Skip to main content
NCBI home page
PLOS One logoLink to PLOS One
. 2021 Jan 28;16(1):e0246202. doi: 10.1371/journal.pone.0246202

Prevalence of anemia among Saudi patients with solid cancers at diagnosis in King Faisal Hospital, Taif Province, Kingdom of Saudi Arabia

Mazen Almehmadi 1, Magdi Salih 1,*, Tariq E Elmissbah 1, Abdulaziz Alsharif 1, Naif Alsiwiehri 1, Khalid Alzahrani 1, Alaa Shafie 1, Haytham Dahlawi 1
Editor: Colin Johnson2
PMCID: PMC7842985  PMID: 33507998

Abstract

Objectives

The aim of this study was to estimate the prevalence of anemia among patients newly diagnosed with solid malignancies at King Faisal Hospital in Taif Province, Kingdom of Saudi Arabia.

Methods

A descriptive, cross-sectional, hospital-based study was conducted from December 2017 to March 2020. A total of 320 patients newly diagnosed with solid malignancy were examined to assess anemia prevalence.

Results

Of 320 patients with solid cancers, 245 (76.6%) were female and 75 (23.4%) were male. The median (interquartile range) age of 57 (45 ─ 66) years, range between 16 and 108 years. The types of cancer included were breast (29.1%), female genital tract (20.0%), colorectal (25.3%), head and neck (10.3%), urinary bladder (4.7%), prostate (5.0%), lung (2.5%), liver (2.2%) and lymphoma (0.9%). The prevalence of anemia at diagnosis of cancer was 44.1% across all cancer types. A higher anemia prevalence was noted in colorectal (n = 46/81, 56.8%) (p = 0.047).

Conclusion

Patients with colorectal or female genital tract cancers had a higher anemia prevalence (56.8% and 43.8%, respectively) than did patients with other cancers.

Introduction

The frequency of anemia in cancer patients is high, although there is huge inconsistency in the rates reported at the time of cancer diagnosis, ranging from 39% to more than 80% [1–4], and a further 13% of nonanemic cancer patients develop anemia during the management of their malignancy [5]. Anemia is a clinical status indicated by a reduced red blood cell (RBC) mass with consequent low hemoglobin (HGB) and hematocrit amounts. Physiologically, it is defined as a reduction in the oxygen-carrying ability of the blood, which leads to tissue hypoxia [6]. Complete blood count, is used to record the number of blood cells. Anemia is reported as low levels of RBCs contained in blood and low levels of blood HGB. RBC count and HGB concentration [7]. Normal adult hematocrit values vary between 40% and 52% for men and 37% and 47% for women. Normal adult HGB values are generally 13 to 18 g/dL for men and 12 to 16.5 g/dL for women [8].

Anemia is serious in cancer patients as it may worsen health in this already frail group [9], and it has been associated with poorer medical outcomes [10, 11]. The prevalence of cancer-associated anemia varies depending on the malignancy’s nature, stage, duration and spread and on the type and schedule of treatment [12, 13]. Cancer-associated anemia confers general adverse consequence mainly in anemic patients with lung, prostate, or head and neck cancers or lymphoma, which have a substantial decrease in survival time compared to their nonanemic counterparts [14]. Therefore, it is accepted that management of anemia is necessary. Sadly, suitable management is often not undertaken, which may be due to the severity of the underlying malignancy. It is essential to recognize the incidence of anemia among cancer patients to support the most appropriate treatment plans. Studies assessing the occurrence of anemia in cancer patients in the Asian context are scarce, and the precise rates in the Kingdom of Saudi Arabia are not well-established. Therefore, the aim of this study is to estimate the prevalence of anemia in solid cancer patients at diagnosis in King Faisal Hospital in the city of Taif.

Materials and methods

Study population

Documents were examined for patients admitted to King Faisal Hospital, Taif Province, Kingdom of Saudi Arabia, from December 2017 to March 2020 who were recently confirmed with at least one of the following cancers: breast, female genital tract, colorectal, head and neck, lung, urinary bladder, liver, prostate or lymphoma. A total of 320 patient records were identified. Inclusion criteria were as follows: male or female of any age; histopathologic confirmation of cancer; primary malignancy with no previous anticancer treatment; and presence of all data from medical history and examinations. Patients were excluded for the following reasons: a history of hematological disease or bone marrow malignancy or anemia of any cause or of chronic renal disease; or patient had received a blood transfusion or was on follow-up for chemotherapy, radiotherapy or surgery.

Data collection

Data on age, gender, tumor diagnosis and blood cell tests were examined. Anemia was defined as HGB concentration <11.5 g/dL for females and <13.0 g/dL for males [15]. Based on this measurement, study groups were divided into two main groups: anemic and nonanemic. All study participants were measured for RBC, HGB and PCV. Parameters were determined using the hematology analyzer Cell-Dyn 1800 (Abbott Laboratories Diagnostics Division, USA). Performance of the hematology analyzer was controlled by running quality control measures alongside the study participants’ samples.

