{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:10:14Z","timestamp":1792696214680,"version":"4.5.0"},"reference-count":23,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi240946-4\"><jats:title>Importance<\/jats:title><jats:p>Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240946-5\"><jats:title>Objective<\/jats:title><jats:p>To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240946-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240946-7\"><jats:title>Exposure<\/jats:title><jats:p>Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240946-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240946-9\"><jats:title>Results<\/jats:title><jats:p>The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; <jats:italic>P<\/jats:italic>\u2009=\u2009.002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; <jats:italic>P<\/jats:italic>\u2009=\u2009.04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; <jats:italic>P<\/jats:italic>\u2009=\u2009.02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) were independently associated with higher incidence of DSD. Using the minimum <jats:italic>P<\/jats:italic> value method, the optimal cutoff for growth rate was found to be 0.68 cm\/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u2009.001) and higher amputation rates (19% vs 7%; <jats:italic>P<\/jats:italic>\u2009=\u2009.008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; <jats:italic>P<\/jats:italic>\u2009=\u2009.006).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi240946-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm\/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.31530","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T15:02:21Z","timestamp":1725462141000},"page":"e2431530","source":"Crossref","is-referenced-by-count":6,"title":["Growth Rate and Outcomes in Locally Recurrent Extremity and Truncal Soft Tissue Sarcoma"],"prefix":"10.1001","volume":"7","author":[{"given":"George Z.","family":"Li","sequence":"first","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Seier","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Xuan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray","family":"Brennan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol D.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee M.","family":"Crago","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"issue":"2","key":"zoi240946r2","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1097\/SLA.0b013e3182367aa7","article-title":"A postoperative nomogram for local recurrence risk in extremity soft tissue sarcomas after limb-sparing surgery without adjuvant radiation.","volume":"255","author":"Cahlon","year":"2012","journal-title":"Ann Surg"},{"issue":"9325","key":"zoi240946r3","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1016\/S0140-6736(02)09292-9","article-title":"Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial.","volume":"359","author":"O\u2019Sullivan","year":"2002","journal-title":"Lancet"},{"issue":"4","key":"zoi240946r4","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1097\/SLA.0b013e318155a9ae","article-title":"Long-term results of prospective trial of surgery alone with selective use of radiation for patients with T1 extremity and trunk soft tissue sarcomas.","volume":"246","author":"Pisters","year":"2007","journal-title":"Ann Surg"},{"issue":"1","key":"zoi240946r5","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1200\/JCO.1998.16.1.197","article-title":"Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity.","volume":"16","author":"Yang","year":"1998","journal-title":"J Clin Oncol"},{"issue":"8","key":"zoi240946r6","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1245\/s10434-020-09564-6","article-title":"Unplanned excision of extremity and trunk wall soft tissue sarcoma: to re-resect or not to re-resect?","volume":"28","author":"Danieli","year":"2021","journal-title":"Ann Surg Oncol"},{"issue":"29","key":"zoi240946r7","doi-asserted-by":"publisher","first-page":"3236","DOI":"10.1200\/JCO.2013.53.9452","article-title":"Comparison of local recurrence with conventional and intensity-modulated radiation therapy for primary soft-tissue sarcomas of the extremity.","volume":"32","author":"Folkert","year":"2014","journal-title":"J Clin Oncol"},{"issue":"20","key":"zoi240946r8","doi-asserted-by":"publisher","first-page":"3440","DOI":"10.1200\/JCO.2008.16.6249","article-title":"Impact of intensity-modulated radiation therapy on local control in primary soft-tissue sarcoma of the extremity.","volume":"26","author":"Alektiar","year":"2008","journal-title":"J Clin Oncol"},{"issue":"3","key":"zoi240946r9","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1245\/ASO.2005.03.045","article-title":"Prognostic factors for survival in patients with locally recurrent extremity soft tissue sarcomas.","volume":"12","author":"Eilber","year":"2005","journal-title":"Ann Surg