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ANAEMIA IN CANCER PATIENTS UNDERGOING RADIOTHERAPY AND CHEMOTHERAPY AT THE NATIONAL HOSPITAL ABUJA, NIGERIA Dr. Chinedu Simeon Aruah: MD,MPH, FWACS INTERNATIONAL CONFERENCE ON NUCLEAR MEDICINE AND RADIATION THERAPY, COLOGNE GERMANY, July14th-15th ,2016 OUTLINE OF THE PRESENTATION Brief Background Rationale for the study-Why did we carry out this study in the first place Objectives Methodology Findings Conclusion and Recommendations Selected references BACKGROUND AFRICA AND CANCER BURDEN BACKGROUND -1 Cancer is an emerging public health problem in Africa According to International Agency for Research on Cancer 715,000 new cancer cases and 542,000 deaths occurred in 2008 in Africa These number are projected to nearly double by 2030 simply due to aging, population growth and change in life style modifications. Majority of cancers in Africa are diagnosed at an advanced stage of disease because of lack of screening and early detection services. Also limited awareness of early signs and symptoms of cancer among the public and healthcare providers are contributory. BACKGROUND -2 NIGERIA POPULATION AND CANCER BURDEN Population in 2012 – 166.6 million People newly diagnosed with cancer (excluding NMSC) /yr – 102,000 Age – standardise rate, incidence per 100,000 people /yr – 100.1 Risk of getting cancer before age of 75 – 10.4% People die from cancer /yr – 71,600 Source – Nigeria Cancer Organization Resources/Cancer Index. www.cancerindex.org NOTE:These figures are likely to increase because total population in Nigeria was estimated at 178.5million people in 2014. BACKGROUND - 3 Anaemia is commonly encountered in cancer patients undergoing therapy in Radiation Oncology centres. Aetiology and pathophysiology of anaemia in cancer patients are usually mutifactorial. Apart from the disease burden, commonly used treatment modalities such as radiotherapy, chemotherapy and chemoradiation in these centres are known to contribute to already existing anaemia. Many cancer patients present with anaemia prior to radiotherapy and chemotherapy and may even experience anaemia or worsening of anaemia at some point during treatment. However, the problem of anaemia is often ignored because patients may experience only functional anaemia defined as haemoglobin level less than 12g/dl especially among Caucasians. However, this Hb value tend to be less in Africans because of underlying aneamia ab nitio. Currently, haemoglobin level of 10g/dl is being used as borderline value and administration of radiotherapy or chemotherapeutic agents without adequate haematological support may tilt the patient into clinical anaemia. BACKGROUND -4 Ludwig et al.3 examined 9,118 cancer patients using Hb concentration level less than 12g/dl as the baseline value to study frequency of anaemia in various cancer types. The results of these studies were expressed in percentages: Breast cancers - 26%, Lung cancer 48%, Colorectal 33%, Head and Neck - 46%, Gynaecological - 43%, Lymphoma and Myeloma - 47%, Leukaemia 53%, Urogenital - 43% and others - 37%. Also, studies done by Ludwig et al3 on anaemia prevalence in patient receiving different cancer treatment with anaemia defined as Hb concentration level less than 12g/dl was quite significant. The results were as follows: chemotherapy - 75%, combination of chemotherapy