Clinical study of chemotherapy induced febrile neutropenia: talcott's versus multinational association for supportive care in cancer risk ...
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International Journal of Research in Medical Sciences
Gaur R et al. Int J Res Med Sci. 2021 Jan;9(1):236-242
www.msjonline.org pISSN 2320-6071 | eISSN 2320-6012
DOI: https://dx.doi.org/10.18203/2320-6012.ijrms20205851
Original Research Article
Clinical study of chemotherapy induced febrile neutropenia: talcott’s
versus multinational association for supportive care in cancer risk
assessment scoring systems
Rachana Gaur1, Rahul Bhardwaj1*, Sandeep Sharma1, Krishna Kumar Rathnam2
Department of Ophthalmology, Regional Institute of Ophthalmology, Sitapur, Uttar Pradesh, India
Department of Medical Oncology, Meenakshi Mission Hospital and Research Centre, Madurai, Tamil Nadu, India
Received: 15 November 2020
Revised: 15 December 2020
Accepted: 16 December 2020
*Correspondence:
Dr. Rahul Bhardwaj,
E-mail: rahulbharadwaj227@gmail.com
Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background: Cancer is a leading cause of death worldwide, accounting for 8.2 million deaths in 2012. Febrile
neutropenia (FN) is fever associated with abnormally low neutrophil count signifying an immunocompromised state
secondary to malignancy or its treatment. The aim of this study was to evaluate clinical outcome of chemotherapy
induced febrile neutropenia.
Methods: This was a hospital based prospective, descriptive observational study. Patients of either sex, age (18-90
years), with cancer on chemotherapy, single oral temperature ≥101°Fahrenheit (38.3°C) or a temperature ≥100.4°
Fahrenheit (38.0° C) for ≥ one hour with absolute neutrophil countsGaur R et al. Int J Res Med Sci. 2021 Jan;9(1):236-242
country which gives an incidence of 92.4 per lac to January 2018. The study was approved by the
population. Same year 6.83 lac persons died of cancer.3 It institutional review board of the parent institution and
is reported that breast cancer is proportionately on the adhered to the tenets of the Declaration of Helsinki.
increase in a few metropolitan areas of India. 4 Informed consent was obtained from all patients before
undertaking treatment options.
The Indian Society of Medical and Pediatric Oncology
(ISMPO) released guidelines for fever with neutropenia Patients of either sex, age (18-90 years), with cancer on
in 2002. Febrile neutropenia (FN) is fever associated with chemotherapy, single oral temperature ≥ 101° F
abnormally low neutrophil count signifying an (Fahrenheit) (38.3°C) or a temperature ≥100.4° F (38.0°
immunocompromised state secondary to malignancy or C) for ≥ one hour with absolute neutrophil counts < 500
its treatment and is a common and often critical condition cells/mm3 or < 1000 cells/mm3 with a predicted decrease
that adversely affects the prognosis of patients. It is a to less than 500 cells/mm3 in the next 24 hours, only with
medical emergency.5 first febrile episode occurring during study period and
prior or concurrent radiation therapy were included in this
There have been major advances in prevention and study.
treatment of FN, this still remains one of the most feared
complications of cancer chemotherapy. Prognosis is Patients with FN, not on chemotherapy, age 14 days). The Common Toxicity Criteria
of the National Cancer Institute established a scale of Patients were classified into low and high risk category
four grades for neutropenia, which are, Grade 1/Mild on the basis of Talcott’s (I to III- high risk; IV- low risk
(ANC ≥1500 toGaur R et al. Int J Res Med Sci. 2021 Jan;9(1):236-242 ± 15 years, (range 18 to 77 years), 31(35.6%) were male duration. Maximum, 65 (75%) patients had neutropenia and 56(64.4%) were female. The highest number were in for ≤ 7 days, 15 (17%) had for 8-14 days, 4 (5%) for 15- between 40-49 years (23%) and overall 80.5% were less 21 days, 3 (3%) for >21 days. than 60 years. Among 87 patients, 70 (80.5%) were less than 60 years and 17 (19.5%) were ≥60 years. Among 70 Table 2: Clinical and Investigation findings of study who were
Gaur R et al. Int J Res Med Sci. 2021 Jan;9(1):236-242 Table 4 shows the Talcott’s and MASCC risk predicting The recovery duration of median fever and neutropenia in tool versus outcome, p values for Talcott’s and MASCC Talcott’s versus MASCC model have been shown in were significant (
Gaur R et al. Int J Res Med Sci. 2021 Jan;9(1):236-242
shown in Table 7. P value was not significant (>0.05) as Validation of MASCC and Talcott's model has been
the data became smaller. Fever and neutropenia duration shown in Table 10.
for solid tumor and hematological malignancy, have been
shown in Table 8, 9.