Statistical analysis

Data were entered in computer using SPSS 16.0 software (SPSS Inc., Chicago, IL) for Windows continuous data (age, HB, RBC and PCV) were checked for normality using Shapiro Wilk test. Variables were not normally distributed and were shown as median (interquartile) and Kruskal–Wallis test was used to compare between different tumor types. Proportions were compared by Chi square test. P value < 0.05 was considered to be significant.

Ethical considerations

The study received ethical approval from the Directorate of Health Affairs in Taif, registration number HAP-02-T-067, Taif, Kingdom of Saudi Arabia. All patient personal data were fully anonymized.

Results

A total of 320 cancer patients were analyzed: 245 (76.6%) females and 75 (23.4%) males. In terms of age, most of the study group (129, 40.3%) fell in the 56–74 years group, with the age range 16 to 108 years, a median (interquartile range) age of 57 (45 ─ 66) years. The types of cancer included were breast (29.1%), female genital tract (20.0%), colorectal (25.3%), head and neck (10.3%), urinary bladder (4.7%), prostate (5.0%), lung (2.5%), liver (2.2%) and lymphoma (0.9%). The HGB levels ranged from 4.8 g/dL to 18.8 g/dL with a median (interquartile range) of 12.9 (11.0 ─ 14.3) g/dL (Fig 1).

Fig 1. The hemoglobin levels and cancer types.

Fig 1

Open in a new tab

The median (interquartile range) HGB for male patients was 12.100 (6.6–17.3) g/dL and for female patients was 13.00 (4.8–18.8) g/dL. Anemia was identified in 141 (44.1%), of the 320 patients and median (interquartile) concentration of HGB was 10.5 g/dL in these anemic patients, whereas it was 14.2 g/dL in the 179 nonanemic patients. Generally, the prevalence of anemia at cancer diagnosis was 44.1% across cancer types, and higher anemia prevalence was noted in colorectal (n = 46/81, 56.8%) (OR = 0.60; 95% CI 0.36–0.98) (p = 0.047), (Fig 2 and Table 1).

Fig 2. Prevalence of anemia among cancer types.

Fig 2

Open in a new tab

Table 1. Prevalence of anemia and factors among newly diagnosed solid cancer patients at King Feisal Hospital at Taif Provinces Kingdom of Saudi Arabia during December 2017 to March 2020 (n = 320).

N (%) N (%) Odds ratio (95% Confidence) Chi-Square
Tumor types Anaemic Non anaemic P value
(N = 141) (n = 179)
Breast cancer 26 (28.0) 67 (72.0) 2.02 (1.23 ─ 3.39) <0.001
Female genital tract cancer 28 (43.8) 36 (56.2) 1.01 (0.58 ─ 1.75) 0.955
Colorectal cancer 46 (56.8) 35 (43.2) 0.60 (0.36 ─ 0.98) 0.047
Head and nick cancer 13 (39.4) 20 (60.6) 1.21 (0.58 ─ 2.58) 0.568
Lung cancer 5 (62.5) 3 (37.5) 0.47 (0.09 ─ 2.08) 0.288
Urinary bladder cancer 6 (40.0) 9 (60.0) 1.18 (0.40 ─ 3.64) 0.745
Liver cancer 4 (57.1) 3 (42.9) 0.59 (0.10 ─ 2.90) 0.896
Prostate cancer 11 (68.8) 5 (31.2) 0.36 (0.11 ─ 1.04) 0.052
Lymphoma 2 (66.7) 1 (33.3) 0.39 (0.01 ─ 5.23) 0.432
Gender
Female 94 (38.4) 151 (61.6) 1.26 (0.90 ─ 1.78) 0.173
Male 47 (62.7) 28 (37.3) 0.47 (0.28 ─ 0.79) 0.003
Open in a new tab

Female patients had a higher median (interquartile range) HGB level than male patients (13.00 (11.4 ─14.3) g/dL for female and 12.10 (10.3 ─14.4) g/dL for male, p = 0.265), a higher median (interquartile range) RBC count (4.81(4.25 ─ 5.25) •1012/L for female and 4.70 (4.12 ─ 5.19)•1012/L for male, p = 0.293) and a higher median (interquartile range) PCV value (39.60 (35.15 ─ 43.80)% for female and for 36.90 (31.90 ─ 44.00)% male, p = 0.125). In terms of cancer types, patients with breast cancer showed the highest median (interquartile range) HGB level (13.50 (12.40 ─ 14.75) g/dL). The median (interquartile range) RBC count was also highest in breast cancer patients (4.92 (4.49 ─ 5.26)•1012/L), and no patient with breast cancer had a PCV level lower than 13.90% (range 13.90–51.90%). In terms of lowest median (interquartile range) values, urinary bladder cancer patients had the lowest median (interquartile range) RBC (4.39 (3.97 ─ 4.77)•1012/L), lymphoma patients had the lowest median (interquartile range) HGB concentration (10.30 (9.50 ─ 0.00)g/dL) and PCV value (33.50 (28.10 ─ 0.00)%) (Table 2).

