Lung Cancer in Peru.

Peru is a South American nation with a growing and aging population of 31 million people with a life expectancy at birth of 76.7 years. The country is divided into 25 regions, 79% of the population is urban, and Lima, the capital, concentrates more than a third of the population.1Instituto Nacional de Estadística e InformáticaPerú: perfil sociodemográfico. Informe nacional. Censos Nacionales 2017. Lima 2018.https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1539/libro.pdfDate accessed: December 1, 2019Google Scholar Although Peru is an upper-middle-income country, health expenditure represents only 5.1% of the gross domestic product, which is lower than the average of Latin America and the Caribbean (LATAM) (8.56%).2The World BankData. 2019.https://data.worldbank.org/indicator/NY.GDP.MKTP.CDDate accessed: December 1, 2019Google Scholar Out-of-pocket health expenditure is 30.9%.3Falconi DP, Bernabé E. Determinants of catastrophic healthcare expenditure in Peru [e-pub ahead of print]. Int J Health Econ Manag. https://doi.org/10.1007/s10754-018-9245-0. Accessed February 28, 2020.Google Scholar Peru has a comprehensive National Cancer Plan and two population-based cancer registries in Lima and Arequipa. The Peruvian health care system is fragmented into public and private sectors, leading to considerable disparities. The public sector is further divided into a subsidized regimen and a contributory regimen. Within the subsidized regimen, the provision of health services is covered by Seguro Integral de Salud (SIS) in the network of establishments, hospitals, and institutes of the Ministry of Health (MOH), including the Peruvian National Cancer Institute (INEN) and the two regional cancer institutes. The contributory regimen corresponds to the social security system (EsSalud) that provides services in its own establishments for the salaried population and their families. The private sector is composed of multiple private insurers, private clinics, and medical centers and offers services for the population with capacity to pay. Overall, SIS and the social security cover 44% and 25% of the population, respectively, whereas only 5% of the population has a private insurance.1Instituto Nacional de Estadística e InformáticaPerú: perfil sociodemográfico. Informe nacional. Censos Nacionales 2017. Lima 2018.https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1539/libro.pdfDate accessed: December 1, 2019Google Scholar However, this general overview covers marked national variation. The rural population is affiliated to SIS and the social security in 76% and 6%, respectively. In contrast, whereas 10% of Lima’s population has a private insurance, those affiliated to this type of insurance do not reach 5% in 21 of 25 regions.4Instituto Nacional de Estadística e InformáticaPoblación afiliada a algún seguro de salud. Sobre la base de los Censos Nacionales 2017. Lima 2018.https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1587/libro01.pdfDate accessed: December 27, 2019Google Scholar Recently, the government made a great step toward universal health insurance, as it authorized the affiliation of all persons without any health insurance who reside in Peruvian territories to SIS, regardless of their socioeconomic status.5Decreto de urgencia Nº 017-2019: Decreto de urgencia que establece medidas para la cobertura universal de saludLima, Peru: Diario Oficial El Peruano; 2019.https://cdn.www.gob.pe/uploads/document/file/431389/1831446-1.pdfDate accessed: March 1, 2020Google Scholar Lung cancer is the sixth most common cancer and the second cause of cancer deaths in Peru. According to Globocan statistics, 3210 new cases and 2844 deaths were projected in 2018, with standardized incidence and mortality rates of 9.5 and 8.9, respectively, and a mortality-incidence ratio of 0.93. Lung cancer incidence in Peru is lower than the LATAM average.6Ferlay J. EM LF Colombet M. et al.Cancer today Lyon, France: International Agency for Research on Cancer; 2018.https://gco.iarc.fr/todayDate accessed: December 1, 2019Google Scholar A nationwide health information system (REUNIS-MINSA) now provides visual data on several diseases, including lung cancer mortality rates by regions, showing significant differences across the board and ranging from 2.7 to 17.5 per 100,000 inhabitants (Fig. 1). The regions with the highest mortality are Callao, Lima, and Arequipa,7Ministerio de Salud, REUNISRepositorio único nacional de información en salud. Lima 2015.https://www.minsa.gob.pe/reunis/Date accessed: December 14, 2019Google Scholar and this distribution has been maintained since 2005.8Flores C.J. Torres-Roman J.S. Mas L. et al.Spatio-temporal distribution of lung cancer mortality rate in Peru: 2005-2014.J Clin Oncol. 