Cancer care in times of conflict: cross border care in of patients from

Muhammed Aasim Yusuf1,*, Shoaib Fahad Hussain2,*, Faisal Sultan1, Farhana Badar1 and Richard Sullivan2

1 Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan 2 Conflict and Health Research Group, Institute of Cancer Policy, King’s College London, London, United Kingdom *Joint First Authors.

Abstract

Armed conflict in Afghanistan has continued for close to 40 years and has devastated its health infrastructure. The lack of a cancer care infrastructure has meant that many Afghans seek cancer care in neighbouring countries, like Pakistan. There remains a signifi- cant lack of empirical data on the new therapeutic geographies of cancer in contemporary conflicts. This retrospective single centre study explores the therapeutic and clinical geographies of Afghan cancer patients who were treated at the Shaukat Khanum Memorial Cancer

Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan over a 22-year-period Research (1995 to 2017) covering major periods of conflict and relative peace. Data was available for 3,489 Afghan patients who received treatment at SKMCH&RC. The mean age at presentation was 42.7 years, and 60% were men. 30.2% came from Kabul and Nangarhar districts of Afghanistan, which have relatively short travel times to Pakistan, but patients from all parts of Afghanistan migrated to SKMCH&RC for treat- ment. Overall, 34.1% were diagnosed with upper gastrointestinal malignancies and 55.7% presented with late stage III/IV cancer. A wide range of treatments were provided, with 25.4% of patients receiving a combination of chemotherapy and radiation treat- ment. 52.7% of all patients were lost to follow-up. Outcomes were more favourable for children with cancer, 42% of whom had a complete response to therapy. Complex migration patterns, mixed political economies (refugees, forced and unforced migrants) and models of care that must be adapted to the realities of the patients rather than notional international standards all reflect the new therapeutic geographies that Correspondence to: Muhammed Aasim Yusuf long-term conflict creates. This requires significant new domestic and international (e.g., Email: [email protected] United Nations High Commissioner for Refugees) policy and practises for providing cancer ecancer 2020, 14:1018 care in today’s contemporary conflict ecosystems that frequently cross national borders. https://doi.org/10.3332/ecancer.2020.1018

Keywords: Afghanistan, Pakistan, cancer, migration, conflict and health, global health Published: 05/03/2020 Received: 22/11/2019 Publication costs for this article were supported by ecancer (UK Charity number 1176307). Copyright: © the authors; licensee Introduction ecancermedicalscience. This is an Open Access article distributed under the terms of the Armed conflicts cause massive disruption including loss of life, injuries, the destruction of Creative Commons Attribution License (http:// vital infrastructure and forced migration, with all the resulting short and long term socio- creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and economic, political and health consequences. The world is witnessing the highest levels reproduction in any medium, provided the original of human displacement due to persecution, conflict and human rights abuses in modern work is properly cited. ecancer 2020, 14:1018; www.ecancer.org; DOI: https://doi.org/10.3332/ecancer.2020.1018 1 Research Centre, Lahore. hospitals, Afghan migrantsincreasingly presentto major apex cancer centres astheShaukat such Memorial Khanum Cancer Hospital and complex therapeuticgeographies, asseeninother conflict-affected countries [6] . In additionto a variety of smaller andmany public private poor healthcare infrastructure hasmeant that Afghan migrants continue to cross borders to present within Pakistan alongill-defined and population Pakistanwithin numbered over 3.3millionpeople SocialistRepublics in 1979,millionsof from people Afghanistancrossed thisborder to seekrefuge inPakistan [1]. At itspeak,therefugee Pakistan shares along,andinplaces, stilldisputed border with Afghanistan. Following theinvasion of Afghanistan by theUnion of Soviet burden for caringfor migrant populations includingrefugees cancerwith falls onhostcountries andonout-of-pocket payments. sioner for Refugees (UNHCR); deficit,an 83%funding with canonlythe UNHCR afford to few fund cancer cases[5].Globally, mostof the [3, 4].In somecountries,as Lebanon, such refugees only receive secondary or tertiary care if fundedby theUnited Nations High Commis- Migrant populations are usually unfamiliar health systemswith inother countries andare often not enrolled informal healthcare programmes humanitarian medicine affectingrefugee andmigrant populations, especially cancer, have received littleattention both politically, and theecosystemwithin of well ascontrollingand infectiousas malnutrition health issuessuch public diseaseoutbreaks. However, non-communicable diseases(NCDs) refugeemultiple crises,mostly through United Nationsagencies (UN) andnon-governmental organisations providing acute medicalcare as history approximatelywith refugees 65.6million anddisplaced people worldwide in2016[1]. The international community hasmanaged ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 raphy andcare of suchmigrant populations seeking care inahostcountry. a retrospective unselectedregistry hospital analysis of thesepatients to understand andilluminate the complex socio-demographics, geog- Afghanistan. Yetis knownlittle geographicclinical, the about and socio-demographic features of migrants of Afghan origin.Here, we present Nearlyof 30% allpatientsin Lahorehospital seen inthe comefrom Khyber Pakhtunkhwa, theadjoiningtribalareas of Pakistan, andfrom [2]. in clinicsseekingtreatment. Pakistan. In 2017almost45,000new cancer patients attended oneof our walk- There are anestimated 170,000to 200,000new cancer diagnosesevery year in management. patients with asuspectedor establishedcancer diagnosiscanattend for further SKMCH&RC alsooperates anetwork of walk-in clinicsallover Pakistan which WALK-IN CLINICS may helpameliorate thedifficultiesthesepatients face. speak andFarsi which helpsprovide informal psychosocial supportand For geographical reasons, staff andmany patients who access thesefacilities to 300patients. provide free accommodation andmealsas well asindividualcarer support,for up dation, leadingto theemergence of SKMCH&RC-affiliated hostel facilities which Many patients, including Afghan patients, are unableto afford private accommo modation near oneof our hospitals. tive/outpatient procedures requiring many patients to seektemporary accom- Most chemotherapy andradiation treatments provided at SKMCH&RC are elec ACCOMMODATION PANEL B:SUPPORTING AFGHAN PATIENTS emphasis onaccepting thosemostlikely to becurable. SKMCH&RC accepts patients basedondiagnosisandcancer stage with an PANEL A: PATIENT SELECTION CRITERIA [1]. The continuation of conflict within Afghanistan since 2001coupled to the - - 2

