Patient- and Caregiver-Reported Outcomes After Limb Salvage or Amputation for Pediatric Bone and Soft Tissue Sarcomas: A Scoping Review

Patient- and Caregiver-Reported Outcomes After Limb Salvage or Amputation for Pediatric Bone and Soft Tissue Sarcomas: A Scoping Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Patient- and Caregiver-Reported Outcomes After Limb Salvage or Amputation for Pediatric Bone and Soft Tissue Sarcomas: A Scoping Review Lindsay Jibb, Juliane Feliciano, Isabella Zaffino, Tessa Palmert, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8379832/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Purpose Children diagnosed with bone tumors or soft tissue sarcomas often undergo limb salvage surgery or amputation, procedures that shape long-term functioning and quality of life (QOL). Patient- and caregiver-reported outcomes (PROs) provide essential insight into physical, psychosocial, and participation impacts, yet existing evidence is dispersed and methodologically heterogeneous. This scoping review mapped the PRO literature for children, survivors, and caregivers following limb surgery and identified gaps limiting clinical care and research advancement. Methods Six databases were searched. Eligible studies included children with bone or soft-tissue sarcomas and their family caregivers that reported PROs or needs related to limb salvage or amputation. Two reviewers independently screened studies and charted data. Quantitative and qualitative findings were summarized descriptively and synthesized narratively across QOL domains. Results Twenty-seven studies fulfilled inclusion criteria. Physical functioning was the most assessed domain, with generally moderate-to-good outcomes and limited differences between limb salvage and amputation. Pain remained common months to years post-surgery. Psychosocial findings were mixed, reflecting peer acceptance but also body image, recreation, and school participation challenges. Only four studies included caregivers, who reported anxiety, depression, financial strain, and shifting family roles. Across studies, PRO measurement was highly heterogeneous, with inconsistent domains of assessment, measurement tool use, and timepoints. Conclusions Children and families experience complex functional and psychosocial impacts after limb surgery, underscoring needs for enhanced rehabilitation, pain care, school reintegration, and caregiver support. A coordinated measurement agenda—including core PRO domains, longitudinal assessment, and family-centered approaches—is essential to strengthen evidence and improve survivorship care. Pediatric oncology Sarcoma Limb salvage Amputation Patient-reported outcomes Quality of life Caregivers Scoping review Figures Figure 1 Figure 2 1. INTRODUCTION Childhood bone tumors and soft tissue sarcomas—most commonly osteosarcoma and Ewing sarcoma—require multimodal therapy that often includes limb-directed surgery. Over the last decades, advances in chemotherapy protocols, prosthetic technology, and surgical techniques, have expanded the use of limb salvage procedures, with amputation remaining necessary in certain clinical contexts ( 1 , 2 ). These approaches aim to maximize survival but inevitably shape the daily functioning and quality of life (QOL) of patients and survivors—affecting mobility, independence, pain, participation at school and in recreation, body image, social relationships, and long-term wellbeing ( 3 – 6 ). Understanding impacts across surgery type from the perspectives of children, survivors, and their family caregivers is essential. Patient-reported outcomes (PROs) capture how health status and treatment effects are experienced in everyday life, while reports from caregivers—who provide practical, emotional, and advocacy support—can illuminate needs that clinician reports and medical record may miss ( 7 , 8 ) Still, despite the critical importance of understanding child function and participation, evidence is dispersed across disciplines and study designs. Outcomes beyond physical function, including psychosocial health, schooling and employment, and caregiver perspectives, are inconsistently assessed and reported. The fields of pediatric surgical oncology care and research lack consensus on which PRO measures (PROMs) are practical to administer and which capture the domains that matter most to children and