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

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Therefore, a comparison between the two experimental interventions in the present study was performed to represent the effectiveness of different treatments or preventative measures. Aim To evaluate the efficacy of oral cryotherapy compared to normal saline mouthwash in reducing alkylating drug-induced mucositis among cancer patients. Methods A Randomized controlled clinical trial-parallel group design was conducted in a tertiary care hospital in the oncology ward of Bhubaneswar, with a total number of 74 participants (of which 37 were administered cryotherapy and 37 were administered normal saline mouthwash) using the WHO mucositis assessment scale. Results Association of mucositis assessment grading with groups was performed on day 1st, 7th day, 14th day and 21st day followed by intervention. The review on 21st day revealed that 70.3% of the cryotherapy group had grade 0 mucositis, which is a big jump from 48.6% on day 14. In contrast, in the normal saline group, the corresponding increase was only 18.9% to 27.0% only. Conclusion 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, as there was a significant association between mucositis grade and group (p<0.001) on day 21. CTRI Trial Registration No CTRI/2023/04/051450 Date of CTRI Trial Registration No.: 10/04/2023 " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-310", "name": "Efficacy of oral cryotherapy compared to normal saline mouth wash..." } } ] } Home Browse Efficacy of oral cryotherapy compared to normal saline mouth wash... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Dash P, R. A, Pradhan C and Pattnaik J. 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.12688/f1000research.159833.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article 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 [version 1; peer review: 1 approved with reservations, 1 not approved] Pritilagna Dash https://orcid.org/0009-0006-9495-2388 1 , Asokan R. 1 , Chandan Pradhan 1 , Jogamaya Pattnaik 2 Pritilagna Dash https://orcid.org/0009-0006-9495-2388 1 , Asokan R. 1 , Chandan Pradhan 1 , Jogamaya Pattnaik 2 PUBLISHED 19 Mar 2025 Author details Author details 1 Medical surgical Nursing Department, Kalinga Institute of Nursing Sciences, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha, 751024, India 2 D.M. Medical Oncology, Kalinga Institute of Nursing Sciences, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha, 751024, India Pritilagna Dash Roles: Conceptualization, Methodology, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Asokan R. Roles: Supervision Chandan Pradhan Roles: Supervision Jogamaya Pattnaik Roles: Supervision OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background The most prevalent, widely recognized, and challenging side effect experienced by cancer patients undergoing chemotherapy is mucositis, which results in considerable morbidity and has the potential to impede the treatment regimen and augment therapeutic costs. Therefore, a comparison between the two experimental interventions in the present study was performed to represent the effectiveness of different treatments or preventative measures. Aim To evaluate the efficacy of oral cryotherapy compared to normal saline mouthwash in reducing alkylating drug-induced mucositis among cancer patients. Methods A Randomized controlled clinical trial-parallel group design was conducted in a tertiary care hospital in the oncology ward of Bhubaneswar, with a total number of 74 participants (of which 37 were administered cryotherapy and 37 were administered normal saline mouthwash) using the WHO mucositis assessment scale. Results Association of mucositis assessment grading with groups was performed on day 1st, 7 th day, 14 th day and 21 st day followed by intervention. The review on 21 st day revealed that 70.3% of the cryotherapy group had grade 0 mucositis, which is a big jump from 48.6% on day 14. In contrast, in the normal saline group, the corresponding increase was only 18.9% to 27.0% only. Conclusion 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, as there was a significant association between mucositis grade and group (p<0.001) on day 21. CTRI Trial Registration No CTRI/2023/04/051450 Date of CTRI Trial Registration No.: 10/04/2023 READ ALL READ LESS Keywords Cryotherapy, chemotherapy, normal saline, mucositis. Corresponding Author(s) Asokan R. ( [email protected] ) Close Corresponding author: Asokan R. Competing interests: No competing interests were disclosed. Grant information: Kalinga Institute of Industrial Technology KIIT-DU/875/24 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2025 Dash P et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Dash P, R. A, Pradhan C and Pattnaik J. 