<?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="research-article" 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.162627.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Demographic, clinical, pathologic and treatment pattern of soft tissue sarcoma at Tikur Anbessa specialized hospital, Ethiopia - retrospective cross-sectional study</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>Mitiku</surname>
                        <given-names>Habtamu Dessie</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/">Software</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/0000-0002-6040-7780</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>Abeje</surname>
                        <given-names>Melesew</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/">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/0009-0007-0352-6074</uri>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Dandena</surname>
                        <given-names>Yonas</given-names>
                    </name>
                    <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; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Statistics, Injibara University, Injibara, Amhara, 40, Ethiopia</aff>
                <aff id="a2">
                    <label>2</label>Department of Clinical Oncology, Bahir Dar University College of Medical and Health Sciences, Bahir Dar, Amhara, 79, Ethiopia</aff>
                <aff id="a3">
                    <label>3</label>Department of Clinical Oncology, Addis Ababa University School of Medicine, Addis Ababa, Addis Ababa, Ethiopia</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:habtamudessie54@gmail.com">habtamudessie54@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>20</day>
                <month>3</month>
                <year>2025</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2025</year>
            </pub-date>
            <volume>14</volume>
            <elocation-id>313</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>8</day>
                    <month>3</month>
                    <year>2025</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 Mitiku HD et al.</copyright-statement>
                <copyright-year>2025</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/14-313/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>Soft-tissue sarcomas are an uncommon group of neoplasms that can be fatal, especially in metastatic settings. Thus, this study aimed to assess the demographic, pathological, clinical, and treatment patterns of soft tissue sarcoma at the Tikur Anbesa Specialized Hospital in Ethiopia.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>A retrospective cross-sectional study was conducted on patients with soft tissue sarcomas who visited the Tihur Anbesa Specialized Hospital, Ethiopia, between August 2017 and August 2021GC. A total of 190 samples were taken. Data from health management information system logbooks and medical records were collected, with only histopathology-confirmed cases included, while those with incomplete data were excluded. Analysis was performed using SPSS version 25, and ethical clearance was obtained from Addis Ababa University College of Health Sciences.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>A total of 320 patients were registered between August 2017 and August 2021; 190 patients were available for this study, and 130 were lost. The median age was 32 years of age and male sex was commonly affected, accounting 61.6%, and female sex accounted 38.4%. The common sites were extremities, accounting for 48.9% of cases. The Commonest presenting symptoms were mass and pain, accounting for 93.2% and 77.9% of cases, respectively. The common histological subtypes were undifferentiated sarcoma, rhabdomyosarcoma, and synovial sarcoma, accounting 50%, 15.8%, and 6.3% cases, respectively. The grade of the lesions was described in 67.3% of patients. Of the lesions whose grade was described, 56.8% were high grade lesions. In all cases, 58.3% of the patients underwent surgery as the primary treatment modality. Only 50.5% of cases were started treatment with curative intent, and 49.5% of the patients started their treatment with palliative treatment.</p>
                </sec>
                <sec>
                    <title>Conclusions</title>
                    <p>The pattern of soft tissue sarcomas showed a heterogeneous distribution in terms of demography, clinical presentation, treatment, and pathological subtypes. The advanced stage of initial clinical presentation and substandard work-up and therapy make it unique from cases reported in other parts of the world.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Soft tissue sarcoma</kwd>
                <kwd>pathological</kwd>
                <kwd>Clinical and treatment patterns</kwd>
                <kwd>Ethiopia</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>This work was supported by the Addis Ababa University of research and the community service, Ethiopia. It is not involved at any stage of the study.</funding-source>
                </award-group>
                <funding-statement>This work was supported by Addis Ababa University of Research and Community Service, Ethiopia. This was not involved in any stage of the study.</funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <def-list>
            <title>Abbreviations and Acronyms</title>
            <def-item>
                <term id="G1">FNAC</term>
                <def>
                    <p>fine needle aspiration</p>
                </def>
            </def-item>
            <def-item>
                <term id="G2">GC</term>
