Non-oncological outcomes following limb salvage surgery in patients with knee sarcoma: a scoping review

Figures & data

Table 1. PICO Table to define the research question and support the inclusion and exclusion criteria for the review.

Population	Adult and paediatric population diagnosed with bone or soft tissue malignant tumour around the knee
Intervention	Limb salvage surgery (LSS)
Comparison	None
Outcome	Functional levels, physical activities, gait, mobility, quality of life, and return to work

Figure 1. PRISMA Diagram for selecting suitable articles.

Table 2. Search terms included for the review.

Term	Keywords/synonym
Sarcoma	Or Bone cancer Or Malignan* Or Osteosarcoma
AND
Knee	Or Distal femur Or Proximal tibia Or Patella
AND
Limb salvage	Or Limb sparing
AND
Functional outcomes	Or Rehabilitation outcomes Or Physical activity Or Gait Or Mobility Or Participation Or Return to work (RtW) OR Quality of life (QoL)

* is a truncation character.

Table 3. Inclusion/exclusion criteria for the review.

Inclusion	Rationale
English language literature	Non-English papers require translation, which is not practical due to limited time and resources.
2009 and onward	To focus on the quality of articles concerned with limb salvage after publication of the clinical recommendations from the European Society of Medical Oncology in 2009, which are widely accepted by global committees and institutions.
Full access available	Limited resources to access the unavailable articles.
Limb salvage for primary bone tumours	The scope of this literature review focuses on outcomes of limb salvage with patients who were diagnosed with cancer; therefore, other conditions such as vascular, trauma and diabetes must be excluded.
Mixed qualitative and quantitative in form of experimental and observational studies, randomised control trials, quasi-experimental research, cohort studies, case-control studies, cross-sectional studies and retrospective chart reviews	Both qualitative and quantitative outcomes were presented in the literature. Qualitative studies were included to consider the outcomes from a population point of view. As the scope of this literature review focused on exploring the outcomes of limb salvage intervention, observational longitudinal studies were limited to cohort studies, case-control studies and high-quality retrospective chart reviews in order to obtain valuable data from such studies [22]. Case series, case reports and expert opinions were excluded so as to focus on high-quality evidence-based practice articles.
Limb salvage procedures including allograft, endoprostheses and both techniques	This literature review focused on limb salvage techniques intended to remove the tumour, as defined in this literature review, with interventions for resuming functional levels. Articles that focused on outcomes or efficacies of procedures or interventions other than limb salvage techniques (which are supposed to reconstruct the limb or enhance the surgical procedure of the limb salvage) were excluded, as they are not the main objective of this literature review.
Limb salvage/sparing procedures	Other procedures which are considered ablative such as amputation and rotationplasty involve wearing an external prosthesis. These were excluded as they are not within the scope of this review. However, articles that included ablative surgery as a comparison group were included.
Articles with more than one measure for functional, physical or QoL outcomes	Single-outcome measurement scores do not provide sufficient context for functional, physical or QoL outcomes, as they might be either a patient-oriented or an objective measure. Therefore, more than one outcome measure was required in the articles concerned with non-oncological outcomes to provide sufficient data for inclusion.

Table 4. Review results: articles identified from methods described.

