DOI: https://doi.org/10.21203/rs.3.rs-809737/v1
Background: For several years, HER2-positive breast cancer was associated with poor outcomes and higher mortality rates than other breast cancer subtypes. Nevertheless, the advent of Trastuzumab has significantly changed the treatment paradigm of HER2-positive breast cancer. However, it is not an affordable treatment option in sub-Saharan African countries. Besides, there was a lack of comprehensive data about the survival outcomes of HER2-positive breast cancer patients in our setting. Hence, the present study aimed to determine the survival outcomes among HER2-positive breast cancer patients at the Oncology Department of Kenyatta National Hospital.
Methods: A hospital-based retrospective cohort design was used to evaluate the survival outcomes, and associated factors among patients with HER2-positive breast cancer admitted between 2015 and 2019 at Kenyatta National Hospital. A total of 50 eligible HER2-positive breast cancer patients were included in the study. In the pre-designed data abstraction tool, the data were collected by reviewing the medical records of the patients. The data were entered and analyzed using the Statistical Package for the Social Sciences version 27 software. The mean survival time was estimated using Kaplan Meier survival analysis. Cox regression analysis was employed to estimate the predictors of mortality among HER2-positive breast cancer patients.
Results: The study showed that the overall survival rate was 30%, with a significant decrease in the percentage survival rate across the five years. More than half of the study participants (26, 52%) showed cancer progression during the last follow-up period. The present study showed that the mean cancer-specific survival rate among the study patients was 26.74±18.395 months. The study showed that the mean survival time of patients aged below 60 years (32.513 months), without co-morbidities (34.40 months), and the early stage of the disease (50.639 months) was higher than their counterparts. Multivariate cox-regression analysis revealed that advanced stage (AHR=13.1, 95% CI=2.6-66.6, P=0.002 and distant metastasis (AHR=15.0, 95% CI=3.6-62.8, P≤0.001) were the significant predictors of mortality among HER2 positive breast cancer patients.
Conclusions: The overall survival rate of HER 2 positive breast cancer was 30%. Advanced stage and distant metastasis were the significant predictors of mortality among HER2-positive breast cancer patients.
Cancer is a combination of diseases exhibited by unlimited growth and spread of malignant cells if not managed adequately (1). The primary type of cancer that affects most women is breast cancer, among the many forms of cancer identified worldwide and responsible for most lives lost (2). Breast cancer remained the major public health concern globally accounted for 1,960,682 new cases and 611,625 deaths (3).
Cancer is becoming an issue of concern for many Kenyans today, with its prevalence rising rapidly over the past few years. Cancer is the third major cause of death in Kenya, with the other two being infectious and cardiovascular disease (4). Furthermore, breast cancer accounted for 16.1% of total cancer cases in Kenya in 2020 (5).
HER2-positive breast cancer is a type of breast cancer that tests positive for a protein known as receptor 2 of the human epidermal growth factor, promoting cancer cell growth. It is a highly aggressive, fast-growing type of cancer that accounts for about 20% of breast cancers (6). Being an aggressive type of cancer, growth control is intensive compared to HER2-negative breast cancer (7). This has an overall impact on the treatment outcomes and the general patient survival rate. Furthermore, in an advanced-stage disease with metastasis, it becomes harder to achieve the desired treatment outcomes in HER2-positive breast cancer (8). For several years, HER2-positive breast cancer was associated with poor outcomes and higher mortality rates than other subtypes of breast cancer. Nevertheless, the advent of Trastuzumab has significantly changed the treatment paradigm of patients who have HER2-positive breast cancer (9). Yamashiro et al reported that the five and ten-year overall survival rates were 96% and 92.7%, respectively, among HER2-positive breast cancer patients after trastuzumab treatment (10). Furthermore, a previous systematic review also reported that a significant improvement in overall survival was observed among trastuzumab-treated HER2-positive breast cancer patients (11). A study in the United States reported that the four-year survival rate among HER 2 positive breast cancer patients was 90.3% (12). Besides, a previous systematic review also revealed that the overall survival outcomes were relatively higher among HER2-positive breast cancer patients (11). Even though trastuzumab is the frontline adjuvant treatment in HER2-positive breast cancer patients in achieving better outcomes, it is not an affordable treatment option in sub-Saharan African countries (13). Because of the expensive nature of trastuzumab treatment, most patients in our setting did not get this treatment for the optimal control of their condition. Besides, there was a lack of comprehensive data about the survival outcomes of HER2-positive breast cancer patients in our setting. Hence, the present study aimed to determine the survival outcomes and associated factors among HER2-positive breast cancer patients at the Oncology Department of Kenyatta National Hospital (KNH).
