Efficacy of oral cryotherapy compared to normal saline mouth wash on reducing alkylating drug induced mucositis among cancer patients at selected tertiary care hospital, Bhubaneswar

Introduction

Cancer is the second most fatal disease in India, accounting for approximately 7% of deaths annually. In Odisha, an estimated 50,000 cancer patients are identified annually. Department of Health and Family Welfare sources stated that each year, around 35,000–36,000 cancer patients are admitted to the Acharya Harihar Regional Cancer Centre in Cuttack, while 15,000–16,000 state patients are admitted to various cancer facilities outside of the state. The disease claims the lives of about one-third of the sufferers.¹

According to projections, the anticipated cancer burden in India for the year 2021 is 26.7 million, with an expected increase to 29.8 million by 2025. Additionally, for the year 2022, the estimated cancer incidence in India was 14,61,427.² It is noteworthy that in India, there is a likelihood of one in nine individuals developing cancer during their lifetime.² Chemotherapy is one of the most widely used treatments for cancer patients^3,4 and is usually prescribed for patients with non-localized cancer cells; it also has the potential to metastasize or spread to various parts of the body.^5,6

Mucositis is a common complication of cancer treatment that typically manifests four–five days following the initiation of chemotherapeutic drugs and is characterized by the identification of erythematic regions inside the oral cavity.⁷ Ulcers gradually emerge, progressively increasing in size, and resulting in the formation of extensive ulcerative areas subsequently after seven–ten days of chemotherapy.^8,9 The management of mucositis is primarily based on adjunctive therapies, maintenance of oral cleanliness, sufficient fluid intake, and application of mouthwashes.⁷

Cryotherapy is considered the foremost standard intervention because of its affordability, safety, and absence of any adverse effects.¹⁰ The concept underlying oral cryotherapy is that the application of ice cubes to the oral cavity can induce vasoconstriction, thereby reducing the potential for damage to the oral mucosa resulting from chemotherapeutic agents.^11,12 Ice cubes of 5cc(5cc=5 ml) were arranged for cryotherapy to study group A, which was moved easily within the mouth during chemotherapy infusion at each 5 minutes interval. Upon dissolution, the ice cubes were replaced with fresh ones.^13,14

To assess the efficacy of the intervention, another Study group-B was taken where the participants were instructed to keep the normal saline (NS) mouthwash inside the mouth for 2-5 minutes,^15–17 according to their tolerance level,¹⁸ and the participants were instructed to gargle normal saline mouthwash twice daily for 15 minutes.¹⁹ NS (NaCl 0.9% solution) is a non-irritant, isotonic oral cleanse; because of its low toxicity, safety, and physiological characteristics, it is advantageous for preserving adequate oral hygiene.^20,21

Methods

Results

All 74 participants successfully completed the study without any lapses. A total of 74 participants were enrolled: 37 in study group A and 37 in study group B.

The distribution of participants according to different demographic variables and oral care practices is shown in Table 1.1. The majority of the participants were over 40 years of age (54.1%). The distribution of participants by gender was 48.6% male and 51.4% female. The maximum proportion of participants was graduates or above, with a share of 58.1%. In terms of occupational status, 36.5% were daily wage earners. The majority of participants brushed their teeth once daily (54.1%). About 3/4^th participants used commercial toothpaste for oral care and the remaining 1/4^th used medicated tooth paste.

None of the demographic variables were significantly associated with the Cryotherapy and Normal saline groups.

The clinical profiles of the study participants are presented in Table 1.2. Overall, only 29.7%,29.7%,50% had a history of smoking, alcoholism, and tobacco chewing, respectively. Among the study participants, the maximum proportion (approximately 20.3%) had CA in the lungs. The maximum proportion of participants had stage II carcinoma (36.5%). The most commonly used drugs were oxaliplatin and irinotel, type of Chemo drug followed by premetaxil and pamorzuman (20.3%). About 1/3^rd of the participants had been diagnosed with CA for more than 9 months. None of the variables in the clinical profile differed significantly between the two groups.