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.12688/f1000research.159833.1 ) First published: 19 Mar 2025, 14 :310 ( https://doi.org/10.12688/f1000research.159833.1 ) Latest published: 19 Mar 2025, 14 :310 ( https://doi.org/10.12688/f1000research.159833.1 ) Introduction “ There’s always hope beyond what you see .” 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 Objectives ✓ To assess the efficacy of oral cryotherapy compared to normal saline mouthwash in reducing alkylating drug-induced mucositis in cancer patients. ✓ Associate mucositis in cancer patients receiving alkylating agents with sociodemographic variables. Research hypothesis H1: There will be a significant reduction in mucositis between study group A receiving cryotherapy and study group B receiving normal saline mouthwash at a significance level of 0.05. Methods Design and setting A Randomized controlled clinical trial was conducted using a parallel group design at the oncology ward, cancer hospital, KIMS, Bhubaneswar. Sample Eligible criteria included cancer patients receiving cytotoxic chemotherapeutic drugs (alkylating agents), aged from 20 to 60 years, who were interested in taking part in the trial and were present during the intervention. Participants with any kind of dental problems, stage IV mucositis, oral cancer, or oral surgery were excluded from the study. Intervention For study group A - Ice cubes of 5cc(5cc=5 ml) were arranged for cryotherapy, which was moved easily within the mouth during chemotherapy infusion at each 5 minutes interval. A total 60 minutes procedure was planned, where intervention was given for 30 minutes (5 minutes intervention and 5 minutes rest, to avoid discomfort to the patient). Upon dissolution, the ice cubes were replaced with fresh ones. Standard oral care was advised by using a soft toothbrush and mild tooth paste–2-3 times per day. 10 , 13 For study group B , the participants were instructed to keep the normal saline mouthwash inside the mouth for 2-5 minutes, according to their tolerance level. A total 30 minutes procedure was planned, where intervention was given for 15 min at each 5 minutes interval and another 15 minutes rest to avoid discomfort. The participants were also instructed to gargle normal saline mouthwash twice daily for 15 minutes. Standard oral care was advised by using a soft toothbrush and mild tooth paste–2-3 times per day. 20 , 21 Instrument Data were collected using a sociodemographic data tool that contains a self-structured questionnaire regarding age, sex, educational level, occupational status, number of times brushing per day, product used for oral care, history of smoking, alcoholism, chewing tobacco, type of cancer, stage of cancer, type of chemotherapeutic drugs advised, and duration of diagnosis of cancer. In addition, the WHO Health Organization mucositis assessment scale was used to assess mucositis grading among the participants. 15 , 19 Studies indicate that as mucositis appears 4-5 days after the initiation of chemotherapy, the participants were assessed every time on the 1st,7th, 14th, and 21st day, followed by intervention using the WHO mucositis assessment scale, to determine the mucositis grade during the cycle of chemotherapy. 14 , 19 CTRI Trial Registration No.: CTRI/2023/04/051450 Date of CTRI Trial Registration No.: 10/04/2023 Ethical 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 Data analysis The data collected were scrutinized, codified, and entered into IBM SPSS Statistics software (version 24.0; www.spss.co.in ) for analysis. The chi-square test of independence was used to examine the relationship between the groups (cryotherapy and normal saline) and the categorical variables, such as age group, gender, etc., that were determined using the frequency distribution approach. Association of mucositis assessment grading with both the groups was studied by using chi-square test of independence. Cut off value ‘p’<0.05 was consider to indicate statistical significance. To compare the efficacy of the intervention on mucositis reduction, the WHO Health Organization mucositis assessment scale was used, which includes scores from 0 to 4. Grade 0, no mucositis; grade 1, erythema and oral soreness (mild); grade 2, ulcers; oral erythema, able to eat solids (moderate); grade 3, ulcers; liquid diet (severe); grade 4, oral alimentation not possible. 19 , 22 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. Table 1.1. Frequency and percentage distribution of demographic variables of participants. 