Quantitative Changes of Red Blood cells in Cancer Patients under Palliative Radiotherapy-A Retrospective Study

 

M. P. Brundha¹, Pathmashri. V. P², Shantha Sundari³

¹Assistant Professor, Department of Pathology, Saveetha Institute of Medical And Technical Science, Saveetha University, Chennai, India.

²Graduate, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, India.

³Professor, Department of Orthodontics, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, India.

 

ABSTRACT:

Introduction: Radiation can be defined as an emission of energy. Radiations like X-rays, gamma rays, and charged particles are used for cancer treatment. Radiation therapy inhibits the ability of the cancer cells to grow and divide, thus slowing their growth and killing them. Radiation therapy is given in curative or palliative intents. Palliative treatments are not intended to cure. They are given to the patients with advanced stage of cancers to reduce the symptoms and suffering caused by cancer. Exposure to ionizing radiation can cause changes in normal blood cell nature. Anemia is a common complication of myelosuppressive chemotherapy. These types of anemia are treated with repeated blood transfusions. The reduction in the leucocyte count is treated with Colony Stimulating Factors. Materials and Methods: Thirty-two cancer positive patients who underwent palliative radiotherapy for five fractions were included in this study. Complete blood count reports were collected from the clinical lab. RBC count of the sample population was noted and compared before and after radiotherapy. Results were analyzed statistically. Results: Results of the comparison between the RBC counts before and after the first fraction of the radiotherapy showed that there was no significant change. As the fractions of radiotherapy increased the RBC count showed a significant reduction which was statistically also significant. Males showed an RBC count reduction after the completion of radiotherapy than the females. Conclusion: In conclusion, a routine serial blood count determination during the entire course of palliative radiation showed a significant effect on RBC count. Though the advanced radiotherapy technologies were followed, the effect of radiation in the human body is still continuing at a lower level and insists the radiotherapist that a follow-up blood examinations is must for all the cancer patients who are under chemotherapy or radiotherapy.

 

 

 

 

 

 

INTRODUCTION:

Cancer is the abnormal growth of cells even after cessation of the growth provoking signals. They have the unique capability to invade or spread to other parts of the body [1,2]. Some cancers are sensitive to drugs called chemotherapy; some are responding more to radiotherapy. Radiation can be defined as an emission of energy. This emission can be in the form of electromagnetic waves or as moving subatomic particles. Radiation is produced due to atomic decay experienced by a nucleus of an atom or an electron in an atom. Radiation can be classified into ionizing radiation and non-ionising radiation. Ionizing radiation is the rays with sufficient energy to cause ionization of the medium through which it passes and non-ionising radiations are the one which does not cause any changes of the medium through which it travels.

 

Radiations like x-rays are used in the medical field for day to day investigation; Gamma rays are used in radiation therapy for treating cancer by shrinking tumors and killing the cancer cells. Radiation therapy inhibits the ability of the cancer cells to grow and divide, thus slowing their growth and killing them. The forms of radiation used in radiation therapy are high energy waves of radiation known as ionizing radiation. Radiation therapy uses high-energy radiation to shrink tumors and kill cancer cells [3]. Radiations like X-rays, gamma rays are used for cancer treatment. Radiation therapy is sometimes given with curative intent. That is, with the hope that the treatment will cure cancer, either by eliminating a tumor, preventing cancer recurrence, or both. In such cases, radiation therapy may be used alone or in combination with surgery, chemotherapy, or both [3, 4].

 

Radiation therapy may also be given with palliative intent. Palliative treatments are not intended to cure. They are given to the patients with advanced stage of cancers to reduce the symptoms and suffering caused by cancer. The type of radiation therapy prescribed by a radiation oncologist depends on many factors, including;  the type, size, location of cancer also, how far into the body the radiation needs to travel, how close the cancer is to normal tissues that are sensitive to radiation. Other factors include the patient’s age and other medical conditions [5]. Types of radiation therapy include 3D-CRT [3 Dimensional Conformal Radiation Therapy], IMRT [Intensity Modulated Radiation Therapy], SBRT [Stereotactic Body Radiation Therapy], IMPT [Intensity Modulated Proton Therapy], Cyber knife, etc.