Table 1.3 and Figure. 1.1 provide a comparison of mucositis assessment grading between groups on days 1, 7^th day, 14^th day and 21^st day. The review on 21^st day revealed that in comparison to 1^st, 7th and 14^th day, in cryotherapy group there were 70.3% participants with grade 0 mucositis are found, which is a big jump from 48.6% on day 14. In contrast, in the normal saline group, the corresponding increase was from 18.9% to 27.0%, and there is clear evidence that on day 21, the improvement in mucositis grade was much higher in the cryotherapy group than in the normal saline group. There was a significant association between mucositis grade and the group (p<0.001) on day 21. The analysis demonstrated the efficacy of cryotherapy in reducing alkylating drug-induced mucositis.

Figure 1.1. Comparison between efficacy of cryotherapy and normal saline with mucositis grading.

Discussion

One of the most significant harmful effects of cancer treatment is mucositis, which affects an individual’s quality of life, comorbidity, and mortality rates.³ Numerous studies have revealed that oral cryotherapy has a beneficial effect in reducing the incidence of mucositis during chemotherapy. This may be attributed to a reduction in the blood flow to the oral mucosa.¹⁸

The results of the clinical trial were designed in the following sequence: (a) frequency percentage distribution of sociodemographic and clinical variables, and (b) association of mucositis grading with the groups. The results of the present study indicated that there was no significant association found in the sociodemographic and clinical profile data for the cryotherapy and normal saline groups (see Tables 1.1 & 1.2). This result is in accordance with a study by Saad(2022) in Egypt, entitled Supportive cryotherapy nursing intervention to reduce oral mucositis in cancer patients, which revealed no statistically significant differences between the cryotherapy and control groups with respect to any demographic variables.¹⁴

In the present study, after completion of the interventions, a highly statistically significant difference was observed between the groups with respect to the incidence and severity of mucositis on the 1^st, 7^th, 14^th and 21^th day (see Table 1.3). Consistent with the WHO mucositis scale, the results revealed that the percentage of grade-0, in the cryotherapy group was 70.3% at the end of the 21st day, which was 32.4% on the 1^st day of assessment, and in the same time in normal saline group, it was 48.6%. at 21th day which was 21.6% in 1^st day. There is clear evidence that, on day 21,the improvement in mucositis grade was much higher in the cryotherapy group than in the normal saline group. The findings of the experimental study confirmed that there was a significant difference in mucositis reduction among the groups (p<0.001) on day 21, which demonstrates the efficacy of cryotherapy in reducing alkylating drug-induced mucositis. In support of this study, a similar study was conducted by Hanan Mohamed Mohamed Soliman(2019) on the effect of cryotherapy on chemotherapy-induced oral mucositis in Egyptian cancer patients. A randomized controlled trial found that in the majority of patients in the cryotherapy group, oral mucositis was not detected (Grade 0) on the 7th, 14th, and 21st days when compared with the control group (p<.001.¹³

Findings related to the association of demographic variables with mucositis grading at different interventions indicate that at days 1, 7th, 14th and 21th except for age and occupational status, other variables did not have a significant association with the grading of mucositis in both groups. In support of this statement, another study conducted by Saad et al.(2022) in Egypt, entitled Supportive cryotherapy nursing intervention to reduce oral mucositis in cancer patients, revealed no statistically significant differences between the cryotherapy and control groups with respect to any demographic variables.¹⁴

Conclusion

This clinical trial was conducted to evaluate the efficacy of cryotherapy in comparison with normal saline mouthwash in reducing mucositis levels. The results suggested that cryotherapy led to a significant reduction in the oral mucositis level in group A compared to normal saline mouthwash in group B.

Ethics and consent

Prior to administering the questionnaire, written consent was obtained from the participants to ensure their participation. Participation was entirely voluntary, and participants were granted the liberty to withdraw from the study at any time without being obligated to provide justification. Approval was granted by the Institutional Ethics Committee of KIMS, Bhubaneswar.

Ethical committee meeting held on 13.01.2023 - Ref.no.: KIIT/KIMS/IEC/1112/2023