23 Demographic variables Classifications Group Total χ 2 , p Cryotherapy (n=37) Normal saline (n=37) No. % No. % No. % Age 20-30 5 13.5 4 10.8 9 12.2 χ 2 =0.294 p=0.961 30-40 13 35.1 12 32.4 25 33.8 40-50 15 40.5 16 43.2 31 41.9 50-60 4 10.8 5 13.5 9 12.2 Gender Male 22 59.5 14 37.8 36 48.6 χ 2 =3.462 p=0.063 Female 15 40.5 23 62.2 38 51.4 Educational level Primary education 3 8.1 4 10.8 7 9.5 χ 2 =5.273 p=0.153 Secondary education 9 24.3 15 40.5 24 32.4 Graduate 17 45.9 16 43.2 33 44.6 Post graduate 8 21.6 2 5.4 10 13.5 Occupational status Daily wages 9 24.3 18 48.6 27 36.5 χ 2 =5.618 p=0.132 Self employed 8 21.6 8 21.6 16 21.6 Govt. employee 7 18.9 4 10.8 11 14.9 Private employee 13 35.1 7 18.9 20 27 No. of times brushing per day One 17 45.9 23 62.2 40 54.1 χ 2 =3.718 p=0.156 Two 13 35.1 12 32.4 25 33.8 Three 7 18.9 2 5.4 9 12.2 Product used for oral care Medicated tooth paste 10 27 8 21.6 18 24.3 χ 2 =0.294 p=0.588 Commercial tooth paste 27 73 29 78.4 56 75.7 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 1.2. Frequency and percentage distribution of clinical profile of participants. 23 Group Total χ 2 , p Cryotherapy (n=37) Normal saline (n=37) No. % No. % No. % History of Smoking No 24 64.9 28 75.7 52 70.3 χ 2 =1.035 p=0.309 Yes 13 35.1 9 24.3 22 29.7 History of alcoholism No 24 64.9 28 75.7 52 70.3 χ 2 =1.035 p=0.309 Yes 13 35.1 9 24.3 22 29.7 History of chewing tobacco No 18 48.6 19 51.4 37 50 χ 2 =0.054 p=0.816 Yes 19 51.4 18 48.6 37 50 Type of cancer CA Breast 2 5.4 4 10.8 6 8.1 χ 2 =3.135 p=0.872 CA Lungs 9 24.3 6 16.2 15 20.3 CA Gallbladder 4 10.8 5 13.5 9 12.2 CA Colon 5 13.5 5 13.5 10 13.5 CA Stomach 6 16.2 5 13.5 11 14.9 CA Rectum 3 8.1 6 16.2 9 12.2 CA Ovary 4 10.8 4 10.8 8 10.8 Germ cell tumor 4 10.8 2 5.4 6 8.1 Stage of cancer I 8 21.6 16 43.2 24 32.4 χ 2 =4.834 p=0.089 II 14 37.8 13 35.1 27 36.5 III 15 40.5 8 21.6 23 31.1 Type of chemo Drug Etophoside 4 10.8 2 5.4 6 8.1 χ 2 =2.178 p=0.824 Oxaliplatin, irinotel 14 37.8 16 43.2 30 40.5 Epirubicin, docitaxil 4 10.8 4 10.8 8 10.8 Cisplatin, gemicitamin 4 10.8 5 13.5 9 12.2 Cyclophosamide, paclitaxel 2 5.4 4 10.8 6 8.1 Premetaxil, pamor-zuman 9 24.3 6 16.2 15 20.3 Duration of diag. of cancer ≤ 4 Months 9 24.3 8 21.6 17 23 χ 2 =4.051 p=0.256 4 to ≤ 6 Months 5 13.5 9 24.3 14 18.9 6 to ≤ 9 Months 7 18.9 11 29.7 18 24.3 > 9 months 16 43.2 9 24.3 25 33.8 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. Table 1.3. Comparison between efficacy of cryotherapy and normal saline with mucositis grading. 23 Day Grade Group Total Cryotherapy (n=37) Normal saline (n=37) No. % No. % No. % 1st 0-no mucositis 12 32.4 8 21.6 20 27 χ 2 =4.615 p=0.202 1-mild 15 40.5 11 29.7 26 35.1 2-moderate 6 16.2 14 37.8 20 27 3-severe 4 10.8 4 10.8 8 10.8 7th 0-no mucositis 16 43.2 10 27 26 35.1 χ 2 =2.455 p=0.483 1-mild 10 27 12 32.4 22 29.7 2-moderate 7 18.9 11 29.7 18 24.3 3-severe 4 10.8 4 10.8 8 10.8 14th 0-no mucositis 18 48.6 7 18.9 25 33.8 χ 2 =13.471 p=0.004 1-mild 12 32.4 8 21.6 20 27 2-moderate 5 13.5 17 45.9 22 29.7 3-severe 2 5.4 5 13.5 7 9.5 21st 0-no mucositis 26 70.3 10 27 36 48.6 χ 2 =20.428 p=<0.001 1-mild 8 21.6 7 18.9 15 20.3 2-moderate 3 8.1 13 35.1 16 21.6 3-severe 0 0 7 18.9 7 9.5 Figure 1.1. Comparison between efficacy of cryotherapy and normal saline with mucositis grading. Association of demographic variables with mucositis grading The association of demographic variables with mucositis assessment grading on day 1,7th, 14th and 21th in the cryotherapy and normal saline groups was carried out. Except for age and occupational status, other variables such as sex, educational level, number of times brushing per day, and product used for oral care did not have a significant association with the grading of mucositis in either group. 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. Delimitations ✓ Adults (male/female), aged 20 to 60 years, receiving only chemotherapy, and those willing to participate in the study and who were present during the therapy were included in this study. ✓ This study was limited to participants who received alkylating agents only. Limitations ✓ Hindrance in some participants’ involvement due to fear and anxiety. ✓ Lack of patience and cooperation among participants. Relevance to clinical practice ✓ Specialized nurses caring for cancer patients must emphasize the reduction of mucositis by administering oral cryotherapy to patients undergoing chemotherapy. ✓ Nurses’ knowledge of the impact of cryotherapy can influence problem management and facilitate the implementation of standardized measures. 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 Data availability Underlying data Figshare: Checklist for “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”, DOI: https://doi.org/ 10.6084/m9.figshare.28410299.v1 . 