Lung Cancer in Armenia

Davit Zohrabyan, MD^a,b [email protected] ∙ Nune Karapetyan, MD, MPH^a,c ∙ Samvel Danielyan, MD, PhD^a ∙ … ∙ Parandzem Khachatryan, MD, PhD^m,n ∙ Armen Mkhitaryan, MD, PhDⁿ ∙ Gregory P. Kalemkerian, MD^o … Show moreAffiliations & NotesArticle Info

Cover Image - Journal of Thoracic Oncology, Volume 18, Issue 4

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Introduction

Located at the crossroads between Europe and Asia, the Republic of Armenia ranks as an upper-middle–income country with a population of 2.97 million and a population density of 104.39 people/km².¹ According to World Bank 2021 data, Armenia’s gross domestic product per capita is $4670.¹ Although Armenia consists of 10 provinces, the population is concentrated in the capital city, Yerevan, with 1.1 million inhabitants.²

After Armenia gained independence from the Soviet Union in 1991, the prevailing Semashko-style health care system was decentralized, leading to the functional disintegration of the primary health care system.³ Since then, Armenia has been involved in three wars, the last one in 2020 during the COVID-19 pandemic, resulting in further deterioration of the economy and the health care system. On the basis of the World Bank’s 2019 estimate, total spending on health care in Armenia was 11.3% of GDP. Nevertheless, the governmental share of these costs is low, with private health care expenditures, primarily out-of-pocket patient payments, accounting for nearly 85% of total health care spending, making Armenia’s health care system one of the most poorly financed in the world.⁴^,⁵ The Armenian Ministry of Health (MoH) administers Basic Benefit Packages (BBPs) to provide health care to vulnerable populations, but the BBP budget routinely runs out during the year resulting in the loss of access to primary health care for many citizens. In 2019, the national government developed an initiative to introduce a system of Universal Health Insurance that is due to be implemented in 2024.⁶^,⁷

Several companies offer Armenians private health insurance on a voluntary basis. This Voluntary Health Insurance (VHI) is available as individual, family, or corporate packages, but most insurers operate mainly through larger employers (e.g., international agencies or corporations), leaving most older individuals without access to VHI. When available, VHI may cover a wide range of medical services, including diagnostic and therapeutic interventions for cancer. Nevertheless, insurance beneficiaries frequently have substantial difficulty claiming reimbursement owing to suboptimal VHI documentation.⁶

Epidemiology

Cancer statistics for Armenia are usually obtained from the Globocan database or the Armenian MoH’s annual reports. Nevertheless, the data in the national cancer registry are incomplete and may not reflect the true cancer incidence in Armenia. According to the Statistical Yearbook of Armenia 2022, the prevalence of respiratory tract and pulmonary malignancies was 3328 in 2021.⁸ Lung cancer had the highest incidence and mortality rates among all types of cancer (excluding nonmelanoma skin cancer), accounting for 14.3% (n = 1320) of new cases and 20.1% (n = 1226) of cancer-related deaths.⁹ In men, lung cancer was the most frequent cancer, accounting for 22.5% of new cases, whereas in women, lung cancer accounted for 5% of new cases and was the fifth most common cancer (after breast, colorectal, uterine, and stomach cancers). With age-standardized mortality rates of 175.7 and 93.4 per 100,000 men and women, respectively, lung cancer ranks first in men and fifth in women. Overall, the World Health Rankings report that Armenia has the 26th highest lung cancer mortality rate in the world.^9–11

Tobacco Control

In 2021, the Armenian MoH, the United Nations Development Program, and the WHO jointly developed a report calculating the burden of tobacco use on the national economy.¹² This report noted that 28% of the Armenian population between the ages of 18 and 69 years used some form of tobacco, with 51% of men and 3% of women being current smokers (Fig. 1).¹² It was estimated that tobacco use was responsible for 5500 deaths per year in Armenia.¹² Other studies have found that Armenia has the second highest percentage of male smokers in the WHO European Region^12–14 (Fig. 2). After ratifying the WHO Framework Convention on Tobacco Control in 2004, Armenia implemented smoke-free policies in selected public settings, including public transportation and educational, cultural, and health care facilities. In February 2020, this policy was expanded to restrict tobacco use in all public spaces, with a ban on smoking in cafés and restaurants taking effect in March 2022.¹⁴^,¹⁵

**Figure 1** Smoking prevalence in Armenia by province.¹² Source: United Nations Development Program. Website: the Case for Investing in WHO FCTC Implementation in Armenia. FCTC, Framework Convention on Tobacco Control.