A retrospective cohort study design was employed among HER 2 positive breast cancer patients admitted at the Kenyatta National Hospital between 2015 and 2019. The study was carried out for a period of two months (February- March 2021). The hospital is located on hospital road, upper Hill Nairobi. The critically ill section has about 30-40 beds available for the patients. Kenyatta National Hospital is Kenya's oldest and largest public referral hospital. It is also the teaching hospital of the College of Health Sciences, University of Nairobi. In the year 1901, the Kenyatta National Hospital was originally founded as the Native Civil Hospital, with a maximum bed capacity of about 40 patients. In the year 1952, the hospital was renamed King George VI hospital. The hospital was later renamed after Jomo Kenyatta, Kenya’s first president.
The medical records of all HER2 positive breast cancer patients admitted at the oncology Department of KNH in the years 2015 and 2019 who fulfilled the inclusion criteria were involved in the study.
Inclusion criteria
Exclusion criteria
The sample size for the study was all HER2-positive breast cancer patients treated in the oncology Department from 2015 to 2019 and fit the inclusion criteria. Hence, a total of 50 HER2-positive breast cancer patients were involved in the study. A consecutive sampling technique was employed in the study.
A data abstraction tool was designed in reference to previous studies of the standard methods of reporting cancer treatment outcomes. The patients' records were obtained from the Health Information Department of Kenyatta National Hospital. Pertinent information such as patient's sociodemographic, clinical characteristics, the type of treatment given, status of the tumor size after treatment, status of the patient in the last follow-up period and survival time were recorded after reviewing the medical records of the patients. Outcomes were measured in terms of mortality, mean survival estimates, remission, and degree progression.
To ensure the validity of the data abstraction tool, a pretest was conducted on 5% of the sample population. The pretest was conducted one week before the actual day of conducting the study. All the required adjustments were performed in the data abstraction tool before implementing in the main study.
The dependent variable for this particular study was the survival outcomes of the patients. Demographic variables such as; age, gender, level of education, occupation, marital status, and Patient characteristics such as; comorbidity, number of medications, histological type of breast cancer, stage of breast cancer, and treatment regimens formed the independent variables.
The data were entered and analyzed using the Statistical Package for the Social Sciences version 27 software. The mean survival time was estimated using Kaplan Meier survival analysis. Cox regression analysis was employed to estimate the predictors of mortality among HER2-positive breast cancer patients. P-value ≤0.05 was considered statistically significant.
Cancer-specific survival: is defined as the time interval from the date of primary cancer
diagnosis to the date of cancer related-death or last follow-up.
Cancer-specific survival after metastasis: defined as the time interval from the date of the first radiographic metastasis to the date of cancer related-death or last follow-up.
Complete remission: defined as no evidence of disease on repeat scanning after treatment
Metastasis-free survival: defined as the time interval from the date of primary cancer diagnosis to the first radiographic metastasis.
Non-response: defined as failure to achieve partial remission.
Partial remission: defined as a reduction in tumor volume of at least 50% compared with
pretreatment imaging.
Progressive disease: defined as increased size of the tumor despite therapy.
The mean age of the study participants was 45.44 ± 12.218 years, with a majority of the patients being below 60 years (N = 40, 80%). Among the 50 study participants, 35(70%) were married, 7(14%) were single, 7(14%) were divorced, while 1(2%) was widowed. Half of the study population (25, 50%) had attained tertiary education, while only 6(12%) had primary education. A larger percentage of the population (22%) were housewives and private employees, while 2(4%) were merchants. The majority (42, 84%) of the study participants had no history of substance abuse, 7(14%) had a history of alcohol abuse, and 1(2%) was a cigarette smoker. Half of the study population (25, 50%) had a family history of cancer, while the other half did not (Table 1).
