Historically, amputation was the primary surgical treatment for osteosarcoma of the extremities; however, with advancements in surgical techniques and chemotherapies limb salvage has replaced ...amputation as the dominant treatment paradigm. This study assessed the type of surgical resection chosen for osteosarcoma patients in the twenty-first century.
Utilizing the largest registry of primary osteosarcoma, the National Cancer Database (NCDB), we retrospectively analyzed patients with high grade osteosarcoma of the extremities from 2004 through 2015. Differences between patients undergoing amputation and patients undergoing limb salvage are described. Unadjusted five-year overall survival between patients who received limb salvage and amputation was assessed utilizing Kaplan Meier curves. A multivariate Cox proportional hazard model and propensity matched analysis was used to determine the variables independently correlated with survival.
From a total of 2442 patients, 1855 underwent limb salvage and 587 underwent amputation. Patients undergoing amputation were more likely to be older, male, uninsured, and live in zip codes associated with lower income. Patients undergoing amputation were also more likely to have larger tumors, more comorbid conditions, and metastatic disease at presentation. After controlling for confounders, limb salvage was associated with a significant survival benefit over amputation (HR: 0.70; p < 0.001). Although this may well reflect underlying biases impacting choice of treatment, this survival benefit remained significant after propensity matched analysis of all significantly different independent variables (HR: 0.71; p < 0.01).
Among patients in the NCDB, amputation for osteosarcoma is associated with advanced age, advanced stage, larger tumors, greater comorbidities, and lower income. Limb salvage is associated with a significant survival benefit, even when controlling for significant confounding variables and differences between cohorts.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of ...a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes.
For many cancer types, survival is improved when patients receive management at treatment centers that encounter high numbers of patients annually. This correlation may be more important with less ...common malignancies such as sarcoma. Existing evidence, however, is limited and inconclusive as to whether facility volume may be associated with survival in soft tissue sarcoma.
The purpose of this study was to examine the association between facility volume and overall survival in patients with soft tissue sarcoma of the extremities. In investigating this aim, we sought to (1) examine differences in the treatment characteristics of high- and low-volume facilities; (2) estimate the 5-year survival by facility volume; and (3) examine the association between facility volume and of traveling a further distance to a high-volume center and overall survival when controlling for confounding factors.
The largest sarcoma patient registry to date is contained within the National Cancer Database (NCDB) and captures > 70% of new cancer diagnoses annually. We retrospectively analyzed 25,406 patients with soft tissue sarcoma of the extremities in the NCDB from 1998 through 2012. Patients were stratified based on per-year facility sarcoma volume and we used univariate comparisons and multivariate proportional hazards analyses to correlate survival measures with facility volume and various other patient-, tumor-, and treatment-related factors. First, we evaluated long-term survival for all variables using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multiple patient, tumor, and treatment characteristics were compared between the two facility-volume groups and then included them in the multivariate proportional hazards model. Of the 25,406 patients analyzed, 3310 were treated at high-volume centers (≥ 20 patients annually) and 22,096 were treated at low-volume centers. Patient demographics were generally not different between both patient cohorts, although patients treated at high-volume centers were more likely to have larger and higher grade tumors (64% versus 56% size ≥ 5 cm, 28% versus 14% undifferentiated grade, p < 0.001).
When controlling for patient, tumor, and treatment characteristics in a multivariate proportional hazards analysis, patients treated at high-volume facilities had an overall lower risk of mortality than those treated at low-volume centers (hazard ratio, 0.81 0.75-0.88, p < 0.001). Patients treated at high-volume centers were also less likely to have positive margins (odds ratio OR, 0.59 0.52-0.68, p < 0.001) and in patients who received radiation, those treated at high-volume centers were more likely to have radiation before surgery (40.5% versus 21.7%, p < 0.001); there was no difference in the type of surgery performed (resection versus amputation) (OR, 1.01 0.84-1.23, p = 0.883).
With the largest patient cohort to date, this database review suggests that certain patients with soft tissue sarcoma of the extremities, particularly those with large high-grade tumors, may benefit from treatment at high-volume centers. Further investigation is necessary to help improve the referral of appropriate patients to high-volume sarcoma centers and to increase the treatment capacity of and access to such centers.
Level III, therapeutic study.
