology community and all other domains of cancer control is the burden of cancer in low- and middle-income countries. Low-income countries had a 2010 per capita gross national income of US $1,005 or less, and for middle-income countries the range was US $1,006 to $12,275. 1 Nations falling into these income groups are often described as developing countries. This chapter will describe the unique characteristics of cancer in this setting and the challenges to health service provision. It will also provide reasons for hope that the global challenge of cancer can be met. Global Burden of Disease Based on projections for 2008, an estimated 14% of all deaths worldwide are due to cancer. 2 In comparison to the worldwide burden of cancer, cardiovascular disease and other chronic conditions are responsible for, respectively, 30% and 19% of deaths globally. In total, 63% of mortality worldwide is the result of noncommunicable disease. Eighty percent of these deaths occur in low- and middle-income countries (LMCs). 2 In low-income countries, where deaths from communicable disease and other related causes are common, chronic dis- ease was the cause of almost as many deaths in 2008 and is expected to surpass them by 2015 or earlier. 2 In 2008, 56% of cancers worldwide occurred in less devel- oped countries, as did 64% of all cancer deaths. 3 The burden of cancer in developing countries relates to increasing life expec- tancy in developing countries, population growth patterns, and rising incidence of risk factors for chronic diseases in develop- ing countries. 4,5 For example, an estimated 65% of people ≥ 60 years of age lived in less developed countries in 2010, and this is expected to rise to 79% by 2050. 4 The growing burden of cancer and other noncommunicable diseases in LMCs repre- sents a significant epidemiologic transition and a dual chal- lenge for disease control efforts. Epidemiology of Cancer Worldwide Worldwide, there were 12.7 million new cases of cancer and 7.6 million cancer deaths in 2008. 3 Lung cancer is the most common cause of cancer worldwide (1.61 million new cases in 2008), followed by breast cancer (1.38 million) and colorectal cancer (1.24 million) (Fig. 28.1). 3 Lung cancer is also the most common cause of cancer death, with 1.38 million deaths in 2008. 3 Gastric cancer (0.74 million) and liver cancer (0.70 mil- lion) are the second and third most common causes of cancer death, respectively. Age-standardized incidence rates of cancer in developed countries are nearly double the rates in devel- oping countries, though mortality rates are far more similar. These findings reflect variation in prevalence and distribution of major risk factors and limitations in early detection and treatment resources in developing countries. 6 Although cervix cancer is the 10th most commonly diag- nosed cancer among women in developed countries, it is sec- ond only to breast cancer in developing nations. 3 This reflects a lack of sufficient prevention of cervical cancer in many LMCs. Cervix cancer is an extremely common cancer in Latin America, Sub-Saharan Africa, and parts of Asia such as India (Fig. 28.2). 3 Gastric cancer and hepatocellular carcinoma are also common

Male

More developed regions

Less developed regions

Lung Prostate Colorectum Stomach Liver Oesophagus Bladder Non-hodgkin lymphoma Leukaemia Lip, oral cavity Kidney Pancreas Larynx Brain, nervous system Other pharynx Breast Colorectum Cervix uteri Lung Stomach Corpus uteri Liver Ovary Thyroid Non-hodgkin lymphoma Oesophagus Leukaemia Pancreas Brain, nervous system Kidney

Incidence Mortality

800,000

600,000

400,000

200,000

0

200,000

400,000

600,000

800,000

Female

More developed regions

Less developed regions

Incidence Mortality

800,000

600,000

400,000

200,000

0

200,000

400,000

600,000

800,000

Figure 28.1.  Estimated number of new cancer cases (incidence) and deaths (mortality) worldwide in 2008. Data are shown for more developed and less developed countries by cancer site and sex, ranked by global cancer incidence. (From Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008 v1.2, cancer incidence and mortality worldwide. IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer, 2010. Available at: http://globocan.iarc.fr, with permission.)

