Accuracy of Time to Treatment Initiation Data in Musculoskeletal Soft Tissue Sarcoma.

Background: Time to treatment initiation (TTI) is a quality metric in cancer care. The purpose of this study is to determine the accuracy of TTI data from a single cancer center registry that reports to the National Cancer Database (NCDB) for sarcoma diagnoses. Methods: A retrospective analysis of a single Commission on Cancer (CoC)-accredited cancer center's tumor registry between 2006 and 2016 identified 402 patients who underwent treatment of a musculoskeletal soft tissue sarcoma and had TTI data available. Registry-reported TTI was extracted from the tumor registry. Effective TTI was manually calculated by medical record review as the number of days from the date of tissue diagnosis to initiation of first effective treatment. Effective treatment was defined as oncologic surgical excision or initiation of radiation therapy or chemotherapy. Registry-reported TTI and effective TTI values were compared for concordance in all patients. Results: In the entire cohort, 25% (99/402) of patients had TTI data discordance, all related to surgical treatment definition. For patients with a registry-reported value of TTI = 0 days, 74% (87/118) had a diagnostic surgical procedure coded as their first treatment event, with 73 unplanned incomplete excision procedures and 14 incisional biopsies. In these patients, effective TTI was on average 59 days (P < 0.001). For patients with a registry-reported value of TTI >0 days, only 4% (12/284) had discordant TTI values. Conclusions: Nearly three-fourths of patients with a registry-reported value of TTI = 0 days in a large, CoC-accredited cancer center registry had a diagnostic procedure coded as their first treatment event, though their effective treatment had not yet started. These data suggest that TTI is likely longer than what is reported to the NCDB. Redefinition of what constitutes surgical treatment should be considered to improve the accuracy of data used in measuring TTI in sarcoma.

Does PET/CT Aid in Detecting Primary Carcinoma in Patients with Skeletal Metastases of Unknown Primary?

BACKGROUND: Patients older than 40 years presenting with osteolytic bone lesions are likely to have a diagnosis of carcinoma, even if they had no prior cancer diagnosis. For patients with no prior cancer diagnosis, there is a well-accepted algorithm to determine a potential primary site. That algorithm, however, leaves approximately 15% of people without a detectable primary tumor site, making treatment decisions extremely difficult. Positron emission tomography (PET) fused with CT, more commonly known as PET/CT, has emerged as an important staging modality for many other malignancies but has been used in a very limited fashion in musculoskeletal oncology. QUESTIONS/PURPOSES: We asked (1) What is the ability of PET/CT to detect the source of the primary tumor in patients with a skeletal metastasis of unknown primary? (2) How does PET/CT perform in detecting metastases in other sites in patients with a skeletal metastasis of unknown primary? METHODS: A retrospective analysis between 2006 and 2016 of the pathology database of a single tertiary center identified 35 patients with a biopsy-proven skeletal metastasis (histologically confirmed carcinoma or adenocarcinoma) and a PET/CT scan that was performed after the standard diagnostic evaluation of the primary cancer site. Patients were identified through use of our pathology database to identify all biopsy-proven bone carcinomas. This was then cross referenced with our imaging database to identify all patients who were at any time evaluated with PET/CT. During this time, we identified 1075 patients with biopsy-proven metastatic bone disease through our pathology database. Any indication for a PET/CT was included, and was most often done for staging of the identified malignancy or evaluation for the unknown source. Data regarding the ability of PET/CT to find or confirm the primary cancer and all metastatic sites were evaluated. The standard diagnostic evaluation (history and physical, laboratory evaluation, CT of the chest/abdomen/pelvis and whole body bone scan) identified the primary cancer in 22 of the 35 patients. Among the 35 patients, there were a total of 176 metastatic sites of disease identified, with 115 identified with the standard diagnostic evaluation (before PET/CT). RESULTS: Among patients with a skeletal metastasis of unknown primary, PET/CT was unable to identify the primary cancer in 12 of 13 patients. PET/CT confirmed the site of the known primary cancer in all 22 patients. There were 176 total metastatic sites. Of the 115 metastases known before PET/CT, PET/CT failed to identify three of 115 (3% false-negative rate). CONCLUSIONS: PET/CT may not provide any additional benefit over the standard evaluation for identification of the primary cancer in patients with a skeletal metastasis of unknown primary, although it may have efficacy as a screening tool equivalent or superior to the standard diagnostic algorithm for evaluation of the overall metastatic burden in these patients. LEVEL OF EVIDENCE: Level III, diagnostic study.

What Demographic and Clinical Factors Are Associated with In-hospital Mortality in Patients with Necrotizing Fasciitis?

