<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="other" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.146012.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Study Protocol</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>An observational prospective study of mucocutaneous adverse effects of chemotherapeutic drugs and radiotherapy</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Rusia</surname>
                        <given-names>Kaveri</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Software</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-6484-5844</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Madke</surname>
                        <given-names>Bhushan</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Software</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Dermatology, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, 442001, India</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:kaverirusia12@gmail.com">kaverirusia12@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>1</day>
                <month>3</month>
                <year>2024</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2024</year>
            </pub-date>
            <volume>13</volume>
            <elocation-id>149</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>16</day>
                    <month>2</month>
                    <year>2024</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Rusia K and Madke B</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/13-149/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>There is an enormous advancement in chemotherapeutic drugs and radiotherapy. With the advancement, the adverse effects in patients receiving chemotherapeutic drugs and radiotherapy have also increased. Hence identifying and treating adverse effects of chemotherapeutic drugs and radiotherapy is of utmost importance for patients. This study will help us to find out the various mucocutaneous adverse effects associated with various new chemotherapeutic drugs and radiation.</p>
                    <p>Our objective is to find out the frequency of mucocutaneous manifestation in patients receiving chemotherapy and radiotherapy and also to know and assess the various patterns and severity of mucocutaneous involvement in chemotherapy and radiotherapy.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>This will be an observational prospective study that will be conducted in a tertiary care cancer hospital [Siddharth Gupta Memorial Cancer Hospital] and patients coming to OPD of AVBRH in the Department of Dermatology from 15th December 2023 to 15 September 2024, who will be presenting with the mucocutaneous adverse effects. Detailed History and Cutaneous examination will be performed and graded according to Common Terminology Criteria for Adverse Events v5. The various mucocutaneous adverse effects will be compiled and grading will be done. This study will help us to find out the various mucocutaneous adverse effects associated with various new chemotherapeutic drugs and radiation.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>We will study the various mucocutaneous manifestations in patients with solid organ malignancy or hematological malignancy receiving chemotherapy and radiotherapy.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Chemotherapeutic drugs</kwd>
                <kwd>Radiation</kwd>
                <kwd>mucocutaneous adverse effects</kwd>
                <kwd>nail discoloration</kwd>
                <kwd>alopecia</kwd>
                <kwd>hormone therapy</kwd>
                <kwd>radiation dermatitis</kwd>
                <kwd>chemotherapy</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>none</funding-source>
                </award-group>
                <funding-statement>The author(s) declared that no grants were involved in supporting this work.</funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec4" sec-type="intro">
            <title>Introduction</title>
            <p>Our understanding of cancer and treatment approaches has advanced significantly over the years. The management of cancer has become more difficult as cancer prevalence rises, making it a challenge for modern clinical care. Cancer patients are currently being treated using a variety of methods, including radiotherapy, chemotherapy, combination therapy, immunotherapy, and hormone therapy.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> Modernized equipment and increasingly sophisticated restorative regimens have revolutionized functionality and greatly reduced, but not eliminated, the negative effects they produce on the body. The negative effects of chemotherapy on the skin, nails, and hair can significantly lower the quality of life and cause therapy to be discontinued. significant advancements. The creation of anticancer agents has seen significant advancements. The importance of genetic changes is particularly highlighted by the development of targeted treatments for the treatment of solid cancers. Through this advancement, cancer patient&#x2019;s chances of survival and quality of life have increased, and hematological and non-specific toxicities have decreased in tandem. A new and broad spectrum of dermatologic adverse effects have, however, also emerged as a result of the introduction of newer drugs.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>Hyperpigmentation, alopecia, radiation recall, hand-foot syndrome, hypersensitivity, extravasation injuries, and nail dystrophies are among the most common cutaneous reactions. Although most post-chemotherapy side effects are not life-threatening, they can nonetheless be stressful for the patient, especially if they result in baldness. In rapidly growing cells like skin, adnexa, and mucous membranes, chemotherapeutic drugs&#x2019; toxicities, and unfavorable effects can be noticed. While other adverse effects including erythema, hyperpigmentation, rash, and hypersensitivity happen less frequently, the side effects that occur in these rapidly reproducing cells are typically dose-dependent. The administration of chemotherapy medications needs to be done cautiously since extravasation of intravenous chemotherapy medications might result in serious skin irritation and necrosis.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <p>Phototoxicity, the recall phenomenon, and radiation enhancement are three examples of cutaneous adverse effects that are linked to the interaction between chemotherapy and radiation. Other, less common side effects such as sclerodermiform dermatitis, Raynaud&#x2019;s phenomenon, and hypersensitivity syndrome are also discussed. Sometimes cutaneous side effects are rather exclusive to a particular class of medication. Taxanes are most frequently connected to capillary leak syndrome. Perhaps as a result of the drug&#x2019;s prolonged use, hydroxyurea causes certain odd cutaneous side effects (ulcerations, pseudodermatomyositis). Despite the frequent and occasionally severe mucocutaneous adverse effects of chemotherapy, stopping the offending medication is rarely necessary. However, dose adjustments or measures to prevent some of these adverse effects are still required.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup>
            </p>
            <p>Alopecia is one of the most frequent dermatologic adverse effects of chemotherapy. Drugs frequently target the rapidly producing hair cells. As a result, the production of hair shafts is lost, resulting in weak, frizzy hair. The scalp&#x2019;s terminal hair follicles, which produce hair more quickly than axillary, pubic, or slower-growing brow, eyelash, or axillary hair, are more affected. Chemotherapy-induced alopecia is reversible, and hair regrowth occurs with a change in texture and color (switching from straight to curly).