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Chapter 28 Radiation Oncology in the Developing World

B. Breast cancer Estimated age-standardized incidence rate per 100,000

A. Cervix cancer Estimated age-standardized incidence rate per 100,000

<21.3

<28.6

<38.7

<56.5

<109.2

<7.0

<12.9

<20.2

<29.6

<56.3

C. Lung cancer Estimated age-standardized incidence rate per 100,000

D. Gastric cancer Estimated age-standardized incidence rate per 100,000

Techniques, Modalities, and Modifiers in Radiation Oncology

<3.2

<8.1

<17.1

<26.1

<52.0

<3.8

<5.8

<8.2

<13.0

<41.4

Figure 28.2.  Global variation in estimated age-standardized cancer incidence per 10 5 in 2008 for specific cancers based on International Agency for Research on Cancer statistics. Incidence is grouped by country quintile with higher incidence indicated by darker color. Rates for both sexes are shown for lung and stomach cancer. A: Cervix cancer rates are highest in Latin America, Sub-Saharan Africa, and parts of Asia including India. B: Breast cancer rates are high among high-income countries. Among low- and middle-income countries, rates are high in parts of Latin America and lower in parts of Africa and Asia. C: Lung cancer rates are high in both developed and developing parts of the world, including China, Southeast Asian countries, and parts of South America. D: Rates of stomach cancer are highest in East Asia. High rates are found in Latin America, other parts of Asia, and Eastern Europe. (From Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008 v1.2, cancer incidence and mortality worldwide. IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer, 2010. Available at: http://globocan.iarc.fr, with permission.)

role of occupational and environmental exposures to cancer in developing countries requires continued exploration. 24 In many developing countries, cancer often presents in advanced stages, due to factors such as lack of comprehensive screening and poor access to effective treatments. 25 As a result, case fatality rates are much higher in developing countries, with rates for breast and cervical cancer in low-income coun- tries being more than double rates in high-income countries. 26 With cervical cancer being so common in developing countries and the high frequency of advanced cancer presentations requiring local therapy, radiation therapy has an extremely important role in developing countries. The following sections will describe radiation oncology in developing countries in terms of access, quality, and economics.

40-year delay between the peak in smoking rates in a popula- tion and the peak in tobacco-related mortality. 12 Thus, an increasing rate of tobacco-related malignancies is expected in LMCs during the next half century. 13,14 Over 26% of cancers in developing countries are attributed to infectious causes. 15 Hepatitis B is a major risk factor for hepatocellular carcinoma in developing countries. Other factors are hepatitis C 16 and aflatoxin produced from Aspergillus in cer- tain poorly preserved foods. 17 Human papillomavirus (HPV) and Helicobacter pylori are important etiologic agents, and there are numerous other infectious agents relevant to cancer in the developing world. These include Epstein-Barr virus, HIV, schisto- somiasis, human T-cell leukemia virus type 1 (HTLV-1), and human herpesvirus 8 (HHV-8). 15 ,18 The prevalence of infectious causes is notable given the preventability of many of these causes through public health measures (e.g., hepatitis B, HPV vaccines). There are a number of other factors that are relevant to pat- terns of global cancer incidence. Diet 19 and obesity are risk fac- tors for some cancers. 20 This is notable given increasing trends in unhealthy diet and sedentary lifestyle among developing countries. 21 The impact of genetic polymorphisms on patterns of global cancer incidence has not been fully elucidated, but there is some suggestion of their relevance. 22,23 Similarly, the

Global Status of Access to Radiation Therapy

Access to radiation therapy is a multifactorial issue. Availability of machines and personnel for treatment is a key part of access to care. Other considerations include spatial accessibility, acceptability, affordability, accommodation, and awareness. 27,28

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Section II Techniques, Modalities, and Modifiers in Radiation Oncology

10

1

Africa LA EE Asia High income

80% prediction limit

0.1

Figure 28.3.  Megavoltage machines per million population ver- sus gross national income per capita on a log-log scale. Countries are divided by income more than US $12,000 (high income) and then by region: Africa, Latin America (LA), Eastern Europe (EE), and Asia. The solid line is a linear regression line and dotted lines are the 80% confidence limit. The vertical dotted line represents the cutoff for high income. (From Levin V, Tatsuzaki H. Radiotherapy services in countries in transition: gross national income per capita as a significant factor. Radiother Oncol 2002;63:147–150, with per- mission from Elsevier.)