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Figure 1. Afghan migrants treated at SKMCH&RC ( major increase inconflict in Afghanistan (Figure). 1B (Figure). 1A Thereold 19-year was arapid increase≤ inthenumber of Afghan migrants presenting from 2008onwards, coinciding with a The mean age at presentation was 42.7 years and median age was 45 years. 60% of patients were male and 12% were children aged address in Afghanistan (Table A1). being requested to obtainfurther investigations. diagnostic Final analysis isbasedontheremaining 3,489patients of which 87.4%hadan receive any further care at SKMCH&RC for various reasons thediagnosis ofincluding benign disease and not returning for follow-up after between 1995 and 2017. This represents 4.84%of all new patients (n=83,477)seenat SKMCH&RC [8]. 550of thesepatients didnot A totalof 4,039patients were identifiedas Afghan nationals,i.e., having provided an Afghan address at thetimeof initialregistration Results sex, cancer diagnosis, stage, treatment provided andfollow-up data, where available. A retrospective review was performed by two independent reviewers, lookingat patient demographics, includingaddress within Afghanistan, over a22-year period who were either identified as Afghan nationals or provided an Afghan address at thetimeof initialregistration. the system [7].Data of patients registered between 1stDecember 1995and1stDecember 2017 were collected to identify cancer patients Since 2000,allpatientdata has beenentered directly intosystem, this with paper chartsprior to thishaving beenscannedandarchived into entry and viewing of results, as well ascriticalalerts. SKMCH&RCelectronica custom-built uses recordmedical system which includesmodulesfor patient registration, clinicalinformation, order Methods n =3,489)from 1995to 2017.(A) Age distribution. (B) Frequency of Afghan patients by year. 3

Research (Figure 2, followed(21.2%) by NangarharBalkh (12.7%), (5.8%). and Khost (7.4%) The province of originfor 19.2%of paediatric patients was unknown Table A6). The province of originfor 19.3%of patients was unknown. The largest number of paediatric patients alsocamefrom Kabul The largest number came from Kabul (20.9%)followed by Nangarhar (9.3%), Balkh (6.2%), Ghazni (5.3%) and Herat (5.3%) (Figure 2, estimated (from Google Maps Drivingbetween times Lahore, Pakistan and various provinces of Afghanistan from which themajority of Afghan migrants originated were ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Figure 2.Distribution of patients by province of originin Afghanistan. (A) Overall. (B) Paediatric only. most common cancers amongadultmalesandfemales (Table 1a 20.1% of female patients presented with breast cancer. Male genital, gynaecological, lower GI and oropharyngeal malignancies were the next Further analysis ofpatients adult revealed that42% of patients male and36.8%of female patients presented Upperwith GImalignancies. phoblastic leukaemia(18%)andnon-Hodgkin lymphoma(16.3%), were themostcommon cancers inpaediatric cases(n=417)Figure 3B lowed by breast (7%)andcolorectalcancer (6%)(Figure 3A).Haematological malignancies,includingHodgkin lymphoma(20.1%),acute lym- Upper gastrointestinaloesophageal including malignancies, (23%)andgastriccancer (12.1%), were themostcommon cancers (n=3,489),fol- hours for Ghazni and23–26hours for Herat. Each of theother provinces together accounted for lessthan5%of thepatients. Table A6). Data ondistributionby gender hasbeenprovided in ™ ) were calculated as follows: 11–15 hours for Kabul; 8–13 hours for Nangarhar; 17 hours for Balkh; 13–14 ). Table A7. ). 4