 

3D-CRT and IMRT use imaging tests to create a treatment pathway. These machines deliver external radiations at multiple different angles at the tumor in order to destroy it. In the case of IMRT, the machine not just delivers external radiation but can also deliver multiple angles of radiation with different intensities at different parts of the tumor, thus produces a more effective treatment. But these devices require immobilization of the patient. In case IMPT instead of using a beam of photons, a beam of protons are used. But this is technique sensitive and very expensive. SBRT- stereotactic body radiation therapy is also called as stereotactic radiosurgery does not involve any surgery. In this oncologist uses very precise computer techniques to deliver radiation to the tumor in different parts of the body.

 

Cyber knife the latest method of treatment which combines robotics with computer software to target and eradicate the tumor cells in a very precise manner leaving the surrounding healthy normal tissues untouched. It works by targeting multiple radiation beams at different angles focused on a particular point and it also does not require any patient immobilization. Hence the patient movements are not restricted.

 

Exposure to ionizing radiation can cause changes in normal blood cell nature. Normal count of RBC is 4.7-6.1 million cells per cubic millimeter for men and 4.2-5.4 million cells per cubic millimeter for women. Red blood cells carry oxygen throughout your body. Increase in RBC level than the normal level leads to a condition called Polycythaemia and Decrease in RBC level than the normal level leads to Anemia. Red blood cells have the ability to carry oxygen; it is measured by the amount of hemoglobin in the blood. If the level of hemoglobin is low, then it is considered as anemic and body works much harder to supply oxygen to your tissues. This can make the anemic patient feel fatigued [6]. Anemia is a common complication of myelosuppressive chemotherapy that results in a decreased functional capacity and quality of life (QOL) for cancer patients [7].  These types of anemia are treated with repeated blood transfusions. The reduction in the leucocyte count is treated with Colony Stimulating Factors [8]. The dose of radiotherapy and the frequency of the radiotherapy decides the severity of the anemia [9]. This study was done to analyze the quantitative changes of RBCs in cancer patients who underwent Palliative Radiotherapy.

 

MATERIALS AND METHODS:

This study was done to assess the change in red cell count of the patients who are under radiation therapy at Rai Clinic, Saveetha Dental College Campus in Chennai. In this study, thirty-two cancer positive patients were randomly selected with the following inclusion and exclusion criteria.

 

Inclusion criteria:

1.    Cancer positive patients under palliative radiotherapy.

2.    Patients who completed all 5 fraction of radiotherapy regularly without any delay in treatment.

3.    Patients who underwent routine and regular blood examination after each fraction of radiotherapy.

 

Exclusion criteria:

1.    Patients with missed radiotherapy cycles (irregular treatment)

2.    Patients who had treated with colony stimulating factor for myelosuppression or blood transfusions.

3.    Patients with missed lab reports or not under regular follow up with blood examination.

 

The technique of radiation used was 3DCRT technique for all the patients. Complete Blood Count reports were collected from the clinical lab, Saveetha Dental College with the consent of patients and the counts were collected before radiotherapy and collected for 5 fractions.

 

RESULTS:

The RBC values of all thirty two patients undergoing palliative radiotherapy with 5 fractions are given below (Table 1). Statistically the values and averages of before and after each fraction of radiotherapy were analysed with a paired t-test. The gender variation also analysed statistically.

 

Tables of the article Quantitative changes in the RBCs in cancer patient under palliative radiotherapy.