Megavoltage machines per million population

1,000

10,000

100

Gross national income per capita (US$)

The most pertinent elements of access to radiation therapy in developing countries are discussed here. Availability of equipment and personnel for radiation ther- apy are common limiting factors in developing countries. Less than 5% of global medical spending on cancer is in developing countries. 29 This is despite developing countries containing over 80% of the world’s population 4 and almost 80% of the world’s premature death, disability, and ill health from cancer. 2 Insufficient medical training programs make it difficult to address the lack of key personnel for radiation oncology. 30–33 ,34 International Atomic Energy Agency (IAEA) data suggest that developing countries only have about a third of the world’s 12,206 megavoltage radiation therapy units despite an esti- mated need for between double and triple the current num- ber. 35 There are currently 23 countries with populations over 1 million with no known machines, mostly in Africa. 35 The greatest limitations in machine supply are strongly associated with low national economic status (Fig. 28.3). 36 Given the expected rise in cancer incidence in LMCs, these large mismatches between need and availability will only increase if current machine supply is not improved. In addition to machine availability, one must also consider the need for other physical resources. These include clinical space, bunkers, other equipment (brachytherapy, simulation, immobilization, treatment planning, beam modification, dosimetry, quality assurance), a reliable power supply for linear accelerators, and the availability of parts (and technical support) for machine maintenance and repair. 37 The state of radiation therapy resources varies between developing countries and regions. 31,32,36,38 Some selected exam- ples are provided for illustration. In 1999, Levin et al. 38 docu- mented the availability and distribution of radiation therapy equipment in Africa. Only 22 of 56 countries in Africa were con- fidently known to have megavoltage radiation therapy facilities. In total, more than 400 million Africans had effectively no access to radiation therapy. Although machine supply has since modestly increased, there are still dramatic shortfalls in machine supply in Sub-Saharan Africa. 35 In the Asia and Pacific Region, Tatsuzaki and Levin 31 found an 82-fold variation in the number of megavoltage machines per million population for 1999. China’s and India’s machine supply has increased in recent years, though capacity is still well below what is needed to treat all patients (Table 28.1). 3,35,39 Workforce resources vary considerably between countries, and

most countries have less than two radiation oncologists per 1,000 incident cancers annually. 3 , 33 , 35 More physicists are required if radiotherapy capacity is to expand in the Asia Pacific region. 33 In the era of multidisciplinary cancer therapy, for instance, for head and neck squamous cell carcinoma, availability of other elements of diagnosis and therapy such as surgical oncol- ogy, medical oncology, oncology nursing, pathology, radiology, rehabilitation, supportive care, and palliative care are all important to effective cancer management. 40 Without adequate pathology and radiology, it is not possible to effectively diagnose cancer and distinguish curative from palliative cases. The need for surgical capacity is especially noted, given its central role in curative treatment of the most common cancers globally, espe- cially in their early stages. Access to palliative care, including pain control for moderate to severe pain, is also a major issue. The World Health Organization (WHO) estimates 5 billion peo- ple live in countries with limited or no access to narcotic anal- gesics and other controlled substances, with an estimated 5.5 million patients with terminal cancer dying each year without adequate treatment. 41 Spatial accessibility refers to the geographic accessibility of medical treatments. Available information suggests spatial accessibility is a major issue in LMCs. 35 ,42 With radiation ther- apy centers often in large cities, rural populations may face substantial financial challenges when traveling into cities for the duration of radiation treatment. Acceptability of available options can impact an individu- al’s willingness to take advantage of services and adhere to recommended therapies. For example, a small study from Cameroon found beliefs, fears, cultural factors, and awareness were among explanations for delay in seeking medical atten- tion for cancer. 43 Values surrounding effects of pelvic radiation treatment on fertility, loss of hair with some chemotherapy, and anatomic changes associated with surgery such as mastec- tomy are some potential factors in need of further description and quantification in developing countries. Culturally appro- priate cancer control plans sensitive to a region’s social and political concerns are needed, including initiatives to overcome stigma and improve awareness. 44 Affordability of radiation therapy and other forms of cancer therapy are a major concern in LMCs. 45 Households often have limited or no health insurance coverage, especially in low- income and lower middle-income countries and more often

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Chapter 28 Radiation Oncology in the Developing World

oping countries, commonly cancer, cardiovascular dis- ease, chronic lung disease, and mental illness, impose a major strain on current resources and health care models. Challenges to the structure of cancer control and radiation therapy in limited-resource settings may also include insuffi- cient priority of cancer control among some gov- ernments and donor agen- cies with many competing priorities. Other issues may include political or social instability, conflict, corrup- tion, and fragmented ser- vice provision. The process of health care refers to what occurs while care is provided. For radiation oncology, this includes technical ele- ments of quality assur- ance, treatment prescrip- tion, treatment planning, and treatment delivery. It

