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A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins.

ABSTRACT: The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82 and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78 and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence.

SUBMITTER: Mueller JL

PROVIDER: S-EPMC4575838 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins.

Mueller Jenna L JL Fu Henry L HL Mito Jeffrey K JK Whitley Melodi J MJ Chitalia Rhea R Erkanli Alaattin A Dodd Leslie L Cardona Diana M DM Geradts Joseph J Willett Rebecca M RM Kirsch David G DG Ramanujam Nimmi N

International journal of cancer 20150603 10

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error ...[more]

PMID: 25994353

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Project description:Soft tissue sarcomas (STS) are rare malignant tumors often associated with poor outcomes and high local recurrence rates. Current tools for intraoperative and definitive margin assessment include intraoperative frozen section and permanent pathology, respectively. Indocyanine green dye (ICG) is a historically safe fluorophore dye that has demonstrated efficacy for intraoperative margin assessment in the surgical management of both breast and gastrointestinal cancers. The utility of ICG in the surgical management of sarcoma surgery has primarily been studied in pre-clinical mouse models and warrants further investigation as a potential adjunct to achieving negative margins. This study is a prospective, non-randomized clinical study conducted on patients with confirmed or suspected STS. Patients younger than 18 years, with a prior adverse reaction to iodine or fluorescein, or with renal disease were excluded from the study. Intravenous ICG was infused approximately three hours prior to surgery at a dosage of 2.0-2.5 mg/kg, and following tumor resection, the excised tumor and tumor bed were imaged for fluorescence intensity. When scanning the tumor bed, a threshold of 77% calibrated to the region of maximum intensity in the resected tumor was defined as a positive ICG margin, according to published protocols from the breast cancer literature. ICG results were then compared with the surgeon's clinical impression of margin status and permanent pathology results. Out of 26 subjects recruited for the original study, 18 soft tissue sarcomas (STS) were included for analysis. Three subjects were excluded for having bone sarcomas, and five subjects were excluded due to final pathology, which was ultimately inconsistent with sarcoma. The average age of patients was 64.1 years old (range: 28-83), with an average ICG dose of 201.8 mg. In 56% (10/18) of patients, ICG margins were consistent with the permanent pathology margins, with 89% specificity. The use of ICG as an intraoperative adjunct to obtaining negative margins in soft tissue sarcoma surgery is promising. However, studies with larger sample sizes are warranted to further delineate the accuracy, optimal dosage, timing, and types of sarcoma in which this diagnostic tool may be most useful.

Project description:BackgroundIn contrast to other head and neck cancers, the impact of histological thyroid specimen margin status in differentiated thyroid cancer (DTC) is not well understood. The aim of this study was to investigate the prognostic value of margin status on local recurrence in DTC.MethodThe records of 3664 consecutive patients treated surgically for DTC between 1986 and 2010 were identified from an institutional database. Patients with less than total thyroidectomy, unresectable or gross residual disease, or M1 disease at presentation and those with unknown pathological margin status were excluded from analysis. In total, 2616 patients were included in the study; 2348 patients (90%) had negative margins and 268 patients (10%) had positive margins. Microscopic positive margin status was defined as tumor present at the specimen's edge on pathological analysis. Patient, tumor, and treatment characteristics were compared by Pearson's chi-squared test. Local recurrence free survival (LRFS) was calculated for each group using the Kaplan Meier method.ResultsThe median age of the cohort was 48 years (range 7-91 years) and the median follow-up was 50 months (range 1-330 months). Age, sex, and histology types were similar between groups. As expected, patients who had positive margins were more likely to have larger tumors (p<0.001), extrathyroidal extension (ETE) (p<0.001), multicentric disease (p<0.001), or nodal disease (p<0.001) and were more likely to receive adjuvant radioactive iodine therapy (p<0.001) as well as external beam radiotherapy (p<0.001). The LRFS at 5 years for patients with positive margins status was slightly poorer compared with patients with negative margins (98.9% vs. 99.5%, p=0.018). Twelve patients developed local recurrence-8/2348 (0.34%) patients with negative margins and 4/263 (1.52%) patients with positive margins. Univariate predictors of LRFS were sex (p=0.006), gross ETE (<0.001), and positive margins (p=0.018). However, when controlling for presence of gross ETE on multivariate analysis, microscopic positive margin status was not an independent predictor of LRFS (p=0.193).ConclusionPatients with resectable, M0 disease that undergo total thyroidectomy have an excellent five year LRFS of 99.4%. Microscopic positive margin status was not a significant predictor for local failure after adjusting for ETE or pathological tumor (pT) stage.

Dataset Information

A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins.

Publications

A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins.

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