There is increasing evidence that perioperative factors, including type of anesthesia, may be an important consideration regarding oncological disease progression. Previous studies have suggested ...that regional anesthesia can improve oncological outcomes by reducing the surgical stress response that occurs during tumor resection surgery and that may promote metastatic progression. The purpose of this study is to provide the first robust investigation of the impact of adding regional anesthesia to general anesthesia on oncological outcomes following sarcoma resection. One hundred patients with bone sarcoma were retrospectively analyzed in this study. After adjusting for confounding variables such as age and grade of the tumor, patients with bone sarcoma receiving regional anesthesia in addition to general anesthesia during resection had improved metastasis free survival (multivariate hazard ratio of 0.47 and p = 0.034). Future studies are needed to confer the beneficial effect of regional anesthesia, and to further investigate the potential mechanism. Clinical significance: The results from this study provide evidence that regional anesthesia may be advantageous in the setting of bone sarcoma resection surgery, reducing pain while also improving oncological outcomes and should be considered when clinically appropriate.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In the United States, race and socioeconomic status are well known predictors of adverse outcomes in several different cancers. Existing evidence suggests that race and socioeconomic status may ...impact survival in soft tissue sarcoma (STS). We investigated the National Cancer Database (NCDB), which contains several socioeconomic and medical variables and contains the largest sarcoma patient registry to date. Our goal was to determine the impact of race, ethnicity and socioeconomic status on patient survival in patients with soft tissue sarcoma of the extremities (STS-E).
We retrospectively analyzed 14,067 STS-E patients in the NCDB from 1998 through 2012. Patients were stratified based on race, ethnicity and socioeconomic status. Univariate and multivariate analyses were used to correlate specific outcomes and survival measures with these factors. Then, long-term survival between groups was evaluated using the Kaplan-Meier (KM) method with comparisons based on the log-rank test. Multiple variables were analyzed between two groups.
Of the 14,067 patients analyzed, 84.9% were white, 11% were black and 4.1% were Asian. Black patients were significantly more likely (7.18% vs 5.65% vs 4.47%) than white or Asian patients to receive amputation (p = 0.027). Black patients were also less likely to have either an above-median education level or an above-median income level (p < 0.001). In addition, black patients were more likely to be uninsured (p < 0.001) and more likely to have a higher Charleson Comorbidity Score than white or Asian patients. Tumors were larger in size upon presentation in black patients than in white or Asian patients (p < 0.001). Black patients had significantly poorer overall survival than did white or Asian patients (p < 0.001) with a KM 5-year survival of 61.4% vs 66.9% and 69.9% respectively, and a 24% higher independent likelihood of dying in a multivariate analysis.
This large database review reveals concerning trends in black patients with STS-E. These include larger tumors, poorer resources, a greater likelihood of amputation, and poorer survival than white and Asian patients. Future studies are warranted to help ensure adequate access to effective treatment for all patients.
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STUDY DESIGN.Retrospective review.
OBJECTIVE.To determine if adjuvant radiation therapy (RT) improves overall survival (OS) following surgical resection of chordomas.
SUMMARY OF BACKGROUND DATA.The ...role of RT for the treatment of chordomas remains incompletely described. Previous studies have not found adjuvant RT to improve OS, but these studies did not group patients based on surgical margin status or radiation dose or modality. We used the National Cancer Database to investigate the role of RT in chordomas following surgical resection.
METHODS.Patients were stratified based on surgical margin status (positive vs. negative). Utilizing the Kaplan–Meier method, OS was compared between treatment modalities (surgical resection alone, therapeutic RT alone, and surgical resection plus therapeutic RT). OS was subsequently compared between patients treated with palliative dose (<40 Gy), low dose (40–65 Gy), and high dose (>65 Gy) RT. Similarly, OS was compared between advanced RT modalities including proton beam therapy (PBT) and intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery (SRS), and external beam radiation therapy (EBRT). A multivariable model was used to determine adjusted variables predictive of mortality.
RESULTS.One thousand four hundred seventy eight chordoma patients were identified; skull base (n = 567), sacral (n = 551), and mobile spine (n = 360). Surgical resection and therapeutic adjuvant RT improved 5-year survival in patients with positive surgical margins (82% vs. 71%, P = 0.03). No clear survival benefit was observed with the addition of adjuvant RT in patients with negative surgical margins. High dose RT was associated with improved OS compared with palliative and low dose RT (P < 0.001). Advanced RT techniques and SRS were associated with improved OS compared with EBRT. In the multivariate analysis high dose advanced RT (>65 Gy) was superior to EBRT.
CONCLUSION.Patients with positive surgical margins benefit from adjuvant RT. Optimal OS is associated with adjuvant RT administered with advanced techniques and cumulative dose more than 65 Gy.Level of Evidence4
Cartilaginous neoplasms can be challenging to grade; there is a need to create an evidence-based rubric for grading. The goal of this study was to identify histopathologic features of chondrosarcoma ...that were associated with 5-year survival and to compare these to traditional patient, tumor and treatment variables.
This was a retrospective review of all patients undergoing surgical resection of a primary chondrosarcoma with at least 2 years of follow up. All specimens were independently reviewed by two pathologists and histopathologic features scored. Univariate and multivariate analyses were performed utilizing Kaplan Meier and proportional hazards methods to identify variables associated with 5-year disease specific survival (DSS) and disease free survival (DFS).
We identified 51 patients with an average follow up of 49 months eligible for inclusion. 30% of tumors were low grade, 45% were intermediate grade, and 25% were high grade. In a univariate analysis considering histopathologic factors, higher tumor mitotic rate (HR 8.9, p < 0.001), tumor dedifferentiation (HR 7.3, p < 0.001), increased tumor cellularity (HR 5.8, p = 0.001), increased tumor atypia (HR 5.8, p = 0.001), LVI (HR 4.7, p = 0.04) and higher tumor necrosis (HR 3.7, p = 0.02) were all associated with worse 5-year DSS. In a multivariate analysis controlling for potentially confounding variables, higher tumor necrosis was significantly associated with disease specific survival survival (HR 3.58, p = 0.035); none of the factors were associated with DFS.
This study provides an evidence-based means for considering histopathologic markers and their association with prognosis in chondrosarcoma. Our findings suggest that necrosis and LVI warrant further study.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Tumor-induced osteomalacia is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. Phosphaturic mesenchymal tumors represent a rare etiology of ...tumor-induced osteomalacia. Nonspecific symptoms of fatigue, bone pain, and musculoskeletal weakness make the diagnosis elusive and lead to a delay in surgical treatment.
Questions/purposes
In this case series, the following three questions were asked: (1) How do the clinical presentation and features of phosphaturic mesenchymal tumors delay the diagnosis? (2) What is the clinical course after surgical treatment of phosphaturic mesenchymal tumors? (3) How frequently do phosphaturic mesenchymal tumors recur and are there factors associated with recurrence?
Methods
This study retrospectively reviewed the cases of five adults diagnosed and treated for phosphaturic mesenchymal tumors. Patients were identified through an internal orthopaedic oncology database with clinical, surgical, and histologic data obtained through a systematic chart review.
Results
Five patients presented with a long-standing history of osteomalacia, generalized fatigue, pain, and weakness before the diagnosis was reached at an average of 7.2 years (range, 2–12 years) after initial symptom onset. The diagnosis appeared to be delayed owing to the cryptic medical presentation, difficulty in locating tumor by imaging, and confirming histologic appearance. Two patients treated with wide surgical resection did not experience recurrence compared with three patients who did show recurrent signs and symptoms after marginal excision. A postoperative increase in fibroblast-derived growth factor-23 was associated with recurrent disease.
Conclusions
Although uncommon, the diagnosis of phosphaturic mesenchymal tumor should be considered in any patient who presents with hypophosphaturic osteomalacia and no other physiologic cause. Definitive treatment is early, wide surgical resection.
Level of Evidence
Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.
Navigation with fluorescence guidance has emerged in the last decade as a promising strategy to improve the efficacy of oncologic surgery. To achieve routine clinical use, the onus is on the surgical ...community to objectively assess the value of this technique. This assessment may facilitate both Food and Drug Administration approval of new optical imaging agents and reimbursement for the imaging procedures. It is critical to characterize fluorescence-guided procedural benefits over existing practices and to elucidate both the costs and the safety risks. This report is the result of a meeting of the International Society of Image Guided Surgery (www.isigs.org) on February 6, 2015, in Miami, Florida, and reflects a consensus of the participants' opinions. Our objective was to critically evaluate the imaging platform technology and optical imaging agents and to make recommendations for successful clinical trial development of this highly promising approach in oncologic surgery.
Vascularized fibula epiphyseal flap was first described in 1998 for proximal humeral reconstruction in children/infants. The authors aim to review their international, multi-institutional, long-term ...outcomes.
An international, multi-institutional review (2004 to 2020) was conducted of patients younger than 18 years undergoing free vascularized fibula epiphyseal transfer for proximal humeral reconstruction. Donor- and recipient-site complications, pain, and final ambulatory status were reviewed. Growth of the transferred bone was assessed under the guidance of a pediatric musculoskeletal radiologist.
Twenty-seven patients were included with a median age of 7 years (range, 2 to 13 years). Average follow-up was 120 ± 87.4 months. There were two flap failures (7.4%). Recipient-site complications included fracture n = 11 (40.7%), avascular necrosis of the fibula head n = 1 (3.7%), fibular head avulsion n = 1 (3.7%), infection n = 1 (3.7%), and hardware failure n = 1 (3.7%). Operative fixation was necessary in one patient with a fracture. The case of infection necessitated fibula explantation 2 years postoperatively, and ultimately, prosthetic reconstruction. Sixteen patients developed peroneal nerve palsy (59.3%): 13 of these cases resolved within 1 year (81% recovery), and three were permanent (11.1%). One patient (3.7%) complained of upper extremity pain. Longitudinal growth was confirmed in all but three cases n = 24 (88.9%) at an average rate of 0.83 ± 0.25 cm/year.
The vascularized fibula epiphysis for proximal humerus reconstruction in children preserves the potential for future growth and an articular surface for motion. Peroneal nerve palsy is common following harvest, although this is often transient. Future efforts should be geared toward reducing postoperative morbidity.
Therapeutic, IV.
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