and radiotherapy - 72%, concomitant chemotherapy and Radiotherapy - 62%, No treatment - 40% and radiotherapy alone - 38%. Rationale-Why this study? Anaemia is one of the predisposing factors to poor patient outcome in cancer treatment More than 50% of cancer patients will receive either radiotherapy or Chemotherapy or both in the course of their treatment It has been difficult to establish global or National benchmark on the baseline haemoglobin of patients selected for cancer therapy especially at different stages of the tumours Various centers use different levels but there is a need to establish a national cut-off point Establishing a uniform benchmark will inform a global best practice and increase the patient’s outcome and quality of life AIMS AND OBJECTIVES: The aim of the study was to carry out a prospective study on pattern of anaemia in cancer undergoing Radiotherapy and Chemotherapy. patients METHODOLOGY: The research was a prospective study The study consisted of 201 cancer patients of both sexes with histopathologically confirmed malignancies (solid cancers). Ethical clearance was obtained from the National Hospital Abuja Study was completed within a period of 8 months Those who met the inclusion criteria were selected and followed up in the course of the study. The patient were encouraged to fill consent form Patients’ baseline or pre-treatment Haemoglobin(Hb) were taken on the first day of consultation. Patients were distributed into three treatment arms, Radiotherapy alone, Chemotherapy alone and Chemoradiation therapy. Their Hb were measured once every 2 weeks during therapy. The blood film pictures of the patients were examined in the course of treatment. The whole process was terminated after 3 consecutive Hb reading or after week 6 Anaemia was classified for this study into: Less than 10g/dl 10 - 10.9g/dl 11 - 12 g/dl 12 g/dl and above - Severe anaemia moderate anaemia mild anaemia no anaemia. RESULTS AND ANALYSIS Table 1A: Demographic of the study population Variable Chemotherapy Radiotherapy Chemo radiotherapy Age Number % Number % Number % 25 – 34 17 17.0 11 17.5 7 18.4 35 – 44 36 36.0 19 30.2 9 27.7 45 – 64 22 22.0 10 15.9 8 21.1 55 – 64 21 21.0 11 17.5 10 26.3 65 – 74 3 3.0 8 12.7 3 7.9 75+ 1 1.0 4 6.3 1 2.6 Total 100 100 63 100 38 100 Table lB is demography of the study population based on sex distribution. Chemotherapy Radiotherapy Chemo radiotherapy Male 12 12.0 5 7.9 11 28.9 Female 88 88.0 58 92.1 27 71.1 Total 100 100 63 100 38 100 Variable Sex Table 2: Percentage Distribution of Tumour site and treatment type Tumour Site Chemotherapy Radiotherapy Chemo radiotherapy Number % Number % Number % Breast 68 68.0 30 47.6 - - Gastrointestinal 9 9.0 - - - - Head and Neck 4 4.0 5 7.9 14 36.8 Urogenital 6 6.0 10 15.9 - - Gynaecological 6 6 14 22.2 24 63.2 Musculoskeletal (Sarcomas) 5 5.0 2 3.2 - - Lung 3 3.0 2 3.2 - - Total 100 100 63 100 38 100 TABLE 3: The result showed majority of the patients presented with stage III tumour in chemotherapy group, radiotherapy group and chemoradiation with a percentage of 72%, 74.6% and 71.1% respectively. Stage Chemotherapy Chemo radiotherapy Radiotherapy Number % Number % Number % 1 2 2.0 1 1.6 1 2.6 2 24 24.0 15 23.8 10 26.3 3 72 72.0 47 74.6 27 71.1 4 2 2.0 - - - - Total 100 100 63 100 38 100 Table 4a: Percentage distribution of Hb by duration of treatment