Table 6: Talcott’s and MASCC model for solid tumor.
Good outcome Poor outcome
Model Total p
RWOC RWC Death
Talcott’s model
Low risk 27 0 0 27
High Risk 16 0 2 18 0.076
Total 43 0 2 45
MASCC model
Low risk 41 0 0 41
0.000
High Risk 2 0 2 4
Total 43 0 2 45
Table 7: Talcott’s and MASCC model for hematological malignancy.
Good outcome Poor outcome
Total p
RWOC RWC Death
Talcott’s model
Low risk 3 0 0 3
0.638
High Risk 21 15 3 39
Total 24 15 3 42
MASCC model
Low risk 18 0 0 18
0.094
High Risk 6 15 3 24
Total 22 17 3 42
Table 8: Fever and neutropenia duration for solid tumor.
Talcott’s low Talcott’s high MASCC low MASCC high
Model P P
risk (n=27) risk (n=18) risk (n=41) risk (n=4)
Mean Fever Duration (in
1 2 0.108 1 1 0.457
days)
Mean Neutropenia
1 2 0.567 2 2 0.380
duration (in days)
Table 9: Fever and neutropenia duration for hematological malignancy.
Talcott’s low Talcott’s high MASCC low MASCC high
Model P P
risk (n=3) risk (n=39) risk (n=18) risk (n=24)
Mean Fever Duration (in
2 9 0.439 6 11 0.231
days)
Mean Neutropenia
2 10 0.250 6 12 0.099
duration (in days)
Table 10: Validation of MASCC and Talcott's model.
Estimate Lower-Upper 95% CIs
Parameter
MASCC Talcott's MASCC Talcott's
Sensitivity 88.06% 44.8% 77.28 - 94.33 32.7-57.41
Specificity 100% 100% 79.95 - 100 79.95-100
Positive Predictive Value 100% 100% 92.38 - 100 85.86-100
Negative Predictive Value 71.43% 35% 51.13 - 86.04 23.24-48.94
Continued.
International Journal of Research in Medical Sciences | January 2021 | Vol 9 | Issue 1 Page 240Gaur R et al. Int J Res Med Sci. 2021 Jan;9(1):236-242
Estimate Lower-Upper 95% CIs
Parameter
MASCC Talcott's MASCC Talcott's
Diagnostic Accuracy 71.08 78.05% 60.57 - 79.93 67.95-85.64
Death rate among Patients at low risk 0 0
Misclassification 9.2% 42.53%
Patients at low risk 67.82% 34.48%
DISCUSSION In our study, among Talcott’s high-risk patients,
37(64.9%) had fever resolution without complication,
Incidence of FN in our study was 17%. In a study by Roy 15(26.3%) with complication, 5(8.8%) died before fever
et al incidence was 13.3%, 15% in Bhavik Doshi et al, resolution. In Talcott’s et al validation study high risk,
19.4% in Schelenz s. et al study,14% in Crawford J et al had 34% complication rate, low risk had only a 5% risk
study.13-16 of developing a medical complication.19
The mean age in our study population was 45±15 years, In our study, among MASCC high risk patients 8(28.6%)
(range 18 to77 years). Male to female ratio was 31: 56, had fever resolution without complication, 15(53.6%)
(0.55). Overall number of females (56/64.4%) were more with complication and 5 (17.8%) died before fever
than males (31/35.6%). In Roy et al study mean age was resolution. Uys et al study showed 98.3% fever resolution
41.2 years, range 16 to 72 years and male to female ratio without complication, 1.7% developing a serious
was 79:132.13 Overall female (62.5%) were more than complication in low risk, in high risk group 50%
males (37.5%). James Talcott et al study had 64% recovered without complication, 36% died before fever
females, range 17 to 75 years. M Okera et al had 59% resolution.22
female and 49% male.18,19
In our study, in Talcott’s low risk group, median duration
Overall maximum 24 (27.6%) patients had carcinoma of FN recovery was approximately 1 day (range 1 to 3
breast. As per WHO carcinoma Breast carcinoma is days) and in high risk group, 5 days (range 1 to 30 days).
