Aims. Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients. Methods. Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR). Results. Cell-free was present in 69 of 70 samples above 0.5 ng/ml. Improved disease-free survival was found for patients with lower cfDNA levels (90% vs 48% at one-year for ≤ 6 ng/ml and > 6 ng/ml, respectively; p = 0.005). Digital droplet PCR was performed as a pilot study and mutant alleles were detectable at 0.5% to 2.5% of the wild type genome, and at a level of 0.25 ng tumour DNA. Tumour-specific alterations (ctDNA) were found in five of six cases. Conclusion. This work demonstrates the feasibility and potential utility of cfDNA and ctDNA as biomarkers for bone and
Prediction tools are instruments which are commonly used to estimate the prognosis in oncology and facilitate clinical decision-making in a more personalized manner. Their popularity is shown by the increasing numbers of prediction tools, which have been described in the medical literature. Many of these tools have been shown to be useful in the field of
Objectives. Our objective was to predict the knee extension strength and post-operative function in quadriceps resection for
Objectives. The clinical utility of routine cross sectional imaging of the
abdomen and pelvis in the screening and surveillance of patients
with primary
The NZ Standards of Service Provision for Sarcoma patients were developed by the NZ Sarcoma working group and published by the Ministry of Health (MOH) in 2013. Although not formally enacted by the MOH we aimed to determine the impact of these published standards and referral pathways on disease-specific survival of patients with
Aims. The primary objective of this study was to compare the postoperative infection rate between negative pressure wound therapy (NPWT) and conventional dressings for closed incisions following
Population-based studies from the United States have reported that sarcoma patients living in rural areas or belonging to lower socioeconomic classes experience worse overall survival; however, the evidence is not clear for universal healthcare systems where financial resources should theoretically not affect access to standard of care. The purpose of this study was to determine the survival outcomes of
This study explored psychological functioning and coping styles in adult patients with localized and metastatic extremity
Purpose. The optimal sequencing of radiotherapy (RT) with surgery in
Clear cell sarcoma (CCS) is a rare and highly malignant
Wide resection, with or without adjuvant therapy, is the mainstay of treatment for soft tissue sarcoma of the extremities. The surgical treatment of soft tissue sarcoma can portend a prolonged course of recovery from a functional perspective. However, data to inform the expected course of recovery following sarcoma surgery is lacking. The purpose of this study was to identify time to maximal functional improvement following sarcoma resection and to identify factors that delay the expected course of recovery. A retrospective chart review was performed of all patients undergoing surgical treatment of a soft tissue sarcoma of the extremities between January 1st, 1985 and November 15, 2020 with a minimum of 1 follow up. The primary outcome measure was time to maximal functional improvement, defined as failure to demonstrate improvement on two consecutive follow up appointments, as defined by the functional outcome measures of Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) Score or by achieving 90% of maximum outcome score. We identified 1188 patients who underwent surgical resection of a soft tissue sarcoma of the extremities. Patients typically achieved a return to their baseline level of function by 1 year and achieved “maximal” functional recovery by 2 year's time postoperatively. Patient and tumor factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included older age (p=0.007), female sex (p-0.004), larger tumor size (p < 0 .001), deep tumor location (p < 0 .001), pelvic location (p < 0 .001), higher tumor grade (p < 0 .001). Treatment factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included use of radiation therapy (p < 0 .001), perioperative complications (p < 0 .001), positive margin status (p < 0 .001) and return of disease, locally or systemically (p < 0 .001). Most patients will recover their baseline function by 1 year and achieve “maximal” recovery by 2 years’ time following surgical resection for soft tissue sarcoma of the extremities. Several patient, tumor and treatment factors should be used to counsel patients as to a delayed course of recovery.
