Assessing the effectiveness of palliative radiotherapy for painful bone metastases in low- and middle-income countries: A systematic review.

Palliative radiotherapy (RT) effectively relieves pain in patients with bone metastases (BMs). Furthermore, several clinical trials, in most cases conducted in high-income countries (HICs), proved that single-fraction RT is equally effective compared to multi-fractionated RT. However, the evidence is scarce regarding low/middle-income countries (LMICs), where the diagnosis of BMs could be later and RT techniques less advanced. Therefore, we conducted a systematic literature review to evaluate the efficacy of palliative RT of BMs in the LMIC setting. A literature search was performed independently by two authors on the PubMed, Cochrane and Scopus databases. Overall, 333 records were screened and after the selection process, 11 papers were included in the analysis. Complete pain response rates ranged from 11.5% to 37.1% (median: 22%) for single-fraction RT and from 0% to 35.1% (median: 19%) for multi-fractionated RT. Partial pain response rates ranged from 23.1% to 76.9% (median: 53.8%) for single fraction RT and from 23.8% to 84.6% (median: 65%) for multi-fractionated RT. Four randomized trials compared single-fraction RT with multiple-fraction RT and none of them showed significant differences in terms of pain relief. Our analysis showed that pain response rates after palliative RT recorded in LMIC are like those reported in studies performed in HIC. Even in this setting, RT in single fraction shows comparable pain response rates to multifractional RT.

Dose-Volume Constraints fOr oRganS At risk In Radiotherapy (CORSAIR): An "All-in-One" Multicenter-Multidisciplinary Practical Summary.

BACKGROUND: The safe use of radiotherapy (RT) requires compliance with dose/volume constraints (DVCs) for organs at risk (OaRs). However, the available recommendations are sometimes conflicting and scattered across a number of different documents. Therefore, the aim of this work is to provide, in a single document, practical indications on DVCs for OaRs in external beam RT available in the literature. MATERIAL AND METHODS: A multidisciplinary team collected bibliographic information on the anatomical definition of OaRs, on the imaging methods needed for their definition, and on DVCs in general and in specific settings (curative RT of Hodgkin's lymphomas, postoperative RT of breast tumors, curative RT of pediatric cancers, stereotactic ablative RT of ventricular arrythmia). The information provided in terms of DVCs was graded based on levels of evidence. RESULTS: Over 650 papers/documents/websites were examined. The search results, together with the levels of evidence, are presented in tabular form. CONCLUSIONS: A working tool, based on collected guidelines on DVCs in different settings, is provided to help in daily clinical practice of RT departments. This could be a first step for further optimizations.

Cervical Cancer in Sub-Saharan Africa: A Multinational Population-Based Cohort Study of Care and Guideline Adherence.

BACKGROUND: Cervical cancer (CC) is the most common female cancer in many countries of sub-Saharan Africa (SSA). We assessed treatment guideline adherence and its association with overall survival (OS). METHODS: Our observational study covered nine population-based cancer registries in eight countries: Benin, Ethiopia, Ivory Coast, Kenya, Mali, Mozambique, Uganda, and Zimbabwe. Random samples of 44-125 patients diagnosed from 2010 to 2016 were selected in each. Cancer-directed therapy (CDT) was evaluated for degree of adherence to National Comprehensive Cancer Network (U.S.) Guidelines. RESULTS: Of 632 patients, 15.8% received CDT with curative potential: 5.2% guideline-adherent, 2.4% with minor deviations, and 8.2% with major deviations. CDT was not documented or was without curative potential in 22%; 15.7% were diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Adherence was not assessed in 46.9% (no stage or follow-up documented, 11.9%, or records not traced, 35.1%). The largest share of guideline-adherent CDT was observed in Nairobi (49%) and the smallest in Maputo (4%). In patients with FIGO stage I-III disease (n = 190), minor and major guideline deviations were associated with impaired OS (hazard rate ratio [HRR], 1.73; 95% confidence interval [CI], 0.36-8.37; HRR, 1.97; CI, 0.59-6.56, respectively). CDT without curative potential (HRR, 3.88; CI, 1.19-12.71) and no CDT (HRR, 9.43; CI, 3.03-29.33) showed substantially worse survival. CONCLUSION: We found that only one in six patients with cervical cancer in SSA received CDT with curative potential. At least one-fifth and possibly up to two-thirds of women never accessed CDT, despite curable disease, resulting in impaired OS. Investments into more radiotherapy, chemotherapy, and surgical training could change the fatal outcomes of many patients. IMPLICATIONS FOR PRACTICE: Despite evidence-based interventions including guideline-adherent treatment for cervical cancer (CC), there is huge disparity in survival across the globe. This comprehensive multinational population-based registry study aimed to assess the status quo of presentation, treatment guideline adherence, and survival in eight countries. Patients across sub-Saharan Africa present in late stages, and treatment guideline adherence is remarkably low. Both factors were associated with unfavorable survival. This report warns about the inability of most women with cervical cancer in sub-Saharan Africa to access timely and high-quality diagnostic and treatment services, serving as guidance to institutions and policy makers. With regard to clinical practice, there might be cancer-directed treatment options that, although not fully guideline adherent, have relevant survival benefit. Others should perhaps not be chosen even under resource-constrained circumstances.