Table 2. Cancer types, categorization based on RBC count.

Hb amount and PCV% at King Feisal Hospital at Taif Provinces (N = 320).

Cancer types RBC m/μL Hb g/dl PCV%
N (%) Median (25% ─ 75%) Median (25% ─ 75%) Median (25% ─ 75%)
Breast 93 (29.1%) 4.92 (4.49 ─ 5.26) 13.50 (12.40 ─ 14.75) 41.50 (38.40 ─ 44.65)
Female genital tract 64 (20.0%) 4.83 (4.15 ─ 5.35) 12.65 (10.70 ─ 14.17) 39.40 (33.32 ─ 43.72)
Colorectal 81 (25.3%) 4.64 (4.15 ─ 5.14) 12.10 (10.20 ─ 14.30) 35.90(30.70 ─ 42.85)
Head and nick 33 (10.3%) 4.72 (4.21 ─ 5.18) 12.50 (11.20 ─ 14.35) 40.40 (34.65 ─ 44.70)
Lung 8 (2.5%) 4.59 (4.29 ─ 6.02) 13.25 (11.60 ─ 16.32) 40.75 (34.75 ─ 48.95)
Urinary bladder 15 (4.7%) 4.39 (3.97 ─ 4.77) 12.50 (11.20 ─ 13.70) 37.10 (32.80 ─ 40.30)
Liver 7 (2.2%) 5.14 (3.31 ─ 5.21) 13.30 (8.00 ─ 15.20) 38.20 (25.10 ─ 47.10)
Prostate 16 (5.0%) 4.97 (3.60 ─ 5.59) 11.35 (9.47 ─ 14.07) 38.10 (29.72 ─ 43.20)
Lymphoma 3 (0.9%) 3.74 (3.26 ─ 0.00) 10.30 (9.50 ─ 0.00) 33.50 (28.10 ─ 0.00)
Total 320 (100%) Kruskal Wallis test P value 0.057 Kruskal Wallis test P value = 0.018 Kruskal Wallis test P value = 0.003
Open in a new tab

Red blood cell count (RBC). Hemoglobin level (Hb). Packed cell volume (PCV). Number (N). Percentage (%). Interquartile Range (25% ─ 75%).

Discussion

Anemia in cancer patients is a consequence of the malignant tumor, anticancer therapy, bleeding, malnutrition, hemolysis, or endocrine syndromes. In the present study, 320 treatment-naive, recently diagnosed solid cancer patients at King Faisal Hospital, Taif Province, Kingdom of Saudi Arabia, were assessed for anemia. This study found the frequency of anemia in these patients across tumor types was 44.1%, which is much higher than the rates in China (18.98%), but only marginally higher than Australia (39.3%), the US (35%), and Thailand (41%) [16–19]. Nevertheless, our result is lower than the rates found by researchers in Europe (54.4%), India (54.7%) and Belgium (55.7%) [20–22]. The variation of frequencies in our study is a result of differences in the description of anemia, the study group composition and the investigation period.

The most common cancers noted in our study were breast (93/320, 29.1%) followed by colorectal cancer (81/320, 25.3%). Our results are similar to those from studies conducted in Thailand and Ethiopia, where breast cancer (26.2%) and colorectal cancer (26.7%) were the leading cancers among the detected tumor varieties [21], respectively. The prevalence of anemia varied by tumor type, with our study demonstrating that 68.8%, 56.8% and 43.8% of prostate, colorectal and female genital tract cancer patients, respectively, were anemic. These rates are lower than those in the US, 78% of prostate cancer patients were reported as anemic; in Norway, 74.7% of colorectal cancer patients were reported as anemic; and in Australia, 65% of female genital tract cancers patients were anemic at admission [23–26]. The differences in rates between our study and these other studies may result from differences in the characterization of anemia and differences in study strategies used. Female patients and patients older than 56 years constitute more than 50% of anemic study group. We found comparable results in China, Belgium and Sudan [16, 22, 27]. In this study, females were more likely to be anemic than males because female genital tract and breast cancers accounted for nearly half of the reported cancer cases. One of the complications of female genital tract cancer is bleeding, which can lead to anemia or at least to lowered levels of HGB subsequent to iron deficiency. In the present study, this might be the most common cause of anemia, as anemia caused by breast cancer only is doubtful. The main likely cause for the higher anemia percentage among older patients compared to younger patients is the set of functional alterations that occur as one ages. These lead, for instance, to a degeneration in hematopoietic stem cell reserves and proliferation ability, which leads to suppression of erythropoiesis. Anemia incidence also varied by tumor type. Higher anemia rates were seen in colorectal and female genital tract carcinomas (32.6% and 19.8%, respectively). The conceivable primary explanation for this result in colorectal tumors is that the disturbance of digestive function led to unseen and long-duration blood loss [16]. The likely reason for the high rate among gynecologic cancer patients is that the main complication of female genital tract cancer is vaginal bleeding.