Myxofibrosarcoma (MFS) is the second most common subtype of soft tissue sarcoma (STS) and is associated with a high rate of local recurrence after resection. These tumours frequently present with peri-lesional edema, termed “tumour tails” on staging MRI scans [1]. Tumour tails(TT) may contain satellite neoplastic cells or can represent benign reactive edema. There are no clear radiological features to distinguish malignant from reactive peri-lesional edema which limits accurate surgical planning, resulting in either high rates of inadvertently positive resection margins and local recurrences or overly-aggressive resections which negatively impact function and increase morbidity [2]. The objective of this pilot study was to prospectively study a cohort of MFS patients with TTs in an attempt to identify radiological features that predict which type of edema is malignant and requires resection together with the main tumour mass. Patients diagnosed with MFS on biopsy at an orthopaedic oncology referral centre between January 1-December 31 2018 who also had TTs on staging MRI scans were prospectively recruited for the study. Tumours were treated with wide surgical excision, including the TTs, and (neo)adjuvant radiotherapy as per institutional protocol. Staging MRI scans were reviewed in a blinded fashion by two musculoskeletal radiologists to distinguish malignant from reactive TTs. The main tumour mass underwent standard histological evaluation while the regions encompassing the TTs were photographed and sectioned into grids. Each tissue section was examined histologically for the presence of satellite neoplastic cells based on morphological criteria. Radiological and histological findings were compared. Six patients met the inclusion criteria and underwent analysis. All tumours were located in the extremities and were deep to fascia. Mean age at presentation was 67 years (range 51 – 85), with a male:female ratio of 4:2. All patients received radiotherapy (50 Gy), either pre- (n=4) or post-operatively (n=2) based on multidisciplinary tumor board discussion or enrolment in a prospective clinical trial. Radiologically, TTs were labelled as malignant in four patients (66.7%) and as benign TTs in two others. The tails were recognised to be malignant due to the differing signal characteristics to reactive edema on mixed MRI sequences. The radiological evaluation correlated exactly with histological analysis, as satellite neoplastic cells were identified microscopically in the same four cases in which the TTs were designated to be malignant by MRI (specificity&sensitivity=100%). Surgical resection margins were microscopically positive in 50% of cases in the TTs themselves, and 75% of cases in which TTs were designated as malignant on staging MRI. “The malignant nature of peri-lesional edema in MFS, also known as the TT, was accurately predicted in this small pilot study based on specific radiological features which correlated exactly with histologic identification of isolated tumor cells. These findings validate development of a larger prospective study to recruit additional patients with tumor tails beyond just MFS, in order to more robustly study the correlation between the MRI appearance and histological distribution of satellite sarcoma cells in peri-lesional edema in STS. We are already recruiting to this expanded radiological-histological investigation including evaluation of additional novel MRI sequences.
Soft tissue sarcomas (STS) are rare, aggressive malignancies derived from connective tissues such as muscle and fat. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common STS in adults. UPS is an aggressive, highly metastatic sarcoma, and is resistant to chemotherapy. New therapies for UPS are desperately needed. STS have an immune desert tumour immune microenvironment (TIME), characterized by a paucity of tumour infiltrating lymphocytes and subsequent resistance to immunotherapies such as immune checkpoint inhibitors. Strategies capable of creating an immune-rich, inflamed TIME may improve immunotherapy efficacies for sarcoma. Activation of the STING (stimulator of interferon genes) receptor can induce potent innate and adaptive immune responses within immunogenic solid tumours. However, this approach has never been attempted in immune-inert sarcomas. Purpose: To determine the therapeutic anti-tumour effects of STING activation in UPS tumours. We have developed an inducible, immune-competent mouse model of UPS. We evaluated intra-tumoural injection of the murine STING receptor agonist, DMXAA, into UPS-bearing immune-competent mice. DMXAA was injected into palpable UPS tumours of the hindlimb. Tumour volume and bioluminescence imaging was recorded bi-weekly. DMXAA treated UPS tumours were also evaluated for necrosis and immune infiltration at defined time points. UPS tumours developed necrosis and lymphocytic infiltration 72 hours after DMXAA treatment. A single intra-tumoural dose of DMXAA into UPS tumours resulted in durable cure in 50% of mice. All survivors rejected a re-challenge of the UPS tumours in both the contralateral hindlimb and lung, suggesting adaptive immunity. The therapeutic effects of DMXAA were mitigated in lymphocyte deficient Rag2 knockout mice. STING therapy is a promising immunotherapeutic opportunity for immune-inert sarcomas. Our data warrants further preclinical investigations in other sarcoma models and in combination with other immune-based therapies.
For soft tissue sarcoma patients receiving preoperative radiation therapy, wound complications are common and potentially devastating; they may result in multiple subsequent surgeries and significant patient morbidity. The purpose of this study was to assess the feasibility of intraoperative indocyanine green fluorescent angiography (ICGA) as a predictor of wound complications in resections of irradiated soft tissue sarcoma of the extremities. A consecutive series of patients of patients with soft tissue sarcoma of the extremities or pelvis who received neoadjuvant radiation and a subsequent radical resection received intraoperative ICGA with the SPY PHI device (Stryker Inc, Kalamazoo MI) at the time of closure. Three fellowship trained Orthopaedic Oncologic Surgeons were asked to prospectively predict likelihood of wound complications based on fluorescence. Retrospective analysis of fluorescence signal along multiple points of the wound length was performed and quantified. The primary endpoint was wound complication, defined as delayed wound healing or wound dehiscence, within 3 months of surgery. An a priori power analysis demonstrated that 5 patients were necessary to achieve statistical significance. Univariate and multivariate statistical analyses were performed to identify predictors of wound complications. 14 patients were consecutively imaged. The diagnosis was undifferentiated pleomorphic sarcoma in 9 (64.3%) of patients; 11 (78.6%) tumors were high grade. There were 6 patients with wound complications classified as “aseptic” in 5 cases and secondary to hematoma in 1 case. Using the ICGA, blinded surgeons correctly predicted wound complications in 75% of cases. In the area of wound complication, the mean % of maximal signal for wound complications was 49% during the inflow phase and 48% during the peak phase. The mean % maximal signal for peri-incisional tissue without wound complications was 77% during the inflow phase and 83% during the peak phase (p=0.003 and p<0.001). During the inflow phase, a mean ratio of normal of 0.62 maximized the area under the curve (AUC=0.90) for predicting wound complications with a sensitivity of 100% and specificity of 77.4%. During the peak phase, a mean ratio of normal of 0.55 maximized the area under the curve (AUC=0.95) for predicting wound complications with a sensitivity of 88.9% and a specificity 100%. Intraoperative use of indocyanine green fluorescent angiography may help to predict wound complications in patients undergoing resection of preoperatively irradiated soft tissue sarcomas of the extremities and pelvis. Future studies are necessary to validate this technology in a prospective manner and to determine if interventions can be instituted to prevent predicted wound complications.
Major wound complication risk factors following soft tissue sarcoma resection. Wound-healing complications represent an important source of morbidity in patients treated surgically for soft tissue sarcomas (STS). The purpose of this study was to determine which factors are predictive of major wound complication rates following STS resection, including tumour site, size, grade, and depth, as well as radiotherapy and chemotherapy. We reviewed 256 cases of STS treated surgically between 2000 and 2011. The primary outcome was occurrence of major wound complications post STS resection. Major wound complications were more likely to occur post STS resection with larger tumour diameters (p = 0.001), high grade tumours (p = 0.04), location in the proximal lower extremity (p = 0.01), and use of preoperative radiotherapy (p = 0.01). Tumours located in the adductor compartment were at highest risk of complications. We did not demonstrate a significant difference in complications rates based on method of closure. Diabetes, smoking, obesity, tumour diameter, tumour location in the proximal lower extremity, and preoperative radiotherapy were independent predictors on multivariate analysis. There are multiple predictors for major wound complications post STS resection. A more aggressive resection of irradiated soft tissues, combined with primary reconstruction, should be considered in cases with multiple risk factors.
The patient's subjective experience of disease is an increasing focus in health care delivery. Health-related quality of life (HRQoL) is defined as a “functional effect of a medical condition and its consequent treatment”; it is both self-reported and multi-dimensional. While functional outcome is well researched among the soft tissue sarcoma (STS) population, few studies have focused on HRQoL, which gives a broader understanding of the psychological, somatic, social and physical toll of cancer and its treatment from the patient's viewpoint. The biologic and anatomic heterogeneity of sarcomas are considerable, just as the treatments are diverse, we surmise that the indicators of patient HRQoL differ and are not captured in existing generic HRQoL tools for cancer. The study objectives were to explore the domains of HRQoL and functioning in adult patients diagnosed with extremity STS from the patient's perspective from active care through survivorship through qualitative inquiry, so as to form the basis for the development of a patient-derived, sarcoma-specific, preference based HRQoL tool. Study design is a sequential exploratory mixed methods study of patient experience in localized or metastatic adult extremity STS (2007 and 2017). The study was conducted at a high-volume sarcoma centre. Qualitative descriptive design was grounded in an integrated knowledge translation approach and aimed at identifying HRQoL domains through in-person and electronic focus groups, and individual semi-structured interviews in both English and French (N=28). The interview guide topics were selected based on existing knowledge about PROs and HRQoL life, including (a) impact of diagnosis on employment or acquisition of academic/vocational skills; (b) physical and psychological functioning; (c) symptom burden; (d) treatment preferences; (e) knowledge of and use of existing resources; (f) impact on family time and resources; and (g) overall experience. Data was analyzed using inductive thematic networks approach using the qualitative software N-Vivo 12. Codes were generated by 2 independent qualitative experts capturing key concepts of HRQoL that is impacted by STS. Basic themes were clustered into organizing themes, and merged into global domains. Attention was paid to deviant cases and within-group dynamics during focus group discussion analysis. Discrepancies or inconsistencies in coding were resolved in consensus meetings. Final sample size was determined when data saturation was reached and no new themes emerged. Qualitative reduction of identified items to reach a consensus framework was facilitated by a moderator during multi-disciplinary panel meetings comprised of sarcoma experts, patient partners, allied health staff and other stakeholders. Twenty-nine patients with biopsy-proven localized or metastatic STS of the extremity participated (69% lower extremity STS; mean age 56 years, 25% with local recurrence, 21% metastatic, 18% amputation). Inductive thematic network analysis revealed five function-related domains HRQoL for patients with STS. The functional domains were mapped to the Wilson & Cleary Model and experience domains were mapped to the Picker Institute's Through Patient's Eyes model. This is a critical step toward developing disease specific outcome measures. Patient-centered research is crucial to understanding the impact of surgery, adjuvant therapy and the associated complications for patients with extremity STS, and thereby improving the quality of care provision. This study offers a unique perspective on what domains and sub domains are most impactful on HRQoL and provides the basis for our on-going development of a disease-specific, preference-based HRQoL measure.
The modified Glasgow Prognostic Score (mGPS) is a validated prognostic indicator in various carcinomas as demonstrated by several meta-analyses. The mGPS includes pre-operative CRP and albumin values to calculate a score from 0–2 that correlates with overall outcome. Scores of 2 are associated with a poorer outcome. Our aim was to assess if the mGPS is reliable as a prognostic indicator for soft tissue sarcoma (STS) patients. All patients with a STS diagnosed during years 2010–2014 were identified using our prospectively collected MSK oncology database. We performed a retrospective case note review examining demographics, preoperative blood results and outcomes (no recurrence, local recurrence, metastatic disease and death). 94 patients were included. 56% were female and 53% were over 50 years. 91% of tumours were high grade (Trojani 2/3) and 73% were >5cm. 45 patients had an mGPS score of 0, 16 were mGPS 1 and 33 were mGPS 2. On univariate analysis, an mGPS of 0 or 2 was statically significant with regards to outcome (p=0.012 and p=0.005 respectively). We have demonstrated that pre-treatment mGPS is an important factor in predicting oncological outcome. A score of 0 relates to an improved prognosis whilst a score of 2 relates to an increased risk of developing metastases and death. mGPS as a prognostic indicator was not affected by either the tumour size or grade. We believe that a pre-operative mGPS should be calculated to help predict oncological outcome and in turn influence management. Further work is being undertaken with a larger cohort.
High grade sarcoma present a systemic metastatic progression in approximaly 50% of cases. The effectiveness of palliative chemotherapy as a treatment of systemic metastases is still controversed. The main objectif of this study is to assess disease progression and survival of patients diagnosed with metastatic soft tissue sarcomas treated with palliative chemotherapy, analyse chemotherapy treatment patterns and response to different lines of treatment. Retrospective chart review of 75 patients treated with palliative chemotherapy for metastatic soft tissue sarcomas between 2003 and 2013 at Maisonneuve-Rosemont Hospital. Data for control group of 40 patients with metastatic soft tissue sarcomas not treated with chemotherapy was collected retrospectively. Collected data include demographic data, overall survival, time free survival, type of chemotherapy treatment, surgical treatment and adverse reaction to palliative chemotherapy. Overall survival was analysed with Kaplan-Meier test. Categorial variable were compared with Log-Rank test. Seventy-five patients (37% female; mean age 50.4 years) received minimally one line of chemotherapy for their metastatic sarcomas. The regimens most commonly used in first-line were doxorubicin (48%) and doxorubicin combined with ifosfamide (21.3%). Favorable response was achieved by 38.7% in first-line and 27.9% in second-line therapy. Median overall survival with chemotherapy treatments was more than two times overall survival without treatments. Median overall survival was 19 months with chemotherapy treatments and 7 months without chemotherapy (p<0.0001). There was no statistically significant difference between survivals for treated and untreated patients with chemotherapy when analysed in term of the histological subtype, age and monotherapy versus combined treatment. Event-free survival was statistically longer during the first year for the group of patients treated with combined chemotherapy (p=0.0125). Results have shown a significantly improved overall survival in all histological groups, resulting in an OS of 19 vs 7 months for the chemotherpy and non chemotherapy group respectively. Nevertheless, patients with favorable response to chemotherapy have poor outcomes. Additional treatment options are needed.
Wound complications are common in patients with soft tissue sarcomas (STS) treated with surgical excision. Limited data is available on predictive factors for wound complications beyond the relationship to neo-adjuvant or adjuvant radiotherapy. Likewise, the association between blood transfusion, patient comorbidities and post-operative outcomes is not well described. In the present study we identified the predictive factors for blood transfusion and wound complications in patients undergoing surgical resection of soft tissue sarcoma from a national cohort. The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent surgical resection of a STS from 2005 to 2013. Primary malignant soft tissue neoplasms were identified using the following ICD-9 codes: 171.2, 171.3 and 171.6. Patients treated with both wide excision and amputation were identified using the current procedural terminology (CPT) codes. Prolonged operative time was defined as greater than 90th percentile of time required per procedure. A multivariable logistic regression model was used to identify associations between patient factors and post-operative wound complications (superficial and deep surgical site infections (SSI), and wound dehiscence). A similar regression model sought to identify prognostic factors for blood transfusion and associations with post-operative outcomes. A total of 788 patients met our inclusion criteria. Of theses, 64.2% had tumours in the lower limb, 23.1% patients had tumours in the upper limb, and 12.7% patients had pelvic tumours. Six hundred and forty patients (81.2%) underwent surgical excision; 148 (18.8%) patients had an amputation. Multivariable logistic regression modeling identified American Society of Anaesthesiologist (ASA) class 3 and 4 (OR=2.3, P=0.03; OR=8.3, P=0.001, respectively), amputation (OR=14.0, P<0.001) and prolonged operative time (OR=4.6, P<0.001) as significant predictors of blood transfusion. Radiotherapy (OR=2.6, P=0.01) and amputation (OR=2.6, P=0.01) were identified as predictors of superficial SSI, whereas ASA class 4 (OR=6.2, P=0.03), prolonged operative time (OR=3.9, P=0.012) and return to the operating room (OR=10.5, P<0.001) were associated with deep SSI. Male gender (OR=1.8, P=0.03), diabetes (OR=2.3, P=0.03), ASA class 3 (OR=2.4, P=0.003), amputation (OR=3.8, P<0.001) and steroids (OR=4.5, P=0.03) were identified as predictors for wound dehiscence and open SSI. A national cohort demonstrates that male gender, diabetes, chronic steroid use, higher ASA score and radiotherapy are associated with an increased incidence of wound complications. One in twenty-three patients undergoing resection of an STS will require a blood transfusion, and this risk is correlated with amputation, prolonged operative time and increased ASA score. Strategies to decrease the risk of blood transfusion and wound complication should be considered for these patient groups.
Aims. The risk of postoperative complications after resection of