3D Specimen Scanning and Mapping in Musculoskeletal Oncology: A Feasibility Study.

BACKGROUND: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists. METHODS: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software. RESULTS: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution. CONCLUSIONS: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map.

Is the Number of National Database Research Studies in Musculoskeletal Sarcoma Increasing, and Are These Studies Reliable?

BACKGROUND: Large national databases have become a common source of information on patterns of cancer care in the United States, particularly for low-incidence diseases such as sarcoma. Although aggregating information from many hospitals can achieve statistical power, this may come at a cost when complex variables must be abstracted from the medical record. There is a current lack of understanding of the frequency of use of the Surveillance, Epidemiology, and End Results (SEER) database and the National Cancer Database (NCDB) over the last two decades in musculoskeletal sarcoma research and whether their use tends to produce papers with conflicting findings. QUESTIONS/PURPOSES: (1) Is the number of published studies using the SEER and NCDB databases in musculoskeletal sarcoma research increasing over time? (2) What are the author, journal, and content characteristics of these studies? (3) Do studies using the SEER and the NCDB databases for similar diagnoses and study questions report concordant or discordant key findings? (4) Are the administrative data reported by our institution to the SEER and the NCDB databases concordant with the data in our longitudinally maintained, physician-run orthopaedic oncology dataset? METHODS: To answer our first three questions, PubMed was searched from 2001 through 2020 for all studies using the SEER or the NCDB databases to evaluate sarcoma. Studies were excluded from the review if they did not use these databases or studied anatomic locations other than the extremities, nonretroperitoneal pelvis, trunk, chest wall, or spine. To answer our first question, the number of SEER and NCDB studies were counted by year. The publication rate over the 20-year span was assessed with simple linear regression modeling. The difference in the mean number of studies between 5-year intervals (2001-2005, 2006-2010, 2011-2015, 2016-2020) was also assessed with Student t-tests. To answer our second question, we recorded and summarized descriptive data regarding author, journal, and content for these studies. To answer our third question, we grouped all studies by diagnosis, and then identified studies that shared the same diagnosis and a similar major study question with at least one other study. We then categorized study questions (and their associated studies) as having concordant findings, discordant findings, or mixed findings. Proportions of studies with concordant, discordant, or mixed findings were compared. To answer our fourth question, a coding audit was performed assessing the concordance of nationally reported administrative data from our institution with data from our longitudinally maintained, physician-run orthopaedic oncology dataset in a series of patients during the past 3 years. Our orthopaedic oncology dataset is maintained on a weekly basis by the senior author who manually records data directly from the medical record and sarcoma tumor board consensus notes; this dataset served as the gold standard for data comparison. We compared date of birth, surgery date, margin status, tumor size, clinical stage, and adjuvant treatment. RESULTS: The number of musculoskeletal sarcoma studies using the SEER and the NCDB databases has steadily increased over time in a linear regression model (ß = 2.51; p < 0.001). The mean number of studies per year more than tripled during 2016-2020 compared with 2011-2015 (39 versus 13 studies; mean difference 26 ± 11; p = 0.03). Of the 299 studies in total, 56% (168 of 299) have been published since 2018. Nineteen institutions published more than five studies, and the most studies from one institution was 13. Orthopaedic surgeons authored 35% (104 of 299) of studies, and medical oncology journals published 44% (130 of 299). Of the 94 studies (31% of total [94 of 299]) that shared a major study question with at least one other study, 35% (33 of 94) reported discordant key findings, 29% (27 of 94) reported mixed key findings, and 44% (41 of 94) reported concordant key findings. Both concordant and discordant groups included papers on prognostic factors, demographic factors, and treatment strategies. When we compared nationally reported administrative data from our institution with our orthopaedic oncology dataset, we found clinically important discrepancies in adjuvant treatment (19% [15 of 77]), tumor size (21% [16 of 77]), surgery date (23% [18 of 77]), surgical margins (38% [29 of 77]), and clinical stage (77% [59 of 77]). CONCLUSION: Appropriate use of databases in musculoskeletal cancer research is essential to promote clear interpretation of findings, as almost two-thirds of studies we evaluated that asked similar study questions produced discordant or mixed key findings. Readers should be mindful of the differences in what each database seeks to convey because asking the same questions of different databases may result in different answers depending on what information each database captures. Likewise, differences in how studies determine which patients to include or exclude, how they handle missing data, and what they choose to emphasize may result in different messages getting drawn from large-database studies. Still, given the rarity and heterogeneity of sarcomas, these databases remain particularly useful in musculoskeletal cancer research for nationwide incidence estimations, risk factor/prognostic factor assessment, patient demographic and hospital-level variable assessment, patterns of care over time, and hypothesis generation for future prospective studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Trauma-Induced Nanohydroxyapatite Deposition in Skeletal Muscle is Sufficient to Drive Heterotopic Ossification.