2017; 35e20081Crossref Google Scholar According to the Metropolitan Lima Cancer Registry (2010–2012),9Departamento de Epidemiología y Estadística del Cáncer. Instituto Nacional de Enfermedades NeoplásicasRegistro de cáncer de Lima metropolitana. Incidencia y mortalidad 2010–2012. Lima, Peru; 2016.http://www.inen.sld.pe/portal/documentos/pdf/banners_2014/2016/Registro%20de%20C%C3%A1ncer%20Lima%20Metropolitana%202010%20-%202012_02092016.pdfDate accessed: December 13, 2019Google Scholar lung cancer has a standardized incidence rate of 11.2 (13.3 in males and 9.6 in females) and a standardized mortality rate of 9.2 (11.0 in males and 7.8 in females). Most cases (75%) occurred in people older than 60 years. Lung cancer in patients younger than 40 years represents 4.3% of all cases as presented in a recent series.10Galvez-Nino M, Ruiz R, Pinto JA. Lung Cancer in the Young [e-pub ahead of print]. Lung. https://doi.org/10.1007/s00408-019-00294-5. Accessed February 28, 2020.Google Scholar Data from Metropolitan Lima Cancer Registry indicate as well that from 1968 to 2012, lung cancer incidence has decreased in men and increased in women (Fig. 2),9Departamento de Epidemiología y Estadística del Cáncer. Instituto Nacional de Enfermedades NeoplásicasRegistro de cáncer de Lima metropolitana. Incidencia y mortalidad 2010–2012. Lima, Peru; 2016.http://www.inen.sld.pe/portal/documentos/pdf/banners_2014/2016/Registro%20de%20C%C3%A1ncer%20Lima%20Metropolitana%202010%20-%202012_02092016.pdfDate accessed: December 13, 2019Google Scholar although the absolute number of cases is increasing because of population growth and aging. Data on mortality, corresponding to a shorter period (1990–2012), indicate a nonsteady decrease for men and an increase for women. In Lima, standardized lung cancer incidence varies greatly among districts, ranging from 6.34 to 35.97 in the male population and from 5.47 to 21.66 in the female population. When comparing two periods, 2004 to 200511Departamento de Epidemiología y Estadística del Cáncer. Instituto Nacional de Enfermedades NeoplásicasRegistro de cáncer de Lima metropolitana. Incidencia y mortalidad 2004–2005. Lima2014.http://www.inen.sld.pe/portal/documentos/pdf/banners_2014/Febrero/25022014_Libro_RCLM_CD.pdfDate accessed: December 13, 2019Google Scholar versus 2010 to 2012,9Departamento de Epidemiología y Estadística del Cáncer. Instituto Nacional de Enfermedades NeoplásicasRegistro de cáncer de Lima metropolitana. Incidencia y mortalidad 2010–2012. Lima, Peru; 2016.http://www.inen.sld.pe/portal/documentos/pdf/banners_2014/2016/Registro%20de%20C%C3%A1ncer%20Lima%20Metropolitana%202010%20-%202012_02092016.pdfDate accessed: December 13, 2019Google Scholar it was found that incidence has increased, especially in women; four and eight of 49 districts entered the highest tier of incidence in men and women, respectively (Fig. 3).Figure 3Incidence rate per districts in Lima. Reprinted with permission from Departamento de Epidemiología y Estadística del Cáncer. Instituto Nacional de Enfermedades Neoplásicas.9Departamento de Epidemiología y Estadística del Cáncer. Instituto Nacional de Enfermedades NeoplásicasRegistro de cáncer de Lima metropolitana. Incidencia y mortalidad 2010–2012. Lima, Peru; 2016.http://www.inen.sld.pe/portal/documentos/pdf/banners_2014/2016/Registro%20de%20C%C3%A1ncer%20Lima%20Metropolitana%202010%20-%202012_02092016.pdfDate accessed: December 13, 2019Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT) The prevalence of tobacco use in adults in Peru has more than halved from 27% in 200012Pinillos L. Quesquén M. Bautista F. Poquioma E. Tabaquismo: un problema de salud pública en el Perú.Rev Peruana Med Exp Salud Publ. 2005; 22: 64-70Google Scholar to 13.3% in 2010—19.7% in men and 7.8% in women.13Organización Panamericana de la Salud. Informe