Table 1: RBC values of the sample population

Sample	Age	Gender	Before Radio therapy	Fraction1 (RBC count/mm3)	Fraction2 (RBC count/mm3)	Fraction3 (RBC count/mm3)	Fraction4 (RBC count/mm3)	Fraction5 (RBC count/mm3)	Average after Radiotherapy
1	49	F	4.67	4.57	3.9	4.22	4.3	3.9	4.17
2	62	M	4.32	4.3	4.57	3.5	4.5	4.3	4.23
3	60	M	4.1	4.9	3.29	2.96	3.75	3.66	3.71
4	40	F	4	2.96	4.13	4.16	4.6	4	3.9
5	34	F	4.1	3.7	4.19	4.19	3.92	4.28	4.05
6	63	M	4.3	4.74	3.73	5.03	3	3.73	4.04
7	62	M	4.32	4.8	3.23	4.23	4.1	4.26	4.12
8	30	M	4.21	3.38	4.39	4	3.26	4.3	3.86
9	50	F	4.45	4.66	4.54	4.71	3.01	4.37	4.25
10	60	F	4.2	4.05	4.42	4.37	3.33	4.52	4.13
11	45	F	4.12	4.9	4.55	4.16	3.44	4.17	4.24
12	53	M	4.25	4.54	4.16	4.12	3.32	4.62	4.15
13	37	F	4.1	3.72	4.32	4.75	3.81	3.4	4
14	75	F	4.51	5.59	4.56	4.52	4.5	4.7	4.77
15	60	F	3.23	2.61	4.25	4.11	3.98	3.75	3.74
16	45	F	4.2	4.45	4.32	4.42	3.99	3.96	4.228
17	47	M	4	3.33	3.3	4.54	4.28	4	3.89
18	36	M	4.21	3.71	3.96	3.71	3.52	3.9	3.76
19	72	F	3.82	2.5	3.1	2.82	3.15	3.09	2.9
20	64	M	4	3.58	3.11	2.89	3.32	3.67	3.314
21	56	F	4.76	6.45	4.47	4.58	4.01	3.57	4.61
22	56	M	4.12	3.71	3.56	3.3	3.52	3.21	3.46
23	34	M	4	3.58	3.11	2.89	3.23	3.67	3.2
24	56	F	4	4.47	4.58	4.01	3.57	3.69	4.06
25	58	F	4.32	3.18	3.82	3	3.46	3.22	3.33
26	46	M	4.67	4	3.89	3.9	4.22	4.32	4.06
27	40	F	3.7	3.45	4.45	3.56	3.63	3.22	3.662
28	67	F	5.2	5.52	5.34	4.82	4.44	4.3	4.8
29	68	M	4.87	4.89	4.54	4.38	4.29	4.84	4.5
30	59	M	4.56	4.09	4.07	4.97	4.77	4.8	4.54
31	45	M	6	5.63	5.55	5.41	5.88	5.31	5.55
32	50	F	5.89	5.31	4.81	4.84	5.89	5.18	5.2

 

Table 2: Before and after fraction 1 radiotherapy

Group	Group One	Group Two
Mean	4.3500	4.2272
SD	0.5537	0.9246
SEM	0.0979	0.1634
N	32	32

P value : 0.303

Statistically no significant difference between groups

 

Table 3: Before and after fraction 2 radiotherapy

Group	Group One	Group Two
Mean	4.3500	4.1316
SD	0.5537	0.6109
SEM	0.0979	0.1080
N	32	32

P value : 0.03

Statistically  significant difference between the two groups

 

Table 4: Before and after fraction 3 radiotherapy

Group	Group One	Group Two
Mean	4.3500	4.0959
SD	0.5537	0.6881
SEM	0.0979	0.1216
N	32	32

P value : 0.02

Statistically  significant difference between the two groups

 

Table 5: Before and after fraction 4radiotherapy

Group	Group One	Group Two
Mean	4.3500	4.0597
SD	0.5537	0.5671
SEM	0.0979	0.1002
N	32	32

P value : 0.0009

Statistically significant difference between groups

 

Table 6: Before and after fraction 5 radiotherapy

Group	Group One	Group Two
Mean	4.3500	3.9372
SD	0.5537	0.7105
SEM	0.0979	0.1256
N	32	32