Heterotopic ossification (HO), or the pathologic formation of bone within soft tissues, is a significant complication following severe injuries as it impairs joint motion and function leading to loss of the ability to perform activities of daily living and pain. While soft tissue injury is a prerequisite of developing HO, the exact molecular pathology leading to trauma-induced HO remains unknown. Through prior investigations aimed at identifying the causative factors of HO, it has been suggested that additional predisposing factors that favor ossification within the injured soft tissues environment are required. Considering that chondrocytes and osteoblasts initiate physiologic bone formation by depositing nanohydroxyapatite crystal into their extracellular environment, we investigated the hypothesis that deposition of nanohydroxyapatite within damaged skeletal muscle is likewise sufficient to predispose skeletal muscle to HO. Using a murine model genetically predisposed to nanohydroxyapatite deposition (ABCC6-deficient mice), we observed that following a focal muscle injury, nanohydroxyapatite was robustly deposited in a gene-dependent manner, yet resolved via macrophage-mediated regression over 28 days post injury. However, if macrophage-mediated regression was inhibited, we observed persistent nanohydroxyapatite that was sufficient to drive the formation of HO in 4/5 mice examined. Together, these results revealed a new paradigm by suggesting the persistent nanohydroxyapatite, referred to clinically as dystrophic calcification, and HO may be stages of a pathologic continuum, and not discrete events. As such, if confirmed clinically, these findings support the use of early therapeutic interventions aimed at preventing nanohydroxyapatite as a strategy to evade HO formation.

NCCN Guidelines Insights: Bone Cancer, Version 2.2017.

The NCCN Guidelines for Bone Cancer provide interdisciplinary recommendations for treating chordoma, chondrosarcoma, giant cell tumor of bone, Ewing sarcoma, and osteosarcoma. These NCCN Guidelines Insights summarize the NCCN Bone Cancer Panel's guideline recommendations for treating Ewing sarcoma. The data underlying these treatment recommendations are also discussed.

Cost-utility of osteoarticular allograft versus endoprosthetic reconstruction for primary bone sarcoma of the knee: A markov analysis.

BACKGROUND: The most cost-effective reconstruction after resection of bone sarcoma is unknown. The goal of this study was to compare the cost effectiveness of osteoarticular allograft to endoprosthetic reconstruction of the proximal tibia or distal femur. METHODS: A Markov model was used. Revision and complication rates were taken from existing studies. Costs were based on Medicare reimbursement rates and implant prices. Health-state utilities were derived from the Health Utilities Index 3 survey with additional assumptions. Incremental cost-effectiveness ratios (ICER) were used with less than $100 000 per quality-adjusted life year (QALY) considered cost-effective. Sensitivity analyses were performed for comparison over a range of costs, utilities, complication rates, and revisions rates. RESULTS: Osteoarticular allografts, and a 30% price-discounted endoprosthesis were cost-effective with ICERs of $92.59 and $6 114.77. One-way sensitivity analysis revealed discounted endoprostheses were favored if allografts cost over $21 900 or endoprostheses cost less than $51 900. Allograft reconstruction was favored over discounted endoprosthetic reconstruction if the allograft complication rate was less than 1.3%. Allografts were more cost-effective than full-price endoprostheses. CONCLUSIONS: Osteoarticular allografts and price-discounted endoprosthetic reconstructions are cost-effective. Sensitivity analysis, using plausible complication and revision rates, favored the use of discounted endoprostheses over allografts. Allografts are more cost-effective than full-price endoprostheses.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

Intraoperative Raman spectroscopy of soft tissue sarcomas.

BACKGROUND AND OBJECTIVE: Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that are often treated through surgical resection. Current intraoperative margin assessment methods are limited and highlight the need for an improved approach with respect to time and specificity. Here we investigate the potential of near-infrared Raman spectroscopy for the intraoperative differentiation of STS from surrounding normal tissue. MATERIALS AND METHODS: In vivo Raman measurements at 785 nm excitation were intraoperatively acquired from subjects undergoing STS resection using a probe based spectroscopy system. A multivariate classification algorithm was developed in order to automatically identify spectral features that can be used to differentiate STS from the surrounding normal muscle and fat. The classification algorithm was subsequently tested using leave-one-subject-out cross-validation. RESULTS: With the exclusion of well-differentiated liposarcomas, the algorithm was able to classify STS from the surrounding normal muscle and fat with a sensitivity and specificity of 89.5% and 96.4%, respectively. CONCLUSION: These results suggest that single point near-infrared Raman spectroscopy could be utilized as a rapid and non-destructive surgical guidance tool for identifying abnormal tissue margins in need of further excision. Lasers Surg. Med. 48:774-781, 2016. © 2016 Wiley Periodicals, Inc.

Overutilization and Cost of Advanced Imaging for Long-Bone Cartilaginous Lesions.

BACKGROUND: The prevalence and cost of unnecessary advanced imaging studies (AIS) in the evaluation of long bone cartilaginous lesions have not been studied previously. METHODS: A total of 105 enchondromas and 19 chondrosarcomas arising in long bones from July 2008 until April 2012 in 121 patients were reviewed. Advanced imaging was defined as MRI, CT, bone scan, skeletal survey, or CT biopsy. Two blinded radiologists independently reviewed the initial imaging study and determined if further imaging was indicated based on that imaging study alone. The cost of imaging was taken from our institution's global charge list. Imaging was deemed unnecessary if it was not recommended by our radiologists after review of the initial imaging study. The difference in cost was calculated by subtracting the cost of imaging recommended by each radiologist from the cost of unnecessary imaging. The sensitivity and specificity for distinguishing enchondromas from chondrosarcomas was calculated. A minimum of 2 years from diagnosis of an enchondroma was required to monitor for malignant transformation. RESULTS: Of patients diagnosed with an enchondroma, 85 % presented with AIS. The average enchondroma patient presented with one unnecessary AIS. The radiologists' interpretations agreed 85 % of the time for enchondromas and 100 % for chondrosarcomas. The sensitivity and specificity for distinguishing enchondromas from chondrosarcomas was 95 % for one radiologist and 87 and 95 % for the other. The average unnecessary cost per enchondroma patient was $1,346.18. CONCLUSIONS: Unnecessary AIS are frequently performed and are a significant source of expense. The imaging algorithms outlined in this study may reduce unnecessary AIS.

MFH and high-grade undifferentiated pleomorphic sarcoma-what's in a name?

BACKGROUND AND OBJECTIVES: In 2002, with the advent of better classification techniques, the World Health Organization declassified malignant fibrous histiocytoma (MFH) as a distinct histological entity in favor of the reclassified entity high-grade undifferentiated pleomorphic sarcoma (HGUPS). To date, no study has evaluated comparative outcomes between patients designated historically in the MFH group and those classified in the new HGUPS classification. Our goal was to determine the presence of clinical prognostic implications that have evolved with this new nomenclature. METHODS: Sixty-eight patients were retrospectively evaluated between January 1998 and December 2007. Forty-five patients diagnosed with MFH between 1998 and 2003 were compared to 23 patients in the HGUPS group, from 2004 to 2007. Primary prognostic outcomes assessed included overall survival, metastatic-free, and local recurrence-free survival. RESULTS: Five-year survivorship between MFH and HGUPS populations, using Kaplan-Meier or competing risk methods, did not show statistical difference for overall survival (60% vs. 74%, P=0.36), 5-year metastasis-free survival (31% vs. 26%, P=0.67), or local recurrence-free survival (13% vs. 16%, P=0.62). CONCLUSION: Despite new classification nomenclature, there appears to be no identifiable prognostic implications for sarcomas that remain in the unclassifiable HGUPS group, as compared to the previously accepted MFH group.

Gastrointestinal stromal tumors, version 2.2014.

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

Soft tissue sarcoma, version 2.2014.

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

Medical malpractice and sarcoma care--a thirty-three year review of case resolutions, inciting factors, and at risk physician specialties surrounding a rare diagnosis.

BACKGROUND: We reviewed medico-legal cases related to extremity sarcoma malpractice in order to recognize those factors most commonly instigating sarcoma litigation. METHODS: Over one million legal cases available in a national legal database were searched for malpractice verdicts and settlements involving extremity sarcoma spanning 1980-2012. We categorized verdict/settlement resolutions by state, year, award amount, nature of the complaint/injury, specialty of the physician defendant, and academic affiliation of defendant-amongst other variables. RESULTS: Of the 216 cases identified, 57% of case resolutions favored the plaintiff, with a mean indemnity payment of $2.30 million (range $65,076-$12.66 million). Delay in diagnosis (81%), unnecessary amputation (11%), and misdiagnosis (7%) accounted for the majority of complaints. The greatest numbers of claims were filed against primary care specialties (34%), orthopaedic surgeons (23%), and radiologists (12%). Individual state tort reform measures were not protective against case resolution outcome. CONCLUSIONS: Reported medico-legal claims involving sarcoma care continue to rise, with mean indemnity payments approaching 10 times that for other reported medical/surgical specialties. Primary care and orthopaedic specialties are the most commonly named physician defendants, citing a delay in diagnosis. This suggests further education in the front line diagnosis and management of sarcomas is needed.

Does postoperative infection after soft tissue sarcoma resection affect oncologic outcomes?

BACKGROUND AND OBJECTIVES: Prior studies have demonstrated postoperative infection may confer a survival benefit after osteosarcoma resection. Our aim was to determine whether infection after soft tissue sarcoma resection has similar effects on metastasis, recurrence and survival. METHODS: A retrospective review was conducted; 396 patients treated surgically for a soft tissue sarcoma between 2000 and 2008 were identified. Relevant oncologic data were collected. Fifty-six patients with a postoperative infection were compared with 340 patients without infection. Hazard ratios and overall cumulative risk were evaluated. RESULTS: There was no difference in survival, local recurrence or metastasis between patients with or without a postoperative infection. Patients were evenly matched for age at diagnosis, gender, smoking status, and diabetes status. Tumor characteristics did not differ between groups in tumor size, location, depth, grade, margin status, stage, and histologic subtype. There was no difference in utilization of chemotherapy or radiation therapy between groups. From our competing risk model, only positive margin status significantly impacted the risk of local recurrence. An increase in tumor size corresponded to an increased risk of metastasis and death. CONCLUSIONS: Postoperative infection neither conferred a protective effect, nor increased the risk of adverse oncologic outcomes after soft tissue sarcoma resection.

Obesity does not affect survival outcomes in extremity soft tissue sarcoma.

BACKGROUND: Obesity is a growing epidemic and has been associated with an increased frequency of complications after various surgical procedures. Studies also have shown adipose tissue to promote a microenvironment favorable for tumor growth. Additionally, the relationship between obesity and prognosis of soft tissue sarcomas has yet to be evaluated. QUESTIONS/PURPOSES: We sought to assess if (1) obesity affects survival outcomes (local recurrence, distant metastasis, and death attributable to disease) in patients with extremity soft tissue sarcomas; and (2) whether obesity affected wound healing and other surgical complications after treatment. METHODS: A BMI of 30 kg/m(2) or greater was used to define obesity. Querying our prospective database between 2001 and 2008, we identified 397 patients for the study; 154 were obese and 243 were not obese. Mean followup was 4.5 years (SD, 3.1 years) in the obese group and 3.9 years (SD, 3.2 years) in the nonobese group; the group with a BMI of 30 kg/m(2) or greater had a higher proportion of patients with followups of at least 2 years compared with the group with a BMI less than 30 kg/m(2) (76% versus 62%). Outcomes, including local recurrence, distant metastasis, and overall survival, were analyzed after patients were stratified by BMI. Multivariable survival models were used to identify independent predictors of survival outcomes. Wilcoxon rank sum test was used to compare continuous variables. Based on the accrual interval of 8 years, the additional followup of 5 years after data collection, and the median survival time for the patients with a BMI less than 30 kg/m(2) of 3 years, we were able to detect true median survival times in the patients with a BMI of 30 kg/m(2) of 2.2 years or less with 80% power and type I error rate of 0.05. RESULTS: Patients who were obese had similar survival outcomes and wound complication rates when compared with their nonobese counterparts. Patients who were obese were more likely to have lower-grade tumors (31% versus 20%; p = 0.021) and additional comorbidities including diabetes mellitus (26% versus 7%; p < 0.001), hypertension (63% versus 38%; p < 0.001), and smoking (49% versus 37%; p = 0.027). Regression analysis confirmed that even after accounting for certain tumor characteristics and comorbidities, obesity did not serve as an independent risk factor in affecting survival outcomes. CONCLUSIONS: Although the prevalence of obesity continues to increase and lead to many negative health consequences, it does not appear to adversely affect survival, local recurrence, or wound complication rates for patients with extremity soft tissue sarcomas. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Surgical Margins in Musculoskeletal Sarcoma.

¼ Negative margin resection of musculoskeletal sarcomas is associated with reduced risk of local recurrence.¼ There is limited evidence to support an absolute margin width of soft tissue or bone that correlates with reduced risk of local recurrence.¼ Factors intrinsic to the tumor, including histologic subtype, grade, growth pattern and neurovascular involvement impact margin status and local recurrence, and should be considered when evaluating a patient's individual risk after positive margins.¼ Appropriate use of adjuvant therapy, critical analysis of preoperative advanced cross-sectional imaging, and the involvement of a multidisciplinary team are essential to obtain negative margins when resecting sarcomas.

The financial burden of reexcising incompletely excised soft tissue sarcomas: a cost analysis.

BACKGROUND: Although survival outcomes have been evaluated between those undergoing a planned primary excision and those undergoing a reexcision following an unplanned resection, the financial implications associated with a reexcision have yet to be elucidated. METHODS: A query for financial data (professional, technical, indirect charges) for soft tissue sarcoma excisions from 2005 to 2008 was performed. A total of 304 patients (200 primary excisions and 104 reexcisions) were identified. Wilcoxon rank sum tests and χ2 or Fisher's exact tests were used to compare differences in demographics and tumor characteristics. Multivariable linear regression analyses were performed with bootstrapping techniques. RESULTS: The average professional charge for a primary excision was $9,694 and $12,896 for a reexcision (p<.001). After adjusting for tumor size, American Society of Anesthesiologists status, grade, and site, patients undergoing reexcision saw an increase of $3,699 in professional charges more than those with a primary excision (p<.001). Although every 1-cm increase in size of the tumor results in an increase of $148 for a primary excision (p=.006), size was not an independent factor in affecting reexcision charges. The grade of the tumor was positively associated with professional charges of both groups such that higher-grade tumors resulted in higher charges compared to lower-grade tumors (p<.05). CONCLUSIONS: Reexcision of an incompletely excised sarcoma results in significantly higher professional charges when compared to a single, planned complete excision. Additionally, when the cost of the primary unplanned surgery is considered, the financial burden nearly doubles.

Tumor size increase following preoperative radiation of soft tissue sarcomas does not affect prognosis.

BACKGROUND AND OBJECTIVES: Administration of preoperative radiotherapy for extremity soft tissue sarcoma improves local control, while allowing for a more conservative surgical resection. During radiation treatment tumor size typically decreases or remains constant. In a subset of patients, however, a size increase in the tumor occurs. Our goal was to investigate the prognosis of patients who had a size increase of at least 20% over the course of preoperative radiotherapy versus those who did not. METHODS: This retrospective study evaluated 70 patients treated for localized primary STS of the extremities between January 2000 and December 2008. Kaplan-Meier curves for disease-specific and metastasis-free survival were calculated for both groups. RESULTS: Sixty-one patients had stable or decrease local tumor size following preoperative radiotherapy and nine patients had an increase of at least 20% in tumor size. There were no statistically significant differences found in disease-specific survival and metastasis-free survival (Gray's test, P = 0.93 and P = 0.68, respectively) among the two groups. CONCLUSION: Our results indicate that a 20% increase in tumor size following preoperative radiotherapy did not result in a worse outcome for patients when compared to those who had stable or decrease local tumor size following preoperative radiotherapy.

Incomplete excisions of extremity soft tissue sarcomas are unaffected by insurance status or distance from a sarcoma center.

BACKGROUND: Soft tissue sarcomas (STS) continue to be excised inappropriately without proper preoperative planning. The reasons for this remain elusive. The role of insurance status and patient distance from sarcoma center in influencing such inappropriate excisions were examined in this study. METHODS: This retrospective review of a single institution prospective database evaluated 400 patients treated for STS of the extremities between January 2000 and December 2008. Two hundred fifty three patients had a primary excision while 147 patients underwent re-excision. Wilcoxon rank sum test and either χ(2) or Fisher's exact were used to compare variables. Multivariable regression analyses were used to take into account potential confounders and identify variables that affected excision status. RESULTS: Tumor size, site, depth, stage, margins, and histology were significantly different between the primary excision and re-excision groups; P < 0.05. Insurance status and patient distance from the treatment center were not statistically different between the two groups. Large and deep tumors and certain histology types predicted appropriate referral. CONCLUSIONS: Inappropriate excision of STS is not influenced by patient distance from a sarcoma center or by a patient's insurance status. In this study, tumor size, depth, and certain histology types predicted the appropriate referral of a STS to a sarcoma center.

Predictors and clinical significance of local recurrence in extremity soft tissue sarcoma.

BACKGROUND: Limb salvage surgery (LSS) has gained widespread acceptance as the current treatment for treating extremity soft tissue sarcoma (STS) and has been greatly refined since its inception. Combined with improved adjuvant treatment modalities, rates of local relapse have greatly decreased. Nonetheless, local recurrence still occurs and identifying the cause and the subsequent effects of local recurrence can provide valuable insights as LSS continues to evolve. METHODS: This retrospective study evaluated 278 patients treated for STS of the extremities between 2000 and 2006. Of these, 41 patients developed a local recurrence while 247 did not. Tumor characteristics and prognostic outcomes were analyzed. Wilcoxon rank sum test and either χ(2) or Fisher's exact was used to compare variables. Kaplan Meier and Gray's test for cumulative risk were also performed. RESULTS: Patients who had a positive margin were 3.76 times more likely to develop local recurrence when compared to those with negative margins. This corresponds to a 38% risk of local recurrence if the margins were positive after six years vs. 12% if the margins were negative. In patients who underwent a re-excision, the presence or absence of residual disease upon re-excision did not have any bearing on local recurrence (p = 0.27). In comparing patients with and without local recurrence, there was no statistically significant difference in the rate and the proportion encountering distant metastasis and death due to sarcoma (p > 0.05). CONCLUSIONS: Despite advancements in surgery, radiation and imaging, positive margins still occur, and the presence of positive margins following definitive treatment continues to remain as a strong predictor for local recurrence. While local recurrence represents a negative outcome for a patient, its impact on future prognosis is influenced by a variety of factors such as time to local recurrence as well as the tumor's inherent biological characteristics.