We found that a significant number of breast and colorectal cancer patients were anemic in terms of HGB concentration, RBC count, and PCV, but for most of the other cancer patients, these values fell within the normal range of reference values. These outcomes may reflect the normal erythropoietic activity in bone marrow and probably exclude the decreased erythropoietin response and common malnutrition as the leading causes of anemia in solid cancer patients at diagnosis. Therefore, reductions in HGB level, RBC count, and PCV in solid cancer patients may be a result of tumor-induced hemolysis. Bhattathiri showed the relation of red cell indices in oral cancer with clinical staging but did not examine the other solid cancer types. Bhattathiri studied 217 patients with oral cancer and reported decreases in mean HGB level (by 63%), RBC count (43%) and PCV (48.4%) [27].

To our knowledge, this study is the first to assess erythrocyte indices in association with anemia among solid cancer patients at diagnosis in the kingdom.

Limitations

The generalizability of our results may be restricted by the small and inadequate numbers in each cancer-type cluster, which resulted from the inclusion of only newly diagnosed cancers. Shortage of accompanying iron studies, blood cell morphology assessment to characterize anemia types are other limitations of this study we recommend further studies into the impact of anemia on cancer grade and management outcome using cohort study.

Conclusion

In this study, the general prevalence of anemia across tumor types was 44.1%. In considering specific cancer types, patients with colorectal and female genital tract cancers recorded higher anemia prevalence (32.6% and 19.8%, respectively) than patients with other cancers. Female patients and patients ≥55 years old showed higher frequencies of anemia than male patients and patients <55 years.

Supporting information

S1 File. Anemia solid cancers data.

(SAV)

Click here for additional data file. (10.7KB, sav)

Acknowledgments

We would like to express our deep gratitude to Professor Ishag Adam for his advice and assistance in data analysis, and special appreciation to all medical staff in King Faisal hospital for assistance in data collection and lab works.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

Dr. Mazen Almehmadi obtained funding from the deanship of scientific research project no.1-440-6143, Taif University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