**Figure 2** Smoking intensity by country in the WHO European region.¹² Source: United Nations Development Program. Website: the Case for Investing in WHO FCTC Implementation in Armenia. FCTC, Framework Convention on Tobacco Control.

Screening

Lung cancer screening and early detection programs have not been established in Armenia.¹⁶ Nevertheless, low-dose computed tomography (CT) is available in Yerevan and screening can be performed for high-risk people with out-of-pocket payment. The absence of screening programs contributes to the high incidence of late-stage lung cancer and poor outcomes of the disease. The Statistical Yearbook of Armenia 2022 notes that 19% of Armenians with lung cancer present with stage III disease and 62% with stage IV disease.⁸ Considering that lung cancer is the fourth most common cause of death in Armenia,¹⁷ it is crucial to develop a national lung cancer control program that integrates both tobacco control and early disease detection.

Diagnosis

The Armenian MoH has not yet developed nor endorsed national guidelines for the diagnosis and management of lung cancer, and reliable data on diagnostic capacity and efficiency are not available. Diagnostic CT is available in nearly all secondary and tertiary hospitals in Yerevan and in most of the larger cities in outlying provinces. The WHO Cancer Country Profile 2020 reported that Armenia has 37.4 CT scanners and 13.6 magnetic resonance imaging (MRI) scanners per 10,000 patients with cancer.¹⁸ The first and only positron emission tomography scanner was opened in Yerevan in 2020. CT and MRI costs are covered by the BBP for all patients with malignant diseases, but to obtain nationally covered examinations, patients must wait in queue for up to a month for a CT scan and several months for an MRI scan. Positron emission tomography is not covered by the government and must be paid for by the patients.

Pathologic examinations, including histologic, cytologic, and immunohistochemical studies, are routinely available, but only three private centers are currently providing molecular testing, which includes evaluations for EGFR, BRAF, KRAS, ALK, ROS1, NTRK, MET, and RET gene aberrations plus programmed death-ligand 1 (PD-L1) expression. The recent results of molecular diagnostic testing from two of the pathology centers are presented in Figure 3. Next-generation sequencing is available in only one center in Armenia, but it can also be obtained on a send-out basis on an oncologist’s request. In public hospitals, standard histologic assessment is covered by BBP, but the fees for immunohistochemical studies must be paid for by the patient. In private centers, fees for both pathologic evaluation and molecular testing must be covered by the patient.

**Figure 3** Driver mutations identified on NSCLC-specific genetic analyses performed at two pathology centers in Armenia. ∗Data are for January 2022 to November 2022. Neg, negative; Pos, positive.

Education

Yerevan State Medical University After M. Heratsi (YSMU) is the only state-sponsored medical school in Armenia. Graduates of YSMU can apply for a three-year General Oncology residency leading to an “Oncologist” specialization which allows them to practice in Surgical Oncology, Medical Oncology, or Radiation Oncology. Advanced training specifically in Medical Oncology or Radiation Oncology is not currently available in Armenia. Graduates from the Department of Thoracic Surgery residency can also practice General Surgical Oncology.

Treatment

According to Armenian MoH policy, oncology services should engage in a multidisciplinary team (MDT) meeting before the initial treatment of each patient with cancer, though adherence to this policy is inconsistent. Because nationally standardized lung cancer treatment guidelines have not been developed in Armenia, most oncologists rely on international guidelines (e.g., National Comprehensive Cancer Network, European Society for Medical Oncology, American Society of Clinical Oncology) or consensus strategies developed in MDT meetings to determine individual patient management plans. Optimally, the MDT should include a medical oncologist, radiation oncologist, thoracic surgeon, radiologist, and pathologist, but frequently, certain disciplines may not be adequately represented. Because of the lack of national treatment guidelines, treatment strategies may vary from center to center. In July 2022, the Immune Oncology Research Institute initiated a Lung Cancer Working Group, involving international experts and the local lung cancer medical community. This group discusses difficult cases on a biweekly basis, fosters lung cancer research in Armenia, and aims to develop nationally standardized lung cancer management guidelines.

Thoracic Surgery

Surgical treatment of lung cancer is only available in Yerevan, where at least six thoracic surgery centers perform lung cancer resections by means of both open thoracotomies and video-assisted thoracoscopic surgery. Robotic surgery is not yet available in Armenia. Mediastinoscopy is available, but it is rarely performed owing to the high out-of-pocket cost. Bronchoscopy with endobronchial ultrasound-guided biopsy is not yet available in Armenia. Therefore, nodal staging is mainly reliant on radiographic studies.

