{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:25:03Z","timestamp":1792013103743,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T00:00:00Z","timestamp":1385337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Neurofibromatosis Clinical Trials Award for FY2007","award":["W81XWH-05-1-0615"],"award-info":[{"award-number":["W81XWH-05-1-0615"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with Neurofibromatosis Type 1 (NF1) have an increased risk of developing tumors of the central and peripheral nervous system, including plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. There are no standard treatment options for PN other than surgery, which is often difficult due to the extensive growth and invasion of surrounding tissues. Mammalian Target of Rapamcyin (mTOR) acts as a master switch of cellular catabolism and anabolism and controls protein translation, angiogenesis, cell motility, and proliferation. The NF1 tumor suppressor, neurofibromin, regulates the mTOR pathway activity. Sirolimus is a macrolide antibiotic that inhibits mTOR activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>We conducted a 2\u2010stratum phase II clinical trial. In stratum 2, we sought to determine whether the mTOR inhibitor sirolimus in subjects with NF1 results in objective radiographic responses in inoperable PNs in the absence of documented radiographic progression at trial entry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No subjects had better than stable disease by the end of six courses. However, the children's self\u2010report responses on health\u2010related quality of life questionnaires indicated a significant improvement in the mean scores of the Emotional and School domains from baseline to 6 months of sirolimus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study efficiently documented that sirolimus does not cause shrinkage of non\u2010progressive PNs, and thus should not be considered as a treatment option for these tumors. This study also supports the inclusion of patient\u2010reported outcome measures in clinical trials to assess areas of benefit that are not addressed by the medical outcomes. Pediatr Blood Cancer 2014;61:982\u2013986. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.24873","type":"journal-article","created":{"date-parts":[[2013,11,25]],"date-time":"2013-11-25T10:51:19Z","timestamp":1385376679000},"page":"982-986","source":"Crossref","is-referenced-by-count":79,"title":["Sirolimus for non\u2010progressive NF1\u2010associated plexiform neurofibromas: An NF clinical trials consortium phase II study"],"prefix":"10.1002","volume":"61","author":[{"given":"Brian","family":"Weiss","sequence":"first","affiliation":[{"name":"Division of Oncology Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte C.","family":"Widemann","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology National Cancer Institute Bethesda 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