  • 1.Huang XZ, Yang YC, Chen Y, Wu CC, Lin RF, Wang ZN, et al. Preoperative anemia or low hemoglobin predicts poor prognosis in gastric cancer patients: a meta-analysis. Disease markers. 2019. January 1: 7606128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Ludwig H, Van Belle S, Barrett-Lee P, Birgegård G, Bokemeyer C, Gascón 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. European journal of cancer. 2004. October 1;40(15):2293–306. 10.1016/j.ejca.2004.06.019 [DOI] [PubMed] [Google Scholar]
  • 3.Knight K, Wade S, Balducci L. Prevalence and outcomes of anemia in cancer: a systematic review of the literature. Am J Med. 2004. April 5;116(7):11–26. [DOI] [PubMed] [Google Scholar]
  • 4.Madeddu C, Gramignano G, Astara G, Demontis R, Sanna E, Atzeni V, et al. Pathogenesis and treatment options of cancer related anemia: perspective for a targeted mechanism-based approach. Frontiers in physiology. 2018. September 20;9:1294 10.3389/fphys.2018.01294 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Tchekmedyian NS. Anemia in cancer patients: significance, epidemiology, and current therapy. Oncology (Williston Park). 2002;16(9 Suppl 10):17–24. [PubMed] [Google Scholar]
  • 6.Terri D. Johnson-Wimbley. Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol. 2011. May;4(3):177–184. 10.1177/1756283X11398736 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Spivak JL. Anaemia and erythropoiesis in cancer. Adv Stud Med 2002;2:612–19. [Google Scholar]
  • 8.Abella V., Scotece M., Conde J., Pino J., Gonzalez-Gay M., Gómez-Reino J., et al. Leptin in the interplay of inflammation, metabolism and immune system disorders. Nat. Rev. Rheumatol. 2017;13(2):100–109. 10.1038/nrrheum.2016.209 [DOI] [PubMed] [Google Scholar]
  • 9.Henry DH. Parenteral iron therapy in cancer-associated anemia. Hematology Am Soc Hematol Educ Program. 2010;(1):351–356. 10.1182/asheducation-2010.1.351 [DOI] [PubMed] [Google Scholar]
  • 10.Henke M, Sindlinger F, Ikenberg H, Gerds T, Schumacher M. Blood hemoglobin level and treatment outcome of early breast cancer. Strahlenther Onkol. 2004; 180(1):45–51. 10.1007/s00066-004-1123-7 [DOI] [PubMed] [Google Scholar]
  • 11.Hoff CM, Lassen P, Eriksen JG, Hansen HS, Specht L, Overgaard M, et al. Does transfusion improve the outcome for HNSCC patients treated with radiotherapy?—results from the randomized DAHANCA 5 and 7 trials. Acta Oncol. 2011; 50(7):1006–1014. 10.3109/0284186X.2011.592650 [DOI] [PubMed] [Google Scholar]
  • 12.Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001; 91(12):2214–2221. [PubMed] [Google Scholar]
  • 13.Mercadante S, Gebbia V, Marrazzo A, Filosto S. Anaemia in cancer: pathophysiology and treatment. Cancer treatment reviews. 2000; 26(4):303–11. 10.1053/ctrv.2000.0181 [DOI] [PubMed] [Google Scholar]
  • 14.Glaspy J. The impact of epoetin alfa on quality of life during cancer chemotherapy: a fresh look at an old problem. Seminars in hematology. 1997; 34(3 Suppl 2):20–6. [PubMed] [Google Scholar]
  • 15.Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?. Blood. 2006;107(5):1747–1750. 10.1182/blood-2005-07-3046 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Cheng K, Zhao F, Gao F, Dong H, Men HT, Chen Y, et al. Factors potentially associated with chemotherapy-induced anemia in patients with solid cancers. Asian Pac J Cancer Prev. 2012. January 1;13(10):5057–61. 10.7314/apjcp.2012.13.10.5057 [DOI] [PubMed] [Google Scholar]
  • 17.Birgegård G, Aapro MS, Bokemeyer C, Dicato M, Drings P, Hornedo J, et al. Cancer-related anemia: pathogenesis, prevalence and treatment. Oncology. 2005;68(Suppl. 1):3–11. [DOI] [PubMed] [Google Scholar]
  • 18.Bahl A, Sharma DN, Basu J, Rath GK, Julka PK. Pre-Treatment anemia evaluation in Cancer patients attending Radiotherapy Clinic: Results from a single Indian Center. Indian journal of medical sciences. 2008. October 1;62(10):417–20 10.4103/0019-5359.44022 [DOI] [PubMed] [Google Scholar]
  • 19.Ludwig H, Belle S, Barrett-Lee P, Birgegård G, Bokemeyer C, Gascón 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;40:2293–306. 10.1016/j.ejca.2004.06.019 [DOI] [PubMed] [Google Scholar]
  • 20.Harrison L, Shasha D, Shiaova L, White C, Ramdeen B, Portenoy R. Prevalence of anemia in cancer patients undergoing radiation therapy. Seminars in oncology. 2001. April;28(Suppl. 8): 54–59. 10.1016/s0093-7754(01)90214-3 [DOI] [PubMed] [Google Scholar]
  • 21.Kifle E, Hussein M, Alemu J, Tigeneh W. Prevalence of anemia and associated factors among newly diagnosed patients with solid malignancy at Tikur Anbessa specialized hospital, radiotherapy center, Addis Ababa, Ethiopia. Advances in hematology. 2019. October 20;2019 10.1155/2019/8279789 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Verbeke N., Beguin Y., Wildiers H., et al. “High prevalence of anemia and limited use of therapy in cancer patients: a Belgian survey (Anaemia Day 2008),” Supportive Care in Cancer, vol. 20, pp. 23–28, 2012. 10.1007/s00520-010-1045-0 [DOI] [PubMed] [Google Scholar]
  • 23.Nalesnik JG, Mysliwiec AG, Canby-Hagino E. Anemia in men with advanced prostate cancer: incidence, etiology, and treatment. Reviews in Urology. 2004;6(1):1 [PMC free article] [PubMed] [Google Scholar]
  • 24.Edna TH, Karlsen V, Jullumstro E, Lydersen S. Prevalence of anaemia at diagnosis of colorectal cancer: assessment of associated risk factors. Hepato-gastroenterology. 2012. May 1;59(115):713–6. 10.5754/hge11479 [DOI] [PubMed] [Google Scholar]
  • 25.Seshadri T, Prince HM, Bell DR, Coughlin PB, James PP, Richardson GE, et al. The Australian Cancer Anaemia Survey: a snapshot of anaemia in adult patients with cancer. Medical journal of Australia. 2005. May;182(9):453–7. 10.5694/j.1326-5377.2005.tb06784.x [DOI] [PubMed] [Google Scholar]
  • 26.Mahdi Hassan F, A Weeda E. Anemia in elderly sudanese lung cancer patients treated with chemotherapy. The Open Lung Cancer Journal. 2010. July 20;3(1): 34–37. [Google Scholar]
  • 27.Bhattathiri VN. Relation of erythrocyte and iron indices to oral cancer growth. Radiother Oncol 2001; 59(2): 221–6. 10.1016/s0167-8140(01)00326-7 [DOI] [PubMed] [Google Scholar]

Decision Letter 0

Colin Johnson

18 Nov 2020

PONE-D-20-28573

Prevalence of Anemia among Saudi Patients with Solid Cancers at Diagnosis in King Faisal Hospital, Taif Province, Kingdom of Saudi Arabia

PLOS ONE

Dear Dr. Salih,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Specifically, concerns were raised over the statistical analysis, and both reviewers had suggestions to improve the readability of the manuscript.