Cervical cancer in Ethiopia - predictors of advanced stage and prolonged time to diagnosis.

INTRODUCTION: In Ethiopia, most cervical cancer patients present at advanced cancer stages, long time after they experience first symptoms. We investigated possible predictors of long time spans between symptom onset and pathologic diagnosis (patient intervals). We also aimed to seek out predictors for advanced cancer stage diagnosis. METHODS: We conducted a retrospective cohort study among 1575 cervical cancer patients who were registered at Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia between September 2008 and September 2012. Cox proportional hazards regression was used to find predictors of long patient intervals. Cumulative odds ordinal logistic regression was used to identify predictors of cancer stage at diagnosis. RESULTS: Median patient interval was 30 weeks, with the interval substantially longer in patients residing in rural than urban areas. Longer patient intervals were associated with more advanced cancer stages at pathologic diagnosis. HIV-positive women had an almost 1.5 times increased risk of diagnosis at a more advanced stage. CONCLUSION: Cervical cancer patients are diagnosed after long time periods leading to advanced stages at diagnosis. Measures to raise awareness about cervical cancer, to increase screening and to shorten the time interval from recognition of symptoms to diagnosis are urgently needed.

Addis Ababa population-based pattern of cancer therapy, Ethiopia.

Cancer in Sub-Saharan Africa is becoming an important challenge for health services due to rising numbers of patients. In Addis Ababa with around 3.5 million inhabitants, more than 2000 cases are diagnosed annually. In this retrospective population-based cohort study we assessed completeness of and waiting time for cancer-therapy among patients registered in the Addis Ababa City Cancer Registry (AACCR), Ethiopia. Patient hospital files were retrieved to complete the data from AACCR. A total of 588 files were found (51% of those diagnosed from January to March 2012 and 2014). We analyzed completeness and waiting time of chemotherapy and radiotherapy; with completeness defined as ≥85% therapy received according to local guidelines. Analysis was done for the five most common cancer-types commonly treated with chemotherapy (breast, colorectal, non-Hodgkin`s lymphoma, lung and ovarian) and the four most common cancer-types commonly treated with radiotherapy (breast, cervical, head and neck and rectal). In our study, half of the patients (54.1%) received adequately dosed chemotherapy and 24.5% of patients received adequately dosed radiotherapy. The median waiting time was 2.1 months (Range: 0 to 20.72) for chemotherapy and 7 months (Range: 0.17 to 21.8) for radiotherapy. This study underscores the need for health system measures to improve cancer-directed therapy in Ethiopia, especially concerning radiotherapy.

Adequacy of Pathologic Reports of Invasive Breast Cancer From Mastectomy Specimens at Tikur Anbessa Specialized Hospital Oncology Center in Ethiopia.