Patients with stage I to II NSCLC routinely undergo surgical resection with mediastinal lymph node sampling, possibly followed by adjuvant systemic therapy depending on pathologic findings. Patients with stage III NSCLC are usually evaluated by an MDT. If the patient is deemed to have potentially resectable disease, then they receive neoadjuvant systemic therapy followed by surgical resection. If their disease is deemed unresectable, then definitive radiotherapy (RT) with concurrent chemotherapy is usually recommended. For those with stage IIIA disease, the treatment plan usually depends on nodal staging. For T3N1 disease, surgery may be considered as the primary treatment option, followed by adjuvant systemic therapy. If nonbulky N2 lymph nodes are involved, then neoadjuvant chemotherapy or chemoimmunotherapy may be recommended. Surgeons typically prefer to avoid perioperative RT to minimize the risk of intraoperative and postoperative complications.

Open surgical procedures for cancer are covered by the national government. However, fees for video-assisted thoracoscopic surgery and other equipment-associated resources must be covered by the patients.

Radiation Therapy

Currently, RT is centralized in two medical centers in Yerevan. In 2020, a third RT unit in Gyumri, Armenia’s second largest city, was closed owing to limited capacity and outdated equipment. One of the active RT centers operates on a public basis at the National Center of Oncology. This facility uses both cobalt-60 and a 6-MV linear accelerator with the capacity for three-dimensional conformal RT. RT planning is done with either conventional or CT simulators, and both two-dimensional– and three-dimensional–planning software are available. This center’s staff consists of seven radiation oncologists, four residents, five medical physicists, and five radiation therapists. The other active facility, the Center of Radiation Therapy by the IRA Medical Group, operates on a private basis with three radiation oncologists, one resident, three medical physicists, and three radiation therapists. This facility is equipped with a 6-MV/15-MV linear accelerator capable of delivering three-dimensional conformal RT and intensity modulated RT. Currently, stereotactic body radiation therapy is not available in Armenia, but it is due to be implemented in two years. Table 1 presents the number of RT courses done for lung cancer at each of these centers in the past 2 years. RT at the National Center of Oncology is covered by BBP, whereas at the private facility, governmental co-payments can be provided.

Year	National Center of Oncology		Center of Radiation Therapy
Year	2D-RT (n)	3D-RT (n)	3D-RT (n)	IMRT (n)
2020	55	28	33	7
2021	81	31	35	9
Total	136	59	68	16

Table 1

Radiotherapy Courses for Patients With Lung Cancer in Armenia, 2020 and 2021

2D, two-dimensional; 3D, three-dimensional; IMRT, intensity modulated radiotherapy; RT, radiotherapy.

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Systemic Therapy

Systemic anticancer therapy is usually administered according to internationally accepted guidelines. Most of the anticancer drugs included in the WHO 22nd Model List of Essential Medicines are registered in Armenia¹⁹ (Table 2). Hence, evidence-based systemic therapy is generally available for patients with lung cancer.

NSCLC	SCLC
Cisplatin	Cisplatin
Carboplatin	Carboplatin
Gemcitabine	Etoposide
Docetaxel	Paclitaxel
Vinorelbine	Docetaxel
Etoposide	Irinotecan
Pemetrexed^a	Vinorelbine
Paclitaxel	Cyclophosphamide
Crizotinib	Gemcitabine
Alectinib	Doxorubicin
Atezolizumab^a	Atezolizumab^a
Ado-trastuzumab emtansine^a

Table 2

Antineoplastic Agents for Lung Cancer Registered in Armenia¹⁹

Drugs not included in the WHO 22nd Model List of Essential Medicines.

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Currently, 13 centers provide systemic anticancer therapy in Armenia, of which 11 are in Yerevan, one is in Gyumri, and one is in Vanadzor, the third largest city in the country. Because of the imbalanced distribution of treatment centers and challenges in transportation, the number of patients receiving systemic therapy in the outer provinces is significantly lower than those being treated in the capital. A general lack of trust by the population in physicians working outside of Yerevan also complicates the provision of adequate oncologic care.

Immunotherapy became available in Armenia in 2019, and the increased availability of PD-L1 expression testing has contributed to the frequent, evidence-based administration of immune checkpoint inhibitors. As noted earlier, molecular diagnostic testing for the full range of lung cancer-specific genetic aberrations is also available, allowing patients the opportunity to benefit from appropriate targeted therapy agents.