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 system; NHL:non-Hodgkin lymphoma. Figure 3.Distribution by site.Overall (A) (B) Paediatric. ALL:acute lymphoblasticleukaemia;CML:chronic myeloid leukaemia;CNS: central nervous Table 1a.Distribution of adultpatients by cancer typeandgender. Other leukaemia Other haematopoietic Other and unspecified Acute lymphoblasticleukaemia Bone Thyroid andother endocrineglands Biliary tract Chronic lymphocyticleukaemia Soft tissues Chronic myeloid leukaemia Hodgkin lymphoma Renal andurinary system Respiratory system andintrathoracic organs Non-Hodgkin lymphoma Eye and CNS Skin Lip, oral cavity andpharynx Lower GI Genital organs Breast Upper GI Cancer type (n =1,801) 757 (42.0) 103 (5.7) 130 (7.2) 145 (8.1) 153 (8.5) 13 (0.7) 12 (0.7) 22 (1.2) 21 (1.2) 24 (1.3) 22 (1.3) 23 (1.3) 28 (1.6) 43 (2.4) 66 (3.7) 68 (3.8) 73 (4.1) 84 (4.7) 3 (0.2) 9 (0.5) 2 (0.1) Male No. (%) (n =1,271) 255 (20.1) 468 (36.8) 124 (9.8) 49 (3.9) 14 (1.1) 17 (1.3) 25 (2.0) 22 (1.7) 23 (1.8) 16 (1.3) 29 (2.3) 53 (4.2) 40 (3.1) 58 (4.6) 61 (4.8) Female 0 (0.0) 2 (0.2) 2 (0.2) 4 (0.3) 6 (0.5) 3 (0.2) 5

Research Table 3b tion). More thantwo-thirds of paediatricpatients were treated CTXalone,inkeepingwith with thenature of cancer diagnoses(Figure, A1 Tablesand A4for A3 treatmentoutcomes for and female male adult patients, respectively, and relapseddisease and17.3% stable or hadprogressive disease. We were unable to assessdiseaseoutcome in25.9%of paediatric patients (see outcome in20.3% of patients. 42%of paediatricpatients achieved acomplete response to therapy, 10.3%partially responded, 4.6%had respondedto therapy,relapseddisease and27.8% had stable 7.8% or hadprogressive disease(Table A2). We were unableto assessdisease surgery,therapy hormone andimmunotherapy. (HTX) of 33.2% theoverall study cohort achieved acomplete response, 10.8%partially patients were treated chemotherapywith or acombinationof chemotherapy (CTX) andradiotherapy (XRT). Other treatment options included Patientsreceived arange of treatmentsin keeping heterogeneitythe with of cancer diagnoses(Figure 4, died duringthestudy period.Further analysis for cancer stage andpatient outcomes by gender ispresented in ments.of30.4% and 29.5%of adult paediatricpatients were beingactively followed 6.9%of up. and15.1%of adults paediatric patients had Overall, 52.7%of patients,53.9% of including and 43.2%of adults paediatric patients, were lostto follow-uplikely dueto travel require- stage for 14.7%of adultsand37.2%of paediatric patients was not documented. analysis ofcohort the by age grouprevealed thatof58% and 39.1%of adults paediatric patients presented with advanced disease.Cancer 55.7% of allpatients (n=3,489)presented advancedwith disease(Stage andin17.4%,cancer IIIandIV) stage was not documented. Further cers affecting female children (Table 1b cancers affecting malechildren whereas bone, renal and urinary system andgynaecological malignancies were thenext mostcommon can- ing female children. Bone cancer, renal andurinary system andeye andcentral nervous system malignancies were thenext mostcommon wascommon themost cancer affectingmale children, whereas acute lymphoblasticleukaemia(17.1%) was themostcommon cancer affect- above,As discussed haematological malignancies werecommon themost cancers affecting paediatric patients. Hodgkin lymphoma(23.8%) ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 ). Table 1b.Distribution of paediatric patients by cancer typeandgender. Other haematopoietic Biliary tract Upper GI organs Respiratory system andintrathoracic Other and unspecified Other leukaemia Soft tissues Thyroid andother endocrineglands Lower GI Lip, oral cavity andpharynx Chronic myeloid leukaemia Genital organs Eye and CNS Renal andurinary system Bone Non-Hodgkin lymphoma Acute lymphoblasticleukaemia Hodgkin lymphoma ). Cancer type 33 (11.2) 54 (18.4) 54 (18.4) 70 (23.8) (n =294) 21 (7.1) 22 (7.5) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.3) 2 (0.7) 3 (1.0) 2 (0.7) 5 (1.7) 5 (1.7) 6 (2.0) 8 (2.7) 8 (2.7) Male No. (%) 15 (12.2) 16 (13.0) 14 (11.4) 21 (17.1) 14 (11.4) (n =123) Table A5for thepaediatric migrantpopula- 11 (8.9) Female 2 (1.6) 1 (0.8) 1 (0.8) 1 (0.8) 2 (1.6) 1 (0.8) 8 (6.5) 3 (2.4) 1 (0.8) 3 (2.4) 2 (1.6) 7 (5.7) Table 3a Table A8. ). More thantwo-thirds of 6