families. A comprehensive map of what has been studied, how it has been measured, and where the gaps remain is required to inform practice and guide research, including by directing PRO measure selection and administration, as well as family-centered supports. By charting the nature of research in this area and identified child-, survivor-, and caregiver-reported post-surgical outcomes, a coherent agenda for interdisciplinary clinicians and researchers working at the intersection of pediatric oncology, surgery, and rehabilitation can be developed. This review was guided by the following research questions: ( 1 ) What health outcomes, reported by children diagnosed with bone tumors or soft tissue sarcomas, survivors of such cancers, and their family caregivers, are associated with having undergone limb salvage surgery or cancer-related amputation? ( 2 ) What gaps exist in the evidence related to measuring PROs in these groups that might limit current clinical care efforts or future evidence generation? 2. METHODS 2.1 Framework The scoping review followed the framework developed by Levac et al. (2010), encompassing inc question formation, study identification and selection, data charting, and synthesis ( 9 ). Reporting adhered to the PRISMA Extension for Scoping Reviews and the PRISMA Extension for Searching guidelines ( 10 , 11 ) ( Appendix 1 ). The review protocol was pre-published on Open Science Framework ( https://osf.io/f8a94 ). 2.3 Study Identification A health sciences librarian developed and executed de novo searches on June 26, 2024, across Ovid MEDLINE, CINAHL, APA PsycInfo, Cochrane CENTRAL, Social Services Abstracts, and ASSIA, using tailored subject headings and keywords without filters or limits. The MEDLINE strategy was peer reviewed using PRESS (Peer Review of Electronic Search Strategies) guidelines ( 55 ) before translation to other databases. Search completeness was assessed through retrieval of known studies and dual screening the first 200 records per database. Reference lists of included studies and relevant reviews were also screened. Search strategies are presented in Appendix 2 . 2.4 Eligibility Criteria Eligibility was defined using the PCC (Population, Concept, Context) framework. The population was children and adolescents (≤ 18 years at surgery) who underwent limb salvage or amputation for bone or soft-tissue cancers, and their family caregivers (individuals providing primary parental care but not necessarily biological parents). The concept was studies of childhood bone tumors and soft tissue sarcomas, as classified in the International Classification of Childhood Cancer (3rd edition) reporting PROs (defined as health information coming directly from patients or caregivers) and needs (subjective states prompting use of medical or other resources). The context was all healthcare settings and qualitative or quantitative study designs, excluding single case reports (< 10 participants), commentaries, protocols, discussion papers, book chapters and conference abstracts. No restrictions were applied by data or language; for non-English studies, translation was planned. Studies without explicit age ranges were included if the mean plus SD was ≤ 18.9 years. 2.5 Study Screening Records were managed in Covidence. Duplicate were removed and titles, abstracts, and full texts were independently screened by two reviewers, with disagreements resolved by a third reviewer. 2.6 Data Abstraction and Charting A standardized Excel abstraction form with an embedded coding manual was piloted on five studies and revised iteratively. Two reviewers independently abstracted data, with disagreements resolved by consensus. Study authors were contacted for clarification where necessary. Extracted data items were publication metadata, study design data, and participant characteristics. Health outcomes were coded with details on measurement tools and reported results. 2.7 Data Synthesis and Reporting Quantitative data were summarized descriptively. Qualitative data were synthesized descriptively and organized in a matrix of outcomes and needs by participant type and domain. Given heterogeneity in study design, results were synthesized narratively with subgroup patterns explored where data permitted. 