                <def>
                    <p>gregorean callender</p>
                </def>
            </def-item>
            <def-item>
                <term id="G3">IAEA</term>
                <def>
                    <p>International atomic energy Agency</p>
                </def>
            </def-item>
            <def-item>
                <term id="G4">IHC</term>
                <def>
                    <p>Immunohistochemistry</p>
                </def>
            </def-item>
            <def-item>
                <term id="G5">MD</term>
                <def>
                    <p>Medical Doctor</p>
                </def>
            </def-item>
            <def-item>
                <term id="G6">MDT</term>
                <def>
                    <p>Multidisciplinary Team</p>
                </def>
            </def-item>
            <def-item>
                <term id="G7">NCDB</term>
                <def>
                    <p>National cancer database</p>
                </def>
            </def-item>
            <def-item>
                <term id="G8">NF1</term>
                <def>
                    <p>Neurofibromatosis type 1</p>
                </def>
            </def-item>
            <def-item>
                <term id="G9">STS</term>
                <def>
                    <p>soft tissue sarcoma</p>
                </def>
            </def-item>
            <def-item>
                <term id="G10">TASH</term>
                <def>
                    <p>Tikur Anbessa Specialized Hospital</p>
                </def>
            </def-item>
            <def-item>
                <term id="G11">WHO</term>
                <def>
                    <p>World Health Organization</p>
                </def>
            </def-item>
        </def-list>
        <sec id="sec5" sec-type="intro">
            <title>Introduction</title>
            <p>Soft tissue sarcomas (STS) are a rare group of cancers, accounting for 1% of all solid tumors and 15% of all malignant tumors in children.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>,
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> The World Health Organization (WHO) has recognized approximately 70 histological subtypes.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> The global incidence of soft tissue and extraosseous sarcomas is estimates 96201 in 2021.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> The incidence of STS varies in different countries and regions, with 13,460 new cases and 5350 deaths reported in 2021,
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> 13,130 new cases in Europe,
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup> 2.91 per 100000 in china. Studies conducted in Nigeria have estimated rates of approximately 0.8 cases per 100,000 individuals for males and 0.5 cases per 100,000 individuals for females.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> Nonetheless, the lack of comprehensive cancer registries and diagnostic facilities in these countries hinders accurate assessment of the true prevalence and incidence rates of STS in the region.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>,
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup>
            </p>
            <p>Sub-Saharan Africa, particularly Ethiopia, faces several challenges in terms of healthcare infrastructure and resources for the diagnosis and management of soft tissue sarcoma. She designed and promised several national initiatives to avert the challenges of cancer prevention, diagnosis, and treatment. Since there is no documented evidence in Ethiopia, the prevalence and incidence of soft tissue sarcomas are unknown. As Evidence shows that due to the etiology is unknown and a certain genetic association on average, a general practitioner may only see one sarcoma in their career
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup> and 10% familial neurofibromatosis (linked to mutations in the NF1 gene),
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup> familial retinoblastoma (RB gene mutations),
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup> and Li-Fraumeni syndrome (TP53 gene mutations),
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>
                </sup> are associated with an increased risk. Additionally, previous radiation therapy can predispose patients to certain sarcomas such as angiosarcomas.</p>
            <p>Due to the heterogeneous sites of origin of STS, it is difficult to clearly define the clinical features of the disease (increasing size, a size greater than 5 cm, and pain). As the size increases, the risk of malignancy is more likely to be sarcomas.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> The standard approach for the diagnosis of a suspicious mass is percutaneous core needle biopsy. Several cores should be taken to maximize the diagnostic yield. However, incisional biopsy may be necessary on rare occasions, and excision biopsy may be the most practical option for small superficial lesions. To ascertain the grade and stage of the tumor, a histological diagnosis should be undertaken in accordance with the 2013 WHO Classification.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup>
            </p>
            <p>The diagnosis of pathology is based on immunohistochemistry and morphology. Molecular pathology, such as fluorescent in situ hybridization or reverse transcription polymerase chain reaction, should increasingly be used in conjunction with it to validate diagnoses that are characterized by a particular genetic abnormality, such as an activating mutation, chromosomal translocation, or chromosomal amplification.