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Figure 4.Distribution by treatment strategy. Table 2b.Distribution of study cohort by selectoutcomes. Table 2a.Distribution of study cohort by cancer stage. Died Discharged Active treatment Active follow-up Unknown/not applicable Stage IV Stage III Stage II Stage I Stage 0 Select outcomes Cancer stage Adults ( Adults ( 1172 (38.2) 451 (14.7) 607 (19.8) 578 (18.8) 258 (8.4) 935 (30.4) 213 (6.9) 187 (6.1) 6 (0.2) 80 (2.6) n =3,072) n =3,072) No. (%) No. (%) Paediatric (n=417) Paediatric (n=417) 155 (37.2) 123 (29.5) 77 (18.5) 55 (13.2) 86 (20.6) 44 (10.6) 63 (15.1) 33 (7.9) 18 (4.3) 0 (0.0) 7

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 rarely encountered patients who hadreceived chemotherapy, andthere are currently nofunctionalradiotherapy facilities in Afghanistan. investigations in Afghanistan, includingabiopsy, to establishacancer diagnosis. Although some patients underwent surgical treatment, we SKMCH&RC. The majority of patients presenting to our from institution Afghanistan were treatment naïve. Most patients underwent initial This study provides abasicdemographicprofileand clinical for Afghan cancer patients who were treated between 1995and2017at nicable diseases,NCDs andtrauma with limited healthcare resources andconstant insecurity [2,12,13]. consequences portionately affectLow- and Middle-Income Countries, especially refugee populations, with damaginglong-term healthandsocio-economic NCDs, ofspectrum the include which cancers, are predicted to constitute over 80%of theglobalburden of diseaseby 2020and disprowill - Discussion Table 3b. Treatment data for themostcommon cancers affecting children. CTX=chemotherapy, XRT =radiotherapy. [9–11]. This is particularly relevant for conflict-affected regions which face a triple burden of disease encompassing commu- HTX =hormonetherapy. Table 3a. Treatment data for themostcommon cancers affecting adults.CTX=chemotherapy, XRT =radiotherapy, +Surgery CTX+XRT CTX+Surgery CTX+XRT Surgery Radiotherapy Chemotherapy Chemotherapy Radiotherapy Surgery CTX+XRT CTX+Surgery XRT+Surgery CTX+XRT+Surgery Hormone therapy HTX+CTX HTX+XRT HTX+Surgery HTX+CTX+Surgery HTX+CTX+XRT +Surgery HTX+CTX+XRT

Leukaemia (n =89) 89 - - - - -

(n =1,225) Upper GI Hodgkin lymphoma 308 481 103 276 37 13 6 1 ------(n =84) 17 66 1 - - (n =257) Breast 121 10 21 43 21 14 5 4 8 2 1 2 5

- Non-Hodgkin lymphoma

Lower GI (n =206) (n =68) 63 47 16 48 26 62 1 2 2 - - 3 1 1 2 - - - - -

Lip, oral cavity andpharynx

(n =49) Bone (n =188) 24 11 7 6 1 - 107 36 24 11 7 2 1 ------Renal andUrinary organs (n =37)