sobre Control del Tabaco en la Región de las Américas. A 10 años del Convenio Marco de la Organización Mundial de la Salud para el Control del Tabaco. Washington, DC: Organización Panamericana de la Salud; 2016. https://iris.paho.org/bitstream/handle/10665.2/28380/9789275318867_spa.pdf?sequence=1&isAllowed=y. Accessed December 2, 2019.Google Scholar This is lower than the current prevalence of smokers in the LATAM region, which has also decreased from 28% in 2000 to 17.4% in 2015.14Organización Panamericana de la SaludDisminuye el consumo de tabaco, pero se debe hacer más para proteger a las personas y reducir las muertes por enfermedades cardíacas que generan fumar y la exposición a su humo.https://www.paho.org/per/index.php?option=com_content&view=article&id=4044:disminuye-el-consumo-de-tabaco-pero-se-debe-hacer-mas-para-proteger-a-las-personas-y-reducir-las-muertes-por-enfermedades-cardiacas-que-generan-fumar-y-la-exposicion-a-su-humo&Itemid=1062Date accessed: December 2, 2019Google Scholar Likewise, current cigarette and tobacco smoking among youth (aged 13–15 y) has decreased from 19.4% in 2007 to 9.7% in 2014.15World Health Organization Regional Office for South-East Asia Global Youth Tobacco Survey (GYTS) 2014: Indonesia Factsheet. WHO Regional Office for South-East Asia, 2015https://apps.who.int/iris/handle/10665/205147Date accessed: March 2, 2020Google Scholar These results suggest that tobacco control policies as outlined in the following are having a progressive impact. Peru ratified the WHO Framework Convention on Tobacco Control (WHO FCTC) in November 2004,16Organización Mundial de la Salud Convenio Marco de la OMS para el Control del Tabaco. OMS, Geneva, Switzerland2003https://goo.gl/P3O9LzDate accessed: March 2, 2020Google Scholar,17Decreto Supremo Nº 054-2004-RE: Decreto Supremo que ratifica el “Convenio marco de la OMS para el control de Tabaco” Diario Oficial El Peruano, Lima, Peru2004https://es.scribd.com/document/362228977/Decreto-Supremo-054-2004-REDate accessed: March 1, 2020Google Scholar and enforced it in 2005. Significant progress has been made in adhering to the framework through the endorsement of laws guaranteeing a 100% smoke-free public environment and regulating tobacco advertising, packaging, and labeling.18Ley 29571: Código de Protección y Defensa del Consumidor Diario Oficial El Peruano, Lima, Peru2010https://www.indecopi.gob.pe/documents/20195/177451/CodigoDProteccionyDefensaDelConsumidor%5B1%5D.pdf/934ea9ef-fcc9-48b8-9679-3e8e2493354eDate accessed: March 1, 2020Google Scholar, 19Resolución Ministerial N° 469-2011-MINSA: "Normativa Gráfica para el uso y aplicación de las advertencias sanitarias en envases, publicidad de cigarrillos y de otros productos hechos con tabaco" Diario Oficial El Peruano, Lima, Peru2011https://www.gob.pe/institucion/minsa/normas-legales/243544-469-2011-minsaDate accessed: March 1, 2020Google Scholar, 20Ley 29517: Ley que modifica la ley Nº 28705 Ley general para la Prevención y Control de los Riesgos del Consumo del tabaco, para adecuarse al Convenio Marco de la Organización Mundial de la Salud OMS para el Control del tabaco, N° 29517 Diario Oficial El Peruano, Lima, Peru2010https://www.gob.pe/institucion/minsa/normas-legales/245512-29517Date accessed: March 1, 2020Google Scholar In Peru, tobacco advertising within 500 m from a health or education establishment is banned. The amount of nicotine, tar, and monoxide must be disclosed in the cigarette packages, and 50% of both sides of the packages must include graphic and text warnings, which are rotated every 12 months. In addition, the use of the terms “light” or “soft” is prohibited. Importantly, retail sale or sale in packages less than five cigarettes and selling to people under 18 years old is illegal. Nevertheless, there are pending commitments to fully implement the WHO FCTC, to integrate smoking control programs and strategies into a National Tobacco Control Plan, which is still nonexistent, to develop a tobacco cessation program, to take action to avoid interference from the tobacco industry, and to increase taxation further to reduce tobacco demand. In 2018, the tax per pack of cigarettes was increased to 61%, which is the highest recorded in the country.21Decreto Supremo Nº 112-2016-EF: Modifican el Literal B del Nuevo