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>The Palmar-plantar erythrodysesthesia, also called the hand-foot condition, is characterized by erythematous, painful lesions on the skin that affect the palms and soles. and was first noticed in patients receiving high doses of cytarabine medication.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> After 2 to 12 days of medication exposure, the patient often has a burning feeling on their hands and feet, which is followed by a severe erythema that is symmetrical and well-defined. The dorsal and lateral fingers, as well as the periungual skin, are frequently affected after the lesions are initially noticed on the thenar and hypothenar eminences of the palms.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> Eventually, the entire hand or foot may be affected, causing swelling and potentially the appearance of vesicles or bullae. After weeks to years of radiation, doxorubicin, in particular, causes the development of radiation dermatitis. Dermatologic symptoms can be desquamation, vesicle development, and maculopapular eruptions with erythema. From a minor rash to a serious case of skin necrosis, reactions can vary in severity. Nail alterations for chemotherapy patients happen regularly. The presence of transverse ridges is indicative of cyclic damage to the nail matrix.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>Ionizing radiation is a crucial therapeutic option for cancer patients. Tissues can undergo a variety of functional and structural changes as a result of radiation. The overall radiation dose, the amount of tissue exposed, and the duration between radiation doses are just a few of the variables that affect how much radiation damage there is. The highly oxygenated cells and proliferative cells are the most vulnerable to radiation damage. The most radiosensitive cells in the integumentary system are basal keratinocytes, hair follicle stem cells, and melanocytes.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup>
            </p>
            <p>Hypersensitivity responses, contact dermatitis, vasculitis, and fixed drug eruptions are frequent misdiagnoses for the skin symptoms brought on by chemotherapy and radiotherapy. Patients receiving chemotherapy and radiotherapy frequently experienced changes in skin, nails, hair, and mucosa as serious side effects. To increase patient compliance, it is crucial to understand the range and presentation of mucocutaneous symptoms in those undergoing chemotherapeutic medicines and radiation therapy.</p>
            <p>With the introduction of newer modalities and upgradation in the treatment of cancer there is an increase in the survival rate of cancer patients but at the same time, there is an increase in adverse effects of chemotherapeutic drugs and radiotherapy. The administration of chemotherapeutic drugs can lead to a host of mucocutaneous manifestations ranging from adverse effects that are specific to drugs like flagellate dermatitis caused by bleomycin to non-specific toxic reactions like painful erythema involving hands and feet, intertriginous areas by a variety of drugs like Cytarabine, Doxorubicin, Capecitabine, Paclitaxel. The skin manifestations caused by chemotherapy and radiotherapy are often misdiagnosed as hypersensitivity reactions, contact dermatitis, vasculitis, and fixed drug eruptions. Therefore, it is important to identify the various presentations of mucocutaneous manifestations in patients receiving chemotherapeutic drugs and radiotherapy to improve the compliance of the patient.</p>
        </sec>
        <sec id="sec5">
            <title>Objectives</title>
            <p>
                <list list-type="bullet">
                    <list-item>
                        <label>&#x2022;</label>
                        <p>To find out the frequency of mucocutaneous manifestation in patients receiving chemotherapy.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>To find out the frequency of mucocutaneous manifestation in patients receiving radiotherapy.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>To know the various patterns of mucocutaneous involvement in chemotherapy.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>To know the various patterns of mucocutaneous involvement in radiotherapy.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>To assess the severity of mucocutaneous involvement with the chemotherapeutic drugs.</p>
                    </list-item>
                </list>
            </p>
        </sec>
        <sec id="sec6" sec-type="methods">
            <title>Methods</title>
            <sec id="sec7">
                <title>Study design</title>
                <p>An observational prospective study.</p>
                <p>Setting: Tertiary care cancer hospital [Siddharth Gupta Memorial Cancer Hospital] or Acharya Vinoba Bhave Rural Hospital, Sawangi</p>
                <p>Location: Rural Central India</p>