2.8 Patient and Public Involvement This review was initiated by a patient and public partner (LD) and funded by the Strategy for Patient-Oriented Research–Evidence Alliance (SPOR-EA), which is jointly supported by the Canadian Institutes of Health Research (CIHR) and 41 public and not-for-profit partners across Canada ( 12 ). The SPOR-EA invited public submissions of research questions to guide literature reviews and the topic of PROs in the context of pediatric oncological surgery was proposed by LD based on her experience of as mother of a child with a cancer-related amputation (ED) and the need to improve access to high-quality evidence. The project was co-led LD and LJ with contributions from ED. Partners were full team members, providing input across every review phase – such as the creation of the search strategy, study screening, data interpretation, and dissemination of findings. Patient and public partner contributions are reported using the Guidance for Reporting Involvement of Patient and the Public (GRIPP)-2 short form ( 13 ) ( Appendix 3 ). 3. RESULTS 3.1 Study Characteristics The search identified 11,403 records, of which 27 were included (Fig. 1). Studies were published between 1989 and 2023 (Fig. 2) and conducted in North America (United States, Canada), Europe (Netherlands, United Kingdom, Italy, France, Spain, Germany), Asia (China, Turkey, Iran), South America (Brazil, Peru), and Australia. Study details are summarized in Table 1, with extracted data presented in Appendix 4 . Designs varied considerably, with cross-sectional (n = 11; 41%) (14–24) and retrospective (n = 8; 30%) studies most common (25–32). Three studies (11%) were prospective or longitudinal cohorts (33–35), two (7.4%) were descriptive (7.4%) (38, 40), one was a case-control (4%) (36), and two were randomized controlled trials (7%) (34, 37). Sample sizes ranged from 11 to 181 participants (median: 37; IQR: 20-72.5). Table 1 Characteristics of Included Studies and Population Study Characteristics Patient Characteristics Caregiver Characteristics Outcome Measure Author and Year Country Study Design Sample Size & Sex/Gender Age at Surgery in Years (Mean, SD) Diagnosis Surgery Type Surgery Location Sample Size & Sex/Gender Tools Used Bekkering et al., 2010 Netherlands Cross-sectional, multi center n = 33 (17M, 16F) 10.5 (SD = 2.5) Osteosarcoma n = 26, Ewing Sarcoma: n = 7 Limb salvage n = 23, amputation n = 10 Lower limb n = 33 N/A TACQOL Bekkering et al., 2011 Netherlands Cross-sectional n = 82 (41M, 41F) 14.2 (SD = 4.1) Osteosarcoma n = 67, Ewing's Sarcoma n = 15 Limb salvage n = 55, amputation n = 27 Lower limb n = 82 N/A TESS and Baecke Questionnaire Cooper et al., 2020 USA Cross-sectional n = 30 (14M, 16F) 12.97 (SD = 2.77) Osteosarcoma n = 17, Ewing Sarcoma n = 7, Chondrosarcoma n = 1, Soft Tissue Sarcoma n = 5 Limb salvage n = 27 NR N/A PROMIS Short Form v1.0 Eiser et al., 1997 United Kingdom Cross-sectional n = 41 (24M, 17F) NR Malignant Primary Bone Tumor n = 41 Limb salvage n = 41 Lower limb n = 41 NR SF-36 and interviews Forni et al., 2012 Italy Descriptive quali-quanitative study n = 20 (12M, 8F) NR NR Limb salvage n = 20 Lower limb n = 20 N/A SF-36 and interviews Ginsberg et al., 2007 USA Prospective multi-site study n = 91 (48M, 43F) 14.52 (SD = 4.06) Ewing Sarcoma n = 14, Osteosarcoma n = 77 Limb salvage n = 69, amputation n = 22 Lower limb n = 91 N/A TESS and SF-36 Han et al., 2012 China Cross-sectional n = 120 (79M, 41F) 14.1 (SD = 4.6) Osteosarcoma n = 94, Ewing sarcoma n = 26 Limb salvage n = 52 Lower limb n = 120 N/A SF-36 Henderson et al., 2010 USA Retrospective, descriptive n = 15 (8M, 7F) 10.6 (range, 4–15) Primary bone sarcoma n = 15 Limb salvage n = 15 Lower limb n = 15 NR PODCI Henderson et al., 2012 USA Retrospective review n = 38 (19M, 19F) 10.4 (range, 4–15) Osteosarcoma n = 31, Ewing sarcoma n = 7 Limb salvage n = 38 Lower limb n = 38 NR PODCI and MSTS Hopyan et al., 2006 Australia Retrospective cohort study Lower extremity osteosarcoma and Ewing sarcoma Lower limb N/A SF-36 and TESS Jamshidi et al., 2019 Iran Case-control n = 43 (19M, 24F) Ewing Sarcoma n = 43 Limb salvage n = 43 Lower limb n = 19, upper limb n = 26 N/A MSTS Jaraway et al., 2013 Canada Retrospective exploratory descriptive study n = 13 (3M, 10F) Range: 6–16 Bone cancer n = 23 Limb salvage n = 13 Lower limb n = 13 n = 22 (9M, 13F) 5-scale Likert and open-ended interview Meng et al., 2022 China Observation Cohort Study, Longitudinal n = 56 (37M, 19F) 12.0 (SD= 3.2) Osteosarcoma n = 56 Limb salvage n = 38, Amputation n = 18 Lower limb n = 52, Unspecified n = 4 n = 104 (49M, 55F) HADS-A and HADS-D Piscione et al., 2014 U.S.A Mixed Methods; Cross Sectional n = 21 (11 M, 10 F) NR Osteosarcoma n = 16, Ewing sarcoma n = 5 Limb salvage n = 18 Amputation = 3 Lower extremity n = 21 N/A ASKp Piscione et al., 2019 Canada Mixed Methods: Longitudinal n = 181 (44 M,110 F) NR Osteosarcoma n = 57, Ewing sarcoma n = 28, Other n = 8 Limb salvage: n = 86, Amputation n = 7 Lower extremity n = 154, Upper extremity n = 27 N/A pTESS- Leg, pTESS-Arm Sainsbury et al., 2014 Canada Mixed Method; Retrospective n = 18 10 (Range = 1.5–17) Osteosarcoma n = 9, Ewing sarcoma n = 8, Adamantinoma n = 1 Limb salvage n = 18 Lower extremity n = 18 N/A Telephone survey (including components of SF-12 and PedsQL), Gillette Functional Assessment Questionnaire Smith et al., 1995 USA Quantitative, Retrospective n = 67 NR NR Amputation n = 67 NR N/A Patient medical records and physician notes Stevenson et al., 2018 United Kingdom Quantitative, Retrospective n = 11 NR Ewing Sarcoma n = 6, Osteosarcoma n = 5 Limb salvage n = 11 Upper limb n = 11 N/A TESS Tabone et al., 2005 France Quantitative, Observational n = 37 (25 M, 12 F) NR Osteosarcoma n = 19, Ewing sarcoma. N = 18 Limb salvage n = 15, Amputation n = 2, Not specified n = 17 NR NR CHQ Tacyildiz et al., 2021 Turkey Quantitative; Retrospective n = 39 (24 M, 15 F) Osteosarcoma n = 39 Limb salvage n = 34, Amputation n = 5 NR N/A Unspecified Questionnaire Tebbi et al., 1989 Brazil Mixed Method; Cross-sectional n = 33 (16 M, 17 F) 12.9 (SD = 2.7) NR Amputation n = 33 Lower extremity n = 33 N/A Interview Tran et al., 2023 Canada Quantitative; Secondary analysis of a multicenter, blinded RCT n = 150 (98 M, 52 F) (total study: n = 597) NR Primary bone sarcoma n = 146, Giant cell tumor n = 3, Soft-tissue sarcoma n = 1 Limb salvage n = 150 Lower extremity n = 150 N/A TESS Tunn et al., 2004 Germany Quantitative; Cross sectional n = 78 NR Osteosarcoma n = 78 Amputation n = 44, Limb salvage n = 34 Lower Extremity n = 78 N/A TESS-LE and Unspecified Questionnaire Vasquez et al., 2022 Peru Quantitative; Cross sectional n = 19 (8 M, 11 F) NR Osteosarcoma n = 17, Ewing sarcoma n = 2 Limb salvage n = 15, Amputation n = 4 Lower extremity n = 19 N/A SF-36 Tirado et al., 2011 Spain Quantitative; Cross sectional n = 17 (8 M, 9 F) NR Osteosarcoma n = 13, Ewing sarcoma n = 4 Amputation n = 19, Limb salvage n = 12 *Some patients had multiple surgeries Lower extremity n = 17 N/A SF-36 Wang et al., 2018 China Quantitative, Prospective RCT n = 45 (23 M, 22 F) Treatment Group Mean 14.3 (SD = 2.8), Placebo Mean 13.9 (SD = 2.7) Osteosarcoma n = 41, Ewing sarcoma n = 4 Amputation n = 45 Lower extremity n = 45 N/A Visual Analog Scale Weir et al., 2010 USA Quantitative; Cross sectional n = 28 (16 M, 12 F) (total study: n = 123) NR NR Amputation n = 28 NR NR Limb Loss Parent Survey ASKp, Activities Scale for Kids – Performance Version; CCSS, Childhood Cancer Survivor Study; CHQ, Child Health Questionnaire; F, Female; HADS-A, Hospital Anxiety and Depression Scale–Anxiety; HADS-D, Hospital Anxiety and Depression Scale–Depression; M, Male; MSTS, Musculoskeletal Tumor Society; NA, Not applicable; NR, Not reported; PedsQL, Pediatric Quality of Life Inventory; PODCI, Pediatric Outcomes Data Collection Instrument; PROMIS, Patient-Reported Outcomes Measurement Information System; pTESS, Parent Toronto Extremity Salvage Score; SF-12, 12-Item Short Form Health Survey; SF-36, 36-Item Short Form Health Survey; TACQOL, Children’s Quality of Life Questionnaire; TESS, Toronto Extremity Salvage Score; TESS-LE, Toronto Extremity Salvage Score – Lower Extremity; USA, United States of America 3.2 Patient and Survivor Characteristics Characteristics are shown in Table 1. Osteosarcoma (20 studies; 71%) and Ewing sarcoma (15 studies; 54%) were most frequently represented. Where reported, mean age at surgery ranged from 10 to 15 years (15, 33, 39). Limb salvage was described in 22 studies (82%), particularly in more recent cohorts (16, 37). Amputation was described in 16 studies (59%), with older studies focusing exclusively on this approach (23, 31). Lower extremity resections were reported in 20 studies (74%) (14, 15, 17–23, 25–29, 33, 34, 36–39). Upper extremity procedures were examined in three studies (11%), within mixed-site populations (30, 35, 36). Four studies did not report surgical site (15%) (24, 31, 32, 40). 