Purpose Although information from pathology reports is essential to the care of individuals with cancer and to population-level cancer control, no systematic evidence exists regarding the adequacy of breast pathology reporting in Ethiopia. This study audited pathology reports of mastectomy specimens from patients evaluated at the Tikur Anbessa Specialized Hospital Oncology Center in Addis Ababa, Ethiopia. Methods Mastectomy pathology reports from February 2014 through January 2016 were assessed for gross and microscopic information considered by the Breast Cancer Initiative 2.5 (BCI 2.5; formerly the Breast Health Global Initiative) guideline to be necessary for care of patients with breast cancer stratified according to basic, limited, and enhanced resource settings. Results Fewer than two thirds (61.6%) of the 417 reports we reviewed included all four of the BCI 2.5 basic pathology data elements we could evaluate with available data (tumor category, lymph node category, histologic type, and histologic grade). Only 1.0% of reports included all three pathology data elements recommended for limited resource settings (estrogen receptor status, margin status, and lymphovascular invasion). Several elements were significantly more likely to be noted in reports from nonpublic hospitals than from public hospitals. Although only three of 417 reports included checklists or templates, all three of these reports included all of the basic pathology information, and they all included at least two of the three limited pathology elements not already on the basic list. Conclusion More than one third (38.4%) of mastectomy pathology reports did not meet BCI 2.5 standards for basic resource settings. Quality measurement and improvement programs and capacity-building interventions by national pathology and oncology organizations, collaboration with medical and public health organizations in neighboring countries, adoption of synoptic reporting templates, use of electronic pathology reporting, and histotechnology and histopathology training collaborations with laboratories in high-resource regions are recommended.

Characteristics and follow-up of metastatic breast cancer in Ethiopia: A cohort study of 573 women.

OBJECTIVES: There is little information on characteristics, treatment and outcome of metastatic breast cancer (mBC) patients in low-income countries. This study aims to describe mBC in the setting of Ethiopia. MATERIALS AND METHODS: A retrospective cohort study was conducted among all female mBC patients from the only oncologic hospital in Addis Ababa 01/2006 to 12/2010. Time between first metastasis and known death or loss to follow-up for more than six months as surrogate for death were used for Cox proportional hazards model. RESULTS: A total of 573 patients were included; 188 (32.8%) women with de novo mBC (dnmBC) and 385 women with recurrent mBC (rmBC). The average age at time of first metastasis was 43.7 (standard deviation 11.9) years with an average survival probability of twelve months. Negative hormone receptor status, only present in 29% (Hazard ratio HR = 2.28 [95% confidence interval CI 1.56-3.32] p < 0.001), and grade 3 (HR = 1.72 [95% CI 1.15-2.55] p = 0.008) had significant influence on survival. Patients with initial bone metastasis (HR = 0.63 [95% CI 0.48-0.83] p = 0.001) had best chances of survival compared to more common initial visceral metastasis. About 35% of the patients received chemotherapy and 30.5% were on endocrine therapy. CONCLUSION: The lower survival for mBC in Addis Ababa compared to that from Western countries is presumably due to the later presentation at the hospital and lack of standard therapy. An unexpected high proportion of patients with hormone receptor positive mBC encourage consequent utilization of endocrine therapy to improve the quality of palliative care in this cohort.

Vulvar cancer in Ethiopia: A cohort study on the characteristics and survival of 86 patients.