23 This project contains the following underlying data: • CRYOTHERAPY-socio demographic XLS Worksheet.xls • mucositis grade assessment data sheet new.xlsx • NORMA SALINE-socio demographic XLS Worksheet - Copy.xls Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Reporting guidelines Figshare: CONSORT checklist for ‘Checklist for “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”’. Doi: https://doi.org/10.6084/m9.figshare.28410299.v1 . 23 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). References 1. Chatterjee S, et al. : Cancer patterns in Odisha - an important mining state in India. Int. J. Cancer Clin. Res. 2019; 6 : 26–34. Publisher Full Text 2. GLOBOCAN: IARC Cancer Incidence CEO Articles.2020; 8–26. 3. Akbarali HI, Muchhala KH, Jessup DK, et al. : Chemotherapy induced gastrointestinal toxicities. Adv. Cancer Res. 2022; 155 : 131–166. PubMed Abstract | Publisher Full Text | Free Full Text 4. Hong BY, et al. : Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis. BMC Microbiol. 2019; 7 : 66. PubMed Abstract | Publisher Full Text | Free Full Text 5. Huang J, et al. : Experimental chemotherapy-induced mucositis: A scoping review guiding the design of suitable preclinical models. Int. J. Mol. Sci. 2022; 23 (23): 15434. PubMed Abstract | Publisher Full Text | Free Full Text 6. D’Hondt S, et al. : Oral mucositis induced by anticancer treatments: physiopathology and treatments. Ther. Clin. Risk Manag. 2006; 2 (2): 159–168. PubMed Abstract | Publisher Full Text | Free Full Text 7. Thomsen M, Vitetta L: Adjunctive treatments for the prevention of chemotherapy- and radiotherapy-induced mucositis. Integr. Cancer Ther. 2018; 17 (4): 1027–1047. PubMed Abstract | Publisher Full Text | Free Full Text 8. Martins JO d L: Risk factors for oral mucositis during chemotherapy treatment for solid tumors. J. Oral Med. Pathol. 2022; 27 : e319–e329. PubMed Abstract | Publisher Full Text | Free Full Text 9. Peterson DE, Cariello A: Mucosal damage: A major risk factor for severe complications after cytotoxic therapy. Semin. Oncol. 2004; 31 (1): 35–44. 10. Alsulami FJ, Shaheed SU: Oral cryotherapy for management of chemotherapy-induced oral mucositis in hematopoietic cell transplantation: a systematic review. BMC Cancer. 2022; 22 : 442. PubMed Abstract | Publisher Full Text | Free Full Text 11. Riley P, et al. : Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy. Cochrane Database Syst. Rev. 2016; 2016 (12): 1–81. Publisher Full Text 12. Rodrigues B: Effect of cryotherapy in preventing mucositis associated with the use of 5-fluorouracil. Rev. Latino-Am. Enfermagem. 2020; 28 : e3953. Publisher Full Text 13. Soliman HM: The effect of cryotherapy on chemotherapy-induced oral mucositis in Egyptian cancer patients: a randomized controlled trial. J. Nurs. Educ. Pract. 2019; 9 : 63–74. Publisher Full Text 14. Saad AM, Ramadan SS, Mohamed SNH: Supportive cryotherapy nursing intervention toward diminishing oral mucositis and associated pain among patients with cancer. Egypt Nurs. J. 2022; 19 (1): 47–59. Publisher Full Text 15. Kamsvåg K, et al. : Prevention of oral mucositis with cryotherapy in children undergoing hematopoietic stem cell transplantation: a feasibility study and randomized controlled trial. Support Care Cancer. 2020; 28 : 4869–4879. PubMed Abstract | Publisher Full Text | Free Full Text 16. Al-Rudayni AH: Efficacy of oral cryotherapy in the prevention of oral mucositis associated with cancer chemotherapy: systematic review with meta-analysis and trial sequential analysis. Curr. Oncol. 2021; 28 (4): 2852–2867. PubMed Abstract | Publisher Full Text | Free Full Text 17. Oku S, et al. : Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning. Support Care Cancer. 2023; 31 : 521. PubMed Abstract | Publisher Full Text | Free Full Text 18. Maciejewska M, et al. : Ice cream used as cryotherapy during high-dose melphalan conditioning reduces oral mucositis after autologous hematopoietic stem cell transplantation. Nat. J. 2021; 333–349. 19. Askarifa M, et al. : The effects of oral cryotherapy on chemotherapy-induced oral mucositis in patients undergoing autologous transplantation of blood stem cells: A clinical trial. Indian Red Crescent Med. J. 2016; 18 : 1–6. Publisher Full Text 20. The comparative effects of povidone-iodine and normal saline mouthwashes on oral mucositis in patients after high-dose chemotherapy. Support Care Cancer. 2005; 13 : 554–558. PubMed Abstract | Publisher Full Text 21. Hajisalem T: Effect of Achillea millefolium mouthwash on oral mucositis induced by chemotherapy in AML patients. J. Nat. Pharm. Prod. 2019; In Press : 1–7. Publisher Full Text 22. World Health Organisation: Handbook for reporting results of cancer treatment. Geneva: WHO; 1979; pp. 15–22. 23. Dash P: Checklist for “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”. Dataset. figshare. 