Apéndice IV del Texto Único Ordenado de la Ley del Impuesto General a las Ventas e Impuesto Selectivo al Consumo Diario Oficial El Peruano, Lima, Peru2016https://busquedas.elperuano.pe/normaslegales/modifican-el-literal-b-del-nuevo-apendice-iv-del-texto-unico-decreto-supremo-n-112-2016-ef-1376337-2/Date accessed: March 1, 2020Google Scholar,22Decreto Supremo Nº 092-2018-EF: Modifican el Literal B del Nuevo Apéndice IV del Texto Único Ordenado de la Ley del Impuesto General a las Ventas e Impuesto Selectivo al Consumo Diario Oficial El Peruano, Lima, Peru2018https://busquedas.elperuano.pe/normaslegales/modifican-el-literal-b-del-nuevo-apendice-iv-del-texto-unico-decreto-supremo-n-092-2018-ef-1646369-3/Date accessed: March 1, 2020Google Scholar However, the recommendation of the WHO FCTC is 75%. Under the leadership of the MOH, a multisectoral approach has been used to formulate and implement tobacco control actions. For its part, the Ministry of Education has established prevention programs in the school curriculum to prevent the start of tobacco consumption. Local governments carry out marketing inspections and ensure smoke-free environments. It is worth emphasizing the role of the civil society through Comisión Nacional Permanente de Lucha Antitabáquica, an institution with international support that since 1988 has been promoting and advocating for public policies regarding tobacco control, educating human resources, and verifying compliance with the law. The prevalence of smokers among Peruvian patients with lung cancer in recent series has been reported to range between 20%23Ruiz R. Nino M.G. Perez K.R. et al.16–25 Epidemiology of advanced lung cancer in Peru.J Thorac Oncol. 2019; (P2:14(10):S875)Abstract Full Text Full Text PDF Google Scholar and 42%,24Gutierrez JM, Ruiz R, Araujo J, et al. Características epidemiológicas y sobrevida en pacientes con Cáncer de Pulmón en la Clínica Oncosalud-AUNA 2011-2014. Carcinos, in press.Google Scholar which is very low when compared with what is reported by international series (75%–95%),25Pesch B. Kendzia B. Gustavsson P. et al.Cigarette smoking and lung cancer—relative risk estimates for the major histological types from a pooled analysis of case–control studies.Int J Cancer. 2012; 131: 1210-1219Crossref PubMed Scopus (286) Google Scholar indicating that risk factors beyond tobacco must be considered. In rural areas in Peru, crop residues (1.4%), dung (1.8%), and particularly wood (17.3%) are the most used fuels for cooking.1Instituto Nacional de Estadística e InformáticaPerú: perfil sociodemográfico. Informe nacional. Censos Nacionales 2017. Lima 2018.https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1539/libro.pdfDate accessed: December 1, 2019Google Scholar In-house exposure to these fumes increases the risk of respiratory diseases in children (risk ratio [RR] = 2.3, 95% confidence interval [CI], 1.04–5.18) and adult women (RR = 3.2, 95% CI, 1.00–5.59) and of lung cancer also in women (RR = 1.9, 95% CI, 1.1–3.5).26Desai M.A. Mehta S. Smith K.R. Indoor Smoke From Solid Fuels: Assessing the Environmental Burden of Disease at National and Local Levels. World Health Organization, Geneva2004Google Scholar,27Viegi G. Simoni M. Scognamiglio A. et al.Indoor air pollution and airway disease.Int J Tuberc Lung Dis. 2004; 8: 1401-1415PubMed Google Scholar In the country, in 2017, 1,757,409 families (21.3%) cooked by burning biomass as fuel.1Instituto Nacional de Estadística e InformáticaPerú: perfil sociodemográfico. Informe nacional. Censos Nacionales 2017. Lima 2018.https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1539/libro.pdfDate accessed: December 1, 2019Google Scholar To address this issue, the government has developed the National Program of Improved Kitchens28Cooperación Técnico Alemana. Proyecto Energía, Desarrollo y Vida (ENDEV-PERÚ). Manual de capacitación para instalador de cocina mejorada familiar Cooperación Técnica Alemana - GTZ, Lima, Peru2008http://www3.vivienda.gob.pe/dnc/archivos/Estudios_Normalizacion/Manuales_guias/manual-de-cocina-mejorada.pdfDate accessed: March 1, 2020Google Scholar that enhances the cleanliness of the interior environments through efficient combustion and appropriate dimensions of the holes and the chimney. In addition, pollution by particles in environmental air, which reaches a value of 50 μg/m3 in Lima29Gonzales G.F. Zevallos A. Gonzales-Castañeda C. et al.Contaminación ambiental, variabilidad climática y cambio climático: una revisión del impacto en la salud de la población peruana.Rev Peru Med Exp Salud Publica. 