P value : 0.0001

Statistically extremely significant difference between groups

 

Table 7: Before and after radiotherapy among all sample population

Group`	Group One	Group Two
Mean	4.35000	4.07575
SD	0.55366	0.55506
SEM	0.09787	0.09812
N	32	32

P value : < 0.0001

Statistically  significant difference between groups

 

Table 8: Before and after radiotherapy among males

Group	Group One	Group Two
Mean	4.39533	4.02560
SD	0.51025	0.57351
SEM	0.13175	0.14808
N	15	15

P value : 0.0001

Statistically  significant difference between groups

 

Table 9: Before and after radiotherapy among females

Group	Group One	Group Two
Mean	4.31000	4.12000
SD	0.60206	0.55198
SEM	0.14602	0.13388
N	17	17

P value : 0.0667

Statistically no  significant difference between groups

 

The statistical analysis of the RBC values before and after the first fraction of palliative radiotherapy showed that there was no significant difference between the two groups (Table 2) with the p-value of 0.3038. As the fractions crossed the RBC count had significantly reduced and the statistical analysis showed significant difference between the two groups (Table 3, 4, 5 and 6) with the p-value < 0.0001. The overall effect of radiotherapy on RBC count showed in table 7, which highlighted an extreme statistically significant difference between the RBC count before and the average after all five fractions of radiotherapy.

 

In this study we also analysed the effect of radiation on RBC count in males and females separately. The table 8 showed the RBC count of males before and after radiotherapy. The paired t-test showed a significant difference between the two groups. The table 9 showed the RBC count of females before and after radiotherapy. The statistical analysis showed that there is no significant difference between the groups.

 

 

 

 

DISCUSSION:

Radiation therapy and chemotherapy are the two most common method of choice for treating cancer or tumor [10]. In radiation therapy, high energy particles or high energy waves like x-rays, gamma rays or beams of protons or electrons are used to destroy the cancer cells by damaging their DNA and killing them or by preventing its growth. Unlike normal cells, cancer cells grow and divide abnormally at a faster rate. Thus these therapies are focused on destroying the abnormal cancer cells [11]. Radiation works by damaging the DNA of the cancer cells and preventing it from growing and multiplying. During radiation, the normal cells around the site are also affected but the damage is usually minimal and these cells recover soon after the treatment [12]. But the rate at which the normal cells recover depends on the site, duration of radiation and also its intensity. The normal cells around a tumor may be damaged permanently. The most commonly affected cells due to radiation therapy include skin cells, cells lining the mouth, cells lining the gastro intestinal tract and blood cells in the marrow.

 
Chemotherapy is considered one of the most powerful methods of killing the cancer cells. Chemotherapy the whole body is exposed to the drugs but radiation therapy is localized in action and produces very minimal harm to the normal cells. Though the chemotherapy drugs destroy the cancer cells rapidly, they also harm the normal cells and have side effects [13]. The severity of these drugs depends on the general health of the patients, age, type and stage of cancer and also the type of chemotherapy. Some cancer is very sensitive to radiation and their by shrinks or completely gets cured in a cycle. In other cases, it requires a few cycles to get cured completely. For a certain type of cancer radiation therapy and chemotherapy are used together [14].

Chemotherapy drugs like some radio sensitizers help the radiation therapy work well by making the abnormal cancer cells to become more sensitive to radiation [15]. After treatment, most of the side effects may disappear but some may remain permanent. Some most common side effects of chemotherapy include hair loss, mouth sores, chemo brain (memory problem), lower blood cell count, menopause, red urine, digestive distress, anxiety and depression, bone loss, a sensitivity of the skin, sexual dysfunction, etc. In the case of combination therapy, the side effects are worsening [16, 17, and 18].