10 11 7 7 2 - Male genital (n =153) 47 10 29 21 10 10 2 5 4 4 3 1 6 1

8

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 tional organisations canberequested beforehand. Publicawareness, includinginformation on when and where to seekhelp,shouldbemade tors have advocated using national cancer registries to achieve better surveillance and allow forecasting of crises so that aid from interna- acute treatments. Thedeficit funding is compounded by themisconception that all types of cancer have poor prognoses. Several commenta- in lacking Afghanistan.Funding cancer care for refugees hashistorically beenneglected with resources andfundingdirected towards more It isimperative that allstakeholders invest indeveloping arobust national cancer screening andawareness programme, which iscurrently with advanced cancers, includingtumoursthat are significantly cheaper andeasier to treat if they were detected at anearlier stage. placed asubstantial burden onhostcountries’ healthcare systems. As discussed above, asignificant proportion of Afghan patients presented The conflictin Afghanistan has impaired thedevelopment of itshealthinfrastructure andthedisplacement of millions of people which has illness, financialhardship, threats of violence as well as visa andsecurity/checkpoint restrictions asseenin Afghanistan [22,26]. patient once hadarobustoncology programme,facehospitals pharmaceutical critical shortages resulting inlimited dosesof chemotherapy per facilitiesavailable, resultingin more than45%of Syrian patients beingunableto complete their treatment inSyria [23,24].In Iraq, which Syria alone, more than half of hospitalshaveall public been damaged or destroyed and there are no diagnostic imaging or radiation therapy Iraq andSyriaface asimilar situation conflictwith millions ofdisplacing peopleanddestroying thelocaloncology infrastructure [2,22].In also significantly more difficultthanfor Pakistan. free cancer treatment to allpatients experiencinghardship.financial Anecdotally, Afghan patients report that procuring a visa to enter is (Figure 2). Afghan patientsmay chooseto betreated atSKMCH&RC becauseitallows unrestricted access to Afghan patients andprovides presentfrom Afghan provinces thatare notgeographically contiguous with Pakistan, asBalkh such andHerat, which are closer much to Iran factthe thatincluding free treatmentis offered tomajority the of patients (Panel A). We alsonote that asignificant proportion of patients and the Afghan governmentit may [21],but more alsobebecause patients in Afghanistan are aware of theservices provided by SKMCH&RC, presence in Afghanistan, on-goingincluding efforts capacity-building between healthorganisations asthe such World Health Organisation presenting to SKMCH&RC (Figure 1b Nevertheless, there isatrend towards increased care-seeking among Afghan patients highlighted by thesteady riseof Afghan patients of our cohort, including25.3%of paediatric patients. treatment,or for follow-up maywhich explainhigh losstothe follow-upin our cohort,and our inability to assessdiseaseoutcome for 20.3% prolonged treatmentback andforthshuttle must to renew their visas. Consequently, many patients missappointments for investigations, facingpatients.has addedtothese difficulties which the Most visas are issuedfor periodsof 2–4 weeks at atime,andpatients undergoing has alsoimplemented stricter border controls since 2016and Afghan patients are now universally required to obtain a visa to enter Pakistan stan. Patients often travel severalwith relatives, adding to overall cost as well ascausingsignificant disruption to family life at home. Pakistan distances to seek treatment elsewhere. The journey is often dangerous and arduous, given the on-going conflict in various parts of Afghani- There are clearly large numbers of patientsneeding cancer treatment within Afghanistan, many of whom are currently forced to travel long Pakistan with fewer restrictions. border controls atthe Afghanistan-Pakistanborder were virtually non-existent and Afghan nationals were ableto buy andrent property in that dueto aperiodof relative peace inthemid-to-late 1990sfewer Afghan patients presented to Pakistan for cancer treatment. In addition, Our data shows that there was a steep rise in the number of Afghan patients presenting to SKMCH&RC in the early 2000s. It is plausible exacerbated by on-going conflict andinsecurity, financialhardship andlimited access to follow-upor definitive treatment [11]. cancer treatments leadto significant delays inpatients seekingmedicalattention andpresenting advancedwith disease. The situation is allocation in the country Over forty years of conflicthas decimated Afghanistan’s healthinfrastructure andthere isminimaldata ontheburden of diseaseor resource programmes likely contribute to thedevelopment of cancer inthispopulation [11,15–18]. war, poor dieta [24]. This hasforcedto people piece together cancer care across domesticandinternational boundaries whilst navigating personal [19, 20]. The lack of a cancer surveillance programme, the cost of treatment, as well as lack of knowledge about ). This may reflectincreased awareness of cancer among Afghans andtheimpact of theinternational 9

Research OIC [28]. to bolster radiationfacilities,medicine provide and improve technicalsupport cancer care infrastructure amongthe57member states of the effort between the International Atomic Energy Agency, the Organisation of Islamic Cooperation (OIC) and the Islamic Development Bank frominitiatives at aimed improving cancer controlMuslim inthe world astheProgramme such of Action for Cancer Therapy, acollaborative organisations amodelakintowith theSendai Framework for Disaster Risk Reduction shouldbeconsidered [4]. Afghanistan canalsobenefit for secondary andtertiary care, primary preventionand cancer surveillance strategies incorporating mobilehealthclinicsandcivilsociety available to helpdetect andtreat early stage cancer which is less costly and carries better prognosis [4, 27]. In additionto increasing funding ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 informationfor care health policy planners, as well asfor donor agencies within Afghanistan, especially given thepaucity of information others. We have also provided dataofdistribution possible on the cancers within thispopulation. Our data provides important preliminary Our data islikely to behelpfulfor national healthpolicy planners, as well asfor international fundingagencies, and astheUNHCR such cultural andsocietal factors to better inform cancer control policy andtailor cancer awareness campaignsinthecountry. and the toxic remnants of war. Further work is also needed to identify barriers to cancer care-seeking among the Afghan population including ofthe impact dietary and lifestylehabits the within Afghan population, as well asenvironmental factors includingthe effects of munitions Future research should concentrate onbuildingaclearer understanding of theincidence andprevalence of cancers within Afghanistan assess incidence, at leastbetween Afghanistan andPakistan, not previously noted. tumourmost common types, age at presentation andregional inour distribution cohort. There may alsobeimportant differences incancer attempted to draw attention to the problem of cancer diagnosisandtreatment in Afghanistan andto provide someinitialdata asto incidence, understanding theaetiology andepidemiology of cancer in Afghanistan as well theestablishment of cancer services inthecountry. We have We feel our data isimportantin drawing attention to possible scaleof the theproblem andhighlights theimportance of further work in While theexactofmagnitude thecancer problem in Afghanistan isunknown, thisisthelargest dataset of Afghan cancer patients to date. Conclusions is likely to beasource of major discrepancy inthenumbers we have provided. place of residence asasurrogate for Afghan nationality. While there isno way of knowing whether thisisaccurate, we donotfeel that this patients treated at SKMCH&RC may have beenunderestimated. Finally, we have usedtheprovision of an Afghan address asapermanent or documented, and Afghan patients were ableto enter andleave Pakistan with relative ease. As aresult, numbersthe actual of Afghan trols before 2016enabledmany Afghan familiesto live inPakistan inastate of semi-permanent residence beingformallywithout registered patientsin earlier years, may have resulted inanumber of Afghan patients beingtreated beingidentified.without Less stringentborder con- This study hassomeimportant limitations. The useof paper records before 2000,as well asrelatively limited data beingrequested from Limitations to long-term to helpaddress cancer care needsin Afghanistan. EMRO andother donor agencies shouldsupportsuchinitiatives inthemedium- childhood vaccination programmes, cancer treatment often loses out. The WHO With more pressing and visible concerns suchasprimary care, maternal care and • • focusing our efforts on: Afghanistan to helpto establishanational cancer centre inKabul. We will be SKMCH&RC iscurrently engaged indiscussions with theGovernment of PANEL C:ESTABLISHING A CANCERCENTREIN AFGHANISTAN ally extending to therest of Afghanistan. Establishing apopulation-based cancer registry startinginKabul andeventu Training Afghan physicians, nurses andalliedhealthcare professionals. - 10