2014; 31: 547-556Crossref PubMed Google Scholar (far greater than the WHO recommendation of 10 μg/m3), has been estimated to cause more than 600 cases of lung cancer in Peru yearly.30Zolezzi A. Salud y medio ambiente en el Perú actual.Acta Med Peru. 2017; 34: 79-81Crossref Google Scholar In Peru, there is no population screening test for lung cancer; however, the National Cancer Plan includes the diagnosis and staging of patients with presumptive diagnosis of lung cancer. On a private level, there is an isolated effort using low-dose tomography for high-risk individuals. The implementation of a national low-dose tomography screening program is unfeasible at the moment owing to limitations in funding, infrastructure, expertise, and health system response. Late lung cancer diagnosis is the most common presentation. According to a study from INEN, 9.2% and 85.5% of patients with lung cancer from 2010 to 2014 were diagnosed at stages III and IV, respectively.31Ruiz R. Nino M.G. Cruz Z.M. et al.Epidemiology and survival of lung cancer in a Latin American cohort.J Clin Oncol. 2019; 37e13101Crossref Google Scholar In contrast, in a recent publication from a private center, 20% of patients were diagnosed at stage III and 64% at stage IV during the same period of time.24Gutierrez JM, Ruiz R, Araujo J, et al. Características epidemiológicas y sobrevida en pacientes con Cáncer de Pulmón en la Clínica Oncosalud-AUNA 2011-2014. Carcinos, in press.Google Scholar Regarding pathologic diagnosis, adenocarcinoma is by far the most frequent subtype, accounting for 72% of all lung cancer cases.31Ruiz R. Nino M.G. Cruz Z.M. et al.Epidemiology and survival of lung cancer in a Latin American cohort.J Clin Oncol. 2019; 37e13101Crossref Google Scholar In Peru, there are few laboratories that perform molecular diagnosis, most of them in the private sector. Within the public sector, the detection of EGFR mutations by polymerase chain reaction, ALK rearrangements by fluorescence in situ hybridization, and the assessment of programmed death-ligand 1 by immunohistochemistry are covered through the subsidized and contributory regimens but available only at INEN and at the two higher complexity hospitals of the social security. At INEN, 16% and 36% of the samples for EGFR and ALK assessment, respectively, are insufficient. Liquid biopsy and next-generation sequencing are available only in the private sector. The predominant targetable alteration in Peruvian patients with lung cancer is the EGFR mutation representing between 32% and 39% of cases.24Gutierrez JM, Ruiz R, Araujo J, et al. Características epidemiológicas y sobrevida en pacientes con Cáncer de Pulmón en la Clínica Oncosalud-AUNA 2011-2014. Carcinos, in press.Google Scholar,32Mas L. Piscocha C. Landa J. et al.Prevalence of EGFR mutations in the Peruvian population: study in a large cohort of patients with NSCLC.J Clin Oncol. 2017; 35e13076Crossref Google Scholar, 33Galvez-Nino M. Ruiz R. Roque K. et al.P2. 05 Real World data on epidermal growth factor receptor tyrosine kinase inhibitors use in advanced non-small cell lung cancer from a Latin American cohort.J Thorac Oncol. 2019; 14: S1187Abstract Full Text Full Text PDF Google Scholar, 34Mas L. de la Torre J.G. Barletta C. Estado mutacional de los exones. 2011;2;19y 21 de EGFR en adenocarcinoma de pulmón: Estudio en 122 pacientes peruanos y revisión de la evidencia de eficacia del inhibidor tirosina kinasa erlotinib.Carcinos. 2011; 1: 52-61Google Scholar These rates, which are the highest reported for the LATAM region, may be explained to some extent by the important Asian ancestry.35Pinto J.A. Mas L.A. Gomez H.L. High epidermal growth factor receptor mutation rates in Peruvian patients with non–small-cell lung cancer: is it a matter of Asian ancestry?.J Glob Oncol. 