Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study.

BACKGROUND: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. METHODS: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients ("traced cohort"). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). RESULTS: Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83-6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07-2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%-76.3%) and 45.3% (95% CI, 38.9%-51.7%), respectively. CONCLUSIONS: Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.

Guideline Concordance of Treatment and Outcomes Among Adult Non-Hodgkin Lymphoma Patients in Sub-Saharan Africa: A Multinational, Population-Based Cohort.

BACKGROUND: Although non-Hodgkin lymphoma (NHL) is the 6th most common malignancy in Sub-Saharan Africa (SSA), little is known about its management and outcome. Herein, we examined treatment patterns and survival among NHL patients. METHODS: We obtained a random sample of adult patients diagnosed between 2011 and 2015 from 11 population-based cancer registries in 10 SSA countries. Descriptive statistics for lymphoma-directed therapy (LDT) and degree of concordance with National Comprehensive Cancer Network (NCCN) guidelines were calculated, and survival rates were estimated. FINDINGS: Of 516 patients included in the study, sub-classification was available for 42.1% (121 high-grade and 64 low-grade B-cell lymphoma, 15 T-cell lymphoma and 17 otherwise sub-classified NHL), whilst the remaining 57.9% were unclassified. Any LDT was identified for 195 of all patients (37.8%). NCCN guideline-recommended treatment was initiated in 21 patients. This corresponds to 4.1% of all 516 patients, and to 11.7% of 180 patients with sub-classified B-cell lymphoma and NCCN guidelines available. Deviations from guideline-recommended treatment were initiated in another 49 (9.5% of 516, 27.2% of 180). By registry, the proportion of all patients receiving guideline-concordant LDT ranged from 30.8% in Namibia to 0% in Maputo and Bamako. Concordance with treatment recommendations was not assessable in 75.1% of patients (records not traced (43.2%), traced but no sub-classification identified (27.8%), traced but no guidelines available (4.1%)). By registry, diagnostic work-up was in part importantly limited, thus impeding guideline evaluation significantly. Overall 1-year survival was 61.2% (95%CI 55.3%-67.1%). Poor ECOG performance status, advanced stage, less than 5 cycles and absence of chemo (immuno-) therapy were associated with unfavorable survival, while HIV status, age, and gender did not impact survival. In diffuse large B-cell lymphoma, initiation of guideline-concordant treatment was associated with favorable survival. INTERPRETATION: This study shows that a majority of NHL patients in SSA are untreated or undertreated, resulting in unfavorable survival. Investments in enhanced diagnostic services, provision of chemo(immuno-)therapy and supportive care will likely improve outcomes in the region.

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.

Factors associated with late-stage diagnosis of breast cancer among women in Addis Ababa, Ethiopia.

PURPOSE: Stage at diagnosis is a key determinant of breast cancer prognosis. In this study, we characterize stage at diagnosis and determine factors associated with advanced stage at diagnosis among women diagnosed with invasive breast cancer in Addis Ababa, capital city of Ethiopia. METHODS: Stage information was collected from medical records of 441 women with invasive breast cancer seen in seven major health facilities in Addis Ababa, from January 2017 to June 2018; these seven facilities capture 90% of all incident breast cancer cases in the city. We used multivariable Poisson regression model with robust variance to determine factors associated with advanced stage at diagnosis. RESULTS: The predominant tumor histology was ductal carcinoma (83.7%). More than half of the tumors' grade was moderately or poorly differentiated. The median tumor size at presentation was 4 cm. Sixty-four percent of the patients were diagnosed at advanced stage of the disease (44% stage III and 20% stage IV), with 36% of the patients diagnosed at early-stage (5% stage I and 31% stage II). The prevalence of advanced stage disease was significantly higher among women who used traditional medicine before diagnostic confirmation (adjusted prevalence ratio [aPR] = 1.31; p = 0.001), had patient delay of >  3 months (aPR = 1.16; p = 0.042) and diagnosis delay of > 2 months (aPR = 1.24; p = 0.004). But it was lower among women who had history of breast self-examination (aPR = 0.77; p = 0.021). CONCLUSIONS: Advanced stage at diagnosis of breast cancer among women in Addis Ababa is strongly associated with use of traditional medicine and with prolonged time interval between symptom recognition and disease confirmation. Community- and health systems-level interventions are needed to enhance knowledge about breast cancer and facilitate timely diagnoses.