 
The hemopoietic system is sensitive to radiation. A persistent and pronounced hyperplastic marrow is produced in locally irradiated site and there is a reduction in leukocytes and lymphocytes with the small amount of change in red blood cells and platelet. Today, major advances in radiation technology have made it more precise, leading to fewer side effects [19]. Severe anemia is treated with red blood cell transfusions, but mild-to-moderate anemia in patients receiving chemotherapy has traditionally been managed conservatively on the basis of the perception that it was clinically unimportant [7,20]. Doctor or health care provider may prescribe or suggest treating the low red blood count: Iron supplement, Multivitamin, a diet high in protein, a red blood cell transfusion [21].

 

Maria da salete fonseca in the year 2008 conducted a study by weekly monitoring the effects of conventional external beam radiation therapy by means of blood cells count- leukocyte and platelet. According to this study, Maria concluded that the most significant decreases in leukocytes were observed in the fourth week, where total leukocytes, neutrophils, monocytes, and platelets showed a decrease as 53%, 26.8%, 19.4%, 22.2%, 14.6% respectively [22].

 

Friedrich. H in the year 1976 conducted a study on the effect of local radiation therapy on blood cell count by reviewing treatment records and concluded that the average treatment dose was 5200 rads and the WBC count of 9600/mm3 dropped to 7300/mm3 and RBC count of 5.6 to 4.4 million /mm3[23]. This was well correlated with our study that the RBC count had been significantly dropped. Marguerite in the year 1964 studied the long-term effects of therapeutic irradiation upon bone marrow and concluded that among 33 participants only 2 showed complete sternal marrow regeneration, for other 31 it continued to be aplastic. 23 of this patient showed no marrow regeneration for 4 year period following therapeutic irradiation while 4 patients marrow remained aplastic for more than 7 years [24].In another study done by Skyes in 1960 reported that normal peripheral blood counts in all 18 patients who received the radiation in the regional lymphatic system for breast cancer had a confirmed marked hypo cellularity in the irradiation sternal marrow [25].

 

It is observed that patients have undergone radiation therapy, where they are exposed to ionizing radiation. The RBC count has not significantly reduced after the first fraction of radiotherapy. Followed by the second fraction of radiotherapy the RBC count started decreasing significantly but not symptomatically. As the radiotherapy cycles move to third, fourth and fifth fraction, the count of the RBCs was showed a significant difference especially in males than the females.

 

CONCLUSION:

In conclusion, a routine serial blood count determination during the entire course of palliative radiation showed a significant effect on RBC count. Surprisingly as per our study males are affected more than the females during the course of palliation. Though the advanced radiotherapy technologies were followed, the effect of radiation in the human body is still continuing at a lower level and insists the radiotherapist that a follow up blood examinations is must for all the cancer patients who are under chemotherapy or radiotherapy.

 

REFERENCE:

1.       World Health Organization. Cancer Fact sheet N°297".  February 2014.10 June 2014.

2.       National Cancer Institute. Defining Cancer. 10 June 2014. p34.

3.       Lawrence TS, Ten Haken RK. Principles of Radiation Oncology. Philadelphia; Cancer- American cancer society, 2008, Volume 17, 8^th edition, p67-p70

4.       Blank KR. Once-Weekly Dosing of Epoetin- Increases Haemoglobin and Improves Quality of Life in Anemic Cancer Patients Receiving Radiation Therapy Either Concomitantly or Sequentially with Chemotherapy. International Journal of Radiation Oncology and Biological Physics. 1997, 44(4), p317-321

5.       Yang FE. Combined therapy for cancer of the anal canal: a preliminary report. International journal of radiation oncology and biological physics. 1995; 33(5); 607-617.

6.       Groopman JE, Itri LM. Chemotherapy-induced anemia in adults: incidence and treatment.J Natl Cancer Inst.1999; 91: 1616–1634.

7.       Effects of Ionising Radiation on Blood and Blood Components: A Survey. International atomic energy agency.1997, IAEA-TECDOC-934, ISSN 1011-4289.