2025. Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 19 Mar 2025 ADD YOUR COMMENT Comment Author details Author details 1 Medical surgical Nursing Department, Kalinga Institute of Nursing Sciences, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha, 751024, India 2 D.M. Medical Oncology, Kalinga Institute of Nursing Sciences, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University, Bhubaneswar, Odisha, 751024, India Pritilagna Dash Roles: Conceptualization, Methodology, Resources, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Asokan R. Roles: Supervision Chandan Pradhan Roles: Supervision Jogamaya Pattnaik Roles: Supervision Competing interests No competing interests were disclosed. Grant information Kalinga Institute of Industrial Technology KIIT-DU/875/24 The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (1) version 1 Published: 19 Mar 2025, 14:310 https://doi.org/10.12688/f1000research.159833.1 Copyright © 2025 Dash P et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Dash P, R. A, Pradhan C and Pattnaik J. 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.12688/f1000research.159833.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 19 Mar 2025 Views 0 Cite How to cite this report: Kandwal A. Reviewer Report For: 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.5256/f1000research.175618.r375392 ) The direct URL for this report is: https://f1000research.com/articles/14-310/v1#referee-response-375392 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 May 2025 Abhishek Kandwal , Swami Rama Himalayan University, Dehradun, Uttarakhand, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175618.r375392 Dear author, The manuscript has potential and good. few points needs to be address or cleared 1. Mention the randomization method , technique employed, blinding status , 2. Mention data power, ... Continue reading READ ALL Dear author, The manuscript has potential and good. few points needs to be address or cleared 1. Mention the randomization method , technique employed, blinding status , 2. Mention data power, sample size calculation and method used. 3. What was temperature achieved in oral / cheek mucosa by chemotherapy recorded any temperature probe used. ?? if not mention as limitation as temperature reached could not be documented scientifically. 4. Mention in details how ice were placed in mouth , suction used to remove the water , position of patient. 5. Clearly mention that whether all patients completed the protocol or dropped in between or the treatment was discontinued. 6. Clearly mention the what was frequency of chemo cycle used weekly / 3 weekly . 7. Mention on which cycle of chemo the patients enrolled are all receiving their first cycle or are in different number of cycle at time of enrollment . 8. It would have been ideal to compare same chemo patients or do as sub group analysis for better interpretation of results. 9. Update references use latest mucositis guidelines of assessment , parthenogenesis and agents by MASCC guidelines . Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: oral toxicities of cancer management, supportive and palliative cancer care focus on head and neck cancer , I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kandwal A. Reviewer Report For: 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.5256/f1000research.175618.r375392 ) The direct URL for this report is: https://f1000research.com/articles/14-310/v1#referee-response-375392 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Altınışık M. Reviewer Report For: 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.5256/f1000research.175618.r375395 ) The direct URL for this report is: https://f1000research.com/articles/14-310/v1#referee-response-375395 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Apr 2025 Müge Altınışık , Akdeniz University, Antalya, Turkey Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.175618.r375395 The topic is well-chosen; however, there are some unclear aspects. In randomized controlled trials, it is crucial to clearly define and explain the sample and methodology, as this minimizes the potential for bias. Providing such clarity enhances the applicability and ... Continue reading READ ALL The topic is well-chosen; however, there are some unclear aspects. In randomized controlled trials, it is crucial to clearly define and explain the sample and methodology, as this minimizes the potential for bias. Providing such clarity enhances the applicability and usefulness of the findings in clinical practice. The sample included cancer patients receiving cytotoxic chemotherapeutic agents (alkylating agents), aged between 20 and 60 years, who were willing to participate in the study and were present