2017; 3: 429-430Crossref PubMed Scopus (4) Google Scholar ALK rearrangements have been detected in around 10% of cases.24Gutierrez JM, Ruiz R, Araujo J, et al. Características epidemiológicas y sobrevida en pacientes con Cáncer de Pulmón en la Clínica Oncosalud-AUNA 2011-2014. Carcinos, in press.Google Scholar,36Arrieta O. Cardona A.F. Bramuglia G. et al.Molecular epidemiology of ALK rearrangements in advanced lung adenocarcinoma in Latin America.Oncology. 2019; 96: 207-216Crossref PubMed Scopus (13) Google Scholar A small targeted panel performed in 113 patients with lung cancer found mutations in KRAS and BRAF in 15.9% and 1.8% of patients, respectively (unpublished data). The Peruvian Society of Cardiothoracic and Vascular Surgery is composed of 120 active members as of today, with 10 of them being women. Approximately, a quarter of all these specialists are mainly advocated to the Thoracic Surgery subspecialty, and very few have training in Thoracic Surgical Oncology. These specialists are concentrated in Lima and in three regions of Peru (La Libertad, Arequipa, and Lambayeque). Only one center in the country provides specialized training in Thoracic Surgical Oncology. This shortage of specialists results in cardiothoracic surgeons also performing operations for the treatment of cancer and in prolonged waiting times for operation in the public sector. Video-assisted thoracic operation for performing lobectomy is available in highly specialized centers, mostly in Lima, at which thoracic oncology surgeons are available. The equipment for performing video-assisted thoracic operation is available nationwide; however, the scarcity of specialists is the limiting factor for the widespread use of this procedure. Therefore, open thoracotomy is still the most common surgical approach, especially in public centers. Robot-assisted thoracic operation for thoracic malignancies is not available in Peru. At INEN, stages I and II are eligible for primary operation. Patients with stage III receive multidisciplinary care, including chemoradiation and, very occasionally, operation. Thoracic operation for advanced cases with oligometastatic presentation is performed in selected cases, according to what is recommended by multidisciplinary tumor boards. Radiotherapy (RT) is key in the management of early, locally advanced, and metastatic lung cancer. Currently, there are 104 radiation oncologists, 100 radiotherapists, and 40 physicists in Peru. According to the National Institute on Nuclear Energy (IPEN),37Instituto Peruano de Energía Nuclear.https://www.ipen.gob.pe/Date accessed: December 2, 2019Google Scholar 28 centers have RT services and are distributed over six of 25 regions in Peru (Lima, La Libertad, Lambayeque, Arequipa, Junín, and Cusco), with 15 of them located in Lima. Equipment available is limited to 32 high-energy linear accelerators and five cobalt machines; that is 1 U for every 1,031,250 inhabitants. In Lima, the ratio is 1 U for every 504,411 inhabitants, whereas in the rest of the country, there is one machine for every 1,628,333 inhabitants. In all cases, the availability of RT units falls short of the recommended International Atomic Energy Agency ratio of one machine for every 200,000 to 250,000 inhabitants. Approximately 100 more units are needed to close this gap. In the public sector, waiting times for treatment are prolonged. Lima concentrates the six RT centers with capacity to perform special techniques such as intensity-modulated radiation therapy, volumetric modulated arc therapy, stereotactic body radiation therapy, and radiosurgery for the treatment of lung cancer; the two electronic intraoperative contact RT machines and the two CT simulators are able to perform 4-dimensional simulation. All of them but INEN are private. Regarding brachytherapy, there are 11 high dose rate brachytherapy machines37Instituto Peruano de Energía Nuclear.https://www.ipen.gob.pe/Date accessed: December 2, 2019Google Scholar, and only two centers, located in Lima, have experience in performing endobronchial brachytherapy. There is no access to Cyberknife units, tomotherapy, or proton therapy, but a Gammaknife equipment belonging to the private sector is available. In Peru, the regulatory approval of new therapies is given by the General Head of Medicines, Supplies and Drugs (DIGEMID) of the Peruvian MOH. Time from FDA approval to regulatory approval in Peru is becoming shorter (Table 1). However, the regulatory approval of new drugs does not imply access to the subsidized