Table 28.1  Megavoltage Machine Supply AND cancer burden in 17 Asia Pacific Countries

2010 Per Capita Gross National Income ($US)

Population (Millions) 2010

Incident Cancers 2010

Megavoltage (MV) Machines 2011

Incident Cancers per MV Machine

Country

Myanmar

n.a. 640

48.0

69,952 150,271 147,738 119,374 1,001,749 4,603 82,468 25,802 309,582 118,601 2,978,386

6

11,659 10,018 3,358 3,730 2,100 2,302 2,749 2,150 9,105 1,797 1,958 1,563 1,659

Bangladesh

148.7 173.6

15 44 32

Pakistan Vietnam

1,050 1,100 1,340 1,890 2,050 2,290 2,580 4,210 4,260 7,900 19,890 29,050 a 40,920 42,150 43,740 a

87.9

India

1,224.6

477

Mongolia Philippines Sri Lanka Indonesia

2.8

2

93.3 20.9

30 12 34 66

239.9

Thailand

69.1

China

1,348.9

1,521

Malaysia

28.4 48.2

34,386 179,187 21,080 14,495 637,963 112,023

22

Korea, Rep New Zealand

108

4.4 5.1

25 12

843

Singapore

1,208

Japan

126.5 22.3

905 131

705 855

Australia

Total

3,692.6

6,007,660

3,442

n.a., not available. a 2009 data. As a simple estimate, countries with more than 1,000 new cancers annually per radiation machine most likely have a short- fall of radiation machines. 2010 gross national income per capita information provided by the World Bank Group (Atlas method), http:// data.worldbank.org/about/country-classifications. 2010 population data from the World Population Prospects 2010 revision, http://esa. un.org/unpd/wpp/index.htm. Projected cancer incidence in 2010 from GLOBOCAN 2008, http://globocan.iarc.fr/. Reported number of megavoltage radiation machines from Directory of Radiotherapy Centers (DIRAC) August 2011, http://www-naweb.iaea.org/nahu/dirac/ default.shtm.

among the poor in LMCs. 46, 47 This is notable as cancer-related public health care may be inadequate or nonexistent. The cost of travel to the nearest cancer center can itself be another major financial obstacle, and costs of staying for the length of radia- tion treatment in another location can mean lost income and more cost to the patient and family. 45 A family may lose addi- tional income due to caregiver absence from work. 45,48 Awareness of the basic cancer principles and the value of cancer screening and early detection may limit timely access to cancer services for the public in LMCs. A large Union for International Cancer Control (UICC) survey of multiple LMCs found substantial lack of awareness of common preventable causes of cancer and found that a quarter or more of respon- dents in Asia and Africa did not think cancer could be cured. 49 Limited awareness of principles of cancer diagnosis and appro- priate referral among nonspecialist health care workers may be further limiting factors for access to cancer treatment. Health care worker training in oncologic principles may be extremely basic or insufficient in some cases. 50 Key dimensions of quality are described by the Institute of Medicine as safety, effectiveness, patient-centeredness, timeli- ness, efficiency, and equity. 51 Quality can be assessed through consideration of a health system’s structure, process, and out- comes. 52 Elements of structure are physical resources, human resources, and organizational structure. Limitations in physical and human resources in LMCs have already been described. The access issues that relate to late presentation and failure to receive indicated treatment arguably have the greatest impact on outcomes and quality of radiation therapy in developing countries. Quality may be further degraded by the inequitable access of the few available resources between country and city, rich and poor. The organizational structure of health care in developing countries has historically revolved around communicable dis- ease, nutritional deficiencies, and child and maternal health. The additional burden of noncommunicable disease in devel- Quality of Radiation Oncology in Developing Countries