Utilization of Cardiac Surveillance Tests in Survivors of Breast Cancer and Lymphoma After Anthracycline-Based Chemotherapy.

BACKGROUND: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. METHODS AND RESULTS: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74-0.85]; P<0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39-1.69] and odds ratio, 1.42 [95% CI, 1.3-1.53]; P<0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. CONCLUSIONS: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.

A prospective study of tea drinking temperature and risk of esophageal squamous cell carcinoma.

Previous studies have reported an association between hot tea drinking and risk of esophageal cancer, but no study has examined this association using prospectively and objectively measured tea drinking temperature. We examined the association of tea drinking temperature, measured both objectively and subjectively at study baseline, with future risk of esophageal squamous cell carcinoma (ESCC) in a prospective study. We measured tea drinking temperature using validated methods and collected data on several other tea drinking habits and potential confounders of interest at baseline in the Golestan Cohort Study, a population-based prospective study of 50,045 individuals aged 40-75 years, established in 2004-2008 in northeastern Iran. Study participants were followed-up for a median duration of 10.1 years (505,865 person-years). During 2004-2017, 317 new cases of ESCC were identified. The objectively measured tea temperature (HR 1.41, 95% CI 1.10-1.81; for ≥60°C vs. <60°C), reported preference for very hot tea drinking (HR 2.41, 95% CI 1.27-4.56; for "very hot" vs. "cold/lukewarm"), and reported shorter time from pouring tea to drinking (HR 1.51, 95% CI 1.01-2.26; for <2 vs. ≥6 min) were all associated with ESCC risk. In analysis of the combined effects of measured temperature and amount, compared to those who drank less than 700 ml of tea/day at <60°C, drinking 700 mL/day or more at a higher-temperature (≥60°C) was consistently associated with an about 90% increase in ESCC risk. Our results substantially strengthen the existing evidence supporting an association between hot beverage drinking and ESCC.

Time intervals experienced between first symptom recognition and pathologic diagnosis of breast cancer in Addis Ababa, Ethiopia: a cross-sectional study.

OBJECTIVES: This study aimed to estimate the magnitude of patient and diagnostic delays and associated factors among women with breast cancer in Addis Ababa. DESIGN: This is a cross-sectional study. SETTINGS AND PARTICIPANTS: All women newly diagnosed with breast cancer in seven major healthcare facilities in Addis Ababa (n=441) were included in the study. MAIN OUTCOMES AND MEASURES: Patient interval (time from recognition of first symptom to medical consultation) and diagnostic interval (time from first consultation to diagnosis). Patient intervals >90 days and diagnostic intervals >30 days were considered delays, and associated factors were determined using multivariable Poisson regressions with robust variance. RESULTS: Thirty-six percent (95% CI [31.1%, 40.3%]) of the patients had patient intervals of >90 days, and 69% (95% CI [64.6%, 73.3%]) of the patients had diagnostic intervals of >30 days. Diagnostic interval exceeded 1 year for 18% of patients. Ninety-five percent of the patients detected the first symptoms of breast cancer by themselves, with breast lump (78.0%) as the most common first symptom. Only 8.0% were concerned about cancer initially, with most attributing their symptoms to other factors. In the multivariable analysis, using traditional medicine before consultation was significantly associated with increased prevalence of patient delay (adjusted prevalence ratio (PR) = 2.13, 95% CI [1.68, 2.71]). First consultation at health centres (adjusted PR = 1.19, 95% CI [1.02, 1.39]) and visiting ≥4 facilities (adjusted PR = 1.24, 95% CI [1.10, 1.40]) were associated with higher prevalence of diagnostic delay. However, progression of symptoms before consultation (adjusted PR = 0.73, 95% CI [0.60, 0.90]) was associated with decreased prevalence of diagnostic delay. CONCLUSIONS: Patients with breast cancer in Addis Ababa have prolonged patient and diagnostic intervals. These underscore the need for public health programme to increase knowledge about breast cancer symptoms and the importance of early presentation and early diagnosis among the general public and healthcare providers.