regimen, which additionally depends on their incorporation to the Peruvian Essential Medicine List, on the basis of safety, efficacy, and cost-effectivity. For the previous years, this list has included mainly cytotoxic drugs and no biologicals or targeted therapy. It was not until 2017 that erlotinib was included in this list. To overcome this limitation, the MOH authorized its public institutions to acquire and use drugs not included in the Peruvian Essential Medicine List, on the condition that they undergo evaluation by institutional committees and health-technology assessment (HTA) by DIGEMID. However, the implementation of HTA continues to face significant challenges concerned with the fragmentation of the health care system and shortage of resources for a timely evaluation. For this reason, INEN and the MOH in a concerted effort have established the normative mechanisms to enable access to selected high-cost drugs, on the condition that they are present on institutional guidelines.38Resolución Ministerial N° 116-2018-MINSA: Aprobar la Directiva Administrativa N° 249-MINSA/2018/DIGEMID "Gestión del Sistema Integrado de Suministro Público de Productos Farmacéuticos, Dispositivos Médicos y Productos Sanitarios - SISMED" Diario Oficial El Peruano, Lima, Peru2018https://www.gob.pe/institucion/minsa/normas-legales/187637-116-2018-minsaDate accessed: March 1, 2020Google Scholar Currently, the scope of this directive is restricted to INEN but is projected to have national reach.Table 1Time to Drug Regulatory Approval and AccessDrug/IndicationFDA ApprovalNational Regulatory ApprovalAccess for the Subsidized RegimenUse Authorization at INENErlotinib2004200820172017Afatinib20132014NoNoOsimertinib/T790M EGFR mutation20152018No2019Osimertinib/EGFR mutation first line20182019NoNoCrizotinib/ALK mutation20112012NoNoAlectinib20152017No2019Pembrolizumab20152016No2019Nivolumab20152015NoNoAtezolizumab20162017NoNoFDA, Food and Drug Administration; INEN, the Peruvian National Cancer Institute. Open table in a new tab FDA, Food and Drug Administration; INEN, the Peruvian National Cancer Institute. For its part, within the contributory regimen, HTA is performed by its own health-technology agency Instituto de Evaluación de Tecnologías Sanitarias e Investigación, allowing access to selected innovative drugs, most of which provide overall survival or quality of life benefit. Importantly, its methodological and evaluation documents are published online and are accessible to patients and other stakeholders.39ESSALUD, Instituto de Evaluación de Tecnologías en Salud e Investigación Lima.http://www.essalud.gob.pe/ietsi/Date accessed: December 20, 2019Google Scholar The scenario is very different for private institutions, where only regulatory approval is needed for using a drug. However, increasingly, private insurers are also establishing HTA to regulate the use of high-cost medications. A summary of drugs available in Peru is shown in Table 1. Regarding results of systemic therapies, a group of researchers from INEN recently presented real-world data on 55 patients with EGFR mutated lung cancer treated with erlotinib at any line of treatment from 2015 to 2018 and found an overall response rate (ORR) of 65.9% and an unexpectedly prolonged progression-free survival (PFS) of 18 months.33Galvez-Nino M. Ruiz R. Roque K. et al.P2. 05 Real World data on epidermal growth factor receptor tyrosine kinase inhibitors use in advanced non-small cell lung cancer from a Latin American cohort.J Thorac Oncol. 2019; 14: S1187Abstract Full Text Full Text PDF Google Scholar Results from another institution could not confirm these results; with follow-up time of 32.4 months, ORR was 73.6% and median PFS and median overall survival were 12 and 24 months, respectively (unpublished data). Results of immunotherapy use at any line have also been evaluated in a cohort of 68 patients. Although ORR was 38% and PFS was 5.5 m, duration of response was 18.6 months (unpublished data). Lung cancer in Peru is a growing public health problem with characteristics that differ from what occurs in the LATAM region and the world. It is a disease that occurs predominantly in nonsmokers, with a high incidence of adenocarcinoma and EGFR and ALK mutations, the cause of which is not well elucidated yet.