Vulvar cancer (VC) is strongly associated with human papilloma virus (HPV) infections and immunosuppression (e.g., HIV). However, there is limited information on VC patient characteristics and survival in parts of sub-Saharan Africa, including Ethiopia, where chronic HPV and HIV infections are prevalent. The aim of this study is to provide a first view on VC patient characteristics in a sub-Saharan African setting.We present a retrospective analysis of records of 86 VC patients diagnosed between January 2010 and October 2015 at Addis Ababa University Hospital and other major health facilities in Ethiopia. Follow-up for vital status was obtained by telephone contact with patients or relatives. The primary endpoint was all-cause mortality.The median age of the patients was 39 (range: 20-85) years, 83% with known HIV status were positive and 81% presented with FIGO stages 2 or 3. The median follow-up time for surviving patients was 17 months (range: 0.1-65.0 months). The 1- and 2-year survival rates were 80% and 51%, respectively. Approximately 37% of patients received surgery, 38% received radiotherapy, and 33% received chemotherapy. Patients who received therapy had better survival than those who did not [adjusted hazard ratios: surgery, 0.44 (95% CI, 0.19-1.03); radiotherapy, 0.36 (95% CI, 0.14-0.90); chemotherapy, 0.42 (95% CI, 0.15-1.12)].A substantial proportion of VC patients in Ethiopia present at a late stage and receive suboptimal treatment. HIV infections appear to be a common comorbid condition. These conditions result in poor outcomes.

Cervical Cancer in Ethiopia: The Effect of Adherence to Radiotherapy on Survival.

BACKGROUND: Discontinuation of radiotherapy (RT) for cervical cancer (CC) in sub-Saharan Africa is common because of patient- and health service-related reasons. This analysis describes toxicities and the effect of adherence on survival. MATERIALS AND METHODS: A total of 788 patients with CC (2008-2012) who received RT at Addis Ababa University Hospital were included. External beam RT without brachytherapy was performed according to local guidelines. We previously described survival and prognostic factors. Now we analyzed adherence and survival according to total doses received. Adjustment via multivariate cox regression analysis was done. RESULTS: One-year overall survival (OS) after radical RT (n = 180) for International Federation of Gynecology and Obstetrics (FIGO) stages IIA-IIIA was 89% for discontinuation (<72 Gy) and 96% for adherence (≥72 Gy; hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.5-3.3). One-year OS after nonradical RT (n = 389) for FIGO stages IIIB-IVA was 71% for discontinuation (<40 Gy) and 87% for adherence (44-50 Gy; HR, 3.1; 95% CI, 1.4-6.9). One-year OS for FIGO stages IIIB-IVB (n = 219) after one compared with two or more palliative single fractions of 10 Gy were 14% and 73% respectively (HR, 7.3; 95% CI, 3.3-16). Reasons for discontinuation were toxicities, economic background, and RT machine breakdown. Grade 1-2 late toxicities were common (e.g., 30% proctitis, 22% incontinence). Grade 3 early and late toxicities were seen in 5% and 10% respectively; no grade 4 toxicities occurred. CONCLUSION: Patients who adhered to guideline-conforming RT had optimum survival. Better supportive care, brachytherapy to reduce toxicities, socioeconomic support, and additional radiation capacities could contribute to better adherence and survival. IMPLICATIONS FOR PRACTICE: This study presents the effect of adherence on survival of 788 patients with cervical cancer receiving external beam radiotherapy without brachytherapy in Ethiopia. Discontinuation of planned radiotherapy according to local guidelines considerably reduced survival for all International Federation of Gynecology and Obstetrics (FIGO) stages treated (hazard ratios were 1.3, 3.1, and 7.3 for FIGO stages IIA-IIIA and IIIB-IVA and the palliative approach, respectively). Early toxicity (5% grade 3) should be treated to improve adherence. Economic difficulties and machine breakdown should also be addressed to reduce discontinuation and improve survival.

First data from a population based cancer registry in Ethiopia.

BACKGROUND: The Addis Ababa City Cancer Registry, established in September 2011, is the only population-based cancer registry in Ethiopia, covering a catchment population of just over three million habitants. Herein, we report incidence data based on the first two years of registration, 2012-2013. METHODS: Newly-diagnosed cancer cases in the capital city were actively collected from 22 hospitals, clinics, and diagnostic facilities. RESULTS: During 2012-2013, a total of 4139 newly diagnosed cases were recorded, with the majority (67%) occurring in females. Cancers of the breast (31.5%) and cervix (14.1%) were the two most common cancers among females, while colorectal cancers (10.6%) and non-Hodgkin lymphomas (10.2%) were the most common cancers among males. The average annual age-standardized rate for all sites 2012-13 were 136.2 (per 100,000) and 70.7 in females and males, respectively. Female age-standardized rates were 40.6 for breast cancer and 21.5 for cervix, while equivalent rates in males were 7.6 per 100,000 for colorectal cancer and 6.8 per 100,000 for non-Hodgkin lymphoma. CONCLUSION: In general, these incidence patterns were similar to those reported in neighboring countries, which suggests that the majority of cancer cases occurring in Addis Ababa are captured within this starting phase of the registry. However, our finding of colorectal cancer as the most commonly-diagnosed cancer in males is novel and requires further investigation.