                <sup>
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> It might be especially helpful in cases when the histology diagnosis is uncertain or the clinical pathologic presentation is unusual. Nowadays, molecular testing is common to distinguish lipomas from atypical lipomatous tumors or well-differentiated liposarcomas, as well as to confirm diagnoses like Ewing sarcoma, rhabdomyosarcoma, and synovial sarcoma</p>
            <p>Customizing treatment based on each patient&#x2019;s unique histology is becoming more and more feasible. Long-term survival, preventing local recurrence, optimizing function, and reducing morbidity are the main therapeutic objectives. Every patient should have their care overseen by a sarcoma multidisciplinary team (MDT) that has been formally established. The Sarcoma MDT should make decisions regarding surgery, chemotherapy, radiotherapy, and the order of each of these treatments. The sarcoma MDT and the site-specific MDT should have a formal link for site-specific STS (such as gynecoithlogical, head, and neck).
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>
                </sup>
            </p>
            <p>There is great variability in histological subtypes, anatomic sites, and clinical presentation, which makes it a heterogeneous entity and makes it difficult to have a specific histologic diagnosis. Owing to the lack of adequate diagnostics and therapy infrastructure in Ethiopia, early identification of soft tissue sarcoma is challenging. Consequently, most patients in Ethiopia present with advanced-stage disease. Therefore, this study aimed to assess the demographic, clinical, pathological, and treatment patterns of soft tissue sarcoma in Ethiopia.</p>
        </sec>
        <sec id="sec6" sec-type="methods">
            <title>Methods</title>
            <sec id="sec7">
                <title>Study area and setting</title>
                <p>This study was conducted at the Tikur Anbessa Specialized Hospital Radiotherapy Center. It was established 27 years ago with the help of the International Atomic Energy Agency (IAEA). Currently, the center has one LINAC unit. Six full-time consultant oncologists, three medical physicists, and five radiotherapists are currently working at the center. The center started training in clinical oncology in 2013, and currently, 36 residents are enrolled. Activities include inpatient admission for chemotherapy, outpatient clinics for new patient evaluation, and simulation for radiotherapy and contouring. There are two chemotherapy centers, one in the black lion and the newly opened center a few years ago, which is called the Amstegna Health Center.</p>
            </sec>
            <sec id="sec8">
                <title>Study design and period</title>
                <p>A hospital-based retrospective cross-sectional study was conducted on patients with soft tissue sarcoma who were seen from August 2017 to August 2021.</p>
            </sec>
            <sec id="sec9">
                <title>Target population</title>
                <p>All patients with soft tissue sarcoma who were registered at the oncology department of Tikur Anbessa Hospital between August 2017 and August 2021 G. C were included.</p>
            </sec>
            <sec id="sec10">
                <title>Study population</title>
                <p>All cases of histopathologically confirmed soft tissue sarcoma were seen in the Tikur Anbassa Specialized Hospital Radiotherapy Center, and their files were available during the study period.</p>
            </sec>
            <sec id="sec11">
                <title>Inclusion and exclusion criteria</title>
                <p>All patients with soft tissue sarcoma who had pathologically confirmed disease at presentation by biopsy or FNAC and visited within the specified study period were included. On the other hand, patients who lacked three or more of the following variables were excluded: histology type, treatment pattern, margin status, grade, age, and sex.</p>
            </sec>
            <sec id="sec12">
                <title>Sampling and sampling procedure</title>
                <p>Health Management Information System (HMIS) logbooks were used to identify all cases of soft tissue sarcoma that were documented after evaluation at the oncology department. All cases that fulfilled the inclusion criteria were included in this study. A total of 190 patients were considered in this study.</p>
            </sec>
            <sec id="sec13">
                <title>Study variables</title>
                <p>

                    <bold>Outcome variable</bold>
                </p>
                <p>Soft tissue sarcoma distribution.</p>
                <p>

                    <bold>Independent variables</bold>
                </p>
                <p>Demographic variables like (sex, age, religion, marital status, residence, and region), and Clinical and Pathologic variables like (histology, marigin status, treatment type) and treatment type and patterns were considered.</p>
            </sec>
            <sec id="sec14">
                <title>Data collection procedure and data quality</title>
                <p>Medical record charts were collected based on the HMIS records, and all cards that were not in accordance with the inclusion criteria were returned by the primary investigator/supervisor. The supervisor discussed the goal and purpose of the study as well as the questionnaire with the other data collectors. Before data collection, supervisors and data collectors were oriented on the purpose of the study and how to fill in the information on structured (formulated) questionnaires so that there was a common understanding of the objectives of each of the questions. This could minimize personal variation in interpretation. The data collection process was supervised by the principal investigator and the supervisor of the data collectors.</p>
            </sec>
            <sec id="sec15">
                <title>Operational definitions</title>
                <p>

                    <bold>Staging</bold> describes how much cancer is in the body and where it is located. In the 
                    <bold>TNM</bold> system, the overall stage is determined after the cancer is assigned a letter or number to describe the tumor (T), node (N), and metastasis (M) categories, according to the 8th edition AJCC.
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2713;</label>
                            <p>

                                <bold>T</bold> describes the original (primary) tumor size.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2713;</label>
                            <p>

                                <bold>N</bold> tells whether the cancer has spread to the nearby lymph nodes.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2713;</label>
                            <p>

                                <bold>M</bold> indicates whether the cancer has spread (metastasized) to distant regions of the body.</p>
                        </list-item>
                    </list>
                </p>
                <p>

                    <bold>Soft tissue sarcoma</bold> is a broad term for cancers that originate in soft tissues (muscle, tendons, fat, lymph and blood vessels, and nerves).</p>
            </sec>
            <sec id="sec16">
                <title>Data management and analysis</title>
                <p>Data were entered and analyzed using SPSS version 25, and visualization was performed using Power BI software 
                    <ext-link ext-link-type="uri" xlink:href="https://www.microsoft.com/en-us/power-platform/products/power-bi">https://www.microsoft.com/en-us/power-platform/products/power-bi
</ext-link>. The main findings are described using frequencies, percentages, and summary statistics.</p>
            </sec>
        </sec>
        <sec id="sec17" sec-type="results|discussions">
            <title>Results and Discussions</title>
            <sec id="sec18">
                <title>Results</title>
                <p>

                    <bold>Socio-demographic related variables of the study participants</bold>
                </p>
                <p>A total of 190 patients were included in this study. The median age of the participants was 32 years, and the age group 20-40years was the common age group accounting for 51.1%, of the participants. Similarly, 61.6% were Males, and 56.3% participants were married. About 57.4% of the participants were Orthodox by religion and 39.5% self-employed by occupation. Moreover, approximately 34.7% and 30% of the participants were coming from Oromia and Addis Ababa, respectively (
                    <xref ref-type="table" rid="T1">
Table 1</xref>).</p>
                <table-wrap id="T1" orientation="portrait" position="float">
                    <label>
Table 1. </label>
                    <caption>
                        <title>Socio-demographic related variables of the study participants.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">variables</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Classification</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">frequency</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Percentage</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="4" valign="middle">Age</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1-20years</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">31</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">16.5</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">20-40years</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">96</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">51.1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">40-60years</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">51</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">27.1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">60+years</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">12</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">5.3</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="2" valign="middle">Sex</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Male</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">117</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">61.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Female</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">73</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">38.4</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="5" valign="middle">Marital status</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Single</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">60</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">31.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Married</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">107</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">56.3</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Divorced</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">5</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">2.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Widow</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">2</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1.1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Unreported</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">16</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">8.5</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="3" valign="middle">Religion</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Orthodox</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">109</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">57.4</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Muslim</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">42</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">22.1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Protestant</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">37</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">19.5</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="4" valign="middle">Occupation</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Employed</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">21</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">11</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">self-employed
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">75</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">39.5</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Unemployed</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">31</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">16.3</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Not reported</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">63</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">33.2</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="7" valign="middle">Region</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Oromia</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">66</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">34.7</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Addis Ababa</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">57</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">30</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Amhara</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">35</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">18.4</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">SNNP</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">25</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">13.2</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Somalia</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">3</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Harari</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">3</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1.6</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">Tigray</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">1</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">0.01</td>
                            </tr>
                        </tbody>
                    </table>
                </table-wrap>
                <p>

                    <bold>Clinical presentation site, stage pattern, Histology subtypes and Surgical Margin status related characteristics of the study participants</bold>
                </p>
                <p>Approximately 48.9%, 24.7%, and 15.8% of the participant&#x2019;s clinical presentation sites were primary the extremities, trunk, and head and neck, respectively. Likewise, for histological diagnosis at oncology department, 96.8% came with biopsy results and 3.2% came with FNA results alone, and none of patients had IHC at time of initial presentation. The common histological type was undifferentiated sarcoma, accounting 50% followed rhabdomyosarcoma accounting 15.8% and the third most common histology was synovial sarcoma, accounting 6.3% of the cases. The common stage at presentation in this study was stage IV, accounting 36.3% of the cases, followed by stage III, and accounting 23.7% of the cases. In postoperative pathologic review, of 190 of patients, 30 %, 4.7%, 17.9%, and 46.8% were had negative, positive, unknown, and inapplicable for assessing marigin status, respectively (
                    <xref ref-type="fig" rid="f1">
Figure I</xref>). Mass and pain were the common presenting symptoms (77.9%), followed by painless masses 21.6%). Out Of 190 patients, 38(20%) presented with cough from lung metastasis (
                    <xref ref-type="fig" rid="f2">
Figure II</xref>).</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>
Figure I. </label>
                    <caption>
                        <title>Clinical presentation site, stage pattern, Histology subtypes and Surgical Margin status of study participants in percentage.</title>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/178860/2aac9333-5d22-4933-b66d-2fe3d3c3034c_figure1.gif"/>
                </fig>
                <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                    <label>
Figure II. </label>
                    <caption>
                        <title>Clinical presentation symptoms by percentage from primary disease in soft tissue sarcoma diagnosed in August 2017-August 2021.</title>
                    </caption>
                    <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/178860/2aac9333-5d22-4933-b66d-2fe3d3c3034c_figure2.gif"/>
                </fig>
                <p>Most of patients 53% of patients had underwent upfront surgery. Of these, 4.7% had received adjuvant chemotherapy. Only 3.2% received adjuvant radiotherapy, and for 17.9% of patients surgery alone was sufficed. Indeed, approximately 35.3% of patients were administered palliative chemotherapy and 1l.6% of patients were administered both palliative chemotherapy and palliative radiotherapy. When it comes to adjuvant treatment of the 101 patients who underwent surgery 15(14.9%) took adjuvant treatment. 6(5.9%) patients took adjuvant chemotherapy and radiotherapy. While 89(46.9%) took palliative chemotherapy from these patients 22(11.6%) received both palliative chemotherapy and palliative chemotherapy. Approximately 15.2% took radiation treatment for different indications. (75.9%) received palliative radiotherapy, and only 6(21%) received adjuvant radiation. Moreover, the results indicated that no patients underwent palliative surgery, surgery after neoadjuvant therapy, definitive radiotherapy, neoadjuvant radiotherapy, or neoadjuvant chemotherapy. With regard to dose, 6patients as adjuvant treatment, 4/6 received 60 GY radiotherapy, and 2/6 received 50 GY radiotherapy, while 22 palliative radiotherapy patients, 15/22 (68.2%) they took 20 GY in five fraction, 3/22 patients (13.6%), they took 30 GY in 10 fractions, and 4/22/patient dose was not known. Likewise, patients from chemotherapy 52/89 (52%) received AD regimen (adriamycine+dacarbazine), 20/89(22.5%) received AIM regimen (doxorubicin,ifosphamide, and mesna), the other 7 patients (7.8%) took doxorubicin alone, and 10 patients (11.2%) were not known (
                    <xref ref-type="table" rid="T2">
Table 2</xref>).</p>
                <table-wrap id="T2" orientation="portrait" position="float">
                    <label>
Table 2. </label>
                    <caption>
                        <title>Treatment patters among 190 soft tissue sarcoma diagnosed in August 2017-2021 at TASH, Ethiopia.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Treatment pattern</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Underwent upfront n(%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Underwent palliative n(%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Neoadjuvant n(%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Adjuvant n(%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Both adjuvant chemotherapy and radiotherapy after surgery n(%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">
Palliative chemo and palliative radio therapy</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Dose</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Surgery</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">101(53%)
                                    <xref ref-type="table-fn" rid="tfn1">*</xref>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">No</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">No</td>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">6(3.1%)</td>
                                <td colspan="1" rowspan="1"/>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Radiotherapy</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">29(15.2%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">22/29(75.9%)</td>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">6/29(20.69%)</td>
                                <td colspan="1" rowspan="1"/>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <p>

                                        <list list-type="bullet">
                                            <list-item>
                                                <label>-</label>
                                                <p>15/22(68.18%) took 20GY in 5 fraction,3/22(13.64%) took 30 GY in 10 fraction, and 4/22(18.18%) patients dose is not known</p>
                                            </list-item>
                                            <list-item>
                                                <label>-</label>
                                                <p>4/6(66.67%) took 60 GYradiotrapy and 2/6(33.33%) took 50 GY</p>
                                            </list-item>
                                        </list>
                                    </p>
</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Chemotherapy</td>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">89(46.9%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">No</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">15(7.89%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">6(3.1%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">22/89(24.7%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <p>

                                        <list list-type="bullet">
                                            <list-item>
                                                <label>-</label>
                                                <p>52/89(58%) took AD AD regimen (adriamycine+dacarbazine), 20/89(22.5%) took AIM regimen (doxorubicin,ifosphamide and mesna),7/89(7.89%) took doxorubicin alone,10/89(11.2%) regimen not known</p>
                                            </list-item>
                                            <list-item>
                                                <label>-</label>
                                                <p>10/15(66.67%) took AD regimen (doxorubin+dacarbazine, 3/15(20%)patients took AIM regimen (doxorubicin,ifosphamide and mesna), and 2/15(13.33%) regimen not known</p>
                                            </list-item>
                                        </list>
                                    </p>
</td>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <fn-group content-type="footnotes">
                            <fn id="tfn1">
                                <label>*</label>
                                <p>Represents all the surgery 101/190(53%) were radical surgery.</p>
                            </fn>
                        </fn-group>
                    </table-wrap-foot>
                </table-wrap>
            </sec>
        </sec>
        <sec id="sec19" sec-type="discussions">
            <title>Discussions</title>
            <p>The sex ratio in this study was 1.6:1, the most common age of presentation in this study was 20-40 years of age and the median age was 32 years between men and women, which is almost similar to the study conducted by.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup> The male-to-female ratio in benign tumors was 1.2:1, and among malignant tumors, the ratio was 2:1, which is also similar to that reported previously.
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> The most common age at presentation in this study was 20-40 years of age and the median age was 32 years. This result is similar to that of a previous study conducted at Jimma University.
                <sup>
                    <xref ref-type="bibr" rid="ref16">16</xref>
                </sup> In contrast, the results of this study differ from those of a study conducted in Korea, in which the most common age group was 50&#x2013;60 years.
                <sup>
                    <xref ref-type="bibr" rid="ref17">17</xref>
                </sup> This difference may be due to the longer life expectancy in developed countries.</p>
            <p>Mass and pain were the common presenting symptoms (77.9%), followed by painless masses 21.6%). Out Of 190 patients, 38(20%) presented with cough from lung metastasis. This study also had a similar outcome to that of a retrospective study on the clinical presentation of soft tissue sarcoma.
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> Similarly, the extremity was the common site (48.9%), followed by trunk (24.7%) and head and neck (15.8%), which is almost similar to the reviews done by.
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>,
                    <xref ref-type="bibr" rid="ref19">19</xref>
                </sup>
            </p>
            <p>With regard to the types of histology, the common histological type was undifferentiated pleomorphic sarcoma (50%), followed by rhabdomyosarcoma (15.8%), and the third most common histological subtype was synovial sarcoma (6.3%) in this study. The results of this study show that our histology reporting system is not adequate to specify the type of histology and is not sufficient for comparison with other studies.</p>
            <p>The common stage at presentation in this study was stage IV accounting (36.3%) of the cases followed by stage III accounting (23.7%) of the cases. Even if the type of histology was predominantly rhabdomyosarcoma, the current study consistent with.
                <sup>
                    <xref ref-type="bibr" rid="ref20">20</xref>
                </sup> In contrast to our study, a retrospective review of an orthopedic oncology database identified 1170 patients with newly diagnosed STS, the incidence of metastases at diagnosis was 10% (116 patients); 8.3% (96 patients) had lung metastases on chest CT, and 1.7% (20 patients) had metastases elsewhere.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> This difference may be due to the late presentation of our setup in Ethiopia.</p>
            <p>this study, 35.3%, 11.6% of the total cases were treated with palliative chemotherapy and both palliative chemotherapy and radiotherapy, respectively about 48.5% of patients had undergone surgery. Of these, 27.7% of patients had undergone surgery and booked for radiotherapy and 17.9% had undergone surgery alone. The remaining 3.2% of the cases were administered adjuvant radiotherapy. The study has also has less surgical treatment pattern compared with other studies, in which approximately 69% of the cases were treated with surgery. And also In this study, only 3.2% of the patients were administered adjuvant radiation, in contrast to study in which 39.5% of the patients were administered adjuvant radiation after surgery.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>,
                    <xref ref-type="bibr" rid="ref21">21</xref>
                </sup> This difference may be due to the inadequate availability of radiotherapy in our country and late presentation of our cases.</p>
            <p>The Marigin status was performed for patients undergoing surgery in which it was negative in 57% of patients, it was positive 9% of the cases, and 34% of the cases the marigin status of unknown and it contradict with.
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>,
                    <xref ref-type="bibr" rid="ref15">15</xref>,
                    <xref ref-type="bibr" rid="ref21">21</xref>
                </sup> The difference may be that many of our patients&#x2019; marigin statuses were not reported. This may be due to the lack of multidisciplinary discussion.</p>
        </sec>
        <sec id="sec20" sec-type="conclusions">
            <title>Conclusions</title>
            <p>The pattern of soft tissue sarcomas in this cross-sectional study showed a heterogeneous distribution in terms of demography, clinical presentation, treatment, and pathological subtypes. Early detection of these potentially fatal soft tissue sarcoma cases allows oncology practitioners to make better clinical decisions for the best clients. Therefore, this study helps to avert the challenges of this rare cancer by reporting the type of histology and advancing strategies for earlier detection of soft tissue sarcoma.</p>
            <sec id="sec21">
                <title>Strength and weakness of this study</title>
                <p>The strength of this study includes all age groups and both sexes, but pediatric age group, histology subtype diagnosed and the treatment pattern and follow up was not well documented on the chart were a weakness of this study.</p>
            </sec>
        </sec>
        <sec id="sec22">
            <title>Declarations</title>
            <sec id="sec23">
                <title>Ethics approval and consent to participate</title>
                <p>All methods were performed in accordance with relevant guidelines and regulations and ethical approval was obtained from the Institutional Review Board of Addis Ababa University College of Medicine and Health Sciences (Ref-AAU/5986/11/RCS/2021) and date 03/11/2021. Both informed and written consent from the patients was not required because it used secondary data and it waived by the ethical review approval committee, and during data collection, no personal identifiers were used for Confidentiality.</p>
            </sec>
        </sec>
        <sec id="sec24">
            <title>Consent for publication</title>
            <p>Not applicable.</p>
        </sec>
        <sec id="sec25">
            <title>Authors&#x2019; contributions</title>
            <p>HD &amp; MA: conceptualization, Data Curation; Formal Analysis; Methodology; Writing &#x2013; Original Draft Preparation; HD: Software, Visualization, HD, MA &amp; YD: Writing &#x2013; Review and Editing and YD: Validation and supervision.</p>
        </sec>
    </body>
    <back>
        <sec id="sec28" sec-type="data-availability">
            <title>Data availability statement</title>
            <p>The data supporting the findings of this study are not publicly available due to confidentiality agreements and institutional policies. In compliance with these regulations, the dataset will not be shared with third parties. However, with reasonable request and reviewed it will be avail from the author 
                <email xlink:href="mailto:habtamudessie54@gmail.com">habtamudessie54@gmail.com</email>.</p>
        </sec>
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    <sub-article article-type="reviewer-report" id="report374113">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.178860.r374113</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>J&#x00e4;&#x00e4;maa</surname>
                        <given-names>Sari</given-names>
                    </name>
                    <xref ref-type="aff" rid="r374113a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0009-0005-7922-9127</uri>
                </contrib>
                <aff id="r374113a1">
                    <label>1</label>Finland and University of Helsinki, Helsinki, Finland</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>10</day>
                <month>4</month>
                <year>2025</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2025 J&#x00e4;&#x00e4;maa S</copyright-statement>
                <copyright-year>2025</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="relatedArticleReport374113" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.162627.1"/>
            <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>In their article "
                <bold>Demographic, clinical, pathologic and treatment pattern of soft tissue sarcoma at Tikur Anbessa specialized hospital, Ethiopia - retrospective cross-sectional study</bold>" Mitiku et al describe clinically relevant data of 190 soft tissue sarcoma (STS) patients treated in one institution from 2017 to 2021.</p>
            <p> </p>
            <p> They show that a majority of patients (66%) are under 40 years old and male (61,6%). In developed countries, the STS patients are usually older and there is no such clear male predominance. Most patients have been diagnosed due to a growing mass or pain, and a minority due to cough or bleeding.</p>
            <p> </p>
            <p> In their study, they show that most STS affect lower extremity (34%) or trunk (24%) or head and neck region (15%), but the incidence of retroperitoneal or visceral sarcomas is considerably lower than in developed countries. In their study, the authors do not describe which imaging modalities (ie CT-scans, MRI-scans, ultrasound or x-ray-imaging) they have available in their institute, a factor which may have affected the relative low numbers of retroperitoneal and visceral sarcomas. I believe information on the imaging modalities would strengthen the paper.</p>
            <p> </p>
            <p> Also the distribution of histological subtypes in Ethiopia differs somewhat from what we see in western contries. There seems to be more UPS and RMS and less leiomyosarcomas and liposarcomas diagnosed in Etiophia, an interesting fact. In discussion the authors speculate that this may be due to inadequate histology reporting system.</p>
            <p> </p>
            <p> I had some problem understanding the Figure 1 panel of surgical margin status. It seems data on the grade of the tumors (high grade, low grade, unspecified? intermediate grade) as well as surgical margins (negative, positive, unknown and inapplicable) have been added on the same panel. I suggest separating them to 2 different panels.</p>
            <p> </p>
            <p> The treatment data have been summarized in Table 2 of the article. A curative surgery was attempted in 53% of the patients and most of these patients did not receive adjuvant radiotherapy (94%) or chemotherapy (85%).</p>
            <p> </p>
            <p> It would be helpful to divide Table 2. to those patients which were curatively treated and to those who underwent palliative treatment.</p>
            <p> </p>
            <p> Also, I suggest that the authors discuss how well the international STS treatment guidelines such as NCCN or ESMO guidelines can be followed currently in Ethiopia.</p>
            <p> </p>
            <p> As the authors stated, not many studies have been published of STS treatment in Sub-Saharan Africa, and therefore I find the article suitable for acceptance.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Partly</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Yes</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Partly</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Partly</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Clinical oncology, soft tissue sarcomas, medical oncology</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>