                <p>Recruitment: 15
                    <sup>th</sup> December 2023 to 15
                    <sup>th</sup> September 2024.</p>
            </sec>
            <sec id="sec8">
                <title>Study population</title>
                <p>150 patients having malignancy receiving chemotherapy or radiotherapy including both genders and all age groups coming to OPD of Tertiary Care Cancer Hospital [Siddharth Gupta Memorial Cancer Hospital] and OPD of Acharya Vinoba Bhave Rural Hospital, Sawangi will be enrolled.</p>
            </sec>
            <sec id="sec9">
                <title>Sample size</title>
                <p>
                    <disp-formula id="e1">
                        <mml:math display="block">
                            <mml:mi mathvariant="normal">n</mml:mi>
                            <mml:mo>=</mml:mo>
                            <mml:mfenced close="]" open="[">
                                <mml:mrow>
                                    <mml:mi>Z&#x03b1;</mml:mi>
                                    <mml:mo>/</mml:mo>
                                    <mml:mn>2</mml:mn>
                                </mml:mrow>
                            </mml:mfenced>
                            <mml:mn>2</mml:mn>
                            <mml:mspace width="0.25em"/>
                            <mml:mo>&#x00d7;</mml:mo>
                            <mml:mspace width="0.25em"/>
                            <mml:mi mathvariant="normal">P</mml:mi>
                            <mml:mfenced close=")" open="(">
                                <mml:mrow>
                                    <mml:mn>1</mml:mn>
                                    <mml:mo>&#x2212;</mml:mo>
                                    <mml:mi mathvariant="normal">P</mml:mi>
                                </mml:mrow>
                            </mml:mfenced>
                            <mml:mo>/</mml:mo>
                            <mml:mtext>d2</mml:mtext>
                        </mml:math>
                    </disp-formula>
                </p>
                <p>Where Z &#x03b1;/2 is the level of significance at 5% i.e., 95%</p>
                <p>Alpha [&#x03b1;] is 0.05</p>
                <p>The estimated proportion of malignancy [p] is 84%</p>
                <p>Estimated error [d] is 6%</p>
                <p>Sample size [n] = 144</p>
                <p>Sample size [n] = 150</p>
            </sec>
            <sec id="sec10">
                <title>Inclusion criteria</title>
                <p>
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Patients receiving chemotherapy and radiotherapy irrespective of their age and sex.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Patients willing to participate.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec11">
                <title>Exclusion criteria</title>
                <p>
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Patient with mucocutaneous manifestation due to malignancy.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Known Prior primary dermatoses</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Drug reaction due to Non-Chemotherapeutic Drugs</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Mucocutaneous manifestation of Paraneoplastic syndromes</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec12">
                <title>Ethical considerations</title>
                <p>The approval for the study was given by the Institutional Ethics Committee on 15
                    <sup>th</sup> July 2022 [DMIMS (DU)/IEC/2022/24]. Informed consent will be taken from the patients.</p>
            </sec>
            <sec id="sec13">
                <title>Data collection</title>
                <p>All patients will be asked to voluntarily participate and provide their written and signed informed permission. A thorough history will be taken, along with a dermatological examination. Additionally, to other clinical information, mucocutaneous side effects will be included. The parameter includes patient demographic information (age, gender, occupation, address, marital status), cancer diagnosis and prognosis information, and treatment information (drugs/routine, formulation, bolus/infusion, route of administration, frequency of administration, cycles of drug therapy, duration of treatment) as well as information on the drugs used and their dosages. According to this grading, mucocutaneous adverse effects will be classified from Grade 1 to Grade 5. The grading will be based on Common Terminology Criteria for Adverse Events v5. 0.</p>
            </sec>
            <sec id="sec14">
                <title>Statistical analysis</title>
                <p>All the results will be calculated using 
                    <ext-link ext-link-type="uri" xlink:href="https://www.ibm.com/products/spss-statistics">SPSS</ext-link> version 22 (RRID:SCR_002865). Demographic data for the study variable will be tabulated in frequency, percentage, and median for qualitative analysis. Comparative evaluation of chemotherapy and radiotherapy cycles will be analyzed for adverse effects on frequency and percentage basis.</p>