Reference, date of publication & location	Sample	Type of study	Method of research	Outcome measure	Procedure type	Key findings	Limitations
1. [17] 2017 Netherlands	N = 20 Gender: Not specified Mean age = 22.3 (18.2–31.6)	Prospective cohort	Long-term study comparing functional outcomes of participants at 2- and 7-years post-operation	TESS MSTS Baecke questionnaire Time up & down stairs (TUDS) Various walking activities (VWA) 6 min walking test (6MWT)	LSS = 15 (Allografts = 6) (Endoprostheses = 9) Ablative surgery (Amputation and Rotationoplasty) = 5.	The study is an extension to a previous study concerned with young adults’ functional outcomes after surgical intervention (LSS or ablative) for bone sarcoma. Patients reached plateau phase at 2 years follow-up (f/u). No significant changes in functional outcome scores between 2 years and 7 years f/u. No deterioration noted in functional outcomes at 7 years f/u despite the presence of 1 or 2 complications. Mean score of covered walking distance outcome measure was 514 m (471–556), which is lower than the mean score (593) of healthy adult individuals. MSTS: Mean score = 83%, CI (37–100)	Small sample size, as nearly half of the participants in previous study are deceased due to the disease prognosis. The study did not compare the results of the major variables such as the ablative and salvage surgeries, type and technique of the procedure, which leads to the generalisability of the findings with chances of bias. MSTS score was taken only at 7 years f/u.
2. [35] 2016 United Kingdom	N = 76 (43 Male & 33 Female) Mean age = 32 (9–74)	Retrospective cohort	Comparison between intra-articular resection and extra-articular resection in patients with bone and soft-tissue sarcoma	MSTS score Knee ROM	LSS = 63 (EAR = 42) (IAR = 21) Ablative surgery (Amputation and Rotationoplasty)= 13	MSTS: Mean score in LSS = 26, with no significant difference between the intra-groups. However, both LSS intra-groups in general were significantly better than the ablative surgery group (p = 0.04). ROM: IAR mean flexion = 106 (70–130) EAR mean flexion = 103 (60–130) No significant differences between groups	Heterogeneous sample size in terms of surgical procedures, techniques and presence of adjuvant therapies without taking them into account as confounding factors during data analysis. This could lead to measurement or analysis bias. No data reported in regards to extension lag, which is a predictable complication with extra-articular endoprostheses, as reported in other reviewed papers.
3. [18] 2014 China	N = 15 (10 Male & 5 Female) Mean age = 12 (9–16)	Retrospective cohort	Comparison of functional outcomes between two groups of patients: limb preservation with physeal distraction and limb preservation with knee arthroplasty (endoprostheses)	MSTS score TESS score ROM	Physeal distraction (PD) = 6 Knee arthroplasty KA = 9	MSTS: Excellent to good overall functional scores. PD Mean MSTS = 86.67% KA Mean MSTS = 74.67%. No significant difference found between groups TESS: PD score = 82.33% KA score = 76.33% No significant differences of MSTS and TESS scores between groups ROM: PD group has significantly better ROM than KA group (p = 0.05)	Small sample size. Confounding factors as associated complications were not taken into account in the statistical calculations of functional outcomes.
4. [36] 2013 Germany	N = 59 (36 Male & 23 Female) Mean age = 33 (11–74)	Retrospective cohort	Comparison of functional outcomes between extra-articular resection and intra-articular resection groups	MSTS score ROM Oxford knee score	EAR = 55 IAR = 4	MSTS: Assessed in only 46 patients; 13 patients were excluded due to post-operative failure episode within 1st year Mean MSTS score = 22 (10–29) which is considered widely variable Oxford knee score: Completed at latest f/u by 21 participants only; mean score = 32 (10–48), which is considered widely variable. ROM: Recorded in only 38 patients Mean flexion = 72 degree (10–100) Nearly a third of patients had < 90 degree of flexion with one patient reporting gross limitation due to peri-prosthetic infection and revision.	Lack of data on functional outcome scores leading to possible selection, measurement and analytical bias. Weak study design and statistical analysis of functional outcomes. Small sample size of IAR in comparison with EAR due to convince sampling method. Use of only univariate statistical analysis in some other outcome measures.
5. [19] 2012 USA	N = 20 (12 Male & 8 Female) Mean age = 34 (15–76)	Retrospective cohort	Comparison of functional status and QoL between limb salvage and above knee amputation groups	Physiological Cost Index (PCI) Reintegration to Normal Living Index SF-36 TESS	LSS = 14 all with endoprostheses AKA = 6	RNL: Scores in LSS group significantly > than AKA group (p = 0.03) PCI: Significantly better gait performance in LSS group than AKA (p = 0.02) TESS & SF-36: Similar scores in both groups, with no significant differences Overall, high QoL scores were observed in both groups.	Small sample size. Limited and no access of participants to advanced prostheses options such as C-Leg in the AKA group. Confounding factors such as chemo-induced cardiovascular toxicity were not taken into consideration with appropriate statistical tests, especially with the use of PCI as objective outcome measure, which measures cardiovascular performance in relation to gait. The heterogeneity of the LSS group can lead to measurement bias.