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 ing capability, partnerships andresearch intheMiddle andNear East ES/P010962/1. (MENA) This publicationthroughis funded ResearchUK the and Innovation GCRF RESEARCHFOR HEALTH CONFLICTIN (R4HC-MENA);develop - Funding the hospital’s electronic medicalrecords saved informationwithin thehospital system of SKMCH&RC. Colleaguesin our cancer registrydata andclinical management unit, together with information technology colleagues, collected data from Acknowledgments Shaukat KhanumMemorial Cancer Hospital andResearch Centre Institutional Review Board Number: 07-07-17-21. Institutional review None. Disclosure of results at ameeting None to declare. Conflicts of interest List of abbreviations form thenucleusaround which suchservices future. canbeplannedinthe currently available. The nascent efforts now underway to establishcancer services in Afghanistan, with which we are involved, will hopefully XRT UNHCR UN SKCMH&RC OIC NHL NCD HTX GI EMRO CTX CNS CML ALL Radiotherapy United Nations High Commissioner for Refugees United Nations Shaukat KhanumMemorial Cancer Hospital andResearch Centre Organisation of Islamic Cooperation Non-Hodgkin lymphoma Non-communicable disease Hormone therapy Gastrointestinal WHO Regional Office for theEastern Mediterranean Chemotherapy Central nervous system Chronic myeloid leukaemia Acute lymphoblasticleukaemia 11

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Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Appendix Table A3. Treatment outcomes andcancer stage for thetop five cancers affecting adultmalepatients aged ≥19-year old. Stomach Oesophageal Cancer diagnosis Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Treatment outcome of residence. Table A1. Distribution of study cohort by country of birthandcountry Table A2. Distribution of study cohort by treatment response. Total Pakistan Afghanistan Unknown Progression/Relapse Stable disease Partial response Complete response Country of residence Treatment outcome Afghanistan 710 (20.3) 970 (27.8) 273 (7.8) 377 (10.8) 1,159 (33.2) 3,152 2,713 439 (n =3,489) 0 ------Overall Country of birth

4 0 0 0 1 3 8 2 1 1 1 3 I No. (%) Pakistan 337 337 108 (25.9) 72 (17.3) 19 (4.6) 43 (10.3) 175 (42.0) 0 65 26 10 14 53 15 11 18 II 7 8 6 3 Paediatric (n =417) Number of patients 3,489 3,050 Total 166 289 439 57 22 35 21 31 94 63 48 29 55 III Stage 87 22 35 14 11 60 13 28 IV 5 9 6 4 NK/NA 13 12 6 6 0 1 0 5 4 1 1 1 Total 335 124 422 142 70 46 42 53 74 85 40 81 14

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Table A3. Treatment outcomes andcancer stage for thetop five cancers affecting adultmalepatients aged ≥19-year old. NK: not known, NA:not applicable. Table A4. Treatment outcomes andcancer stage for thetop five cancers affecting adultfemale patients aged ≥19-year old. Skin Testicular Colorectal Total Oesophageal Cancer diagnosis Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Total Progression/Relapse Stable disease Partial Response Complete Response Unknown Treatment outcome 0 ------1 0 0 0 0 1 1 0 0 0 0 1 ------7 0 0 0 0 7 I 22 17 19 24 62 44 2 3 0 0 4 1 1 0 0 2 3 0 1 1 8 5 2 3 40 16 II 7 8 1 8 182 24 30 19 18 10 23 49 15 22 73 5 5 0 1 2 3 0 1 4 3 0 2 1 Number of patients 599 110 201 104 117 Stage 279 87 16 37 15 20 12 42 67 57 82 27 44 69 4 4 1 0 6 6 8 5 7 9 9 III 180 22 14 41 82 24 21 12 5 5 1 0 1 0 3 3 0 0 0 1 0 5 0 6 47 23 14 IV 3 3 4 NK/NA (Continued) 30 14 62 19 18 19 4 1 1 7 7 0 2 0 1 1 3 0 0 0 0 3 1 5 9 1 5 1 0 2 1,086 Total 382 118 141 103 201 355 109 155 266 68 32 66 98 56 25 19 19 60 10 41 31 15 13 14 12 85 2 3 9 15