8.       M. E. Gaulden. Biological Dosimetry of Radionuclide and Radiation Hazards. Journal of Nuclear Medicine, 1983 vol 24; issue 2, pp. 160-164. 

8.       Finkelstein SE, Fishman M. Clinical opportunities in combining immunotherapy with radiation therapy. Front Oncol 2012; 2:169.

9.       M. Anderson, S. J. Marsden, E. G. Wright, M. A. Kadhim, T. Goodhead and C. S. Griffin. Complex Chromosome aberrations in Peripheral Blood Lymphocytes as a Potential biomarker of Exposure to High-LET Alpha-Particles.   International Journal of Radiation Biology, 2000, Vol. 76(2), pp. 31-42.

10.     R. J. Dufrain, L. G. Littlefield and E. E. Joiner, Human Cytogenetic Dosimetry: A Dose Response Relationship for Alpha Particle Radiation. Health Physics, Vol.  37, No. 3, 1979, pp. 279-289.

11.     National Research Council of the National Academy. Health Risks from Exposure to Low Levels of Ionising Radiation, Beir VII Phase 2, 2006.

12.     R. W. Field. Radon: An Overview of Health Effects.  Encyclopedia of Environmental Health, 2011 vol 23, issue 7 pp. 745-753.

13.     H. Ismail and M. S. Jaafar, Interaction of Low-Intensity nuclear Radiation Dose with the Human Blood: Using the new Technique of CR-39NTDs for an in Vitro Study. Applied radiation and Isotopes,2011, Vol. 69, No. 3, pp. 559-566. 

14.     Finkelstein SE, Fishman M. Clinical opportunities in combining immunotherapy with radiation therapy. Front Oncol 2010, vol 2(2), 169.

15.     Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer, vol 12(12), p237-251.

16.     Van Nostrand D, Freiats J. Side effects of I-131 for ablation and treatment of well-differentiated thyroid carcinoma. NJ:  humana press, 2006, 89(6), p454. 

17.     Li W, Li ZY, Mao YX, Zhang YT, Zhao YM, Chen  K; Inhibition of MCF-7 breast cancer cellinduced platelet aggregation using a combination of antiplatelet drugs. Oncol Lett,2013, vol 3, issue(5) p675-680.

18.     Kolb HJ; Bone marrow morbidity of radiotherapy, in Plowman PN, McElwain T, Meadows A. Complications of Cancer Management- Oxford 1991, 65(7), p 398.

19.     Camerer E, Qazi AA, Duong DN, Cornelissen I, Advincula  R  and Coughlin SR; Platelets, protease-activated receptors,  and fibrinogen in hematogenous metastasis. Blood; volume 104, issue 004, p397-401.

20.     Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA.  Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994, volume 331 issue 9, page 502

21.     Hank B, Cohen AM, Kelsen DP: Cancer of the anal region; Principles and Practice of Oncology. 1989, volume 12 issue 8; page765.

22.     Sri Vasavi kadiyala. Platelet count in cancer patients under radiation therapy. Int J.Pharm.Sci. 2018, vol 48 issue 1 p52-p53.

23.     Maria da salete fonseca. Weekly monitoring the effects of conventional external beam radiation therapy by means of blood cells count- leukocyte and platelet. Radiologia Brasileira. 2008, volume 41, issue 1, p5509-5512.

24.     Friedrich H.Stutz. Local radiotherapy and peripheral white blood cell count: a review of 203 treatment records. Military medicine, volume 141, issue 6, p390-p391.

25.     Marguerite P.Skyes. Long term effects of therapeutic irradiation upon bone marrow. ORCID. Volume 17, issue 9, p1144-p1150.

26.     Skyes. H. blood lymphocytes after radiation therapy of mammary carcinoma. Acta radiologica therapy physics biology.1974, Volume 13, issue 3, 185-200.

 

 

Accepted on 02.11.2018        © RJPT All right reserved

Research J. Pharm. and Tech 2019; 12(2):687-692.