Cancer History, Health Insurance Coverage, and Cost-Related Medication Nonadherence and Medication Cost-Coping Strategies in the United States.

OBJECTIVES: To evaluate the relationship between cancer history and cost-related medication nonadherence (CRN) as well as cost-coping strategies, by health insurance coverage. METHODS: We used the 2013 to 2016 National Health Interview Survey to identify adults aged 18 to 64 years with (n = 3599) and without (n = 56 909) a cancer history. Cost-related changes in medication use included (1) CRN, measured as skipping, taking less, or delaying medication because of cost, and (2) cost-coping strategies, measured as requesting lower cost medication or using alternative therapies to save money. Separate multivariable logistic regressions were used to calculate the adjusted odds ratios (AORs) of CRN and cost-coping strategies associated with cancer history, stratified by insurance. RESULTS: Cancer survivors were more likely than adults without a cancer history to report CRN (AOR 1.26; 95% confidence interval [CI] 1.10-1.43) and cost-coping strategies (AOR 1.10; 95% CI 0.99-1.19). Among the privately insured, the difference in CRN by cancer history was the greatest among those enrolled in high-deductible health plans (HDHPs) without health savings accounts (HSAs) (AOR 1.78; 95% CI 1.30-2.44). Among adults with HDHP and HSA, cancer survivors were less likely to report cost-coping strategies (AOR 0.62; 95% CI 0.42-0.90). Regardless of cancer history, CRN and cost-coping strategies were the highest for those uninsured, enrolled in HDHP without HSA, and without prescription drug coverage under their health plan (all P<.001). CONCLUSIONS: Cancer survivors are prone to CRN and more likely to use cost-coping strategies. Expanding options for health insurance coverage, use of HSAs for those with HDHP, and enhanced prescription drug coverage may effectively address CRN.

Most Gleason 8 Biopsies are Downgraded at Prostatectomy-Does 4 + 4 = 7?

PURPOSE: Nonrepresentative biopsy sampling of prostate cancers with a biopsy Gleason score of 8 can adversely influence decisions regarding androgen deprivation in men receiving primary radiation therapy. The frequency of and factors associated with downgrading Gleason 8 biopsies at prostatectomy are not well known. MATERIALS AND METHODS: We used records from NCDB (National Cancer Database), a hospital based registry in the United States, of 72,556 men with prostate cancer diagnosed from 2010 to 2013, including 5,474 with Gleason 8 biopsies and no other high progression risk criteria according to NCCN (National Comprehensive Cancer Network®) Guidelines®. The prevalence of Gleason 8 downgrading was calculated. Generalized estimating equation multivariable regression models were used to estimate the prevalence ratios and 95% CIs of downgrading by demographic and clinical factors, and evaluate the association of Gleason 8 downgrading with cT (clinical T) to pathological T category up staging. RESULTS: Of 5,474 Gleason 8 biopsies in men lacking other high progression risk criteria 3,263 (60%) were downgraded, changing the progression risk category from high to intermediate. A higher prevalence of Gleason 8 downgrading was significantly and independently associated with decreasing age, African American race, lower cT category, lower prostate specific antigen quartile and certain combinations of primary and secondary Gleason grades (3 + 5 greater than 4 + 4 greater than 5 + 3). Gleason 8 downgrading in cases of cT less than 3 was independently and significantly associated with a lower prevalence of up staging (prevalence ratio = 0.65, 95% CI 0.61-0.69). CONCLUSIONS: Downgrading Gleason 8 biopsies is common. Patient evaluation based on Gleason 8 biopsies often results in overestimating progression risk and disease extent, which may lead to overtreatment.