also includes the integration of multidisciplinary services needed alongside radiation oncology for effective cancer man- agement. A major process issue in some countries is system- related delay in diagnosis. 53,54 This probably contributes to high rates of advanced disease at presentation. System-related diagnostic delay can relate to weak or nonexistent referral sys- tems or limited resources for diagnosis. It is compounded by patient-related delay in seeking medical attention due to previ- ously described access issues. 55 The additional impact on delay due to waiting times for radiation following radiation oncology consultation requires further characterization in LMCs. The technical process of radiotherapy is a vital element of quality. For this reason, the IAEA and WHO have maintained a postal dose audit program using thermoluminescent devices (TLDs). A report focusing on measurements from developing countries found acceptable results, with most machines cali- brated within the ± 5% dose acceptance limit. Sixteen percent of machines registered measurements outside this range in the first round of testing, with 93% measuring dose within 5% of the standard after the second round. 56 Notably, a dosimetric audit in Latin America and the Caribbean suggested an asso- ciation between on-duty medical physics support and accept- able TLD results. 57 This emphasizes the importance of ade- quate staffing to a radiation department’s quality assurance process. Current reports are too limited to comment on the quality of general patterns of the radiation oncology clinical process in regions of the developing world. There are most certainly specific opportunities for gains. Taking advantage of hypofrac- tionation to increase throughput where there is supportive evidence has not always occurred, as one survey on patterns of palliative radiation for bone metastasis in Africa suggests. 58 Implementation of multidisciplinary decision making among oncologists in LMCs is important but not always present. 59,60 Treatment refusal or nonadherence by patients can be a major problem in some cases and is an important area for quality improvement where it exists. 42,48,61 Audits of the clinical deci- sion-making and the treatment-planning process may provide a useful means of ensuring patient safety, improving pro- cesses, and creating opportunities for continuing educa- tion. 62 ,63 This is particularly important with the introduction of

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Section II Techniques, Modalities, and Modifiers in Radiation Oncology

technology at new locations. For example, initial experience with this approach in a new radiation therapy center in an Asian developing country found suboptimal management in 52% of cases. 62 Adverse event rates in developing countries treating with radiation are largely unknown. A report examining the risk profile of radiation therapy for the WHO could not identify any detailed reports of adverse events from Africa or Asia. 64 It is important to highlight the need for adverse event recording and reporting for the purpose of patient safety and quality improvement for all countries utilizing radiation therapy. Finally, quality of radiation oncology in developing coun- tries relates to outcomes. Of all cancer outcomes, there is the most information on survival. Generally, overall survival for cancer patients is lower, and sometimes dramatically so, for populations in developing countries. In a large multinational series from the International Agency for Research on Cancer (IARC), 5-year age-standardized relative survival for cervix cancer was 79% in Seoul, South Korea, but 46% in Mumbai, India; 22% in The Gambia; and only 13% in Kampala, Uganda. 65 Similarly, for breast cancer, survival rates ranged from 90% in Hong Kong SAR to 13% in The Gambia. When absolute survival was stratified by extent of disease, in many cases, treatment outcomes were still inferior in regions with less developed health services compared to regions with more developed services (e.g., local and regional extent breast cancer and larynx cancer). This may reflect access and quality issues in diagnosis, treatment, and follow-up and/or limitations of the available data. Radiation therapy has been shown to be cost-effective in numerous developed world settings. 66 ,67–68 A study by the Breast Health Global Initiative (BHGI) suggests that a com- prehensive breast cancer program involving early detection and treatment, including radiotherapy, can be cost-effective in developing world settings. 69 Notably, the BHGI study found that it was more cost-effective to invest in early detection in addition to comprehensive cancer therapy resources for breast cancer than in cancer therapy resources alone. This finding reflects the ability of early detection to increase the chances of cure due to earlier stage presentation and to some degree the lower cost of treating earlier stage versus locally advanced dis- ease. In other situations, preventing cancer reduces the num- ber of patients needing treatment, which can also impact on overall cost of therapy for a population. In addition to cost-effectiveness, the actual cost of deliver- ing interventions must be taken into account when planning. Though per-patient costs of radiation can be quite low com- pared to other modalities given the long usage cycle of mega- voltage radiotherapy units, large up-front costs can serve as a major deterrent to establishing services. Unfortunately, there is little context-specific information on the economics of cancer therapies in developing countries. One exception is an IAEA- supported study demonstrating wide variation in the cost of delivering a fraction of radiation between a sample of units in developing and developed countries. 70 For the costs consid- ered, the median cost per fraction delivered by a cobalt machine was less than half that for linear accelerators. Cost variation was most associated with radiation machine cost and machine usage for linear accelerators, and for cobalt machines, machine cost, usage, and personnel cost. Undoubtedly, applications of various radiation therapy techniques and modern equipment will yield opportunities to maximize the cost–benefit ratio of radiation treatment in developing countries. Hypofractionation yields opportunities to treat more patients with the same supply of equipment. 71 Economics of Radiation Therapy in Developing Countries