Oncol"},{"issue":"2","key":"zoi240946r10","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1200\/JCO.1997.15.2.646","article-title":"Association of local recurrence with subsequent survival in extremity soft tissue sarcoma.","volume":"15","author":"Lewis","year":"1997","journal-title":"J Clin Oncol"},{"issue":"6","key":"zoi240946r11","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1097\/SLA.0b013e3181b2468b","article-title":"Predicting outcome by growth rate of locally recurrent retroperitoneal liposarcoma: the one centimeter per month rule.","volume":"250","author":"Park","year":"2009","journal-title":"Ann Surg"},{"issue":"1","key":"zoi240946r12","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/(SICI)1097-0258(20000115)19:1<113::AID-SIM245>3.0.CO;2-O","article-title":"Categorizing a prognostic variable: review of methods, code for easy implementation and applications to decision-making about cancer treatments.","volume":"19","author":"Mazumdar","year":"2000","journal-title":"Stat Med"},{"issue":"1","key":"zoi240946r13","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1186\/s12885-018-4829-0","article-title":"Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.","volume":"18","author":"Keung","year":"2018","journal-title":"BMC Cancer"},{"key":"zoi240946r14","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.725484","article-title":"Case report: response to regional melphalan via limb infusion and systemic PD1 blockade in recurrent myxofibrosarcoma: a report of 2 cases.","volume":"11","author":"Bartlett","year":"2021","journal-title":"Front Oncol"},{"issue":"2","key":"zoi240946r17","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1200\/JCO.2017.75.1610","article-title":"Emerging targeted and immune-based therapies in sarcoma.","volume":"36","author":"Pollack","year":"2018","journal-title":"J Clin Oncol"},{"issue":"7","key":"zoi240946r20","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1200\/JCO.1993.11.7.1276","article-title":"An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas.","volume":"11","author":"Antman","year":"1993","journal-title":"J Clin Oncol"},{"key":"zoi240946r21","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejrad.2021.110082","article-title":"Natural speed of growth of untreated soft-tissue sarcomas: a dimension-based imaging analysis.","volume":"146","author":"Cromb\u00e9","year":"2022","journal-title":"Eur J Radiol"},{"issue":"8","key":"zoi240946r22","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1007\/s00330-015-3654-y","article-title":"Evaluation of several FDG PET parameters for prediction of soft tissue tumour grade at primary diagnosis and recurrence.","volume":"25","author":"Fendler","year":"2015","journal-title":"Eur Radiol"},{"issue":"5","key":"zoi240946r23","first-page":"713","article-title":"Dynamic PET 18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading.","volume":"42","author":"Dimitrakopoulou-Strauss","year":"2001","journal-title":"J Nucl Med"},{"key":"zoi240946r1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-41906-0","volume-title":"Management of Soft Tissue Sarcoma","author":"Brennan","year":"2016","edition":"2nd ed"},{"key":"zoi240946r15","unstructured":"Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. ClinicalTrials.gov identifier: NCT03307616. Updated April 5, 2024. Accessed July 18, 2024. https:\/\/clinicaltrials.gov\/study\/NCT03307616?term=NCT03307616&rank=1"},{"key":"zoi240946r16","unstructured":"A phase II study of concurrent systemic pembrolizumab and isolated limb infusion (ILI) with melphalan and dactinomycin for patients with locally advanced or metastatic extremity sarcoma. ClinicalTrials.gov identifier: NCT04332874. Updated July 11, 2024. Accessed July 18, 2024. https:\/\/clinicaltrials.gov\/study\/NCT04332874?term=NCT04332874&rank=1"},{"key":"zoi240946r18","unstructured":"Phase 2 study of abemaciclib (LY2835219) in dedifferentiated liposarcoma. ClinicalTrials.gov identifier: NCT02846987. Updated December 28, 2023. Accessed July 18, 2024. https:\/\/clinicaltrials.gov\/study\/NCT02846987?term=NCT02846987&rank=1"},{"key":"zoi240946r19","unstructured":"Phase I study evaluating combination therapy with the receptor tyrosine kinase inhibitor plx3397 and sirolimus in patients with unresectable sarcoma and phase II study in malignant peripheral nerve sheath tumors. ClinicalTrials.gov identifier: NCT02584647. Updated March 13, 2024. Accessed July 18, 2024. https:\/\/clinicaltrials.gov\/study\/NCT02584647?term=NCT02584647&rank=1"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2823144\/li_2024_oi_240946_1724777563.04748.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T15:02:32Z","timestamp":1725462152000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2823144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,4]]},"references-count":23,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9,3]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.31530","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,4]]}}}