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Table A5. Treatment outcomes andcancer stage for thetop five cancers affecting paediatric patients aged <19-year old. Table A4. Treatment outcomes andcancer stage for thetop five cancers affecting adultfemale patients aged ≥19-year old. NK: not known, NA:not applicable. Hodgkin lymphoma Total Colorectal Cervical/Uterine Stomach Breast Cancer diagnosis Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Total Unknown Progression/Relapse Partial Response Complete Response Total Progression/Relapse Stable disease Partial Response Complete Response Treatment outcome 4 0 0 0 0 4 1 0 0 0 0 1 3 0 0 0 3 ------35 29 12 16 13 3 2 1 0 0 0 0 0 0 0 0 2 1 0 9 0 0 0 0 0 0 3 0 0 - - - - - I 279 174 176 130 39 42 17 18 11 30 13 15 26 18 7 0 6 1 0 5 5 1 6 1 5 4 1 4 2 25 20 II 0 0 5 406 130 108 75 39 54 37 15 11 10 50 21 10 30 17 Number of patients 4 5 2 3 4 1 1 1 6 6 7 5 8 0 38 31 III 2 1 4 Stage 101 11 45 27 13 18 18 21 14 IV 9 9 5 0 3 1 1 0 2 5 0 3 3 4 5 5 3 1 2 9 6 1 4 0 3 NK/NA 27 11 12 5 8 1 2 1 1 0 0 0 0 2 0 0 0 0 2 3 0 2 0 1 0 3 1 1 7 (Continued) - - - - - 852 133 227 100 335 255 171 Total 57 61 24 22 68 10 16 10 29 86 11 33 15 12 15 39 36 5 7 3 3 9 84 12 65 6 1 16

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Table A5. Treatment outcomes andcancer stage for thetop five cancers affecting paediatric patients aged <19-year old. NK: not known, NA:not applicable. Non-Hodgkin lymphoma Acute lymphoblasticleukaemia Renal Bone Total Table A6. Distribution of study cohort by province of origin. Khost Herat Ghazni Balkh Nangarhar Kabul Province Complete Response Complete Response Progression/Relapse Unknown Total Partial Response Stable disease Progression/Relapse Unknown Total Complete Response Total Unknown Progression/Relapse Stable disease Partial Response Complete Response Partial Response Stable disease Progression/Relapse Unknown Complete Response Total Partial Response Stable disease Progression/Relapse Unknown Total (n =3,489) 730 (20.9) 136 (3.9) 184 (5.3) 186 (5.3) 216 (6.2) 325 (9.3) Overall 16 12 21 3 0 0 0 0 1 2 2 1 3 8 3 0 0 0 1 2 3 1 2 3 - - - - No. (%) 10 31 48 8 0 0 0 2 2 2 5 1 0 1 9 0 1 0 1 4 5 2 5 5 - - - - 17 31 49 11 71 7 0 2 5 1 0 0 1 0 2 1 5 5 ------Paediatric 53 (12.7) 88 (21.1) (n =417) 24 (5.8) 11 (2.6) 14 (3.4) 31 (7.4) 11 23 12 12 22 15 16 14 68 3 6 1 2 1 6 0 2 3 2 4 0 4 2 1 - - - - (Continued) 105 15 52 75 12 17 21 20 58 8 0 0 0 0 1 2 7 2 1 0 1 6 2 1 5 3 3 3 135 313 15 52 75 31 13 19 20 12 68 12 49 10 37 37 48 85 8 1 4 7 4 6 6 2 7 8 17

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Table A7. Distribution of study cohort by gender andprovince of origin. Table A6. Distribution of study cohort by province of origin. Ghazni Balkh Nangarhar Kabul Daykundi Sar-e-Pul Kapisa Panjshir Farah Samangan Bamyan Jowzjan Zabul Helmand Unknown Other (combined) Nuristan Uruzgan Ghor Badghis Nimroz Kandahar Badakshan Takhar Faryab Parwan Paktika Kunar Baghlan Wardak Laghman Logar Kunduz Paktia Province (n =1,801) 326 (18.1) 101 (5.6) 108 (6.0) 152 (8.4) Male

Adults ( n =3,072) 673 (19.3) 130 (3.7) 10 (0.3) 14 (0.4) 17 (0.5) 20 (0.6) 22 (0.6) 22 (0.6) 25 (0.7) 28 (0.8) 32 (0.9) 32 (0.9) 37 (1.1) 41 (1.2) 47 (1.3) 50 (1.4) 49 (1.4) 50 (1.4) 48 (1.4) 74 (2.1) 73 (2.1) 95 (2.7) 94 (2.7) (n =1,271) 316 (24.9) 2 (0.1) 5 (0.1) 5 (0.1) 4 (0.1) 6 (0.2) 7 (0.2) 120 (9.4) 71 (5.6) 77 (6.1) Female - (Continued)