Because all patients with cancer are included in national BBPs, all hospitalization costs and some laboratory expenses are covered by governmental funds. Patients can also receive co-payments to partially cover drug expenses, with up to $700 provided annually to cover drug purchases of each patient with lung cancer. Nevertheless, most chemotherapy drug costs must be covered by the patient or, infrequently, by private health insurance. In addition, patients are not provided with any governmental support for targeted therapy or immunotherapy agents. Nonprofit health organizations and charitable foundations provide substantial funding for anticancer treatments in Armenia. For example, in September 2022, the Max Foundation began a program that provides crizotinib free of charge for all patients with ALK- or ROS1-rearranged NSCLC. In addition, the City of Smile charitable foundation covers all treatment expenses for children, adolescents, and young adults (up to 25 years of age) diagnosed with malignant diseases.

Palliative Care

The Palliative Care Needs Assessment in Armenia study was completed by the International Palliative Care Initiative in 2009 to 2010 and fostered the development and implementation of palliative care in Armenia.²⁰ Since then, the government has made significant efforts to improve the provision of palliative care, including legislative drug policy reforms and updated regulations on oral opioid analgesics. Nevertheless, until very recently, there were only two private palliative care centers in Armenia and a drastic shortage of palliative care financing. In October 2022, a new 30-bed palliative care center opened at the National Cancer Institute, where hospital expenses are covered by the national government. However, patients and their families are still responsible for the costs of the palliative drugs.

One of the main impediments to the widespread introduction of palliative care in Armenia is the lack of adequate training programs.²¹ Since 2017, YSMU has offered a 3-month postgraduate program in palliative care for nurses and physicians, but more comprehensive fellowship programs in palliative care are not available within the country. Poor access to opioids is another outstanding issue. Although narcotic analgesics, including oral morphine, are registered in Armenia, their use is exceptionally limited. The stigma associated with opioid use in Armenian society creates an environment in which physicians are reluctant to prescribe narcotics and patients frequently refuse to use them.²¹

Conclusions

Lung cancer imposes a significant socioeconomic burden on Armenian society. More effective measures to stem the epidemic of tobacco smoking are sorely needed if there is to be any future progress in managing the country’s lung cancer problem.

To assure high-quality, standardized care, it is essential for Armenia to develop nationally accepted lung cancer diagnostic and treatment guidelines and to increase provider access to evidence-based educational resources in the Armenian language. In addition, the design and implementation of separate training programs in Medical Oncology, Radiation Oncology, and Surgical Oncology (including General Thoracic Surgery) would expand the workforce and enhance the expertise of oncology specialists. The expansion of cancer research, including clinical trial development and participation, is also needed for both clinical and scientific advancement. Furthermore, it is necessary to ensure the accessibility of all oncology and palliative care services throughout the country. Eventually, an adequately funded universal health insurance plan must be implemented to provide adequate care for all patients with cancer in Armenia.

CRediT Authorship Contribution Statement

Davit Zohrabyan: Project administration, Supervision, Visualization, Writing—original draft, Writing—review and editing.

Nune Karapetyan: Data curation, Project administration, Visualization, Writing—original draft, Writing—review and editing.

Samvel Danielyan: Project administration, Writing—review and editing.

Tatul Saghatelyan: Conceptualization, Writing—review and editing.

Liana Safaryan, Samvel Bardakhchyan, Martin Harutyunyan, Marine Rushanyan, Gohar Mkrtchyan, Armen Avagyan, Lilit Harutyunyan, Sergey Mkhitaryan, Armen Khanoyan, Amalya Sargsyan, Mariam Mailyan: Writing—review and editing.

Gevorg Tamamyan: Conceptualization, Project administration, Writing—review and editing.

Sergey Badalyan: Visualization, Writing—original draft, Writing—review and editing.

Armine Lazaryan: Data curation, Investigation, Writing—review and editing.

David Mamunts, Anzhela Asadyan, Parandzem Khachatryan: Data curation, Investigation, Visualization.

Armen Mkhitaryan: Data curation, Investigation, Visualization, Writing—review and editing.

Gregory P. Kalemkerian: Conceptualization, Project administration, Supervision, Visualization, Writing—review and editing.

References

The World Bank

Data for Armenia, Upper middle income

https://data.worldbank.org/?locations=AM-XT

Date accessed: September 3, 2022