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    <title language="eng">Long‐term results from the multicentric European randomized phase 3 trial CWS/RMS‐96 for localized high‐risk soft tissue sarcoma in children, adolescents, and young adults</title>
    <abstract language="eng">Background: CWS/RMS‐96 was an international multicenter trial with randomization between two therapy arms of the standard four‐drug therapy (vincristine, ifosfamide, adriamycin, dactinomycin [VAIA]) versus an intensified six‐drug regimen (carboplatin, epirubicin, vincristine, dactinomycin, ifosfamide, and etoposide [CEVAIE]) for high‐risk rhabdomyosarcoma (RMS), extraskeletal Ewing sarcoma (EES), and undifferentiated sarcoma (UDS) in children, adolescents, and young adults aiming to improve their survival. Intensified chemotherapy with CEVAIE did not improve outcome.&#13;
&#13;
Methods: Patients younger than 21 years with a previously untreated localized HR‐RMS, EES, and UDS were enrolled from Cooperative Weichteilsarkom Studiengruppe (CWS) centers in Germany, Austria, Poland, Switzerland, and from Italian Soft Tissue Sarcoma Committee (STSC) centers. Randomization (1:1) to receive either 9 × 21 days cycles of VAIA or CEVAIE was performed separately in CWS and STSC. Hyperfractionated accelerated radiotherapy (32–44.8 Gy) was added at week 9–12 according to histology and response to chemotherapy. A secondary microscopically complete nonmutilating resection was performed if possible. Primary endpoints were response to chemotherapy, event‐free (EFS) and overall survival (OS).&#13;
&#13;
Results: Five hundred fifty‐seven patients (HR‐RMS:n = 416, EES and UDS:n = 141) underwent randomization: VAIA (n = 273) or CEVAIE (n = 284). Radiotherapy was given to 70% of patients in both groups. A secondary resection was performed in 47% and 48% patients, respectively. The 5‐year EFS and OS for the VAIA and CEVAIE treatment arms were 59.8% and 60.8% (p = .89), and 74.2% and 68.3% (p = .16), respectively. No differences in response, toxicity, or second malignancies emerged in the two groups.&#13;
&#13;
Conclusion: The use of an intensified regimen failed to show a significant improvement in tumor response and outcome of patients with localized HR‐RMS, EES, and UDS.</abstract>
    <parentTitle language="eng">Pediatric blood and cancer</parentTitle>
    <identifier type="doi">10.1002/pbc.29691</identifier>
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Intensified chemotherapy with CEVAIE did not improve outcome.&lt;\/jats:p&gt;&lt;jats:p&gt;&lt;jats:bold&gt;Methods&lt;\/jats:bold&gt;: Patients younger than 21\u00a0years with a previously untreated localized HR\u2010RMS, EES, and UDS were enrolled from Cooperative Weichteilsarkom Studiengruppe (CWS) centers in Germany, Austria, Poland, Switzerland, and from Italian Soft Tissue Sarcoma Committee (STSC) centers. Randomization (1:1) to receive either 9 \u00d7 21\u00a0days cycles of VAIA or CEVAIE was performed separately in CWS and STSC. Hyperfractionated accelerated radiotherapy (32\u201344.8\u00a0Gy) was added at week 9\u201312 according to histology and response to chemotherapy. A secondary microscopically complete nonmutilating resection was performed if possible. Primary endpoints were response to chemotherapy, event\u2010free (EFS) and overall survival (OS).&lt;\/jats:p&gt;&lt;jats:p&gt;&lt;jats:bold&gt;Results&lt;\/jats:bold&gt;: Five hundred fifty\u2010seven patients (HR\u2010RMS:&lt;jats:italic&gt;n&lt;\/jats:italic&gt;\u00a0=\u00a0416, EES and UDS:&lt;jats:italic&gt;n&lt;\/jats:italic&gt;\u00a0=\u00a0141) underwent randomization: VAIA (&lt;jats:italic&gt;n&lt;\/jats:italic&gt;\u00a0=\u00a0273) or CEVAIE (&lt;jats:italic&gt;n&lt;\/jats:italic&gt;\u00a0=\u00a0284). Radiotherapy was given to 70% of patients in both groups. A secondary resection was performed in 47% and 48% patients, respectively. The 5\u2010year EFS and OS for the VAIA and CEVAIE treatment arms were 59.8% and 60.8% (&lt;jats:italic&gt;p&lt;\/jats:italic&gt;\u00a0=\u00a0.89), and 74.2% and 68.3% (&lt;jats:italic&gt;p&lt;\/jats:italic&gt;\u00a0=\u00a0.16), respectively. 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    <author>Monika Sparber‐Sauer</author>
    <author>Andrea Ferrari</author>
    <author>Daniel Kosztyla</author>
    <author>Ruth Ladenstein</author>
    <author>Giovanni Cecchetto</author>
    <author>Bernarda Kazanowska</author>
    <author>Giovanni Scarzello</author>
    <author>Gustaf Ljungman</author>
    <author>Giuseppe Maria Milano</author>
    <author>Felix Niggli</author>
    <author>Rita Alaggio</author>
    <author>Christian Vokuhl</author>
    <author>Michela Casanova</author>
    <author>Thomas Klingebiel</author>
    <author>Angelica Zin</author>
    <author>Ewa Koscielniak</author>
    <author>Gianni Bisogno</author>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>CEVAIE</value>
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    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>CWS-96</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>High-risk soft tissue sarcoma</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>Randomization</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>Rhabdomyosarcoma</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>RMS-96</value>
    </subject>
    <subject>
      <language>eng</language>
      <type>uncontrolled</type>
      <value>VAIA</value>
    </subject>
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    <collection role="institutes" number="">VP Vizepräsident</collection>
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