3.3 Caregiver Characteristics Caregivers were included in four studies (15%) (23–25, 39). In all cases, caregivers were mothers or fathers. 3.4 Outcome Measures Outcome measures were heterogeneous (Table 1). Multi-dimensional QOL or functional tools included the: Toronto Extremity Salvage Score (TESS) and parent-proxy TESS (pTESS), used in seven studies (26%) (15, 20, 28, 30, 33, 35, 37); Short Form Health Surveys (SF-12 or SF-36) used in seven studies (26%) (17, 19, 21, 22, 28, 33, 38); Musculoskeletal Tumor Society (MSTS) tool, used in eight studies (30%) (20, 22, 28, 29, 33, 36, 36, 37); and Pediatric Outcomes Data Collection Instrument (PODCI), used in two studies (7%) (26, 29). Other validated instruments less frequently used included the PROMIS short forms (16), the Child Health Questionnaire (CHQ)(40), and the Pediatric Quality of Life Inventory (PedsQL) (27). Psychological or symptom-specific measures were also used to measure PROs, such as the Hospital Anxiety and Depression Scale (HADS) (39) and the pain intensity Visual Analog Scale (34). Eight studies (30%) incorporated qualitative or mixed methods, including interviews, open-ended questionnaires, and telephone surveys (15, 17, 18, 23, 25, 27, 35, 38). One study used medical records and physician notes to source PRO data (31). 3.5 Patient and Survivor Outcomes Twenty-five studies (93%) reported patient or survivor outcomes (Table 2). Outcomes were primarily self-reported (n = 18/25; 72%), with fewer joint patient-caregiver reports (n = 5/25; 20%) or caregivers-only reports (n = 3/25; 12%). Thirty-six distinct PROMs were used, most commonly the TESS (n = 8/25; 32%), SF-36 (n = 7/25; 28%), PODCI (n = 3/25; 12%), and semi-structured interviews (n = 3/25; 12%). Reporting of respondent type (child vs. proxy) was inconsistent and discrepancies between reporters were seldom analyzed. Timing also varied widely; longitudinal outcome trajectories were uncommon, limiting insight into critical windows such as pre-operative period, early rehabilitation, return to school, or transition to survivorship. Table 2 Outcomes Measured Across Studies Physical Functioning Emotional Functioning Social and Occupational Functioning Study General Health Pain Mobility and Function Independence Self-Image & Esteem Mental Health Satisfaction with Surgery Cognition Self-Efficacy Recreational Ability Social & Relational Financial Educational & Occupational Spiritual Acceptance by Others Patient Outcomes Bekkering et al, 2010 X X X X X X X X Bekkering et al., 2011 X X Cooper at al., 2020 X X X X X X Eiser et al., 1997 X X X X X X X X X X Forni et al., 2012 X X X X X X X X Gingsberg et al., 2007 X X X X Han et al., 2012 X X X X X X Henderson et al., 2010 X X X X Henderson et al,, 2012 X X X X X X Hopyan et al., 2006 X X X Jamshidi et al., 2019 X Piscione et al., 2014 X X X X X Piscione et al., 2019 X Sainsbury et al., 2014 X X X X X X X X Smith et al., 1995 X Stevenson et al., 2018 X Tabone et al., 2005 X X X X X X Tacyilidiz et al., 2021 X X X X X Tebbi et al., 1989 X X X X X X X X X X Tran et al., 2023 X Tunn et al., 2004 X X Vasquez et al., 2022 X X X X X X Tirado et al., 2011 X X X X X X Wang et al., 2018 X X Weir et al., 2010 X Caregiver Outcomes Jaraway et al., 2013 --- --- --- --- X X --- X --- --- Meng et al., 2022 --- --- --- --- X --- --- --- Tebbi et al., 1989 --- --- --- --- X --- --- --- Weir et al., 2010 --- --- --- --- --- --- X --- 3.5.1 Physical Functioning Physical functioning was the most evaluated domain, assessed in 23 studies (85%). Within the domain, the most assessed aspects were mobility/function (n = 17/23; 74%), independence (n = 17/23; 74%), and pain (n = 13/23; 56%). Females reported lower physical QOL and general health than males in two studies (21, 22), while no functional differences were observed between limb salvage and amputation groups (15). Survivors generally reported lower health-related QOL (HRQOL) than healthy controls (15, 32). Many patients described being unable to run, having trouble climbing stairs, or struggling to sit on the floor (17, 18). One study found that the physical functioning and pain significantly improved from surgery to 6- and 12-months post-surgery, with overall HRQOL being lower in bone tumor patients than the general