| Variable | Frequency | Percent |
|---|---|---|
| Age (in years) | ||
| ≤ 60 years | 40 | 80.0 |
| ≥ 60 years | 10 | 20.0 |
| Marital status | ||
| Single | 7 | 14.0 |
| Married | 35 | 70.0 |
| Divorced | 7 | 14.0 |
| Widowed | 1 | 2.0 |
| Educational status | ||
| Primary | 6 | 12.0 |
| Secondary | 19 | 38.0 |
| Tertiary | 25 | 50.0 |
| Occupational status | ||
| Housewife | 11 | 22.0 |
| Government employee | 10 | 20.0 |
| Retired | 3 | 6.0 |
| Merchant | 2 | 4.0 |
| Unemployed | 6 | 12.0 |
| Farmer | 4 | 8.0 |
| Daily laborer | 3 | 6.0 |
| Private employee | 11 | 22.0 |
| History of substance abuse | ||
| Alcohol | 7 | 14.0 |
| Smoking cigarette | 1 | 2.0 |
| None | 42 | 84.0 |
| Family history of cancer | ||
| No | 25 | 50.0 |
| Yes | 25 | 50.0 |
Clinical characteristics of the HER 2 positive breast cancer patients
The present study showed that all the study participants had invasive ductal carcinoma histological type of breast cancer. Of the 50 breast cancer patients, 18(36%) were in stage IV, 17(34%) in stage II, 14(28%) stage III, while only one patient was in stage I. Among the study participants, 22(44%) had co-morbidities, while 28(56%) did not have concurrent co-morbidities. Of the 22 patients with co-morbidities, 16(32%) had one, while 6(12%) had two co-morbidities. The Eastern Cooperative Oncology Group (ECOG) performance scale results showed that most patients (35, 70 %) were at scale 5. The largest proportion (64%) of the study patients had no distant metastasis. In comparison, 18(36%) had distant metastasis. The predominant co-morbidity among the study patients was diabetes mellitus (11, 22%) followed by hypertension (14%) and retroviral disease (14%), while the least prevalent was deep vein thrombosis (2, 4%) and anemia (1, 2%) as shown in Table 2.
| Variable | Frequency | Percent |
|---|---|---|
| Stage of cancer | ||
| Stage I | 1 | 2.0 |
| Stage II | 17 | 34.0 |
| Stage III | 14 | 28.0 |
| Stage IV | 18 | 36.0 |
| Co-morbidity | ||
| Present | 22 | 44.0 |
| Absent | 28 | 56.0 |
| Number of co-morbidities | ||
| Zero | 28 | 56.0 |
| One | 16 | 32.0 |
| Two | 6 | 12.0 |
| ECOG performance scale | ||
| 1 | 1 | 2.0 |
| 2 | 8 | 16.0 |
| 3 | 3 | 6.0 |
| 4 | 3 | 6.0 |
| 5 | 35 | 70.0 |
| Any distant metastasis | ||
| No | 32 | 64.0 |
| Yes | 18 | 36.0 |
| Type of co-morbidity | ||
| Diabetes mellitus | 11 | 22 |
| Hypertension | 7 | 14 |
| Retroviral disease | 7 | 14 |
| Deep Vein Thrombosis | 2 | 4 |
| Anemia | 1 | 2 |
Treatment regimen administered to the HER 2 positive breast cancer patients
The treatment regimens administered to the study patients were combination therapy, chemotherapy, surgery, and endocrine (hormonal) therapy. Of the study patients, 31(62%) were on combination therapy, 11(22%) on chemotherapy, while both surgery and endocrine therapy were the least prevalent types of treatment regimen (4, 8%). Most patients had undergone six cycles of chemotherapy (12, 24%). The most dominant type of chemotherapy regimen administered among the study patients was AC (Paclitaxel, Trastuzumab) (16, 32%), while the least administered were TC (Docetaxel, Cyclophosphamide) and AC (Doxorubicin, Cyclophosphamide) (2, 4%) and (1, 2%), respectively. Concerning the number of drugs administered, 80% of the patients were on 5 to 9, 12% on ten or more drugs, while those on less than 5 drugs were 8%, as shown in Table 3.