Hypofractionation for cervical cancer and lung cancer are examples of identified areas for research. 72–74 Investigation of brachytherapy or intraoperative radiation therapy (IORT) may provide means of delivering adjuvant treatments rapidly. High– dose-rate (HDR) brachytherapy markedly increases patient throughput (e.g., for cervical cancer) compared to low–dose- rate (LDR) brachytherapy per machine. 75 An IAEA study of accelerated radiation therapy for head and neck cancer in developing countries suggests an opportunity for increasing effectiveness of treatment without increasing departmental resources, though with increased, but tolerable, acute toxicity. 76 There has been some debate about the relative merits of cobalt-60 versus linear accelerator technology for limited resource settings. The ideal mix of machines will change depending on site-specific considerations and future market dynamics. Regarding the latter, development of lower-cost entry-level linear accelerators and, on the other hand, increases in costs of new and more sophisticated cobalt equipment would affect decision making. 77 It is useful to remember that quality assurance costs, maintenance costs, and associated personnel requirements of cobalt machines are estimated to be substan- tially less than for linear accelerators and reliability is generally higher. 70,77 Translating Knowledge into Action Recognized priorities for action fall into six categories: (a) advo- cacy, (b) investment, (c) planning, (d) capacity building, (e) qual- ity, and (f) research. 47,77–82 The varying resources, priorities, and disease burden seen in countries at different stages of develop- ment mean that there is no single solution that will apply in all cases. 81 In low-income countries with extreme resource limi- tations, a strategy focusing on cost-effective prevention, rais- ing awareness of cancer within the population, monitoring of process and outcomes, good palliative care, and focused early detection and treatment goals would be a reasonable starting point. 83 Advocacy.  An international coalition to support cancer control and cancer care in developing countries is emerging. The UICC plays an important role as an umbrella organiza- tion for advocacy. Other groups range from international agen- cies (e.g., IAEA, WHO, IARC), to national organizations (e.g., U.S. National Cancer Institute), to professional groups (e.g., American Society for Radiation Oncology [ASTRO], European Society for Radiotherapy and Oncology [ESTRO], American Society of Clinical Oncology [ASCO], International Organization for Medical Physics [IOMP]), to nongovernmental organiza- tions (NGOs) (e.g., Lance Armstrong Foundation, International Network for Cancer Treatment and Research [INCTR], Axios International, AfrOx, American Cancer Society), to academic institutions and hospitals (e.g., the Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries [GTF.CCC] convened by Harvard, St. Jude Children’s Research Hospital). Through the advocacy of the UICC and many other partners (e.g., NCD Alliance), the Political Declaration 84 of the United Nations High-Level Meeting on the Prevention and Control of Non-communicable Diseases (September 19–20, 2011) was an important acknowledgment by governments of the global problem of cancer and other non- communicable diseases. It was also a substantial step toward specific and concerted action by the international community. Investment.  The advocacy and work of the many cancer control groups range from local to global, and from grassroots to high-level agencies. All approaches are extremely impor- tant for generating the political will to invest in cancer control. Particularly in middle-income countries, incorporation of can- cer care into public health insurance for those living in poverty

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Chapter 28 Radiation Oncology in the Developing World