Please submit your revised manuscript by Jan 02 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Colin Johnson, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please ensure that you include a title page within your main document. You should list all authors and all affiliations as per our author instructions and clearly indicate the corresponding author.

3. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files

4. Please note that in order to use the direct billing option the corresponding author must be affiliated with the chosen institute. Please either amend your manuscript to change the affiliation or corresponding author, or email us at plosone@plos.org with a request to remove this option.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Comments to the author,

Abstract section,

Line 7- change is to "was". In your objective... newly diagnosed... Does this indicate your study to be prospective?

Line 12- the term incidence preferably good to be replaced by prevalence

Line 15- Add range of your study participants to the age groups

Line 20- P-value in the absence of OR and/or Chi square does not have helpful meaning. So, here the analysis and result should be re-analyzed with the help of OR, chi square and 95% C.I to see association between the variables and to determine clinical significance.

Introduction section,

Line 38-40: the term" erythrocytosis" seems not necessary in this paper as it is not relevant to the topic of study

Line 46: replace adversarial with the word" adverse"

Under Materials and methods section,

What is your actual study population? Is your study participants patient or medical records? How do you process your ethical assurance?

Line 69: You did not cite for referencing cut off value for anemia and again it lacks in reference section

How did you get 320 of your sample size? Sample size calculation is not stated. What type of sampling technique did you use to collect your sample?

What is your study design? Is it retrospective or prospective?

In your analysis part,

Line 84: Even if you mentioned some analytical parameters like Chi square and ANOVA test, it lacks applicability in your findings. What is the value of using ANOVA test?

In result section,

Line 94: 56-74 years

Line 106: What is the operational definition base line? Is it consistent with your objective?

Generally, it is not well stated. Only descriptive statistics were used. Majorly, OR and or Chi-square were missed; re-analysis should be operated especially in Table 1 &2. Even the existing p-value is very vague. I t is not clear how p-value is analyzed. For each variable, there should be p-value except constant variable. Again in Table 1 with gender variable, p-value=0.00. By any means, p-value should no be zero. So, re-construct these tables using OR and/or Chi-square, 95%C.I and/or p-value for each independent variable except the constant one.

Discussion part,

Line 125 & 131: The same reference is cited [20]; in fact it is not the same. Check your citation and references, too for correction.

Line 125-127; 136-138 & 151-153: Unless there is reference for your possible reason of the differences between your findings and others, it seems personal judgment, which is not scientifically acceptable.

Line 164: It is not clear. Does the statement belong to your finding?

In reference section,

Ref No 20 & 22 are the same. Could you address the issue?

Reviewer #2: This study analyzed the prevalence of anemia in newly diagnosed cancer patients in Saudi Arabia. The number of subjects is sufficient to drive the intended analysis. I have the following comments:

1. The introduction should be shortened, eliminating the extended defintiion of anemia which I assume is very familiar to the PLOS ONE audience. I suggest keeping it simple and short, adopting WHO definition (Hb levels).

2. In methods, the division of RBC parameters in "normal", "low" and "high" groups seems pointless and dispensable as it is not used nor discussed throughout the manuscript.

3. In Results, some data presented in the second paragraph are the same reported in the first paragraph, and should be removed.

4. The prevalence of anemia in prostate cancer and lymphoma patients should be cautiously described as the number of subjects was very low in both groups, making it unnapropriate to assume a true high prevalence of anemia in these patients.

5. Please state the unit for frequency in figures 1 and 2 (number or percentage … I assume those are numbers, correct?).

6. I suggest a reformulation of table 2 with respect to the cut-off points adopted for RBC, Hb and PCV, as they were not the same adopted for anemia definition under “Methods”, and should also be different between male and female patients.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: Comments to the author.docx

Click here for additional data file. (12.5KB, docx)
PLoS One. 2021 Jan 28;16(1):e0246202. doi: 10.1371/journal.pone.0246202.r002

Author response to Decision Letter 0

30 Dec 2020

Response to the Comments of Reviewers

December 15, 2020

Subject: Revision and resubmission of manuscript PONE-D-20-28573

Prevalence of Anemia among Saudi Patients with Solid Cancers at Diagnosis in King Faisal Hospital, Taif Province, Kingdom of Saudi Arabia

Dear Dr. Colin Johnson,

Thank you for your letter and the opportunity to revise our paper. The suggestions offered by the reviewers have been immensely helpful. I have included the reviewer comments immediately after this letter and responded to them individually, indicating exactly how we addressed each concern or problem and describing the changes we have made. The revisions have been approved by all authors. The changes are marked in yellow in the paper, and the revised manuscript will be uploaded.