| Variable | Frequency | Percent |
|---|---|---|
| Treatment regimen | ||
| Combination therapy | 31 | 62.0 |
| Chemotherapy | 11 | 22.0 |
| Surgery | 4 | 8.0 |
| Endocrine therapy (Hormonal therapy) | 4 | 8.0 |
| Number of chemotherapy cycles | ||
| 0 | 8 | 16.0 |
| 2 | 2 | 4.0 |
| 3 | 1 | 2.0 |
| 4 | 9 | 18.0 |
| 5 | 1 | 2.0 |
| 6 | 12 | 24.0 |
| 7 | 2 | 4.0 |
| 8 | 9 | 18.0 |
| 9 | 2 | 4.0 |
| 10 | 1 | 2.0 |
| 14 | 2 | 4.0 |
| 16 | 1 | 2.0 |
| Type of chemotherapy regimen | ||
| AC (Paclitaxel, Trastuzumab) | 16 | 32.0 |
| TAC (Docetaxel, Doxorubicin, Cyclophosphamide) | 8 | 16.0 |
| None | 8 | 16.0 |
| TCH (Docetaxel, Carboplatin, Trastuzumab) | 7 | 14.0 |
| AC (Docetaxel, Trastuzumab) | 4 | 8.0 |
| ACP (Doxorubicin, Cyclophosphamide, Paclitaxel) | 4 | 8.0 |
| TC (Docetaxel, Cyclophosphamide) | 2 | 4.0 |
| AC (Doxorubicin, Cyclophosphamide) | 1 | 2.0 |
| Number of drugs given | ||
| < 5 | 4 | 8.0 |
| 5–9 | 40 | 80.0 |
| ≥ 10 | 6 | 12.0 |
The present study showed that the overall survival rate was 30%, with a significant decrease in the percentage survival rate across the five years. The percentage survival rate was 66% for one year, 56% for two years, 48% for three years, 42% for four years, and 30% for five years (Fig. 1).
More than half of the study participants (26, 52%) showed cancer progression during the last follow-up period. Non-responsive, partial remission and complete remission rates were 24%, 14%, and 8%, respectively (Fig. 2).
The present study showed that the mean cancer-specific survival rate among the study patients was 26.74 ± 18.395 months. In contrast, the means of cancer-specific survival after metastasis and metastasis-free survival were 4.26 ± 7.105 and 1.88 ± 3.293 months, respectively (Table 4).
| Survival parameter | Mean | Standard deviation |
|---|---|---|
| Cancer-specific survival | 26.74 | 18.395 |
| Cancer-specific survival after metastasis | 4.26 | 7.105 |
| Metastasis-free survival | 1.88 | 3.293 |
The study showed that the mean survival time among HER 2 positive patients was 32.513 months for those aged below 60 years and 27.100 months for patients 60 years and above. HER 2 positive breast cancer patients with a family history of cancer had a slightly higher mean survival rate of 31.855 months than those with no family history of cancer (29.854 months). The stage of cancer greatly influenced the mean survival rate among the patients, with those in the early stage of the disease had a higher mean survival rate of 50.639 months while those at stage advanced stage had the lowest mean survival rate of 18.76 months. The mean survival rate (34.40 months) of patients without co-morbidities, was higher as compared to that of patients with co-morbidities (27.409 months).
The mean survival rate of study patients according to the history of substance abuse was; 26.333 months for alcohol abusers and 30 months for cigarette smokers, while those who had no history of substance abuse had a mean survival rate of 32.22 months. The mean survival rate for patients with regressed tumor, progressed tumor, and no change in the size was 52.2 months, 21.729 months, and 39.381 months, respectively. Patients with no distant metastasis and diabetes mellitus had a high mean survival rate than those with distant metastasis and diabetes mellitus.
The log-rank test showed that the stage of cancer, size of the tumor, distant metastasis, and diabetes mellitus co-morbidity were all statistically significant differences in (P < 0.05) survival outcomes (Table 5).