            </sec>
            <sec id="sec15">
                <title>Limitations</title>
                <p>It is a hospital-based study, not a population-based study.</p>
            </sec>
            <sec id="sec16">
                <title>Bias</title>
                <p>For the prevention of selection bias, random selection will be followed for the selection of participants.</p>
            </sec>
        </sec>
        <sec id="sec17" sec-type="discussion">
            <title>Discussion</title>
            <p>It is highly common for patients following chemotherapy and radiation therapy to present with a variety of mucocutaneous symptoms. If these symptoms occur frequently, it can lower the patient&#x2019;s quality of life. The adverse effects might be asymptomatic observations, incapacitating symptoms, or a combination of these.</p>
            <p>In a descriptive study of 226 patients, Naveed S et al.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> found that the most common symptom was nail changes (194; 5.84%). Discoloration of nails was more common in patients receiving combination therapy than chemotherapy alone. The second most common manifestation was skin changes (191; 84.51%), followed by hair changes (159; 70.35%), mucosal involvement (34; 15.04%), and other non-specific presentations. The most frequent negative impact on the skin was skin pigmentation. Other skin abnormalities included hirsutism, hypertrichosis, and alopecia.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup>
            </p>
            <p>Susser et al.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup> in a study has found that the most common adverse effect of cancer chemotherapy was Alopecia. Anagen effluvium was most commonly produced by Anticancer agents. Oral mucositis although was a dose-limiting side effect, affects almost 40% of individuals. The drugs most commonly associated with oral mucositis were bleomycin, docetaxel, and daunorubicin.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup>
            </p>
            <p>Biswal SG et al.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup> conducted an observational study of 1000 receiving chemotherapy. Out of 1000 patients, 384 presented with any one of the dermatological manifestations. Anagen Effluvium was the most common affecting 78.6% of patients. The other less common manifestations were Sweet syndrome and Bullous Photodermatitis.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup>
            </p>
            <p>Lalla RV et al.
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup> conducted a study and reported the oral complication in patients receiving chemotherapy and radiotherapy was Oral mucositis affecting 20 to 40% of patients. The pain associated with oral mucositis has led to a reduction in chemotherapy and radiotherapy doses.
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup>
            </p>
            <p>Gabriella et al.
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup> in their study of 100 patients receiving chemotherapeutic drugs. The patients on EGFR inhibitor developed papulopustular reaction [55.8%], dry skin [41.17%], nail alterations [29.41%], and alopecia [17.64%].
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup>
            </p>
            <p>In their descriptive analysis of 53 chemotherapy patients, Pavey et al.
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>
                </sup>found that the most prevalent mucocutaneous adverse effects were changes to the nails (33; 62.2%), then changes to the hair (20; 37.7%), skin (19; 33.9%), and mucosa (2; 3.7%).
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>
                </sup>
            </p>
            <p>In a study conducted by 
                <ext-link ext-link-type="uri" xlink:href="https://pubmed.ncbi.nlm.nih.gov/?term=Utlu+Z&amp;cauthor_id=35126018">Zeynep Utlu</ext-link> et al.
                <sup>
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> total of 128 patients were enllored and divided into two groups one receiving classic chemotherapeutic agents and the other receiving targeted agents The majority of the adverse effects, xerosis, were observed in 93 (72.7%) of the 128 individuals. Alopecia, mucositis, pruritus, pigmentation of skin, and hand-foot erythema were other common adverse effects. In the traditional chemotherapeutic group, xerosis, pruritus, alopecia, and nail alterations were the most frequently reported adverse effects, occurring in 71 (75.5%) individuals, 50 (53.2%), 49 (52.1%), and 43 (45.7%) of the patients. In the targeted chemotherapeutic group, xerosis (22/64.7%), nail alterations (17/50%), alopecia (15/44.1%), and pruritus (13/38.2%) were the most frequently reported adverse effects.