6. [37] 2018 Spain	N = 45 (22 Male & 23 Female) Mean age: DF = 19.7 (10–49) PT = 23.8 (12–55)	Case-control	Comparison of allograft-prostheses composite for reconstruction between distal femur and proximal tibia groups	MSTS score Western Ontario and McMaster Universities (WOMAC) score for QoL Visual Analog Scale (VAS) for pain	DF = 24 PT = 21	Standardised healthcare plan, surgical technique and rehabilitation protocol MSTS: Good overall outcome score Mean of DF & PT = 24 No significant difference found between the groups ROM: Extension lag outcomes: PT Median = 7 degrees (SD 4.0) DF Median = 5 degrees (SD 1.0) PT group has significantly worse extension lag than DF group (p = 0.029). WOMAC & VAS: All patients reported either mild to no pain. No significant differences found between groups. All patients required permanent cane to walk except two patients in PT group who used no walking aid. Only one patient from DF group and four patients from PT group reported a return to previous level of activity.	Possible selection bias due to the retrospective nature and convenience sampling. Limited statistical analysis of functional outcome measures with associated variables such as demographics, stage of disease and surgical technique (e.g. extensor mechanism reconstruction with PT).
7. [20] 2009 Australia	N = 20 (10 Male & 10 Female) Mean age at surgery = 16.1 Control N = 10. Mean age= 24.9	Case–Control	Retrospective evaluation of disease-specific impairment and disability in patients who underwent LSS around the knee due to sarcoma	MSTS TESS ROM Muscle power “knee extensors”	DF = 17 PT = 3 All DF & PT with intra-articular endoprostheses replacement	MSTS: Good to excellent overall score Mean = 25 (SD 3.0) The emotional acceptance and functional ability components ranked the lowest. ROM: Knee flexion was significantly worse in cases when compared to control group (p < 0.01). Mean flex = 120 (85–140) Muscle Power: Knee strength was significantly reduced in cases in comparison with control (p = 0.04) TESS: Overall mild disability score Mean = 86% (SD 3.5) Lowest components of TESS score were kneeling movements, followed by sport participation, then walking upstairs and uphill. TESS score has moderate positive correlation with knee flexion movement and knee extensor strength TESS score has moderate positive correlation with MSTS sub-score of walking capacity (p = 0.02), followed by emotional acceptance (p = 0.01) No statistically significant differences between the prosthetic design and subjective outcome measures for impairment and disability	Small sample size. Lack of recruitment information on control group, their demographics and generally a small number “Half number of the cases included”. Study design does not match the methodology; the methods used in the study are more like a case-series instead of case-control.
8. [38] 2018 Malaysia	N = 20 (8 Male & 12 Female) Mean age = 22.75 (8–44)	Cross-sectional study design with objective and subjective measures	Evaluation of gait pattern with patients who underwent endoprosthetic reconstruction after tumour resection and comparison of the objective data from gait assessment with subjective data from MSTS score	Gait analysis for collecting data on temporal parameters-preferred walking velocity, stride length and duration of stance phase + goniometry of the knee during walking MSTS score	DF = 15 PT = 5	MSTS: Good to excellent score levels Mean = 21 (13–25) 80% of participants (21–25) - Good to excellent 20% of participants (13–20) - Fair to good Lowest component = “Walking ability”; only two patients gave a normal gait score after the surgery while the rest who scored the lowest in walking required a walking aid in outdoor activities. Gait analysis: The participants walked slower when compared with normal gait parameters (p < 0.05), indicating reduced stride length, velocity and stance after the surgery. Comparison between affected and non-affected limb indicated symmetrical stride length & velocity. Asymmetrical stance phase was found significantly reduced (p = 0.00) Knee goniometry during gait analysis: 80% of participants exhibited stiff knee gait 10% of participants had flexed knee gait 10% of participants had normal knee gait ROM: Despite the stiff and flexed knee gait pattern revealed by gait analysis, ROM in all patients was within normal actively and passively: Active ROM mean = 2.25–105 Passive ROM mean = 0–105 No statistically significant difference found between affected and non-affected knee ROM (p > 0.05) Overall MSTS score had significant relationship with velocity aspect in gait analysis (p < 0.05)	Small sample size. No clear recruitment process described, which may lead to selection bias. Age varied widely and was not statistically tested with outcome measure variables. No bivariate or multivariate statistical analysis done in regards to location of resected tumour (distal femur or proximal tibia) with other variables.