| Variable | Mean survival time (months) ± standard error (95% CI) | Log-rank test (p-value) |
|---|---|---|
| Age (in years) | 0.475 | |
| ≤ 60 years | 32.513 ± 3.310(26.025-39.000) | |
| ≥ 60 years | 27.100 ± 7.230(12.929–41.271) | |
| Family history of cancer | 0.806 | |
| No | 29.854 ± 4.071(21.87-37.832) | |
| Yes | 31.855 ± 4.257(23.510-40.199) | |
| Stage of cancer | ≤ 0.001* | |
| Early stage(I&II) | 50.639 ± 2.8 (45.1–56.2) | |
| Advanced stage (III& IV) | 18.76 ± 2.7(13.4–24.2) | |
| Co-morbidity | 0.197 | |
| Present | 27.409 ± 4.105(19.364–35.455) | |
| Absent | 34.40 ± 34.207(26.157–42.650) | |
| History of substance abuse | 0.569 | |
| Alcohol | 26.333 ± 8.119(10.420-42.246) | |
| Smoking cigarette | 30.000 ± .000(30.000–30.000) | |
| None | 32.22 ± 23.395(25.567–38.877) | |
| Size of tumor | 0.004* | |
| Regressed | 52.200 ± 2.105(48.074–56.326) | |
| Progressed | 21.729 ± 3.318(15.225–28.233) | |
| No change | 39.381 ± 5.894(27.830-50.933) | |
| Distant metastasis | ≤ 0.001* | |
| No | 42.947 ± 2.954(37.157–48.738) | |
| Yes | 9.136 ± .843(7.484–10.788) | |
| Diabetes mellitus | 0.035* | |
| No | 34.143 ± 3.479(27.324–40.962) | |
| Yes | 21.455 ± 5.253(11.159–31.750) |
Bivariate analysis of the predictors of survival showed that the stage of cancer, distant metastasis, size of the tumor, remission status, and diabetes mellitus were significant predictors of survival outcomes. In contrast, the multivariate analysis showed that only the stage of cancer and distant metastasis were statistically significant. Bivariate analysis showed that those at an advanced stage (stage III and IV) of cancer were 12.2 times at high hazard of dying than those at an early stage (stage I and II). Those with distant metastasis were 32.1 times more likely to die than those without, while those without diabetes mellitus were 0.5 times more likely to die than those with the diseases shown in Table 6.
| Variable | Bivariate analysis | Multivariate analysis | |||
|---|---|---|---|---|---|
| CHR (95% CI) | P-value | AHR (95% CI) | P-value | ||
| Age (in Years) | |||||
| < 60 years | 1 | 1 | |||
| ≥ 60 years | 0.74(.318-1.717) | 0.482 | 1.6(0.6–4.3) | 0.379 | |
| Stage of cancer | |||||
| Early (I &II) | 1 | 1 | |||
| Advanced (III &IV) | 12.2 (4-1-36.4) | ≤ 0.001* | 13.1 (2.6–66.6) | 0.002* | |
| Distant metastasis | |||||
| No | 1 | 1 | |||
| Yes | 32.1(8.7-118.4) | ≤ 0.001* | 15.0(3.6–62.8) | ≤ 0.001* | |
| Co-morbidity | |||||
| Present | 1 | 1 | |||
| Absent | 1.5(0.79–2.99) | 0.205 | 1.08(0.28–4.27) | 0.909 | |
| Size of tumor | |||||
| Regressed | 1 | 1 | |||
| Progressed | 4.0 (1.4–11.6) | 0.010* | 1.9(0.1–30.4) | 0.638 | |
| No change | 1.3 (0.3–5.3) | 0.697 | 2.6(0.4–15.8) | 0.313 | |
| Remission status | |||||
| Complete remission | 1 | 1 | |||
| Partial remission | 3.3 (0.4–30.1) | 0.294 | 0.3 (0.1–9.6) | 0.523 | |
| Non-response | 3.7 (0.4–30.7) | 0.231 | 0.7 (0.1-7.0) | 0.795 | |
| Progression of the disease | 10.8 (1.4–30.2) | 0.021* | 3.3(0.7–16.3) | 0.151 | |
| Diabetes mellitus | |||||
| Yes | 1 | 1 | |||
| No | 0.5 (0.21–0.97) | 0.043* | 1.22(0.36–4.1) | 0.748 | |
| *Statistically significant p-value < 0.05, CHR: Crude hazard ratio, AHR: Adjusted hazard ratio | |||||
This study was aimed at analyzing the five-year survival rate and predictors of survival among 50 HER 2 positive breast cancer patients at the Kenyatta National Hospital. The study showed that the overall breast cancer survival rate was 30% which was similar to the 5-year survival rate. This finding almost corresponds to a study done in Algeria, showing that the 5-year survival rate was 38.8% (14). This low overall survival rate in our setting may be attributed to many factors, including the lack of early screening program, a higher proportion of advanced-stage cancer at the time of diagnosis, lack of specialized care, and delay in receiving care due to economic constraints. In addition, since most of the study patients (80%) were below 60 years, the poor survival outcomes might be linked to their younger age, as previous study showed that women under 40 years had a more aggressive tumor profile than older patients. Besides, the carcinomas in younger women were characterized by genetic instability, suggesting that the underlying tumor biology in many younger patients has a more aggressive profile and less favorable outcome(15).
