Impact of Margin Status and Local Recurrence on Soft-Tissue Sarcoma Outcomes

Potter, Benjamin K.; Hwang, Paul F.; Forsberg, Jonathan A.; Hampton, Chadwick B.; Graybill, John Christopher; Peoples, George E.; Stojadinovic, Alexander

doi:10.2106/jbjs.l.01149

Cited by 60 publications

(50 citation statements)

References 60 publications

(60 reference statements)

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“…WLE of soft‐tissue sarcomas presents several challenges, including localizing the tumor within its investing tissues and guiding the surgical dissection around the tumor at a uniform distance from the pseudocapsule. These challenges have resulted in a positive margin rate of 22% to 34%, decreasing postoperative survival and increasing tumor recurrence . Development of molecular‐targeted FGS for WLE of soft‐tissue sarcomas may increase the sensitivity and specificity of margin detection and improve outcomes after surgical resection.…”

Section: Introductionmentioning

confidence: 99%

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Preclinical imaging of epidermal growth factor receptor with ABY‐029 in soft‐tissue sarcoma for fluorescence‐guided surgery and tumor detection

Samkoe

Sardar

Bates

et al. 2019

Journal of Surgical Oncology

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Background and Objectives Fluorescence‐guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY‐029 (anti‐EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small‐molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft‐tissue sarcomas with varying levels of EGFR expression and vascularization. Methods Five xenograft soft‐tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY‐029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin‐fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. Results ABY‐029 is retained longer within tumor tissue and achieves higher tumor‐to‐background ratios both in vivo and ex vivo than IRDye 700DX. ABY‐029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast‐to‐noise ratio, but all systems have individual advantages. Conclusions ABY‐029 demonstrates promise to assist in wide local excision of soft‐tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.

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Section: Introductionmentioning

confidence: 99%

“…These challenges have resulted in a positive margin rate of 22% to 34%, decreasing postoperative survival and increasing tumor recurrence. 19,[24][25][26] Development of molecular-targeted FGS for WLE of soft-tissue sarcomas may increase the sensitivity and specificity of margin detection and improve outcomes after surgical resection.…”

mentioning

confidence: 99%

Preclinical imaging of epidermal growth factor receptor with ABY‐029 in soft‐tissue sarcoma for fluorescence‐guided surgery and tumor detection

Samkoe

Sardar

Bates

et al. 2019

Journal of Surgical Oncology

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“…Although negative surgical margins have been determined to be an important factor for improving local recurrence-free survival (LRFS), their impact on disease-specific survival (DSS) is still a subject of debate. Large single-institutional studies investigating the prognostic significance of surgical margins in extremity STS patients have presented inconsistent results [2,[7][8][9][10][11][12][13][14][15][16][17]. However, the implementation of radical surgery in the extremities is often difficult.…”

Section: Introductionmentioning

confidence: 99%

Soft Tissue Sarcomas of the Extremities: Surgical Margins Can Be Close as Long as the Resected Tumor Has No Ink on It

et al. 2017

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In the present retrospective analysis of 643 patients with primary soft issue sarcomas of the extremities, surgical margins could be identified as independent predictors of local recurrence-free, disease-specific, and metastasis-free survival. Given the diminished outcome of patients left with positive margins, surgical efforts should aim to achieve microscopically negative margins whenever feasible. It is noteworthy that only the quality of surgical margins, but not the negative margin width attained, had an influence on the prognosis. Our findings suggest that surgical margins can be close as long as the resected tumor has no ink on it.

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“…The presence of cancer cells at the surface of the excised mass defines a positive margin and is associated with increased recurrence rates and decreased survival rates. [11][12][13][14] Unfortunately, positive margin rates following sarcoma resection with curative intent remain in the range of 22% to 34%. [11][12][13] WLE of subsurface tumors presents several barriers to conventional direct fluorescence visualization because a margin of normal tissue must be maintained around the mass.…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision

et al. 2017

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Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ∼1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ∼1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE.

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Impact of Margin Status and Local Recurrence on Soft-Tissue Sarcoma Outcomes

Abstract: Positive surgical margins are consistently associated with adverse survival-related outcomes in localized soft-tissue sarcomas of the extremity. Local recurrence had a significant impact on overall survival, but not on disease-specific survival.

Cited by 60 publications

References 60 publications

Preclinical imaging of epidermal growth factor receptor with ABY‐029 in soft‐tissue sarcoma for fluorescence‐guided surgery and tumor detection

Preclinical imaging of epidermal growth factor receptor with ABY‐029 in soft‐tissue sarcoma for fluorescence‐guided surgery and tumor detection

Soft Tissue Sarcomas of the Extremities: Surgical Margins Can Be Close as Long as the Resected Tumor Has No Ink on It

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision

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