The prevalence of estrogen receptor-negative breast cancer in Ethiopia.

BACKGROUND: In contrast with breast cancers (BCs) in other parts of the world, most previous studies reported that the majority of BCs in sub-Saharan Africa are estrogen-receptor (ER) negative. However, a recent study using the US SEER database showed that the proportion of ER-negative BC is comparable between US-born blacks and West-African born blacks but substantially lower in East African-born blacks, with over 74% of patients Ethiopians or Eritreans. In this paper, we provide the first report on the proportion of ER-negative BC in Ethiopia, and the relation to progesterone-receptor (PgR) status. METHODS: We analysed 352 female patients with ER results available out of 1208 consecutive female BC patients treated at Addis Ababa-University Hospital, Ethiopia, from June 2005 through December 2010. The influences of age, stage, and histology on the probability of ER-negative tumours were assessed by a log-linear regression model. RESULTS: Of the 352 patients, only 35% were ER-negative. The proportion of ER-negative tumours decreased with advancing age at diagnosis and was not affected by histology or stage. For age, the proportion decreased by 6% for each additional 5 years (stage-adjusted prevalence ratio PR=0.94, 95% CI: 0.89-1.00). About 31% were ER- and PgR-negative, and 69% were ER- and/or PgR-positive. CONCLUSIONS: Contrary to most previous reports in other parts of sub-Saharan Africa, the majority of patients in Ethiopia are ER-positive rather than ER-negative. These findings are in line with low proportions of ER-negative BCs from East African immigrants within the SEER database, and they have clinical implications for management of BC patients in Ethiopia and other parts of sub-Saharan Africa where ER-status is not ascertained as part of routine management of the disease. Since the majority of patients showed ER-positive BC, Tamoxifen-therapy should be given to all patients even with unknown ER status.

Cervical cancer in Ethiopia: survival of 1,059 patients who received oncologic therapy.

BACKGROUND: Almost 500,000 women are newly diagnosed with cervical cancer (CC) every year, the majority from developing countries. There is little information on the survival of these patients. Our primary objective was to evaluate consecutive CC patients presenting over 4 years at the only radiotherapy center in Ethiopia. METHODS: All patients with CC from September 2008 to September 2012 who received radiotherapy and/or surgery were included (without brachytherapy). Vital status was obtained through telephone contact or patient cards. RESULTS: Of 2,300 CC patients, 1,059 patients with standardized treatment were included. At the end of the study, 249 patients had died; surviving patients had a median follow-up of 16.5 months; the 10% and 90% percentiles were 3.0 and 32.7 months, respectively. Mean age was 49 years (21-91 years). The majority of patients presented with International Federation of Gynecology and Obstetrics stage IIb-IIIa (46.7%). Because of progression during the waiting time (median 3.8 months), this proportion declined to 19.3% at the beginning of radiotherapy. The 1- and 2-year overall survival probabilities were 90.4% and 73.6%. If assuming a worst-case scenario (i.e., if all patients not available for follow-up after 6 months had died), the 2-year survival probability would be 45.4%. CONCLUSION: This study gives a thorough 4-year overview of treated patients with CC in Ethiopia. Given the limited treatment availability, a relatively high proportion of patients survived 2 years. More prevention and early detection at all levels of the health care system are needed. Increasing the capacity for external-beam radiation as well as options for brachytherapy would facilitate treatment with curative intention.