9. [21] 2011 Netherlands	N = 82 (41 Male & 41 Female) Mean age = 16.9 (8–25)	Cross-sectional study with objective measures	Evaluation of functional ability and physical activity among children and young adults who underwent limb salvage and ablative surgeries for treating sarcoma around the knee	TESS score Time up & go (TUG) Time up & down stairs (TUDS) 6 min walking test (6MWT) Lie down and stand up (LDSU) Various walking activities (VWA) Baecke questionnaire Activity monitor by ActiLog device	Limb salvage = 39 (Allograft = 24) (Endoprostheses = 15) Ablative surgery = 43 (Amputation = 27) (Rotationoplasty = 16)	TESS: Mean score = 85.3 indicating moderate disability; no significant differences found between the LSS and ablative surgery groups Baecke questionnaire: Mean score = 7.4 indicates moderate limitation No significant statistical difference between the LSS and ablative groups in physical activity aspects of the Baecke Questionnaire and activity monitor measure Performance tests: TUDS & VWA: LSS group had better scores than ablative surgery (p = 0.003, p = 0.004, respectively). Other performance tests showed no statistical difference between the groups.	The study f/u period ranged between 1–5 years, which is relatively short when considering long-term aspects. Heterogeneous treatment protocols may lead to possible procedural or measurement bias.
10. [13] 2017 China	N = 108 (69 Male & 39 Female) Mean age = 25.3 (15–67)	Retrospective chart review	Retrospective study on long-term functional outcomes of cemented mega-prostheses	MSTS ROM	DF = 72 PT = 36	MSTS: Good to excellent overall score Overall mean = 22.9 DF mean = 25.4 PT mean = 20.95 No statistical test was done in this regard. ROM: Knee flexion range (90–120) in patients who developed patella alta, with no mean calculated in this regard nor any statistical tests done with other variables.	Weak and lacking statistical approach in regard to functional outcome measures. No mention of ROM in the cases who did not develop patella alta. Heterogeneous sample for age, tumour type, stage, treatment protocol and surgical procedures.
11. [39] 2014 Japan	N = 14 (9 Male & 5 Female) Mean Age: EAR = 44.4 years (23–65) IAR = 22.4 years (11–58)	Retrospective chart review	Comparison of extra-articular functional outcomes to intra-articular endoprostheses procedures	MSTS ROM	EAR = 6 IAR= 8	MSTS: EAR mean = 21 IAR mean = 26.5 EAR was significantly worse than IAR (p < 0.01) Lowest MSTS components: “walking ability” and “support” 4 patients in EAR group required walking aids, and all patients of IAR walked with no aid ROM: (EAR < IAR) EAR flexion = 84 (60–95) IAR flexion = 95 (90–110) Extension lag < 10 degrees was present in four cases	Small sample size. The mean age of both groups varied noticeably. Possible bias due to confounding factors such as the use of different types of endoprostheses, variable follow-up period and presence of adjuvant treatment in some cases.
12. [40] 2012 China	N = 120 (75 Male & 45 Female) Mean age = 18.9 (5–48)	Retrospective chart review	Evaluation of functional outcomes	MSTS ROM	(DF = 78) (PT = 42)	MSTS: Good to excellent overall score DF mean = 25.7 (SD 2.9) PT mean = 25.0 (SD 2.8) No significant difference (p = 0.21) Lowest components: “functional” and “emotional capacity” ROM: Knee flexion in DF was worse than PT but with no statistical significance (p = 0.12) DF = 103 (SD 27) PT = 112 (SD 30) Extension ROM was significantly worse regarding lag in PT group (18 patients) compared to DF group (nine patients) (p = 0.03) DF = 8 (SD 3) PT = 14 (SD 7)	Lack of rehabilitation program between the patients lead to procedural bias. The authors stated that due to healthcare financial aspects, many osteosarcoma patients underwent amputation surgery because they could not afford the neo-adjuvant therapies required for LSS, which can affect the sampling. Heterogeneous chemotherapy protocols delivered in the study could be highly considered as confounding factors, leading to procedural or measurement bias.
13. [41] 2010 Australia	Case N = 20 (17 DF & 3 PT) all with intra-articular endoprostheses replacement Mean age at surgery = 16.1 Control N = 10.	Case-Control Retrospective outcome study.	Electromyo-graphic assessment of Gait function following limb salvage procedures for bone sarcoma.	Electromyo-graphy. Energy Consumption Measurement (Cosmed KB4 system).	Assessment and comparison of locomotor patterns in Osteosarcoma patients who went intra-articular knee limb salvage surgery via electromyographic and energetic measurement techniques.	EMG: Stance Phase: prolonged activation of rectus femoris and prolonged co-contraction of the rectus femoris and hamstring muscles in the affected limb of the LSS group compared to a control group (p > 0.05). Higher Quadricepts to Hamstring co-contraction index in affected limb than unaffected when compared to control group (p = 0.01). Energy Measure: Gross Energy Expenditure + Net Energy Expenditure + Energetic Cost Measurements were all significantly higher in LSS group (p < 0.01) indicating higher amount of energy used by LSS group during walking activity when compared to control group.	Small Sample Size and uneven comparison between case and control groups. Study design is not well developed and executed.  Confounding factors which lead to cardiopulmonary issues in cancer patients such as adjuvant therapies were not taken into account especially with the use of Energy Consumption Measures.

Abbreviations: LSS: limb salvage surgery; AKA: above knee amputation; PT: proximal tibia; DF: distal femur; IAR: intra-articular replacement; EAR: extra-articular replacement.

Table 5. Summary review of articles with respect to three themes.

	Functional Outcomes	Quality of Life	Gait and Knee Goniometry
Bekkering et al. 2011 [21]	✓	✓	✓
Carty et al. 2009 [20]	✓	✓	✓
Hardes et al. 2013 [36]	✓		✓
Ieguchi et al. 2014 [39]	✓		✓
Malek et al. 2012 [19]	✓	✓	✓
Puerta et al. 2018 [37]	✓	✓
Shaihd et al. 2017 [35]	✓		✓
Singh et al. 2018 [38]	✓		✓
Tan et al. 2012 [40]	✓		✓
Van Egmond-van Dam et al. 2017 [17]	✓	✓	✓
Zhang et al. 2014 [18]	✓	✓	✓
Zhang et al. 2017 [13]	✓		✓
Carty et al. 2010 [41]	✓		✓

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