Phase I Trial of Preoperative Doxorubicin-Based Concurrent Chemoradiation and Surgical Resection for Localized Extremity and Body Wall Soft Tissue Sarcomas

Pisters, Peter W.T.; Patel, Shreyaskumar; Prieto, Víctor G.; Thall, Peter F.; Lewis, Valerae O.; Feig, Barry W.; Hunt, Kelly K.; Yasko, Alan W.; Lin, Patrick P.; Jacobson, Marc G.; Burgess, M. A.; Pollock, Raphael E.; Zagars, Gunar K.; Benjamin, Robert S.; Ballo, Matthew T.

doi:10.1200/jco.2004.01.040

Cited by 73 publications

(51 citation statements)

References 11 publications

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“…Alektiar et al reported a 5-year DFS rate of 55% that did not change with presentation (primary vs recurrent) or grade (low vs high). 10,12 Ballo et al observed no difference in the LCR depending on the receipt of IORT (5-year LCR: 46% without IORT vs 51% with IORT). Concerning the whole group, the 10-year disease-specific survival, DFS, and distant metastasis-free survival rates were 44%, 39%, and 67%, respectively.…”

Section: Hdr-iortmentioning

confidence: 99%

“…This decision was made at the discretion of the treating surgeon. 12 At the University of Alabama, intensity-modulated RT (IMRT) delivered a dose of 45 Gy in 25 fractions. At the same time, a simultaneous integrated boost of 12.5 Gy was delivered to the ''margins at risk'' with the use of IMRT.…”

Section: Hdr-iortmentioning

confidence: 99%

“…The low toxicity rate from this regimen was attributed to tumor-associated bowel displacement away from the RT target volume. 12 In series of patients who did not receive chemotherapy, the toxicity profile was very mild, and hospital admission reportedly was rare. 19,44,55 …”

Section: Toxicitymentioning

confidence: 99%

“…9 Unfortunately, obtaining a microscopically complete resection remains a heavy burden even in the hands of experienced surgeons. 8,[10][11][12][13] After undergoing macroscopically complete surgery alone, local recurrences develop in 20% to 75% of patients, and these can occur even after 5 years of follow-up. 1,8,10,[14][15][16][17][18][19] The estimated survival rate at 5 years varies between 12% and 75%, 6,13,20,21 and the cause of death for these patients usually is local recurrence, which is in sharp contrast to outcomes for patients with sarcoma of the extremities.…”

mentioning

confidence: 99%

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Radiotherapy and surgery—An indispensable duo in the treatment of retroperitoneal sarcoma

Voorde

Delrue

Eijkeren

et al. 2011

Cancer

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The authors undertook a systematic review to designate the role that radiotherapy (RT) might play in the treatment of retroperitoneal sarcomas. Correlating with recent literature, the objective of this review was to evaluate whether there was enough evidence for the authors to develop an institutional treatment protocol concerning the use of RT in the treatment of retroperitoneal sarcoma. Furthermore, this was a call for surgeons to talk to radiation oncologists before performing surgery. The 2 objectives of this review were: 1) to determine the benefit of RT in terms of local control and/or survival in the treatment of retroperitoneal sarcomas and 2) to discover the optimal timing of RT in the treatment sequence. A computerized literature search was performed in the PubMed database, the Cochrane Library database, and reference lists; and journals also were searched by hand to identify all retrospective and prospective reports published since 1998 relating to RT treatment of adult retroperitoneal sarcoma. Mainly, analyses were sought that were based on a 5-year local control rate (LCR), 5-year disease-free survival, and 5-year overall survival (OS). If only 2 years follow-up were available, then the authors also noted this outcome. Toxicity data were collected and analyzed separately. The synthesis of the literature was based on 9 prospectively nonrandomized studies and 10 retrospective studies that, together, reviewed a total of 1426 patients. The 5-year LCR varied from 27% to 62%, and the results from other reports fell in between those values. The 5-year OS rate ranged from 12% to 90%, and complete resection and tumor grade were the most important prognostic factors in most studies. This review resulted in 7 recommendations concerning the use of RT in the treatment of retroperitoneal sarcoma. The authors concluded that there is good evidence from multiple single-institutions studies that RT improves the LCR in patients with retroperitoneal sarcoma. Until now, there has not been a translation of this approach into survival benefit. The current results indicated that preoperative external-beam RT followed by radical surgery seems to be the preferred sequence, and adding intraoperative RT is a safe procedure for dose escalation in the upper abdomen. Cancer 2011;117:4355-