is an important, and challenging, goal to meet. 47 ,85 Given the shortage of national funding for cancer care in poorer coun- tries, international private and public donor support and advo- cacy for tiered pricing will be notably important in improving access to cancer therapy. Planning.  Development of radiation therapy capacity can- not occur in isolation. Radiation therapy resources must be integrated into a broader context of multidisciplinary cancer care and cancer control and into a functional health system capable of tackling the double burden of communicable and noncommunicable diseases afflicting developing countries. 86 A national cancer control plan and collection of cancer regis- try and health data are central in organizing resources in an equitable and appropriate fashion. 87 Notably, the GTF.CCC has published an important resource for planning, advocacy, and priority setting entitled Closing the Cancer Divide: A Blueprint to Expand Access in Low and Middle Income Countries. 88 Prevention (e.g., tobacco control, hepatitis B and HPV vac- cination) and early detection are crucial in reducing the burden of advanced cancers in developing countries. When early detection and prevention are combined with timely access to effective cancer therapy, there is great potential for dramati- cally reducing deaths from cancer in developing countries as well as minimizing national costs of cancer therapy. 47 Numerous relevant resources on cancer control and other noncommuni- cable diseases have been published online by the WHO, includ- ing a series of modules on cancer control planning, 89 and the Framework Convention on Tobacco Control. The IAEA plays a prominent role in quality assurance, safety standards, and dose calibration of radiation therapy equipment internationally. It has also been involved in numer- ous technical cooperation projects and radiation therapy clini- cal trials in developing countries. In 2004, the IAEA launched the Program of Action for Cancer Treatment (PACT) to widen the scope of its work in radiation therapy planning and capac- ity building. Its wide-ranging plan started with the development of sustainable demonstration radiation treatment sites in six countries throughout the developing world (Albania, Nicaragua, Sri Lanka, Tanzania, Vietnam, and Yemen). The PACT program situates the delivery of radiation therapy within a comprehen- sive framework including prevention, early detection, treat- ment, and palliation. Plans sensitive to the target country’s social and political situation are developed through local and international partnerships. Other IAEA initiatives for develop- ing countries include strengthening pediatric radiation oncol- ogy and quality audits. At a global level, breast cancer guidelines stratified by avail- ability of resources have been developed through the Breast Health Global Initiative. 90 This is a useful paradigm for devel- oping resource-appropriate and stepwise, scalable goals and guidelines for cancer care that is being adopted for other can- cers. 91 A related approach has been used by the IAEA to describe additional resource requirements, benefits, and risks for specific approaches in lung cancer treatment, including curative and palliative radiation. 92 Developing innovative means of organizing and funding cancer services is needed. The IAEA’s PACT program offers opportunities to identify successful models of service delivery and planning. A model of radiotherapy service provision utiliz- ing geographically dispersed telemedicine-linked sites with varying levels of capacity has also been proposed by an Indian group to maximize available resources. 93 Another concept that is being explored is utilizing community health workers and primary care to expand cancer-related service provision. Proposed activities are cancer prevention, early detection, some treatment (e.g., systemic therapy), palliation, and follow- up. 47 A social business model is one potential solution to financing radiation therapy services. 94 This is being explored as part of a Bangladesh initiative.

Capacity Building.  The importance of improving human resources for radiation oncology and oncology in gen- eral cannot be overstated given the global workforce short- age of trained health care professionals. Some initial efforts have been made in developing curricula and educational approaches specific to the discipline of radiation medicine. 95,96 The IAEA has been notably involved in these efforts. The issue of loss of trained staff from developing to developed countries is especially important to consider in developing educational programs. Urban regions in LMCs may have high-level exper- tise that can be utilized in developing national training pro- grams. A complementary approach is online training. This is the approach of the Virtual University for Cancer Control and Regional Training Network (VUCCnet) initiative in Africa. A growing number cancer centers, regional groups, and spe- cific nations have been involved in twinning projects build- ing capacity for cancer therapy in limited-resource countries. These initiatives have been particularly strong in pediatric oncology, with demonstrated success. 97,98 They provide an appealing means for broad participation in improving cancer control in developing countries. Numerous oncology societies in developed and developing countries support initiatives to build capacity in developing countries. The African Organization for Research and Training in Cancer (AORTIC) is an Africa-based collaboration with an advocacy, research, and training focus in cancer control for Africa. ESTRO, ASTRO, and a number of other radiation oncol- ogy societies support initiatives for education and capacity building in developing countries. ASCO has developed a num- ber of ongoing initiatives in training, mentoring, and continu- ing education of oncologists in developing countries, including translation by local editors of their flagship journal into 12 languages. 99 The U.S. National Cancer Institute Radiation Research Program is partnering with other oncology groups to develop a capacity-building Cancer Expert Corps. Regional and national initiatives are very important for improving the capacity to treat cancer in developing countries. For example, the Forum for Nuclear Cooperation in Asia (FNCA) organizes radiation therapy protocols in the Asian region for the common problems of cervical cancer and naso- pharyngeal cancer. 100 The FNCA involves Asian countries at a wide range of economic levels. At a national level, the Association of Radiation Oncologists of India (AROI) publishes a scientific journal and supports various educational and pro- fessional activities. 101 Quality.  Embedded within the themes of investment, planning, and capacity building is the implicit theme of struc- ture-related quality improvement. Process-related initiatives in quality are another very important part of ensuring optimal outcomes. These are often referred to indirectly (e.g., safety, effectiveness, patient-centeredness, timeliness, efficiency, equity). 51 Quality improvement relating to process and orga- nizational structure is important as it holds the potential for improving some outcomes more rapidly than other drivers of health, such as economic growth. 102 One important element of quality for radiation oncology in developing countries is safety, given the potential for unsafe treatment to negate any benefit of available treatment. 103 Safety includes the clinical process, the various elements of technical quality assurance, maintenance, worker safety, public safety, and source secu- rity. 104,105 Safety requires investment in appropriate dosimetry equipment, sufficiently trained human resources, and time for quality assurance activities. 105 Internal and external audits, peer review, regulation, accreditation, certification, checklists, adverse event reporting, common protocols, quality improve- ment, and independent checking are examples of interven- tions ensuring safety and quality assurance in radiation oncol- ogy. 64,106,107