during the intervention. To reduce potential bias and achieve more precise results, it would have been beneficial to define the mucositis grade as part of the inclusion criteria—for instance, including only patients with grade 2 or grade 3 mucositis. Another important consideration is the presence of chronic illnesses, which may influence the healing process. For example, a patient with diabetes may experience delayed wound healing, potentially impacting the effectiveness of the intervention. For Study Group A, although the total duration of the intervention was planned as 60 minutes, only 30 minutes involved active cryotherapy application. The intervention was structured as alternating intervals—5 minutes of cryotherapy followed by 5 minutes of rest—to ensure patient comfort. Therefore, the 30 minutes of active application were distributed over a 60-minute session. However, the original phrasing in the study does not clearly convey this structure, and may lead to confusion regarding the actual intervention duration. Although the duration of the intervention (e.g., over a 21-day period or one month) is mentioned in the abstract and conclusion, it is not clearly specified in the intervention section of the methodology. It is essential to explicitly state the total duration of the intervention for each study group within the methodology to ensure clarity, reproducibility, and scientific rigor. Without this specification, the reader may find it difficult to interpret the consistency and continuity of the intervention. It is unclear whether a power analysis was conducted to determine the sample size. Performing such an analysis is crucial to enhance the statistical validity of the study and to minimize the risk of Type II errors. Moreover, the inclusion of a CONSORT flow diagram would have greatly enhanced the transparency of the participant flow throughout the study phases—enrollment, allocation, follow-up, and analysis. This would aid in clarifying the exact number of participants at each stage and provide a clearer understanding of attrition and exclusion, if any. Details regarding the randomization process are not provided. It is essential to specify the type of randomization used—such as simple, stratified, or block randomization—in order to ensure the prevention of selection bias and to uphold methodological transparency. There is no information regarding blinding (masking). It should be clearly stated whether blinding was implemented for participants, researchers, or outcome assessors. If blinding was not feasible due to the nature of the intervention, this should be acknowledged as a study limitation, and its potential influence on the results should be discussed accordingly. In the statistical analysis section, it is not stated whether the data were analyzed using an intention-to-treat or per-protocol approach. Clarifying this aspect is essential for assessing the robustness of the findings. Although p-values are reported, the omission of effect size measures limits the interpretability of the clinical relevance of the findings. Reporting effect sizes alongside p-values would provide a more comprehensive understanding of the magnitude of the observed differences. The method of associating mucositis with sociodemographic variables in cancer patients receiving alkylating agents is not clearly explained. It is essential to describe the statistical approach used to assess the relationship between sociodemographic factors (such as age, gender, occupation, etc.) and mucositis grading. For example, were chi-square tests or regression analysis used to examine these associations? Clarifying this would enhance the clarity and reproducibility of the analysis and provide a more thorough understanding of how these variables may influence the incidence or severity of mucositis in the study population. Discussion The current text mainly reiterates the findings without providing an in-depth interpretation of their significance. There is a lack of explanation regarding why the results turned out the way they did, the mechanisms behind these outcomes, and how they can be explained. A more comprehensive discussion should explore the possible reasons for the observed results and compare them with existing literature to highlight the novelty or consistency of the findings. Additionally, while other studies are mentioned, only their names are cited, and there is no detailed comparison of the methodological similarities and differences, sample variations, or intervention duration. For example, in the referenced studies, was the same intervention used? What was the duration of the intervention in those studies, and how does it compare to the current study? Limitations The study was conducted with a sample size of only 74 participants at a single center. However, the implications of this on the generalizability of the findings have not been discussed. A statement such as, “While the results are promising, the small sample size and single-center design limit the generalizability of the findings,” would have been beneficial to clarify the potential limitations in extending the conclusions to a broader population. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oncology nursing I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Altınışık M. Reviewer Report For: 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.5256/f1000research.175618.r375395 ) The direct URL for this report is: https://f1000research.com/articles/14-310/v1#referee-response-375395 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 19 Mar 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 1 19 Mar 25 read read Müge Altınışık , Akdeniz University, Antalya, Turkey Abhishek Kandwal , Swami Rama Himalayan University, Dehradun, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Kandwal A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 May 2025 | for Version 1 Abhishek Kandwal , Swami Rama Himalayan University, Dehradun, Uttarakhand, India 0 Views copyright © 2025 Kandwal A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Dear author, The manuscript has potential and good. few points needs to be address or cleared 1. Mention the randomization method , technique employed, blinding status , 2. Mention data power, sample size calculation and method used. 3. What was temperature achieved in oral / cheek mucosa by chemotherapy recorded any temperature probe used. ?? if not mention as limitation as temperature reached could not be documented scientifically. 4. Mention in details how ice were placed in mouth , suction used to remove the water , position of patient. 5. Clearly mention that whether all patients completed the protocol or dropped in between or the treatment was discontinued. 6. Clearly mention the what was frequency of chemo cycle used weekly / 3 weekly . 7. Mention on which cycle of chemo the patients enrolled are all receiving their first cycle or are in different number of cycle at time of enrollment . 8. It would have been ideal to compare same chemo patients or do as sub group analysis for better interpretation of results. 9. Update references use latest mucositis guidelines of assessment , parthenogenesis and agents by MASCC guidelines . Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise oral toxicities of cancer management, supportive and palliative cancer care focus on head and neck cancer , I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Kandwal A. Peer Review Report For: 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.5256/f1000research.175618.r375392) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-310/v1#referee-response-375392 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Altınışık M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Apr 2025 | for Version 1 Müge Altınışık , Akdeniz University, Antalya, Turkey 0 Views copyright © 2025 Altınışık M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The topic is well-chosen; however, there are some unclear aspects. In randomized controlled trials, it is crucial to clearly define and explain the sample and methodology, as this minimizes the potential for bias. Providing such clarity enhances the applicability and usefulness of the findings in clinical practice. The sample included cancer patients receiving cytotoxic chemotherapeutic agents (alkylating agents), aged between 20 and 60 years, who were willing to participate in the study and were present during the intervention. To reduce potential bias and achieve more precise results, it would have been beneficial to define the mucositis grade as part of the inclusion criteria—for instance, including only patients with grade 2 or grade 3 mucositis. Another important consideration is the presence of chronic illnesses, which may influence the healing process. For example, a patient with diabetes may experience delayed wound healing, potentially impacting the effectiveness of the intervention. For Study Group A, although the total duration of the intervention was planned as 60 minutes, only 30 minutes involved active cryotherapy application. The intervention was structured as alternating intervals—5 minutes of cryotherapy followed by 5 minutes of rest—to ensure patient comfort. Therefore, the 30 minutes of active application were distributed over a 60-minute session. However, the original phrasing in the study does not clearly convey this structure, and may lead to confusion regarding the actual intervention duration. Although the duration