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.

This study explored psychological functioning and coping styles in adult patients with localized and metastatic extremity soft-tissue sarcoma (STS) from diagnosis through survivorship in a single expert sarcoma center in Canada. Our analyses were driven by three main goals: 1) to develop a better understanding of the affective responses and coping mechanisms in patients who face this rare illness, 2) to identify areas of psychological functioning in which patients with STS experience most difficulties, and 3) to describe how these areas could be best addressed in clinical settings.

This descriptive qualitative study is a part of a larger mixed-methods study on health related quality of life (HRQoL) in adult patients with soft-tissue sarcoma treated between 2003 and 2018. Purposive sampling based on demographic and disease variables from all patients within a prospective database was utilized to ensure a representative patient population. Three formats of data collection were conducted in French and English, 2 online focus groups (total n=12), 2 in-person focus groups (total n=12), as well as individual semi-structured interviews (n=4). Data was analyzed using inductive thematic networks approach using the qualitative software N-Vivo 12. Codes were generated by 2 independent qualitative experts that captured key concepts referring to psychological functioning and coping mechanisms. Basic themes were clustered into organizing themes, which were later merged into a global theme. Attention was paid to deviant cases, and within-group dynamics during focus group discussion analysis. Any discrepancies or inconsistencies in coding were resolved in a consensus meeting. The final sample size was determined when data saturation was reached, and no new themes emerged.

Our analyses of psychological well-being and functioning revealed three main themes, mood, anxiety, and body image concerns. Feelings of depression and low mood were prominent, coinciding with physical symptoms and limitations especially during the phase of treatment and recovery. Women were more likely to report emotional volatility, while men tended to report more preoccupation. Loss of control and independence, anxiety related to illness recurrence, uncertainty about the future and facing one's mortality significantly impacted quality of life. Furthermore, while patients were more concerned with limb functionality, disfigurement and self-consciousness featured prominently in the narrative. Four adaptive coping styles were observed, positive reframing and optimism, finding a purpose, being proactive, and using humor. Among the maladaptive strategies, we noted passive acceptance, and avoidance and denial.

Psychological well-being is an important domain in the HRQoL of adult patients with extremity STS. Physicians and medical workers should encourage adaptive coping mechanisms such as positive reframing and optimism. Patients endorsing higher levels of psychological distress and maladaptive coping styles should be monitored for their well-being and multidisciplinary strategies employed to optimize psychological function and HRQoL.

Background

We have reported an injectable L-pNIPAM-co-DMAc hydrogel with hydroxyaptite nanoparticles (HAPna) which promotes mesenchymal stem cell (MSC) differentiation to bone cells without the need for growth factors. This hydrogel could potentially be used as an osteogenic and osteoconductive bone filler of spinal cages to improve vertebral body fusion. Here we investigated the biocompatibility and efficacy of the hydrogel in vivo using a proof of concept femur defect model.

This is quite an innovative study that should lead to a multicentre validation trial. We have developed an FDG-PET/MRI texture-based model for the prediction of lung metastases (LM) in newly diagnosed patients with soft-tissue sarcomas (STSs) using retrospective analysis. In this work, we assess the model performance using a new prospective STS cohort. We also investigate whether incorporating hypoxia and perfusion biomarkers derived from FMISO-PET and DCE-MRI scans can further enhance the predictive power of the model.

A total of 66 patients with histologically confirmed STSs were used in this study and divided into two groups: a retrospective cohort of 51 patients (19 LM) used for training the model, and a prospective cohort of 15 patients (two patients with LM, one patient with bone metastases and suspicious lung nodules) for testing the model. In the training phase, a model of four texture features characterising tumour sub-region size and intensity heterogeneities was developed for LM prediction from pre-treatment FDG-PET and MRI scans (T1-weighted, T2-weighted with fat saturation) of the retrospective cohort, using imbalance-adjusted bootstrap statistical resampling and logistic regression multivariable modeling. In the testing phase, this multivariable model was applied to predict the distant metastasis status of the prospective cohort. The predictive power of the obtained model response was assessed using the area under the receiver-operating characteristic curve (AUC). In the exploratory phase of the study, we extracted two heterogeneity metrics from the prospective cohort: the area under the intensity-volume histogram of pre-treatment DCE-MRI volume transfer constant parametric maps and FMISO-PET hypoxia maps (AU-IVH-Ktrans, AU-IVH-FMISO). The impact of the addition of these two individual metrics to the texture-based model response obtained in the testing phase was first investigated using Spearman's correlation (rs), and lastly using logistic regression and leave-one-out cross-validation (LOO-CV) to account for overfitting bias.

First, the texture-based model reached an AUC of 0.94, a sensitivity of 1, a specificity of 0.83 and an accuracy of 0.87 when tested in the prospective cohort. In the exploratory phase, the addition of AU-IVH-FMISO did not improve predictive power, yielding a correlation of rs = −0.42 (p = 0.12) with lung metastases, and a relative change in validation AUC of 0% in comparison with the texture-based model response alone in LOO-CV experiments. In contrast, the addition of AU-IVH-Ktrans improved predictive power, yielding a correlation of rs = −0.54 (p = 0.04) with lung metastases, and a change in validation AUC of +10%.