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Section: Hdr-iortmentioning

confidence: 99%

Section: Hdr-iortmentioning

confidence: 99%

Section: Toxicitymentioning

confidence: 99%

mentioning

confidence: 99%

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Radiotherapy and surgery—An indispensable duo in the treatment of retroperitoneal sarcoma

Voorde

Delrue

Eijkeren

et al. 2011

Cancer

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“…Considerations for using adjuvant radiation therapy for local treatment are not specific to synovial sarcomas per se but follow guidelines used for most adult soft tissue sarcomas. Two randomized, controlled trials suggest the usefulness and a trend toward survival benefit of doxorubicin-based chemotherapy for aggregated groups of soft tissue sarcomas [1,63], whereas other studies suggest no such trend [54,61]. Nevertheless, data specific to synovial sarcoma are sparse.…”

Section: Introductionmentioning

confidence: 99%

Synovial Sarcoma: From Genetics to Genetic-based Animal Modeling

Haldar

Randall

Capecchi

2008

Clin Orthop Relat Res

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Synovial sarcomas are highly aggressive mesenchymal cancers that show modest response to conventional cytotoxic chemotherapy, suggesting a definite need for improved biotargeted agents. Progress has been hampered by the lack of insight into pathogenesis of this deadly disease. The presence of a specific diagnostic t(X;18) translocation leading to expression of the unique SYT-SSX fusion protein in effectively all cases of synovial sarcoma suggests a role in the etiology. Other nonspecific anomalies such as overexpression of Bcl-2, HER-2/neu, and EGFR have been reported, but their role in the pathogenesis remains unclear. Using gene targeting, we recently generated mice conditionally expressing the human SYT-SSX2 fusion gene from mouse endogenous ROSA26 promoter in chosen tissue types in the presence of Cre recombinase. These mice develop synovial sarcoma when SYT-SSX2 is expressed within myoblasts, thereby identifying a source of this enigmatic tumor and establishing a mouse model of this disease that recapitulates the clinical, histologic, immunohistochemical, and transcriptional profile of human synovial sarcomas. We review the genetics of synovial sarcoma and discuss the usefulness of genetics-based mouse models as a valuable research tool in the hunt for key molecular determinants of this lethal disease as well as a preclinical platform for designing and evaluating novel treatment strategies.

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Soft Tissue Sarcomas

Maki

Raut

O’Sullivan

2017

Holland‐Frei Cancer Medicine

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Overview The management of soft tissue sarcomas is driven by the anatomic site and histology of the primary and is increasingly affected by the specific genetics of the sarcoma. In this chapter, we focus on the principles of management of this group of over 50 cancer subtypes to highlight commonalities and differences from anatomical constraints of surgery to specifics of adjuvant radiation to identification of systemic therapeutics that are appropriate for each histology. We will discuss in this chapter the etiology, presentation, diagnosis, staging, and multidisciplinary management of patients with sarcomas of soft tissue. Surgery remains paramount to achieve cure for the vast majority of sarcomas. Radiation therapy is used for larger tumors in the appropriate clinical context. The evolution of increasingly sophisticated radiation techniques is highlighted in this chapter. As pertains to systemic therapy, this chapter is written at a time in which first‐line therapies for soft tissue sarcomas may change, raising anew some questions of adjuvant therapy that remain incompletely answered. Where appropriate, we attempt to link specific histologies or molecular changes to therapeutic suggestions, with the understanding and hope that novel agents will supplant the medications that are available but that have not materially affected outcomes for few diagnoses other than GIST in the past several years.

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Phase I Trial of Preoperative Doxorubicin-Based Concurrent Chemoradiation and Surgical Resection for Localized Extremity and Body Wall Soft Tissue Sarcomas

Abstract: Preoperative doxorubicin-based chemoradiation appears safe and feasible. The maximum-tolerated dose of continuous-infusion doxorubicin with standard preoperative radiation was 17.5 mg/m(2)/wk. Pathologic response rates with this regimen are encouraging.

Cited by 73 publications

References 11 publications

Radiotherapy and surgery—An indispensable duo in the treatment of retroperitoneal sarcoma

Radiotherapy and surgery—An indispensable duo in the treatment of retroperitoneal sarcoma

Synovial Sarcoma: From Genetics to Genetic-based Animal Modeling

Soft Tissue Sarcomas

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