                <sup>
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup>
            </p>
            <p>Hospital-based observational research was carried out by Menon A et al.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>
                </sup> with the participation of 100 patients, including 37 female and 63 male patients. Hair was the most often seen adverse impact among the cutaneous side effects, followed by changes in the skin, changes in nails, and mucosal involvement. The most often noted negative effects on the skin were hyperpigmentation and xerosis.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>
                </sup>
            </p>
            <p>Thapa DP et al.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup> performed hospital-based research in which 62 patients in all were included. Eczema accounted for 39% of all dermatoses, with infection coming in at 25%, pruritus at 14%, insect bite hypersensitivity at 3.2%, pilosebaceous unit disorder at 3.2%, urticaria at 3.2%, pigmentary alterations at 3.2%, nail involvement at 3.2%, drug rash at 2%, vesiculo-blistering disorder at 2%, and cutaneous metastases at 2%.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup>
            </p>
            <sec id="sec18">
                <title>Expected outcome variables</title>
                <p>The expected outcome variables include xerosis of skin, hyperpigmentation, and hypopigmentation of skin, erythema multiforme, eczema, photosensitivity, palmoplantar erythrodysesthesia syndrome, purpura, maculopapular rash, acneiform eruptions, urticaria, skin ulceration about the skin. The involvement of hair in the form of Alopecia which is defined as a decrease in the density of hair compared to normal for a given individual at a given age and body location. Other hair abnormalities are hypertrichosis, hirsutism, and changes in hair texture and color. Nail changes can be nail discoloration which is a change in the color of the nail plate, nail loss, and nail ridging. Oral mucosa involvement in the form of oral mucositis, and oral candidiasis. Other miscellaneous changes are pruritus, hyperhidrosis, hypohidrosis, and erythroderma. These changes will then be graded according to the Common Terminology Criteria for Adverse Events v5. 0. into 5 grades from Grade 1 to Grade 5 and will be evaluated for adverse effects in frequency and percentage. Association with the demographic variables will be performed using chi-square and odd analysis.</p>
            </sec>
            <sec id="sec19">
                <title>Study status</title>
                <p>Ethical approval was obtained and recruitment of the study participants has not yet begun.</p>
            </sec>
        </sec>
    </body>
    <back>
        <sec id="sec22" sec-type="data-availability">
            <title>Data availability</title>
            <p>No data are associated with this article.</p>
        </sec>
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    <sub-article article-type="reviewer-report" id="report268034">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.160043.r268034</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Soltani</surname>
                        <given-names>Madjid</given-names>
                    </name>
                    <xref ref-type="aff" rid="r268034a1">1</xref>
                    <role>Referee</role>
                </contrib>
                <aff id="r268034a1">
                    <label>1</label>University of Waterloo, Waterloo, Ontario, Canada</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>14</day>
                <month>5</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Soltani M</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport268034" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.146012.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This article was carefully studied and examines the adverse mucocutaneous effects of chemotherapy and radiotherapy drugs. The author first introduces the different types of these complications, and then describes the mechanisms of their creation. This article also addresses the challenges involved in studying and treating these complications. The strengths of this article include providing a comprehensive overview of these complications, citing authoritative scientific sources, and providing useful information for medical professionals and patients. However, the paper could have been stronger by focusing more on specific complications, patient management and providing a clear summary at the end of the paper. The following are also presented as tips for improving the article:</p>
            <p> 1-&#x00a0;While the background is informative, it doesn't explicitly state how the study adds new knowledge. Consider emphasizing the specific gap you're addressing in the research on mucocutaneous side effects.</p>
            <p> 2-The objectives could be more specific. For example, instead of just "find out the frequency" of side effects, you could focus on comparing frequencies between chemotherapy and radiotherapy or across different patient demographics.</p>
            <p> 3-While you mention using chi-square and odds analysis, you could elaborate on how you'll be using these tests to analyze your data.</p>
            <p> 4-Provide more details on chemotherapy drugs and radiotherapy techniques included in this study.</p>
            <p> 5-It seems that by using more recent articles in this field, you can well describe the background of the research and the work that has been done in this field so far.</p>
            <p>Is the study design appropriate for the research question?</p>
            <p>Partly</p>
            <p>Is the rationale for, and objectives of, the study clearly described?</p>
            <p>Yes</p>
            <p>Are sufficient details of the methods provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Are the datasets clearly presented in a useable and accessible format?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Transport Phenomena in Tissues&#x00a0;Mathematical Cancer Modeling&#x00a0;Biomedical Engineering&#x00a0;Image Based Cancer Modeling&#x00a0;CFD</p>
            <p>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.</p>
        </body>
        <sub-article article-type="response" id="comment11559-268034">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Rusia</surname>
                            <given-names>Kaveri</given-names>
                        </name>
                        <aff>dermatology, datta meghe institute of higher education and research, wardha, maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>14</day>
                    <month>5</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Thank you for your valuable response. I will keep in mind the changes suggested by you.</p>
            </body>
        </sub-article>
        <sub-article article-type="response" id="comment13216-268034">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Rusia</surname>
                            <given-names>Kaveri</given-names>
                        </name>
                        <aff>dermatology, datta meghe institute of higher education and research, wardha, maharashtra, India</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>25</day>
                    <month>1</month>
                    <year>2025</year>
                </pub-date>
            </front-stub>
            <body>
                <p>Thank you for your valuable opinion.</p>
            </body>
        </sub-article>
    </sub-article>
</article>