for patients undergoing Chemotherapy, Radiotherapy and Chemoradiation The table showed treatment from week 0 – week6; where week 0 was defined as time from initial administration of chemotherapy or Radiotherapy or Chemoradiation to the first 2weeks. CHEMOTHERAPY Hb g/dl TREATMENT DURATION Week 0 % Week 2 % Week 4 % Week 6 % <10 - - - - 6 6.0 2 2.0 10 – 10.9 - - - - 10 10.0 14 14.0 11 – 12 61 61.0 80 80.0 74 74.0 62 62.0 12+ 39 39.0 20 20.0 10 10.0 12 12.0 Total 100 100 100 - 100 100 100 100 Mean 12.6 11.92 - 11.29 - 10.89 - Standard Deviation 0.98 1.40 1.05 1.18 RADIOTHERAPY Hb g/dl TREATMENT DURATION Week 0 % Week 2 % Week 4 % Week 6 % <10 - - - - 1 1.6 3 4.8 10 – 10.9 13 20.6 15 23.8 21 33.4 20 31.7 11 – 12 38 60.3 42 66.7 35 55.5 35 55.6 12+ 12 19.1 6 9.5 6 9.5 5 7.9 Total 63 100 63 100 63 100 63 100 Mean 12.6 11.92 11.29 10.89 Standard Deviation 0.98 1.40 1.05 1.18 CHEMORADIATION Hbg/dl TREATMENT DURATION Week 0 % Week 2 % Week 4 % Week 6 % <10 1 2.6 1 2.6 4 10.5 7 18.4 10 – 10.9 2 5.3 2 5.3 13 34.2 15 39.5 11 – 12 15 39.5 25 65.8 18 47.4 12 31.6 12+ 20 52.6 10 26.3 3 7.9 4 10.5 Total 38 100 38 100 38 100 38 100 Mean 12.34 11.78 11.31 11.17 Standard Deviation 0.81 0.91 0.93 0.88 Table 4B: Showing percentage distribution of patients on chemotherapy, Radiotherapy and Chemoradiation blood film picture pattern from week 0 to week 6; while week 0 was defined as the time of initial therapy to the first 2week. CHEMOTHERAPY ALONE Blood Film Picture Treatment Duration (Chemotherapy Alone) Week 0 % of Patients Week 2 % of Patients W % eek of 4 W % of Patients eek Pat 6 ien ts 1. Normocytic 73 73.0 53 53.0 45 Normochromic 2. Hypochromic 45. 28 28.0 0 13 13.0 20 20.0 33 33. 37 37.0 0 3. Macrocytosis 5 5.0 5 5.0 1 1.0 5 5.0 4. Microcytosis 2 2.0 1 1.0 2 2.0 1 1.0 5. Poikliocytosis 1 1.0 - - - - 1.0 6. Anisocytosis 2 2.0 14 14.0 7 7.0 11 11.0 7. Elliptocytosis - - 1 1.0 - - 2 2.0 8. Dimorphic Picture 1 1.0 3 3.0 5 5.0 6 6.0 9. Target Cells 3 3.0 3 3.0 7 7.0 9 9.0 Blast cells - - - - - - - 10. 1 - RADIATION ALONE Blood Film Picture Treatment Duration (Radiation Alone) Week 0 % of Patients Week 2 % of Patients W % W % of Patients ee ee of k 4 Pat k 6 ien ts 1. Normocytic 48 76.2 42 66.7 36 57 36 57.1 Normochromic 2. Hypochromic .1 6 9.5 11 17.5 16 25 17 27.0 .4 3. Macrocytosis 2 3.2 - - 2 3. - - 2 4. Microcytosis 2 3.2 - - - - - - 5. Poikliocytosis 1 1.6 2 3.2 - - - - 6. Anisocytosis 1 1.6 2 3.2 5 7. 2 3.2 4 6.3 4 6.4 9 7. Elliptocytosis 1 1.6 1 1.6 1 1. 6 8. Dimorphic Picture 2 3.2 5 7.9 3 4. 8 9. Target Cells - - - - - - - - 10. Blast cells - - - - - - - - CHEMO-RADIATION ALONE CHEMO-RADIATION Blood Film Picture Week 0 Treatment Duration (Chemoradiation Alone) W % % of Patients Week 2 % of Patients ee of k Pa 4 ti en ts 73.7 22 57.9 10 26 .3 W % of Patients ee k 6 1. Normocytic Normochromic 28 2. Hypochromic 5 13.2 10 26.3 23 60 16 42.1 .5 3. Macrocytosis 1 2.6 2 5.3 3 7.9 4. Microcytosis Poikliocytosis 1 1 2.6 2.6 - - 6. Anisocytosis 1 2.6 4 10.5 7. Elliptocytosis Dimorphic Picture 1 2.6 - - 9. Target Cells - - - - 1 2. 6 - 1 2. 6 2 5. 3 - 1 2. 6 - - - - 10. Blast cells - - - - - - - 5. 