Risk-Adjusted Margin Positivity Rate as a Surgical Quality Metric for Non-Small Cell Lung Cancer.

BACKGROUND: Incomplete lung cancer resection connotes poor prognosis; the incidence varies with patient demographic, clinical, and institutional factors. We sought to develop a valid, survival impactful, facility-based surgical quality metric that adjusts for related patient demographic and clinical characteristics. METHODS: Facilities performing resections for patients diagnosed with stage I to IIIA non-small cell lung cancer in the National Cancer Data Base between 2004 and 2011 were identified. Multivariate logistic regression modeling was used to estimate the expected number of margin-positive cases by adjusting for patient risk mix and calculate the observed-to-expected ratio for each facility. Facilities were categorized as outperformers (observed-to-expected ratio less than 1, p < 0.05), nonoutliers (p > 0.05), and underperformers (observed-to-expected ratio greater than 1, p < 0.05); and their characteristics across performance categories were compared by χ2 tests. Multivariate Cox proportional hazard analyses were conducted, adjusting for patient demographic and clinical characteristics. RESULTS: A total of 96,324 patients underwent surgery at 809 facilities. The overall observed margin-positive rate was 4.4%. Sixty-one facilities (8%) were outperformers, 644 (80%) were nonoutliers, and 104 (13%) were underperformers. One third (36%) of National Cancer Institute-designated facilities, 13% of academic comprehensive cancer programs, 5% of comprehensive community cancer programs, and 13% of "other" facilities achieved outperforming status but no community cancer programs did. Interestingly, 9% of National Cancer Institute-designated facilities and 11% of academic comprehensive cancer program facilities were underperformers. Adjusting for patient demographic and clinical characteristics, outperformers had a 5-year all-cause hazard ratio of 0.88 (95% confidence interval: 0.85 to 0.91, p < 0.0001) compared with nonoutliers, and 0.80 (95% confidence interval: 0.77 to 0.84, p < 0.0001) compared with underperformers. CONCLUSIONS: Facility performance in lung cancer surgery can be captured by the risk-adjusted margin-positivity rate, potentially providing a valid quality improvement metric.

Survival impact of postoperative therapy modalities according to margin status in non-small cell lung cancer patients in the United States.

OBJECTIVE: Unlike complete (R0) resection guidelines, current National Comprehensive Cancer Network (NCCN) adjuvant therapy guidelines after incomplete (R1/R2) resection of non-small cell lung cancer (NSCLC) are based on low-level evidence. We attempted to validate them. METHODS: Patients with pathologic stage I-IIIA NSCLC from 2004 to 2011 in the National Cancer Database were stratified by margin status, NCCN-specified stage groupings, and adjuvant therapy exposure (none, radiotherapy, chemotherapy, or both). Five-year overall survival (OS) and hazard ratios, adjusted for patient and institutional characteristics, were compared. We used a parallel analysis of R0 resections to validate our methodology. RESULTS: We analyzed 3461 R1/R2, and 78,979 R0 resections. After R0 resection, the NCCN-recommended option was associated with the best survival across all stage groups, supporting our analytic approach. Patients with R1/R2 stage IA treated with radiation had a 26% OS, compared with 58% with no treatment (P = .003). In patients with stage IB/IIA(N0) R1/R2, radiation was associated with a 25% OS compared with 47% with no treatment (P = .025) and 62% with chemotherapy (P < .007). Chemoradiation was not associated with a survival benefit in either group. Patients with IIA(N1)/IIB and IIIA had better survival with chemotherapy or chemoradiation. No group had a survival benefit with radiation alone. CONCLUSIONS: NCCN adjuvant therapy guidelines after complete resection, based on high-level evidence, are validated, but not guidelines for patients with incompletely resected early-stage NSCLC, which are based on low-level evidence. Monomodality postoperative radiotherapy was not validated for any stage. Specific studies are needed to determine optimal management after incomplete resection.