commonest in India.4 Talcott et al study carcinoma Breast In MASCC low risk group median time was 1 day (range
(31%) was the most common diagnosis.18 1 to 20) and in high risk group was 9 days (range 1 to 30
days). As per Mezha et al study duration and severity of
In our study 77(88.4%) had ECOG 1 performance status. neutropenia increases the risk of infection and febrile
In some studies, it has been found that poor performance neutropenia.8
status (e.g., WHO Grade > 1), as a measure of frailty, is a
significant risk factor.17 The p value was significant only for MASCC model for
solid tumor. For solid tumor, mean fever and neutropenia
In our study, 64.4% developed FN during 1 st recovery duration was 7 days for Talcott’s
Doshi et al study 50% in M Okera et al study 75% in and MASCC high risk group and ≤7 days for Talcott’s
Mezha M et al study 65% in first 2 cycles.13,14,19,8,20 and MASCC low risk group. Pizzo et al found that
patients whose neutropenia resolved within 7 days were
The maximum number of patients had fever (78.2%) and at low risk, and Bodey et al have consistently found that
neutropenia recovery duration (74.7%) ≤ 7 days. Grade improvement in neutropenia in the first week improves
IV neutropenia was noted in 59.8% and grade III in prognosis. 18,23-25
40.2% patients at the time of presentation. In Roy et al
study the average number of FN days per patient was Limitations: This study was conducted in a single centre
3.46 ± 0.13 days.13 The number of patients with grade IV and therefore the results are not representative of the
neutropenia was 12.7% and grade III was 87.3%. Bhavik general populations.
D. Doshi et al noted 43% grade 3 or 4 neutropenia. 14
CONCLUSION
Growth factor was used in 81.7% patients in our study. M
Okera et al study used growth factor in 63% patients. 19 Neutropenic fever is a potentially life-threatening
Routine use of Growth factor can reduce FN incidence to complication of cancer chemotherapy. MASCC and
50%.21 Talcott’s model can be used to identify low and high risk
patients. MASCC risk index may have a better
Overall 63% patients had comorbidities in our study. In a performance than the Talcott’s model in risk
study by James A Talcott et al 36% had comorbidities.19 classification. However, the Talcott’s model remains a
valid and useful tool because of its simplicity. High risk
International Journal of Research in Medical Sciences | January 2021 | Vol 9 | Issue 1 Page 241Gaur R et al. Int J Res Med Sci. 2021 Jan;9(1):236-242
patients are expected to have longer duration of fever and febrile neutropenic cancer patients. J Clin Oncol.
neutropenia recovery duration. Granulocyte colony 2000;18(16):3038:3051.
stimulating factor can shorten the duration of neutropenia 13. Roy V, Saxena D, Agarwal M, Bahadur AK, Mishra B.
and fever and improve treatment outcomes. Indian J Cancer. 2010;47(4):430-6.
14. Doshi B, Pandya N, Shah C, Gupta A, Makwan M. Der
Funding: No funding sources Pharmacia Lettre. 2012;4(2):584-90.
Conflict of interest: None declared 15. Schelenz S. Annals of Oncology Advance Access
Ethical approval: The study was approved by the published in Oxford J European Oncol Society.
Institutional Ethics Committee 2011;10:1093.
16. Crawford J, Wolff D, Culakova E, Poniewierski MS,
Selby C, Dale D, et al. For the ANC Study Group.
REFERENCES
First-cycle risk of severe and febrile neutropenia in
1. Stewart BW, Wild CP, Christopher P. Wild, World cancer patients receiving systemic chemotherapy:
Cancer Report 2014, International Agency for research results from a prospective nationwide study, American
on cancer, WHO. 2014; 92(3):157. Society of Hematol. 2004;4(7):2210.