No. (%) 31 (10.5) 62 (21.1) (n =294) 12 (7.5) 22 (0.2) Male Paediatric (n=417)

80 (19.2) 15 (3.2) 11 (2.6) 17 (4.1) 4 (1.0) 5 (1.2) 7 (1.7) 4 (1.0) 7 (1.7) 8 (1.9) 5 (1.2) 7 (1.7) 9 (2.2) 9 (2.2) 8 (1.9) ------22 (17.9) 26 (21.1) (n =123) Female 2 (1.6) 9 (7.3)

18

Research ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Table A8. Distribution of study cohort by cancer stage andoutcomes. Stage 0 Cancer stage Stage I Stage II Table A7. Distribution of study cohort by gender andprovince of origin. Unknown Nuristan Uruzgan Nimruz Badghis Ghor Daykundi Sar-e Pul Kapisa Farah Panjshir Bamyan Samangan Helmand Jowzjan Zabul Kandahar Takhar Paktika Badakhshan Parwan Kunar Faryab Baghlan Maidan Wardak Laghman Logar Kunduz Paktia Khost Herat Characteristic 366 (20.3) 10 (0.6) 11 (0.6) 11 (0.6) 13 (0.6) 16 (0.9) 18 (1.0) 19 (1.1) 20 (1.1) 21 (1.2) 22 (1.2) 23 (1.3) 25 (1.4) 26 (1.4) 34 (1.9) 35 (1.9) 36 (2.0) 39 (2.2) 43 (2.4) 48 (2.7) 75 (4.2) 77 (4.3) 94 (5.2) 1 (0.2) 3 (0.2) 3 (0.2) 3 (0.2) 4 (0.2) 5 (0.3) 6 (0.3) 7 (0.4) (n =1,801) 246 (13.7) 140 (7.8) 1 (0.1) Male Adults ( n =3,072) 227 (17.9) 10 (0.8) 10 (0.8) 14 (1.1) 13 (1.0) 19 (1.5) 18 (1.4) 13 (1.0) 31 (2.4) 25 (2.0) 43 (3.4) 29 (2.3) 47 (3.7) 35 (2.8) 79 (6.2) 1 (0.1) 1 (0.1) 2 (0.2) 0 (0.0) 0 (0.0) 1 (0.1) 3 (0.2) 6 (0.5) 5 (0.4) 8 (0.6) 4 (0.3) 9 (0.7) 8 (0.6) 9 (0.7) 9 (0.7) 8 (0.6) (n =1,271) 332 (26.1) 118 (9.3) Female 5 (0.4) No. (%) (Continued) 60 (20.4) 11 (3.7) 14 (2.4) 1 (0.3) 0 (0.0) 1 (0.3) 0 (0.0) 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3) 0 (0.0) 1 (0.3) 1 (0.3) 1 (0.3) 1 (0.3) 2 (0.7) 0 (0.0) 4 (1.4) 5 (1.7) 7 (2.4) 5 (1.7) 2 (0.7) 6 (2.0) 3 (1.0) 4 (1.4) 4 (1.4) 7 (2.4) 8 (2.7) 8 (4.8) 7 (4.1) 39 (13.3) (n =294) 29 (9.9) 0 (0.0) Male Paediatric (n=417) 20 (16.3) 10 (8.1) 0 (0.0) 0 (0.0) 0 (0.0) 1 (0.8) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.2) 1 (0.8) 1 (0.8) 0 (0.0) 0 (0.0) 2 (1.6) 1 (0.8) 0 (0.0) 5 (4.1) 5 (4.1) 1 (0.8) 1 (0.8) 3 (2.4) 2 (1.6) 1 (0.8) 6 (4.9) 0 (0.0) 4 (3.3) 15 (12.2) 16 (13.0) (n =123) Female 0 (0.0) 19

Research Figure A1. Distribution by treatment strategy inpaediatric patients. ecancer 2020, 14:1018; www.ecancer.org; DOI:https://doi.org/10.3332/ecancer.2020.1018 Table A8. Distribution of study cohort by cancer stage andoutcomes. Stage III Stage IV Unknown/Not Applicable Active follow-up Lost to follow-up Patient outcome Active treatment Discharged Died 1,029 (57.1) 704 (39.1) 428 (23.8) 282 (15.7) 483 (26.8) 143 (7.9) 98 (5.4) 48 (2.7) 468 (36.8) 179 (14.1) 628 (49.4) 169 (13.3) 452 (35.6) 89 (7.0) 32 (2.5) 70 (5.5) (Continued) 125 (42.5) 105 (35.7) 68 (23.1) 53 (18.0) 85 (28.9) 41 (13.9) 27 (9.2) 16 (5.4) 18 (14.6) 24 (19.5) 55 (44.7) 50 (40.7) 38 (30.9) 22 (17.9) 6 (4.9) 2 (1.6) 20

Research