The Unique Issues With Brachytherapy in Low- and Middle-Income Countries

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Gynecologic carcinomas, including cervical cancer, present a significant burden on low- and middle-income countries (LMICs). Brachytherapy plays an integral role in the treatment of gynecologic carcinomas, as it is essential for both curative and palliative treatment. However, there are numerous geographic and economic barriers to providing brachytherapy to cancer patients in LMICs. This article examines the role and delivery of brachytherapy in gynecological cancer treatment; brachytherapy capacity in LMICs, including infrastructure, equipment, and human resources considerations; commissioning, training, and clinical implementation of brachytherapy in LMICs; other challenges, and strategies for improvement in brachytherapy delivery in LMICs, including innovation and current and upcoming international initiatives.

Introduction

Cervical carcinoma, although relatively rare in most developed countries, is a significant global health problem. According to the World Health Organization (WHO) 528,000 women are diagnosed each year with cervical carcinoma and 266,000 women succumb to the disease each year, 90% of them in low- to middle-income countries.1 In these areas the incidence: mortality ratio exceeds 50%. This is the equivalent to 1 life lost every 2 minutes, which approximates the number of women who die annually in pregnancy and childbirth. Most of these women are raising their children, and contributing to the economic well-being of their families and communities. Even more alarming, although incidence and death rates are decreasing in high-income countries, cervical cancer deaths are projected to increase by 25% over the next 10 years in low-income countries. The highest rates are in Central and Southern America, East Africa, South and Southeast Asia, and the Western Pacific. In 55 countries, it is the number one cancer killer and most common cancer among women in 45 countries. In 2013, at the World Health Assembly, an action plan for the prevention and control of noncommunicable diseases was agreed upon and cervical cancer control was considered a priority.

Many efforts to eradicate this disease focus on screening and prevention. The cause has been well-established, with the human papilloma virus (HPV) subtypes 16 and 18 causing 70% of cases worldwide. There are 3 vaccines currently available—Gardasil (quadrivalent), Gardasil 9 (nonavalent) and Cervarix. All 3 prevent infections with HPV types 16 and 18 but Gardasil also protects again HPV types 6 and 11, which cause 90% of genital warts.2 Gardasil 9 also adds HPV types 31, 33, 45, 52, and 58. Since the vaccines do not treat pre-existing HPV infection or disease, the vaccination is recommended before sexual activity begins. The vaccine is currently not available in many countries. Other efforts that focus on prevention emphasize screening to detect precancerous disease. Screening in developed countries consists of a Papanicolaou smear and HPV testing. In most low- to middle-income countries, where these techniques may not be available, the cervix is treated with acetic acid and abnormal areas are treated with cryotherapy, a “screen and treat” approach.

Not only does prevention and treatment of noninvasive precursor lesions affect this alarming incidence:mortality ratio, it is also profoundly affected by the lack of adequate treatment once the diagnosis is made. The challenges are innumerable including lack of epidemiologic data in some areas to convince local leaders of the severity of the problem; lack of funding for supplies, equipment and infrastructure; lack of an effective referral system and inequality of access to healthcare for women. Access to linear accelerators (LINACS) in most of the developing world is poor and disparate. For example, Tanzania, with a population of 47.4 million is served by only 2 old cobalt machines, although the charity organization Radiating Hope (www.radiatinghope.org) partnered with the Foundation for Cancer Care in Tanzania to provide a LINACS. For comparison, in the United States (US), there is 1 radiation machine per 100,000 people.3 Guatemala, with a population of 15.8 million, has only 5 radiation centers and 11 radiation machines, or 1 radiation machine per 1.4 million people. There are several clinics (HOPE Radiotherapy Center, International Institute of Advanced Therapies, and Hospital el Pilar) that offer radiation therapy and brachytherapy in Guatemala.4 Although there are numerous studies proving the survival benefit with the addition of brachytherapy to external beam therapy in the primary treatment of cervical carcinoma,5, 6 many countries face unique challenges and struggle to offer this modality as a routine part of gynecologic cancer care.5, 6 For example, in Guatemala, there are 4 brachytherapy delivery systems, but no high-dose-rate brachytherapy equipment.7

In this issue, we would discuss the role and delivery of brachytherapy for carcinoma, the capacity in low- to middle-income countries, challenges with implementation of a brachytherapy program and strategies for improvement.

Section snippets

The Role and Delivery of Brachytherapy in Treatment of Gynecologic Cancers

Brachytherapy plays an integral role in the treatment of gynecologic carcinomas. Placing a brachytherapy source in close proximity to tumor allows a high dose of radiation to the target and minimizes the dose to nearby sensitive organs, making it both safer and more effective than external beam alone.8 For early endometrial carcinoma, cylinder brachytherapy is used to treat the vaginal cuff following primary surgical therapy. However, for the medically inoperable patient with primary uterine

Brachytherapy Capacity in Low- and Middle-Income Countries

Brachytherapy offers a viable method of treating certain cancers in regions of the world where geographic and economic barriers would otherwise prevent cancer patients from receiving fractionated courses of external beam radiotherapy. For cervical cancer, which accounted for 7.5% of cancer-related deaths in women in developing countries in 2012, the combination of external beam radiotherapy and brachytherapy is essential to cure locally advanced cases.11

Low- and middle-income countries (LMICs)

Commissioning, Training, and Clinical Implementation of Brachytherapy in LMICs

The choice of brachytherapy source, whether LDR or HDR, and the platform to be used, is a complex decision and beyond the scope of this article. However, HDR has a number of advantages including ability to perform it in an outpatient setting, smaller source size and applicators, ability to perform dose optimization, and an increase in patient comfort and decreased risk of thromboembolic events. There are disadvantages and possible risks with HDR brachytherapy including expense, requirement for

Other Challenges

Establishing a sustainable pathway for equipment repair and maintenance presents another challenge. In sub-Saharan Africa, up to 70% of medical equipment lies idle because of errors made during acquisition or installation and a lack of adequate training and technical support.32 Of the equipment in use, 25%-35% is not operable because of equipment malfunction, and a lack of capacity in the local environment for repair. An advantage for most LDR techniques is the relative simplicity of the

Local (at Country Level) Engagement

At the country level, recognizing the need for expanding training in brachytherapy and developing strategies simultaneously to target the multiple issues described above is crucial.

Strategic planning, appropriate resource allocation for infrastructure development in a phased manner with strict achievable goals are required at the national level. Simultaneously, brachytherapy personnel team training, including problem-oriented/practical learning initiatives and development of standard operating

Conclusion

Cervical cancer is the fourth most common cancer affecting women worldwide, ~90% of deaths occurring in LMICs.37 In the developing world, cervical cancer is the leading cause of cancer-related deaths in women.38 Thus, much of the global burden of cervical cancer falls on LMICs.

Brachytherapy plays an integral role in the treatment of gynecologic carcinomas.11 Brachytherapy is essential for both the curative and palliative treatment of cervical cancer. However, there are numerous geographic and

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    Conflict of interest: none.

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