Reviewer #1: Comments to the author,

Abstract section,

Comment. Line 7- change is to "was". In your objective... newly diagnosed... Does this indicate your study to be prospective?

Respond: Thank you for your assessment within line7 the suggested correction has been made.

No we mean that our study group were newly diagnosed cancer patient and not subjected to cancer therapy as it has complications that my affects our results

Comment. Line 12- the term incidence preferably good to be replaced by prevalence

Respond: thank you for this excellent observation for line12 the suggested correction has been made and we replaced the word by prevalence.

Comment. Line 15- Add range of your study participants to the age groups

Respond: Thank you! We found your comments helpful and have revised accordingly the suggested correction has been made, and range of study participants to the age groups added

Comment. Line 20- P-value in the absence of OR and/or Chi square does not have helpful meaning. So, here the analysis and result should be re-analyzed with the help of OR, chi square and 95% C.I to see association between the variables and to determine clinical significance.

Introduction section,

Respond

We agree with the reviewer’s assessment of the analysis. Our chi square does make it difficult to fully interpret the data. In addition, in its current form, we agree it would be hard to tell that this measurement constitutes a significant improvement over previously reported values. we reanalyzed our data starting with normality checking using the Shapiro-Wilk’s W test to determine whether our data is normally distributed, the checks showed Value < 0.05 suggest that our data is not normally distributed so that we used the non-parametric tests the Kruskal Walis that is non-parametric test to determines whether the medians and interquartile range of the Hb, PCV and Red blood cell count are different to determine the presence of anemia based on these parameters, and we compare it to different cancers types. We have therefore re-analyzed the data using odds ratio, chi square and 95% C.I as suggested with reviewer.” Please see re-constructed table 1& 2.

Comment. Line 38-40: the term" erythrocytosis" seems not necessary in this paper as it is not relevant to the topic of study

Respond

Thank you very much erythrocytosis" definition was deleted

Comment. Line 46: replace adversarial with the word" adverse" Under Materials and methods section,

Respond

Thank you for comment the word adversarial was replaced with the “adverse"

Comment. What is your actual study population? Is your study participants patient or medical records? How do you process your ethical assurance?

Respond

Thank you very much the actual study populations “were medical records and we processed our ethical assurance by taking permission from local health authorities and pathology department at the hospital (The study received ethical approval from the Directorate of Health Affairs in Taif, registration number HAP-02-T-067, Taif, Kingdom of Saudi Arabia. All patient personal data were fully anonymized)

Comment. Line 69: You did not cite for referencing cut off value for anemia and again it lacks in reference section

Respond

Thank you very much with regard to cite for referencing cut off value for anemia we add the missing reference its number 15 in reference section (its Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?. Blood. 2006;107(5):1747-1750. doi:10.1182/blood-2005-07-3046)

Comment. How did you get 320 of your sample size? Sample size calculation is not stated. What type of sampling technique did you use to collect your sample?

Respond

A sample size of 320 patients was calculated based on the equation and we assumed that 29.5% of the patients with cancer would have anemia.

N= z2*p*(1-p)/e2

N= sample size for infinite population

z= Z score. We considered confidence level 95% then Z score=1.96.

p= % of population probability (assumed to be 29.5%=0. 29.5)

e= desired margin of error. It was taken 5%=0.05.

Comment. What is your study design? Is it retrospective or prospective?

In your analysis part,

Respond

Thank you its retrospective study

Comment. Line 84: Even if you mentioned some analytical parameters like Chi square and ANOVA test, it lacks applicability in your findings. What is the value of using ANOVA test?

In result section,

Respond

Thank you very much and we are sorry for this confusion we agree with the reviewer and reanalyzed the data and deleted this confusion, instead of the ANOVA The Kruskal Wallis test was used the test determines whether the medians of two or more groups are different we explain this above .

Comment.Line 94: 56-74 years

Respond

Thank you the suggested correction has been made

Comment. Line 106: What is the operational definition base line? Is it consistent with your objective?

Generally, it is not well stated. Only descriptive statistics were used. Majorly, OR and or Chi-square were missed; re-analysis should be operated especially in Table 1 &2. Even the existing p-value is very vague. I t is not clear how p-value is analyzed. For each variable, there should be p-value except constant variable. Again in Table 1 with gender variable, p-value=0.00. By any means, p-value should no be zero. So, re-construct these tables using OR and/or Chi-square, 95%C.I and/or p-value for each independent variable except the constant one.

Respond

Thank you so much for comment. In general, a baseline is a well-defined, well-documented reference that serves as the foundation for different assessment, the operational definition of anemia depends on Hemoglobin levels at baseline an individual with baseline Hb concentration at the higher end of normal, decrease in Hb concentration to the lower end of normal might be considered anemic and we used this baseline for classification of anemia in our study group and this liked to the objective of this study.

Regarding statistics comment we agree with reviewer so that we re-analyzed our data we include the OR, chi square and 95% C.I and the association between the anaemia and different types of cancers was determine and we have re-analyzed the data presented in former tables and re-constructed table 1& 2 that include p-value For each variable.