Do cancer survivors change their prescription drug use for financial reasons? Findings from a nationally representative sample in the United States.

BACKGROUND: There is limited evidence from nationally representative samples about changes in prescription drug use for financial reasons among cancer survivors in the United States. METHODS: The 2011 to 2014 National Health Interview Survey was used to identify adults who reported ever having been told they had cancer (cancer survivors; n = 8931) and individuals without a cancer history (n = 126,287). Measures of changes in prescription drug use for financial reasons included: 1) skipping medication doses, 2) taking less medicine, 3) delaying filling a prescription, 4) asking a doctor for lower cost medication, 5) buying prescription drugs from another country, and 6) using alternative therapies. Multivariable logistic regression analyses were controlled for demographic characteristics, number of comorbid conditions, interactions between cancer history and number of comorbid conditions, and health insurance coverage. Main analyses were stratified by age (nonelderly, ages 18-64 years; elderly, ages ≥65 years) and time since diagnosis (recently diagnosed, <2 years; previously diagnosed, ≥2 years). RESULTS: Among nonelderly individuals, both recently diagnosed (31.6%) and previously diagnosed (27.9%) cancer survivors were more likely to report any change in prescription drug use for financial reasons than those without a cancer history (21.4%), with the excess percentage changes for individual measures ranging from 3.5% to 9.9% among previously diagnosed survivors and from 2.6% to 2.7% among recently diagnosed survivors (P < .01). Elderly cancer survivors and those without a cancer history had comparable rates of changes in prescription drug use for financial reasons. CONCLUSIONS: Nonelderly cancer survivors are particularly vulnerable to changes in prescription drug use for financial reasons, suggesting that targeted efforts are needed. Cancer 2017;123:1453-1463. © 2016 American Cancer Society.

Temporal Trends and the Impact of Race, Insurance, and Socioeconomic Status in the Management of Localized Prostate Cancer.

BACKGROUND: Numerous management options exist for patients with prostate cancer; however, recent trends and their influencing factors are not well described. OBJECTIVE: To describe modern patterns of care and factors associated with management choice using the National Cancer Database. DESIGN, SETTING, AND PARTICIPANTS: Patients with localized prostate cancer diagnosed between 2004 and 2012 were included and grouped according to National Comprehensive Cancer Network guidelines into low, intermediate, or high risk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Trend analyses and multivariate logistic regression was used to identify factors associated with management. RESULTS AND LIMITATIONS: There were 598 640 patients who met the study criteria; 36.3% were classified as low risk, 43.8% intermediate risk, and 20.0% high risk. Over the study period, among low-risk patients, observation increased from 9.2% to 21.3%, while radical prostatectomy (RP) increased from 29.5% to 51.1% (p<0.001 for both). In contrast, external beam radiotherapy decreased from 24.3% to 14.5%, while brachytherapy decreased from 31.7% to 11.1%. A similar pattern was seen for patients with intermediate-risk or high-risk disease. Among high-risk patients, RP increased from 25.1% to 43.4% replacing external beam radiotherapy as the dominant therapy. On multivariate analysis, racial minorities, the uninsured, and low-income patients were less likely to receive RP. Low-risk patients in similar subgroups were significantly more likely to be observed. Limitations include potential miscoding or misclassification of variables. CONCLUSIONS: Patterns of care in localized prostate cancer are changing rapidly. While use of observation is increasing in low-risk groups, the use of RP is increasing across all risk groups with a concomitant decline in use of radiotherapy. Socioeconomic factors appear to influence management choice. PATIENT SUMMARY: In this report we identify a recent significant increase in the use of radical prostatectomy for prostate cancer patients. Socioeconomic factors such as race, insurance type, and income may affect treatments offered to and received by patients.