Our results demonstrate that texture-based models extracted from pre-treatment FDG-PET and MRI anatomical scans could be successfully used to predict distant metastases in STS cancer. Our results also suggest that the addition of perfusion heterogeneity metrics may contribute to improving model prediction performance.

Purpose: Lymphoedema is a serious potential complication of the management of extremity soft tissue sarcoma (STS) about which relatively little is known. We aimed to evaluate the incidence of lymphoedema, its severity and associated risk factors following limb salvage for extremity STS.

Method: Lymphoedema severity (EORTC/RTOG) was recorded prospectively in two databases of soft tissue sarcoma patients. Patient’s demographics, tumor characteristics, surgical procedures, radiotherapy dosage, complications and functional outcomes (MSTS, TESS) were also prospectively collected. Charts were also retrospectively abstracted for body mass index (BMI) and medical comorbidities.

Results: 289 patients had sufficient data for analysis (158 male). Mean age was 53 (range 16–88). Mean BMI was 27.4 (range: 15.8–52.1). 209 had lower extremity tumors and 80, upper. Mean tumor size was 8.1 cm (range 1.0–35.6 cm). 77 had no adjuvant radiation, 180 had 50 Gy and 32, 66 Gy. The incidence of lymphoedema was found to be 28.7% (58 mild, 22 moderate, 3 severe). Mean MSTS score was 32 (range: 11–35) and TESS was 89.4 (range: 32.4–100). We grouped cases with lymphoedema grade 0–1 and 2–3. Univariate analysis found significant correlations between the severity of lymphedema and tumor size ≥5 cm (p=0.011), deep location (no patient with a superficial tumor had severe lymphoedema, p=0.001), and radiation dosage 50 vs 66 Gy (p=0.021) but not between upper vs lower extremity (p=0.06).

Conclusion: 9% of STS studied developped significant post-treatment lymphoedema. Large, deep tumors and necessity for 66 Gys were most at risk. This group could be targeted for prophylatic intervention.

Fracture healing continues to pose challenges for researchers and clinicians in the field of trauma and orthopaedic surgery. The future treatment strategies for fracture healing will most likely focus on the use of biologic and biochemical methods in combination with established fixation and mechanical methods. In this study, heparanase (HPSE), a mammalian endo-glycuronidase that promotes angiogenesis through cleavage of the extra cellular matrix (ECM)-heparan sulphate and mobilization of ECM resident growth factors, was investigated for its osteoblasts-stimulating effect.

Osteoblast cells, originated from osteoporotic and healthy human subjects who underwent total knee replacement, were cultured and exposed to HPSE at a series of final concentrations of 1, 3, and 6μg/mL. The cell density, proliferation, alkaline phosphatase (ALP) production and specific activity, and expression of osteogenic genes were examined.

A marked stimulating effect of HPSE in cell density and proliferation was observed in the osteoblastic cultures from both osteoporotic and healthy subjects. The ALP level and its specific activity, a classical osteoblastic marker, were also increased at the presence of HPSE in a dose-dependant manner. The expression of osteogenic pathway genes, particularly bone morphogenic proteins (BMPs), transcription factors SMDs, vascular endothelial growth factor and tissue inhibitor of metallopeptidase (TIMP) were up- or down-regulated, which correlated with the doses of HPSE.

This study is the first to show that HPSE increases cell proliferation and stimulates differentiation in human osteoblasts suggesting that the potential of HPSE as a new biofactor for the treatment of fractures. Further research on HPSE in co-culture of osteoblasts and osteoclasts is under investigation in our laboratory.

Introduction Morbidity associated with wound complications may translate into disability and quality-of-life disadvantages for patients treated with radiotherapy (RT) for soft tissue sarcoma (STS) of the extremities. Functional outcome and health status of extremity STS patients randomized in a phase III trial comparing pre-operative versus post-operative RT is described.

Methods One hundred and ninety patients with extremity STS were randomized after stratification by tumor size dichotomized at 10 cm. Function and quality of life were measured by the Musculoskeletal Tumor Society Rating Scale (MSTS), the Toronto Extremity Salvage Score (TESS), and the Short Form-36 (SF-36) at randomization, six weeks, and three, six, 12, and 24 months after surgery. One hundred and eighty-five patients had function data.

Results Patients treated with post-operative RT had better function with higher MSTS (25.8 v 21.3, P < .01), TESS (69.8 v 60.6, P =.01), and SF-36 bodily pain (67.7 v 58.5, P =.03) scores at six weeks after surgery. There were no differences at later time points. Scores on the physical function, role-physical, and general health sub-scales of the SF-36 were significantly lower than Canadian normative data at all time points. After treatment arm was controlled for, MSTS change scores were predicted by a lower-extremity tumor, a large resection specimen, and motor nerve sacrifice; TESS change scores were predicted by lower-extremity tumor and prior incomplete excision. When wound complication was included in the model, patients with complications had lower MSTS and TESS scores in the first two years after treatment.

Conclusions The timing of RT has minimal impact on the function of STS patients in the first year after surgery. Tumor characteristics and wound complications have a detrimental effect on patient function.