8. - 10 26.3 1 2.6 - 6 15.8 1 2.6 1 2.6 Table 5: Distribution of Means and Standard Deviation of HB by Sex and type of treatment Sex MEAN STANDARD DEVIATION Chemotherapy Radiotherapy Chemo radiotherapy Male 11.72 (0.88) 10.82 (0.95) 12.27 (1.39) Female 11.65 (1.21) 12.14 (1.02) 11.13 (1.14) 95% C.I Mean difference 0.07 ± 2.73 -1.32 ± 2.73 1.14 ± 3.52 t 0.53 -2.96 2.41 P-value p>0.05 (NS) p>0.05 (NS) p>0.05 (NS) Table 6: Percentage Distribution of Hb by prevalence group Hbg/dl Number % <10 40 11.1 10 – 10.9 37 10.3 11 – 12 133 36.9 12+ 150 41.7 Total 360 100 Table 7: Distribution of mean HB, Stand deviation and confidence interval by type of treatment Types of Treatment Mean Standard Deviation Week Week 0 Week 2 Week 4 Week 6 Week 0 Week 2 Week4 Week6 Chemotherapy 13.42 12.42 11.99 11.35 1.2 1.51 1.50 1.32 Radiotherapy 12.55 12.18 12.02 11.83 .90 .93 1.1 1.5 Chemo radiotherapy 12.34 11.78 11.31 11.17 .81 .90 .93 .88 95% C.I Chemotherapy Radiotherapy Chemo radiotherapy Week 0 12.12 – 12.85 12.31 – 12.80 12.17- 12.52 Week 2 11.10 – 11.91 11.93 – 12.42 11.59 – 11.97 Week 4 9.91 – 10.95 11.73 – 12.31 11.11 – 11.51 Week 6 9.60 – 10.62 11.52 – 12.13 10.98 – 11.36 Table 8: Comparison of Prevalence Hb group level and the Baseline Hb of the study group Therapy Baseline Prevalence Chemotherapy 13.42 40 Radiotherapy 12.55 37 Chemo 12.34 133 t-test 1.604 radiotherapy 150 p-value 0.109 Remark Not significant >0.05 DISCUSSION-1 It was found from the study that the prevalence of anaemia in cancer patients undergoing Radiotherapy and Chemotherapy at National Hospital Abuja was 63% of the study group (ie average of 72%, 42.9%, 73.7%). Majority (62.0%) of the 100 patients on chemotherapy had Hb level at the range of 11-l2g/dl by week 6. This agreed with study by Barrett-Lee et al16 which observed that when the patients were analyzed to determine relative risk of anaemia, 62% of patients experienced a Hb decline of 1.5g/dl within a median of 6.1 to 7.2 weeks and 51% had a Hb decline of 2g/dl with a median of 7.3 to 8.3 weeks. . The Hb range at the end of the week 6 study showed that chemotherapy Hb range was 9.60 – 10.62, Radiotherapy 11.52 – 12.13, and Chemoradiation 10.98 – 11.36g/dl. This study was also in agreement with report by Ludwig et al16 which found that cancer patients treated and evaluated after; that anaemia occurred in 50.5% of those who received chemotherapy, 43.5% of patients who received chemoradiation and 28.7% in patients who received radiotherapy. The above observation helped to strengthen our earlier report that chemotherapy had greatest impact on Hb level during therapy. This assertion was supported by three different studies elsewhere (Ludwig et al3 ,Grossi et a119 and Jassen et a1 20) which showed that chemotherapy is a well known bone marrow depressant and acute cytotoxic agent: At the completion of radiotherapy at week 6, 55.6% of the patients had haemoglobin value at the range of 1112g/dl. There was gradual decline in Hb level as the radiotherapy treatment proceeded from week 0 to week 6. The result of this study was in agreement with work done by Harrison et al17 which reported that 41% of patients were anaemic with Hb level less than l2g/dl before starting radiotherapy Out of 38 patients analyzed on Chemoradiation only 4 had Hb level greater than 12g/dl This study was in agreement with studies done by Morris et a115 who studied cancer patients who had chemoradiation involving gynaecological and head and neck tumours. This report was in agreement with study done by MacRae et al18 following evaluation of 104 cancer patients with stage III