Discussion part,

Line 125 & 131: The same reference is cited [20]; in fact it is not the same. Check your citation and references, too for correction.

Respond

Thank you so much the references citation was checked and corrected

Line 125-127; 136-138 & 151-153: Unless there is reference for your possible reason of the differences between your findings and others, it seems personal judgment, which is not scientifically acceptable.

Respond

Thank you so much it’s not personal judgment for our finding in lines 125-127, is supported with well-known scientific information that description of anemia, the study group composition may affects the outcomes 136-138 we cited comparable results from China, Belgium and Sudan please see references numbers (16,22 and 26) and for 151-153 data its eminent that one of the most common causative factor of anemia among female is bleeding either from menstrual cycle or female genital tract tumors

Line 164: It is not clear. Does the statement belong to your finding?

Respond: Thank you so much yes the statement describe our study finding

In reference section,

Ref No 20 & 22 are the same. Could you address the issue?

Respond: Thank you so much for catching these glaring and confusing errors, which we have now corrected in the text and deleted the duplicated reflectance number 22 and rearranged the whole references

Reviewer #2: This study analyzed the prevalence of anemia in newly diagnosed cancer patients in Saudi Arabia. The number of subjects is sufficient to drive the intended analysis. I have the following comments:

1. The introduction should be shortened, eliminating the extended definition of anemia which I assume is very familiar to the PLOS ONE audience. I suggest keeping it simple and short, adopting WHO definition (Hb levels).

Respond

Thank you for reminding us how important it is to present short and scripts in a concise introduction. We agree that definition of anemia is very familiar to readers of journal however onetime we need to start from basic point to recognize our hypothesis.

Changes: We shorten and simplify anemia definition and agreeing WHO meaning. We believe this sets the information out clearly and comparatively and is a format that readers will return to when seeking information on the manuscript’s uncomplicated idea. The changes in text appear in the revised paper.

2. In methods, the division of RBC parameters in "normal", "low" and "high" groups seems pointless and superfluous as it is not used nor discussed throughout the manuscript.

Respond: Thank you so much the reviewer makes a great point: and this division may appear superfluous and confusing to reader so we remove this part from the method section in the revised manuscript.

3. In Results, some data presented in the second paragraph are the same reported in the first paragraph, and should be removed.

Respond: Thank you so much as suggested, the data presented in results have been revised in order to more effectively convey the central idea of the manuscript.

4. The prevalence of anemia in prostate cancer and lymphoma patients should be cautiously described as the number of subjects was very low in both groups, making it inappropriate to assume a true high prevalence of anemia in these patients.

Respond. We agree with the reviewer assessment of lymphoma patients and prostate cancer findings unfitting to adopt high prevalence of anemia in these patients for low number and it’s impossible to fully interpret the data in terms of the prevailing theories the reformed manuscript was revised accordingly.

5. Please state the unit for frequency in figures 1 and 2 (number or percentage … I assume those are numbers, correct?).

Respond. Thank you very much as suggested by the reviewer, we have revised Figure 1 and 2 we reconstructed these figures

6. I suggest a reformulation of table 2 with respect to the cut-off points adopted for RBC, Hb and PCV, as they were not the same adopted for anemia definition under “Methods”, and should also be different between male and female patients.

Respond:

We have re-analyzed the data using odds ratio, chi square and 95% C.I and re-constructed table 1& 2 I hope it’s clearer now

We hope the revised manuscript will better suit PLOS Journal but are happy to consider further revisions, and we thank you for your continued interest in our research.

Sincerely,

Dr. Magdi Mansour Salih

Correspondent author

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (26.3KB, docx)

Decision Letter 1

Colin Johnson

15 Jan 2021

Prevalence of Anemia among Saudi Patients with Solid Cancers at Diagnosis in King Faisal Hospital, Taif Province, Kingdom of Saudi Arabia

PONE-D-20-28573R1

Dear Dr. Salih,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Colin Johnson, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: (No Response)

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I want to appreciate the author in charge of this manuscript for addressing almost all of my comments. So, I recommend this paper to be published even if the decision is up to the editor-in chief. Thank you again.

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Acceptance letter

Colin Johnson

19 Jan 2021

PONE-D-20-28573R1

Prevalence of Anemia among Saudi Patients with Solid Cancers at Diagnosis in King Faisal Hospital, Taif Province, Kingdom of Saudi Arabia

Dear Dr. Salih:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Colin Johnson

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 File. Anemia solid cancers data.

    (SAV)

    Click here for additional data file. (10.7KB, sav)
    Attachment

    Submitted filename: Comments to the author.docx

    Click here for additional data file. (12.5KB, docx)
    Attachment

    Submitted filename: Response to Reviewers.docx

    Click here for additional data file. (26.3KB, docx)

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.

    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES