<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//TaxonX//DTD Taxonomic Treatment Publishing DTD v0 20100105//EN" "../../nlm/tax-treatment-NS0.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:tp="http://www.plazi.org/taxpub" article-type="research-article" dtd-version="3.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">87</journal-id>
      <journal-id journal-id-type="index">urn:lsid:arphahub.com:pub:A116C711-4C18-5A38-8F1E-5E97753A8A64</journal-id>
      <journal-title-group>
        <journal-title xml:lang="en">Folia Medica</journal-title>
        <abbrev-journal-title xml:lang="en">FM</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0204-8043</issn>
      <issn pub-type="epub">1314-2143</issn>
      <publisher>
        <publisher-name>Plovdiv Medical University</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.3897/folmed.66.e122593</article-id>
      <article-id pub-id-type="publisher-id">122593</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Case Report</subject>
        </subj-group>
        <subj-group subj-group-type="scientific_subject">
          <subject>Oncology</subject>
          <subject>Pediatrics &amp; Genetic diseases</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A nine-year-old child with nasopharyngeal cancer treated with concomitant chemoradiotherapy with cisplatin – a case report</article-title>
      </title-group>
      <contrib-group content-type="authors">
        <contrib contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Popov</surname>
            <given-names>Veselin</given-names>
          </name>
          <email xlink:type="simple">dr.v_popov@yahoo.com</email>
          <uri content-type="orcid">https://orcid.org/0000-0002-6423-9665</uri>
          <xref ref-type="aff" rid="A1">1</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Suleyman</surname>
            <given-names>Gulhan</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Spasov</surname>
            <given-names>Neofit</given-names>
          </name>
          <uri content-type="orcid">https://orcid.org/0000-0003-4807-2989</uri>
          <xref ref-type="aff" rid="A1">1</xref>
          <xref ref-type="aff" rid="A2">2</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Pavlov</surname>
            <given-names>Stefan</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
        <contrib contrib-type="author" corresp="no">
          <name name-style="western">
            <surname>Raycheva</surname>
            <given-names>Gabriela</given-names>
          </name>
          <xref ref-type="aff" rid="A1">1</xref>
        </contrib>
      </contrib-group>
      <aff id="A1">
        <label>1</label>
        <addr-line content-type="verbatim">Department of Clinical Oncology, Faculty of Medicine, Medical University of Plovdiv, Plovdiv, Bulgaria</addr-line>
        <institution>Medical University of Plovdiv</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A2">
        <label>2</label>
        <addr-line content-type="verbatim">Clinic of Radiation Oncology, St George University Hospital, Plovdiv, Bulgaria</addr-line>
        <institution>St George University Hospital</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A3">
        <label>3</label>
        <addr-line content-type="verbatim">Department of Pediatrics and Medical Genetics, Medical University of Plovdiv, Plovdiv, Bulgaria</addr-line>
        <institution>Medical University of Plovdiv</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <aff id="A4">
        <label>4</label>
        <addr-line content-type="verbatim">St George University Hospital, Plovdiv, Bulgaria</addr-line>
        <institution>St George University Hospital</institution>
        <addr-line content-type="city">Plovdiv</addr-line>
        <country>Bulgaria</country>
      </aff>
      <author-notes>
        <fn fn-type="corresp">
          <p>Corresponding author: Veselin Popov, Department of Clinical Oncology, Faculty of Medicine, Medical University of Plovdiv, 15A Vassil Aprilov Blvd., 4002 Plovdiv, Bulgaria; Email: <email xlink:type="simple">dr.v_popov@yahoo.com</email></p>
        </fn>
      </author-notes>
      <pub-date pub-type="collection">
        <year>2024</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>30</day>
        <month>06</month>
        <year>2024</year>
      </pub-date>
      <volume>66</volume>
      <issue>3</issue>
      <fpage>421</fpage>
      <lpage>425</lpage>
      <uri content-type="arpha" xlink:href="http://openbiodiv.net/F44D19AF-275F-501B-A66D-E9B019390EB3">F44D19AF-275F-501B-A66D-E9B019390EB3</uri>
      <history>
        <date date-type="received">
          <day>14</day>
          <month>03</month>
          <year>2024</year>
        </date>
        <date date-type="accepted">
          <day>17</day>
          <month>04</month>
          <year>2024</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>Veselin Popov, Gulhan Suleyman, Neofit Spasov, Stefan Pavlov, Gabriela Raycheva</copyright-statement>
        <license license-type="creative-commons-attribution" xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <abstract>
        <label>Abstract</label>
        <p>In recent years, the role of radiation oncology in treating various pediatric cancers has been extensively researched and developed. The dosage of radiotherapy, when combined with chemotherapy, was either reduced in some oncological diseases or modified in other cancers. Despite these changes, due to swift advancements in radiation oncology technology, this combination therapy continues to enhance both overall and progression-free survival rates, maintaining its vital status as a therapeutic approach in precision medicine.</p>
        <p>We report here a nine-year-old patient with nasopharyngeal carcinoma treated according to SIOPE guidelines, which included induction neoadjuvant chemotherapy followed by concurrent chemoradiotherapy with cisplatin. Post-therapy imaging assessments revealed a persistent tumor mass with reduced dimensions on MRI one month after treatment, characterized by absence of contrast enhancement, water diffusion restriction, or lymphadenopathy. Subsequent CT imaging at three months post-radiotherapy showed no signs of disease progression. Repeat MRI scans at four and six months post-treatment demonstrated stable disease without evidence of water diffusion restriction, indicating a positive response to therapy. These results underscore the effectiveness of the multimodal approach in achieving favorable tumor control and therapeutic efficacy in pediatric nasopharyngeal carcinoma.</p>
      </abstract>
      <kwd-group>
        <label>Keywords</label>
        <kwd>chemoradiotherapy</kwd>
        <kwd>cisplatin</kwd>
        <kwd>epipharynx cancer</kwd>
        <kwd>pediatric cancer</kwd>
      </kwd-group>
    </article-meta>
    <notes>
      <sec sec-type="Citation" id="SECID0EXE">
        <title>Citation</title>
        <p>Popov V, Suleyman G, Spasov N, Pavlov S, Raycheva G. A nine-year-old child with nasopharyngeal cancer treated with concomitant chemoradiotherapy with cisplatin – a case report. Folia Med (Plovdiv) 2024;66(3):421-425. doi: <ext-link xlink:type="simple" ext-link-type="doi" xlink:href="10.3897/folmed.66.e122593">10.3897/folmed.66.e122593</ext-link>.</p>
      </sec>
    </notes>
  </front>
  <body>
    <sec sec-type="Introduction" id="SECID0EDF">
      <title>Introduction</title>
      <p>Nasopharyngeal cancer (NPC) is an extremely rare malignancy in children, constituting only 1%–5% of all childhood cancers and accounting for 20%–50% of all primary malignant nasopharyngeal tumors in this age group, according to various worldwide statistics.<sup>[<xref ref-type="bibr" rid="B1 B2 B3">1–3</xref>]</sup> Despite its rarity, NPC poses significant challenges in diagnosis and management due to its association with a multitude of etiological factors. These factors include infectious mononucleosis, Epstein-Barr virus infection, consumption of foods rich in nitrosamines, and various genetic and epigenetic influences that remain poorly understood.<sup>[<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>]</sup> Notably, NPC is particularly uncommon in children under the age of ten, further complicating a timely diagnosis. Consequently, many patients experience delayed diagnosis, leading to local-regional spread of the disease.<sup>[<xref ref-type="bibr" rid="B6">6</xref>]</sup> Complications may arise as the cancer progresses, such as infiltration into the base of the skull potentially resulting in cranial nerve palsy.</p>
      <p>Additionally, facial muscle paralysis or difficulty in jaw movement may manifest, underscoring the severity of NPC in pediatric patients. Understanding the unique characteristics and challenges associated with pediatric NPC is crucial for early detection and effective management strategies. The use of optimal modern radiotherapy techniques helps to achieve a much higher dose of rain tumors and preserve the function and structure of normal organs and tissues adjacent to the tumor. This is of utmost importance to achieve long-term local tumor control, especially in children, where the surrounding healthy tissue must be maximally protected to avoid long-term radiation side effects.</p>
    </sec>
    <sec sec-type="Case report" id="SECID0EHG">
      <title>Case report</title>
      <p><italic>A nine-year-old patient started treatment based on SIOPE nasopharyngeal carcinoma in children and adolescents (final version V.9) with induction neoadjuvant chemotherapy regimens in the pediatric oncology department. The regimens included 5-fluoracil at a dose of 1000 mg/5 days, and on the first day of this regimen 100 mg of cisplatin IV. After this induction therapy, we started radiotherapy with a concomitant weekly infusion of 34.5 mg of cisplatin. Volume-modulated arc therapy (VMAT) technique was used on Elekta Infinity LINAC. The plan included one whole arc, which started from 180 to 360 degrees of turning</italic><bold><italic>(Fig. <xref ref-type="fig" rid="F1">1</xref>)</italic></bold> . <italic>The daily fraction was 1.8 Gy per day, or 725.2 monitor units (MU), and a total dose of 48.6 Gy to the nasopharynx plus bilateral cervical lymph nodes, plus an integrated simultaneous boost of 2.2 Gy to a total of 59.4 Gy in a nasopharyngeal tumor. The dose in critical organs is within tolerance and meets international protocols</italic><bold><italic>(Fig. <xref ref-type="fig" rid="F2">2</xref>)</italic></bold> . <italic>No early or late radiation side effects were observed. Every day, the position of the patient was checked with a cone beam computer tomograph. When radiotherapy was complete, the patient continued treatment with interferon beta-1a.</italic></p>
      <fig id="F1" position="float" orientation="portrait">
        <object-id content-type="arpha">283F443D-8D98-5CF9-A1A2-2BD9B67B015A</object-id>
        <label>Figure 1.</label>
        <caption>
          <p>Radiotherapy treatment plan with VMAT technique in axial, sagittal and coronal planes.</p>
        </caption>
        <graphic xlink:href="foliamedica-66-3-e122593-g001.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1083702.jpg">
          <uri content-type="original_file">https://binary.pensoft.net/fig/1083702</uri>
        </graphic>
      </fig>
      <fig id="F2" position="float" orientation="portrait">
        <object-id content-type="arpha">54A0E1B8-7908-571B-93A8-E05FE7821A14</object-id>
        <label>Figure 2.</label>
        <caption>
          <p>Dose volume distribution in target volumes and critical organs.</p>
        </caption>
        <graphic xlink:href="foliamedica-66-3-e122593-g002.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1083703.jpg">
          <uri content-type="original_file">https://binary.pensoft.net/fig/1083703</uri>
        </graphic>
      </fig>
    </sec>
    <sec sec-type="Results" id="SECID0ECH">
      <title>Results</title>
      <p>Following the completion of therapy, comprehensive imaging assessments were conducted to evaluate the treatment response. One-month post-therapy MRI imaging revealed a persistent tumor mass with reduced dimensions (27/15 mm), notable for the absence of contrast enhancement, water diffusion restriction, or lymphadenopathy. Subsequent imaging with CT of the head, neck, and thorax performed three months post-radiotherapy did not indicate any signs of disease progression. Notably, at the fourth and sixth months following concomitant chemoradiotherapy, repeat MRI scans demonstrated stable disease without evidence of water diffusion restriction, indicating a positive response to treatment <bold>(Fig. <xref ref-type="fig" rid="F3">3</xref>)</bold>. These results suggest favorable tumor control and therapeutic efficacy, highlighting the effectiveness of the multimodal approach in managing pediatric NPC. Continued surveillance and monitoring are essential to assess long-term treatment outcomes and ensure disease stability in this challenging patient population.</p>
      <fig id="F3" position="float" orientation="portrait">
        <object-id content-type="arpha">461C7432-71B6-5D9C-AF41-0E615FA887BC</object-id>
        <label>Figure 3.</label>
        <caption>
          <p>MRI results at 1 (<bold>А</bold>), 4 (<bold>B</bold>), and 6 (<bold>C</bold>) months after treatment.</p>
        </caption>
        <graphic xlink:href="foliamedica-66-3-e122593-g003.jpg" position="float" orientation="portrait" xlink:type="simple" id="oo_1083704.jpg">
          <uri content-type="original_file">https://binary.pensoft.net/fig/1083704</uri>
        </graphic>
      </fig>
    </sec>
    <sec sec-type="Conclusion" id="SECID0EPH">
      <title>Conclusion</title>
      <p>In the pediatric age group, NPC is an exceedingly rare clinical entity, often presenting with advanced loco-regional disease if diagnosed at a late stage.<sup>[<xref ref-type="bibr" rid="B7">7</xref>]</sup> Multimodal treatment approaches are typically employed, with radiotherapy combined with weekly platinum-based chemotherapy serving as a cornerstone.<sup>[<xref ref-type="bibr" rid="B8 B9 B10 B11">8–11</xref>]</sup> Concomitant chemoradiotherapy has shown promise in managing NPC, particularly when employing advanced techniques such as VMAT to precisely target tumor sites while sparing healthy tissues and organs at risk. However, the administration of high doses of radiation poses a significant risk of toxicity, especially in pediatric patients, necessitating careful dose modulation. Strategies such as reducing radiation doses to the nasopharynx through neo-adjuvant or concomitant chemotherapy have been explored to mitigate late toxicity while maintaining effective local tumor control. This comprehensive approach underscores the importance of tailored treatment regimens in pediatric NPC to optimize outcomes while minimizing treatment-related morbidity. Continued research and clinical advancements are imperative to further refine therapeutic strategies and improve the long-term prognosis for children with NPC.</p>
    </sec>
    <sec sec-type="Acknowledgements" id="SECID0EEAAC">
      <title>Acknowledgements</title>
      <p>The authors have no support to report.</p>
    </sec>
    <sec sec-type="Funding" id="SECID0EJAAC">
      <title>Funding</title>
      <p>The authors have no funding to report.</p>
    </sec>
    <sec sec-type="Competing Interests" id="SECID0EOAAC">
      <title>Competing Interests</title>
      <p>The authors have declared that no competing interests exist.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>References</title>
      <ref id="B1">
        <mixed-citation xlink:type="simple">1. Ayan I, Kaytan E, Ayan N. Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol 2003; 4:13–21.</mixed-citation>
      </ref>
      <ref id="B2">
        <mixed-citation xlink:type="simple">2. Deutsch M, Mercado Jr R, Parsons JA. Cancer of the nasopharynx in children. Orphanet J Rare D 2006; 1:23.</mixed-citation>
      </ref>
      <ref id="B3">
        <mixed-citation xlink:type="simple">3. Ingersoll L, Woo SY, Donaldson S, et al. Nasopharyngeal carcinoma in the young: a combined M.D. Anderson and Stanford experience. Int J Radiat Oncol Biol Phys 1990; 19:881–7.</mixed-citation>
      </ref>
      <ref id="B4">
        <mixed-citation xlink:type="simple">4. Vokes EE, Liebowitz DN, Weichselbaum RR. Nasopharyngeal carcinoma. Lancet 1997; 350:1087–91.</mixed-citation>
      </ref>
      <ref id="B5">
        <mixed-citation xlink:type="simple">5. Wolf H, Hausen H, Becker V. EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nat New Biol 1973; 244:245–7.</mixed-citation>
      </ref>
      <ref id="B6">
        <mixed-citation xlink:type="simple">6. Cvitkovic E, Bachouchi M, Armand JP. Nasopharyngeal carcinoma. Biology, natural history, and therapeutic implications. Hematol Oncol Clin North Am 1991; 5:821–38.</mixed-citation>
      </ref>
      <ref id="B7">
        <mixed-citation xlink:type="simple">7. Ayan I, Altun M. Nasopharyngeal carcinoma in children: retrospective review of 50 patients. Int J Radiat Oncol Biol Phys 1996; 35:485–92.</mixed-citation>
      </ref>
      <ref id="B8">
        <mixed-citation xlink:type="simple">8. Guo Q, Cui X, Lin S, et al. Locoregionally advanced nasopharyngeal carcinoma in childhood and adolescence: Analysis of 95 patients treated with combined chemotherapy and intensity‐modulated radiotherapy. Head Neck 2015; 38(S1):E665–72.</mixed-citation>
      </ref>
      <ref id="B9">
        <mixed-citation xlink:type="simple">9. Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998; 16:1310–7.</mixed-citation>
      </ref>
      <ref id="B10">
        <mixed-citation xlink:type="simple">10. Mertens R, Granzen B, Lassay L, et al. Nasopharyngeal carcinoma in childhood and adolescence: concept and preliminary results of the cooperative GPOH study NPC-91. Gesellschaft für Pädiatrische Onkologie und Hämatologie. Cancer 1997; 80(5):951–9.</mixed-citation>
      </ref>
      <ref id="B11">
        <mixed-citation xlink:type="simple">11. Kong L, Zhang YW, Hu CS, et al. Neoadjuvant chemotherapy followed by concurrent chemoradiation for locally advanced nasopharyngeal carcinoma. Chin J Cancer 2010; 29(5):551–5. doi: <ext-link xlink:type="simple" ext-link-type="doi" xlink:href="10.5732/cjc.009.10518">10.5732/cjc.009.10518</ext-link></mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>