Techniques, Modalities, and Modifiers in Radiation Oncology

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Section II Techniques, Modalities, and Modifiers in Radiation Oncology

Research.  There are many fundamental questions that remain unanswered specific to cancer in developing coun- tries. For instance, it cannot be assumed that approaches to treating cancer from developed settings will produce the same results when applied in other countries. Considerations include potential differences in disease bulk, malnutrition, rates of chronic infections such as HIV/tuberculosis/hepatitis B, and genetic polymorphisms affecting disease biology and treatment response. 108–112 Resources for supportive care and quality assur- ance are also considerations. There are many unknowns in can- cer epidemiology and basic science, and, as mentioned, more health services research is emphatically needed into areas such as access, quality, and economics. 87 Supporting research on cancer by investigators in the devel- oping world is important as it can build local research capacity and provide a means of adapting scientific knowledge to local circumstances to meet national health priorities. 113 The U.S. National Cancer Institute has also been involved with numer- ous international collaborations. Protocol-driven clinical research can also strengthen local treatment capacity. The INCTR has been involved in designing clinical trials relevant to developing world situations, as has the IAEA. International research partnerships are essential in the interconnected and interdependent world we live in. 113 Many developing countries have quite advanced resources to sustain research activities; for instance, a number of clinical trials for cervical cancer radiotherapy have occurred in India (e.g., HDR vs. LDR brachytherapy, radiation vs. chemoradiation). 114,115 India is also home of the Advanced Center for Treatment, Research and Education in Cancer (ACTREC), part of the Tata Memorial Center. Regional research collaborations are devel- oping, for example, the FNCA. In addition, of note, a number of research/teaching twinning partnerships between developed and developing countries have been formed. 97,98 ,116 Undoubtedly, industry and development will play an impor- tant role in improving access to quality radiation therapy equip- ment. Equipment that is affordable, safe, and technically suit- able for developing country conditions is needed. 77 The IAEA has taken leadership in advocacy for such equipment, and there is hope that new solutions will proliferate. Creative public–private partnerships will be important, as will be innovative equipment design. This last point has been exemplified by a group in Canada that has pioneered cobalt-60 tomotherapy. 117 Conclusion Cancer in the developing world is an urgent problem, reaching critical proportions. Almost 60% of all cancer cases occur in the developing world. Vast numbers of people in developing coun- tries have either limited access or no access to radiation therapy. At a time when new gains in oncology outcomes in the developed world are incremental, oncologists have the chance to help make some of the largest survival gains in history in the developing world. In addition, the potential for health care gains through cancer prevention and early detection, and the relief of suffer- ing through palliative care are enormous. The poor deserve fair access to quality cancer care. The challenge will now be to deliver this in a thoughtful and contextually appropriate way. Selected References A full list of references for this chapter is available online. 1. World Bank. World Bank country classifications. 2010. Available at: http://data. worldbank.org/about/country-classifications. Accessed August 13, 2011. 2. World Health Organization. Projections of mortality and burden of disease, 2004-2030. 2008. Available at: http://www.who.int/healthinfo/global_burden_ disease/projections/en/index.html. Accessed August 13, 2011. 3. Ferlay J, Shin HR, Bray F, et al. GLOBOCAN 2008 v.1.2, Cancer incidence and mortality worldwide. IARC CancerBase No. 10 [Internet]. 2010. Available at: http://www-dep.iarc.fr. Accessed August 14, 2011. 6. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011;61(2):69–90.

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