BACKGROUND: Necrotizing fasciitis is a rare infection with rapid deterioration and a high mortality rate. Factors associated with in-hospital mortality have not been thoroughly evaluated. Although predictive models identifying the diagnosis of necrotizing fasciitis have been described (such as the Laboratory Risk Indicator for Necrotizing Fasciitis [LRINEC]), their use in predicting mortality is limited. QUESTIONS/PURPOSES: (1) What demographic factors are associated with in-hospital mortality in patients with necrotizing fasciitis? (2) What clinical factors are associated with in-hospital mortality? (3) What laboratory values are associated with in-hospital mortality? (4) Is the LRINEC score useful in predicting mortality? METHODS: We retrospectively studied all patients with necrotizing fasciitis at our tertiary care institution during a 10-year period. In all, 134 patients were identified; after filtering out patients with missing data (seven) and those without histologically confirmed necrotizing fasciitis (12), 115 patients remained. These patients were treated with early-initiation antibiotic therapy and aggressive surgical intervention once the diagnosis was suspected. Demographic data, clinical features, laboratory results, and treatment variables were identified. The median age was 56 years and 42% of patients were female. Of the 115 patients analyzed, 15% (17) died in the hospital. Univariate and receiver operating characteristic analyses were performed due to the low number of mortality events seen in this cohort. RESULTS: The demographic factors associated with in-hospital mortality were older age (median: 64 years for nonsurvivors [interquartile range (IQR) 57-79] versus 55 years for survivors [IQR 45-63]; p = 0.002), coronary artery disease (odds ratio 4.56 [95% confidence interval (CI) 1.51 to 14]; p = 0.008), chronic kidney disease (OR 4.92 [95% CI 1.62 to 15]; p = 0.006), and transfer from an outside hospital (OR 3.47 [95% CI 1.19 to 10]; p = 0.02). The presenting clinical characteristics associated with in-hospital mortality were positive initial blood culture results (OR 4.76 [95% CI 1.59 to 15]; p = 0.01), lactic acidosis (OR 4.33 [95% CI 1.42 to 16]; p = 0.02), and multiple organ dysfunction syndrome (OR 6.37 [95% CI 2.05 to 20]; p = 0.002). Laboratory values at initial presentation that were associated with in-hospital mortality were platelet count (difference of medians -136 [95% CI -203 to -70]; p < 0.001), serum pH (difference of medians -0.13 [95% CI -0.21 to -0.03]; p = 0.02), serum lactate (difference of medians 0.90 [95% CI 0.40 to 4.80]; p < 0.001), serum creatinine (difference of medians 1.93 [95% CI 0.65 to 3.44]; p < 0.001), partial thromboplastin time (difference of medians 8.30 [95% CI 1.85 to 13]; p = 0.03), and international normalized ratio (difference of medians 0.1 [95% CI 0.0 to 0.5]; p = 0.004). The LRINEC score was a poor predictor of mortality with an area under the receiver operating characteristics curve of 0.56 [95% CI 0.45-0.67]. CONCLUSIONS: Factors aiding clinical recognition of necrotizing fasciitis are not consistently helpful in predicting mortality of this infection. Identifying patients with potentially compromised organ function should lead to aggressive and expedited measures for diagnosis and treatment. Future multicenter studies with larger populations and a standardized algorithm of treatment triggered by high clinical suspicion can be used to validate these findings to better help prognosticate this potentially fatal diagnosis.Level of Evidence Level III, therapeutic study.

Immediate Versus Staged Soft Tissue Reconstruction After Soft Tissue Sarcoma Resection Has Similar Wound and Oncologic Outcomes.

BACKGROUND: The aim of this study was to compare the wound complication rate and oncologic outcome in patients undergoing immediate versus staged soft tissue reconstruction after soft tissue sarcoma (STS) resection. METHODS: This is a retrospective analysis of a single sarcoma referral center between 2006 and 2016 which identified a cohort that underwent resection of an extremity or trunk STS with reconstruction surgery (split thickness skin graft or flap coverage). Patients were divided into 2 groups based on the reconstruction timing: immediate (same day) versus staged (later date). Demographic characteristics, wound complications, and oncologic outcomes were compared. RESULTS: Of the 491 patients who underwent resection of an extremity or trunk STS, 81 (16%) received reconstructive surgery, with 26 patients undergoing immediate reconstruction and 55 patients undergoing staged reconstruction. Overall wound complication (58% vs 45%, P = 0.347) and infection rates (35% vs 25%, P = 0.602) were similar between immediate and staged groups, respectively. Likewise, local recurrence (8% vs 7%, P = 1.000), metastasis (19% vs 20%, P = 0.755), and all-cause mortality (27% vs 27%, P = 1.000) rates after reconstruction was similar. Patients in the staged group with positive margins after resection were re-excised before definitive reconstruction, whereas those in the immediate group were not. The staged group required fewer surgical intensive care unit stays after resection surgery (22% vs 58%, P = 0.006). The mean ± SD final follow-up was 38 ± 33 months. CONCLUSIONS: Wound complication rates and oncologic outcomes remain similar, regardless of timing for reconstruction. Staged reconstructions were associated with fewer surgical intensive care unit stays, while also affording opportunity for reintervention after positive margins with little additional morbidity.

A versatile cancer cell trapping and 1D migration assay in a microfluidic device.

Highly migratory cancer cells often lead to metastasis and recurrence and are responsible for the high mortality rates in many cancers despite aggressive treatment. Recently, the migratory behavior of patient-derived glioblastoma multiforme cells on microtracks has shown potential in predicting the likelihood of recurrence, while at the same time, antimetastasis drugs have been developed which require simple yet relevant high-throughput screening systems. However, robust in vitro platforms which can reliably seed single cells and measure their migration while mimicking the physiological tumor microenvironment have not been demonstrated. In this study, we demonstrate a microfluidic device which hydrodynamically seeds single cancer cells onto stamped or femtosecond laser ablated polystyrene microtracks, promoting 1D migratory behavior due to the cells' tendency to follow topographical cues. Using time-lapse microscopy, we found that single U87 glioblastoma multiforme cells migrated more slowly on laser ablated microtracks compared to stamped microtracks of equal width and spacing (p < 0.05) and exhibited greater directional persistence on both 1D patterns compared to flat polystyrene (p < 0.05). Single-cell morphologies also differed significantly between flat and 1D patterns, with cells on 1D substrates exhibiting higher aspect ratios and less circularity (p < 0.05). This microfluidic platform could lead to automated quantification of single-cell migratory behavior due to the high predictability of hydrodynamic seeding and guided 1D migration, an important step to realizing the potential of microfluidic migration assays for drug screening and individualized medicine.