non-small cell chemoradiotherapy. lung cancer (NSCLC) undergoing Conclusion and key Recommendation While pre-treatment Hb level measurement is very important, it is the on-treatment Hb level that is very critical as patients with initial adequate Hb value may easily be tilted into anaemia as their treatment progress. At 95% confidence interval, evaluation of effect of therapy on Hb level in the three arms showed that none of the values reached statistical significance ie P-value < 0.05. However, the impact of Chemotherapy on Hb level was more significant than in other treatment arms, hence Chemotherapy – 9.60-10.62g/dl, Radiotherapy 11.5212.13g/dl, and Chemoradiation 10.98-11.36g/dl. We recommend a benchmark of 11g/dl minimum for any patient being selected for both radiotherapy, chemotherapy and chemoradiation in Nigeria. LIMITATIONS: Paucity of published data in this area in Nigeria was a major challenge The sample size also might not be adequate for generalization The type of patients in the study may also be a challenge and bias considering that the center is in a big urban city and constitute patients with well-fed families This results might show a different finding if done in a poor rural community Financial limitation did not allow the expansion of this research to hospitals in poor rural settings in Nigeria AUTHORS DR. ARUAH S.C1 (Corresponding author) DR. OYESEGUN R2. (Radiation Oncology Department, NHA) DR. OGBE OCHE3, (Haematology Department, NHA) DR. IGBINOBA F4. (Radiation Oncology Department, NHA) DR JAWA Z.M.5, (Nuclear Medicine Department NHA) DR. OKOYE O.G.6, (Surgery Department, NHA) DR. AISHA ISMAILA7, (Nuclear Medicine Department NHA) DR. ONYISHI T.N.8 (HistoPathology Department ESUTTH, Enugu) SELECTED REFERENCES: Miller C B et al; “Decreased erythropoietin response in patients with the anaemia of cancer” National England Journal of Medicine (1990); 322:pp. 1689-1692. National Comprehensive Cancer Network (NCCN) Clinical Practice Guideline in Oncology Cancer and Chemotherapy induced anaemia V3. 2009. Ludwig H, Van Belles, Barrett-lee P et al. The European Cancer Anaemia Survey (ECAS): A large multinational prospective survey defining the prevalence, incidence and treatment of anaemia in cancer patients Eur J Cancer (2004); 40:2293-2306. Daniel Santini, Bruno Vincenzi, Annalisa Navajas et al. A new Dose-Intense epoietin Alfa Regimens Effective in Anaemia Cancer Patients Receiving Chemotherapy: An open-label, Non Randomized pilot study. Anti Cancer Research 2005; 25:669—674. Natacha Verbeke, Yves Beguin, Hans Wildiers, J.L Canon, Greet Bries, Andre Bosly, Simon Van Belle. Hight prevalence of anaemia and limited use of therapy in cancer patients: a Belgium Survey (Anaemia day 2008). Support Care Cancer, 2012; 20:23 —28. S.A Laurie, K. Ding, M. Whitehead, R. Feid, N. Murray, F.A Shepherd and L. Seymour. The impact of anaemia on outcome of chemoradiation for limited small-cell lung cancer: a combined analysis of studies of the National Cancer Institute of Canada Clinical 2007; 18:1051 — 1055. Pilar M, Samper Ots, Julia Munoz, Albert Biete, Maria Jose Ortiz et al. PITASOR Epidemiological study: Prevalence, incidence and treatment of anaemia in radiation therapy oncology department in Spain. Clin Transl Oncol 2011; 13:322-327. Laura Doni, Alessandra Penn, Luigi Manzione, Vittorio Gebbia, Rodoifo Mattioli,