The stage of cancer was also seen to have an impact on the overall survival rate of the study population. The majority of advanced stage (III and IV) patients had a death record, and a few were censored. The late disease stage is associated with larger tumor size and a lower rate of response to medication. Advanced stage of the disease is associated with reduced patient physiological function-ability, hence resultant low survival rate. In addition, the stage of cancer at the time of diagnosis is a significant predictor of survival since diagnosis at an earlier stage (I and II) contributes to a quicker response to treatment owing to the small size of the tumor and absence of metastasis (16).
The size of the tumor was also an important determinant of the mean survival time of the HER 2 positive breast cancer patients, which indicated that the majority of the patients had a progressed tumor size, thus a high fatality rate. This may have been attributed to the high cost of trastuzumab which is the most effective regimen for the HER 2 positive breast cancer patients. A previous study showed that the effective use of trastuzumab significantly improves the overall survival rate of HER 2 positive breast cancer patients (17). In contrast, most of the patients in our setting were on an alternative chemotherapy regimen that did not include trastuzumab hence slower or no response to treatment and subsequent progression of the tumor.
Numerous studies have shown that the presence of co-morbidity during or around the time of diagnosis most often measured by a comorbidity index, such as the Charlson Comorbidity Index (CCI), subsequently result in a low mean survival rate of HER 2 breast cancer patients (18). Similarly, the present study showed that the mean cancer-specific survival rate among the study patients was shorter (26.74 ± 18.395 months). This shorter cancer-specific survival rate might be linked to the larger percentage of (44%) coexisting co-morbidities among the study participants. The presence of co-morbidities subjects the patient to different and many drugs, which may become too much for the patient to take, hence compromising patient compliance. According to a study done in Botswana, HIV-positive patients, who were also HER 2-breast cancer positive, have a twofold reduction in the survival rate. This was different from the HIV-negative patients, who had higher chances of survival. This was linked to immunosuppression by HIV that even predisposed other patients to infections. However, little difference was observed in stage IV cancer patients, whose death rate was still high regardless of their HIV status (19). As from the study carried out at Kenyatta National Hospital, the outcomes were similar to these and, therefore, explain the reduced survival rate in HIV-positive breast cancer patients in the study setting.
On the other hand, diabetes mellitus was also a contributing factor to a decreased overall survival rate in our setting. This can be due to the development of diabetes mellitus complications that may compromise the patient from getting cancer treatments such as adjuvant chemotherapy and radiotherapy due to a resultant increase in chemotherapy toxicity. In addition, uncontrolled blood sugar levels may result in hyperglycemia, and thus survival decreases as glycemic control decreases (19).
In conclusion, the overall survival rate of a confirmed diagnosis of HER 2 positive breast cancer was 30% in the study setting. Advanced stage and distant metastasis were the significant predictors of mortality among HER2-positive breast cancer patients.
AHR: Adjusted hazard ratio
CHR: Crude hazard ratio
ECOG: Eastern Cooperative Oncology Group
HER 2: Human epidermal growth factor receptor 2
KNH: Kenyatta National Hospital
Ethics approval and consent to participate
The actual data collection was conducted after approval from the University of Nairobi/Kenyatta National Hospital Ethics and Research Committee (Approval number: UP8/01/2021). All patient information was treated with the utmost confidentiality. The patients' names were not recorded, and each patient was identified only based on study numbers and their initials. Patient files were not removed from the premises, and the data collected was used for the intended purpose only. No patient consent was needed for this study as secondary data was the main source of information for this study.
Consent for publication
We have obtained approval to publish from the Ethics committee.
Availability of data and materials
The datasets used during the current study are available from the corresponding author on a reasonable request.
Competing interests
The authors declare that they have no conflicts of interest.
Funding
There was no funding to conduct this project
Authors' contributions
GT and AD were involved from the conception to the final manuscript preparation. All authors reviewed the manuscript.
Acknowledgements
The authors would like to acknowledge the Oncology Department of Kenyatta National Hospital for permitting us to conduct this study.