2. Weir HK, Thompson TD, Soman A, Moller B, 17. Wilson-Royalty M, Lawless G, Palmer C, Brown R.
Leadbetter S, White MC. Meeting the healthy people Predictors of chemotherapy-related severe or febrile
2020 objectives to reduce cancer mortality, Preventive neutropenia: a review of the clinical literature. J Oncol
chronic disesase. 2015;12:140482. Pharm Pract. 2002;7:141-7.
3. Globocan 2013, India Fact sheet, section of cancer 18. Talcott JA, Finberg R, Mayer RJ, Goldman L. The
information, International Agency for research on medical course of patients with fever and neutropenia:
cancer, WHO, Lyon, France, 2013. clinical identification of a low-risk subgroup at
4. WHO, 1999, Health situation in the south –East Asia presentation. Arch Intern Med. 1988;148:2561-8.
Region, Regional Office for SEAR, New Delhi 1994- 19. Talcott JA, Siegel RD, Finberg R, Goldman L. Risk
1997. assessment in cancer patients with fever and
5. Indian Society of Medical and Pediatric Oncology. neutropenia: a prospective, two-center validation of a
Indian Guidelines-Febrile Neutropenia 2002. prediction rule. J Clin Oncol. 1992;10:316-22.
6. Naurois JDE, Novitzky-Basso I, Gill MJ, Marti F, 20. Caggiano V, Stolshek BS, Delgado DJ, Carter WB.
Cullen MH, Roila F. Management of febrile First and all cycle febrile neutropenia hospitalizations
neutropenia: ESMO Clinical Practice Guidelines. Ann (FNH) and costs in intermediate grade non-Hodgkins
Oncol. 2010;21(Suppl 5):252-6. lymphoma (IGL) patients on standard-dose CHOP
7. Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown therapy [abstract 1810]. Blood. 2001;98:431a.
AE, Calandra T. 2002 guidelines for the use of 21. Zidan J, Shetver L, Gershuny A, Abzah A, Tamam S,
antimicrobial agents in neutropenic patients with Stein M, et al. Prevention of chemotherapy-induced
cancer. Clin Infect Dis. 2002;34(6):730-51. neutropenia by special honey intake. J Clin Oncol.
8. Meza L, Baselga J, Holmes FA, Liang B, Breddy J. 1998;16:3179-90.
Proc Am Soc Clin. Oncol. 2002;21:2840. 22. Uys A, Rapoport BL, Anderson R. Febrile neutropenia:
9. Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin a prospective study to validate the Multniational
SA, Barajas- Figueroa LJ, Wiens BL, et al. First and Association for Supportive Care in Cancer (MASCC)
subsequent cycle use of pegfilgrastim prevents febrile risk-index score. Supp Care Cancer. 2004;2:555-60.
neutropenia in patients with breast cancer: A 23. Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG,
multicenter, double-blind, placebo-controlled phase III Levine AS, Deisseroth AB, et al. Duration of empiric
study. J Clin Oncol. 2005;23:1178-1184. antibiotic therapy in granulocytopenic patients with
10. Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. cancer. Am J Med. 1979;67(2):194-200.
Current trends in the epidemiology of nosocomial 24. Bodey GP, Buckley M, Sathe YS, Freireich EJ.
blood stream infections in patients with haematological Quantitative relationships between circulating
malignancies and solid neoplasms in hospitals in the leukocytes and infection in patients with acute
United States. Clin Infect Dis. 2003;36(9):1103-110. leukemia. Ann Intern Med. 1966;64(2):328-40.
11. Blay JY, Chauvin F, Cesne ALe, Anglaret B, Bouhour 25. Anaissie EJ, Fainstein V, Bodey GP. Randomized trial
D, et al. Early lymphopenia after cytotoxic of beta-lactam regimens in febrile neutropenic cancer
chemotherapy as a risk factor for febrile neutropenia. J patients. Am J Med. 1988;84:581-9.
Clin Oncol. 1996;14:636-63.
Cite this article as: Gaur R, Bhardwaj R, Sharma S,
12. Klastersky J, Paesmans M, Rubenstein EB, Boyer M,
Rathnam KK. Clinical study of chemotherapy
Elting L, Feld R, et al. The Multinational Association
for Supportive Care in Cancer risk index: a induced febrile neutropenia (FN): talcott’s versus
multinational scoring system for identifying low-risk multinational association for supportive care in
cancer (MASCC) risk assessment scoring systems.
Int J Res Med Sci 2021;9:236-42.
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