of the intervention (e.g., over a 21-day period or one month) is mentioned in the abstract and conclusion, it is not clearly specified in the intervention section of the methodology. It is essential to explicitly state the total duration of the intervention for each study group within the methodology to ensure clarity, reproducibility, and scientific rigor. Without this specification, the reader may find it difficult to interpret the consistency and continuity of the intervention. It is unclear whether a power analysis was conducted to determine the sample size. Performing such an analysis is crucial to enhance the statistical validity of the study and to minimize the risk of Type II errors. Moreover, the inclusion of a CONSORT flow diagram would have greatly enhanced the transparency of the participant flow throughout the study phases—enrollment, allocation, follow-up, and analysis. This would aid in clarifying the exact number of participants at each stage and provide a clearer understanding of attrition and exclusion, if any. Details regarding the randomization process are not provided. It is essential to specify the type of randomization used—such as simple, stratified, or block randomization—in order to ensure the prevention of selection bias and to uphold methodological transparency. There is no information regarding blinding (masking). It should be clearly stated whether blinding was implemented for participants, researchers, or outcome assessors. If blinding was not feasible due to the nature of the intervention, this should be acknowledged as a study limitation, and its potential influence on the results should be discussed accordingly. In the statistical analysis section, it is not stated whether the data were analyzed using an intention-to-treat or per-protocol approach. Clarifying this aspect is essential for assessing the robustness of the findings. Although p-values are reported, the omission of effect size measures limits the interpretability of the clinical relevance of the findings. Reporting effect sizes alongside p-values would provide a more comprehensive understanding of the magnitude of the observed differences. The method of associating mucositis with sociodemographic variables in cancer patients receiving alkylating agents is not clearly explained. It is essential to describe the statistical approach used to assess the relationship between sociodemographic factors (such as age, gender, occupation, etc.) and mucositis grading. For example, were chi-square tests or regression analysis used to examine these associations? Clarifying this would enhance the clarity and reproducibility of the analysis and provide a more thorough understanding of how these variables may influence the incidence or severity of mucositis in the study population. Discussion The current text mainly reiterates the findings without providing an in-depth interpretation of their significance. There is a lack of explanation regarding why the results turned out the way they did, the mechanisms behind these outcomes, and how they can be explained. A more comprehensive discussion should explore the possible reasons for the observed results and compare them with existing literature to highlight the novelty or consistency of the findings. Additionally, while other studies are mentioned, only their names are cited, and there is no detailed comparison of the methodological similarities and differences, sample variations, or intervention duration. For example, in the referenced studies, was the same intervention used? What was the duration of the intervention in those studies, and how does it compare to the current study? Limitations The study was conducted with a sample size of only 74 participants at a single center. However, the implications of this on the generalizability of the findings have not been discussed. A statement such as, “While the results are promising, the small sample size and single-center design limit the generalizability of the findings,” would have been beneficial to clarify the potential limitations in extending the conclusions to a broader population. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests No competing interests were disclosed. Reviewer Expertise Oncology nursing I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Altınışık M. Peer Review Report For: 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 [version 1; peer review: 1 approved with reservations, 1 not approved] . F1000Research 2025, 14 :310 ( https://doi.org/10.5256/f1000research.175618.r375395) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-310/v1#referee-response-375395 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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