population (21). Patient and survivor functional independence in was evaluated through general indicators (e.g., need for assistive devices) and specific tasks such as housework, childcare, and physically navigating different terrains. Three longitudinal studies documented improvements in independence over time (21, 23, 37), with others noting that independence was closely linked to mobility aid use (15, 23, 27). Pain was common and persisted months or years post-surgery (23, 32). Pain was described both as continuous and episodic (e.g., occurring after physical exertion or in cold weather) (17). Limb-sparing procedures were associated with pain, hypersensitivity, numbness, and stiffness (18). Three investigations explicitly assessed phantom limb pain (23, 31, 34). One study found that pediatric cancer amputees were four times more likely to report phantom limb pain than those with trauma-related amputations, especially amongst those exposed to chemotherapy (31). Another study found that gabapentin was effective in preventing acute post-operative phantom limb pain (34). 3.5.2 Social and Occupational Functioning Sixteen studies (59%) evaluated patient or survivor social and occupational functioning. The outcomes most frequently examined were in the social or relational domains (n = 11/16; 69%), which included family involvement, peer relationships, and social activities. Social functioning improved following surgery, particularly among males treated with limb-sparing procedures (21, 22, 29, 32). Social confidants were primarily identified as mothers, with peers described as being helpful, fearful, avoidant, and pitying after surgery (23). Survivors also described social discomfort, noting that others appeared uneasy discussing their illness (23). Educational and occupational outcomes were reported in seven studies (n = 7/16, 44%). School challenges included learning difficulties, absenteeism, and repeating grades (15, 17). Compared to non-amputees and healthy siblings, amputees were less likely to graduate high school or college (32). School absences among amputees were commonly attributed to fear of injury or difficulties using stairs (17, 24). Employment outcomes, assessed in three studies (n = 3/16, 19%), indicated lower employment rates among survivors relative to siblings (17, 23, 32). Although one study found no overt hiring discrimination, survivors reported job loss due to their surgery or restricted mobility (23). While many survivors reported their opportunities as constrained, some described their experiences as influencing career choices, particularly toward health and social sciences (17). Recreational ability was measured in five studies (n = 5/16, 31%), with children often reporting minimal difficulties with activities of daily living such as bathing or dressing (27). However, significant restrictions were reported for high-demand tasks such as sports and physical recreation, often accompanied by regret and frustration (15, 17, 18, 27). Financial impacts were described in one study (n = 1/16, 6%) with survivors describing prostheses as expensive to purchase and maintain (23). No studies assessed spiritual outcomes. 3.5.3 Emotional Functioning Emotional functioning was assessed in 15 studies (58%). Mental health outcomes were assessed in 13 studies (n = 13/15, 87%). One study reported that survivors sought psychiatric help to address intense fears of disease recurrence (17), with one showing improvement in mental health outcomes with time post-surgery (10). Self-image and self-esteem were examined in eight studies (n = 8/15, 53%). Findings included dissatisfaction with physical appearance, prostheses, or scars, alongside challenges with maturation. While many patients were satisfied with their physical appearance overall, perceptions of body image varied widely (26). Attitudes toward scars varied and included embarrassment, indifference, and pride (17, 27, 38). Three studies highlighted clothing restrictions and embarrassment in specific contexts such as swimming (17, 23, 38). Two studies suggested that self-acceptance was initially difficult but improved with age (26, 38). Self-esteem was generally comparable across ages and genders, with slightly higher ratings among patients without internally implanted devices (i.e., endoprostheses) (26, 40). Self-efficacy was examined in two studies (n = 2/15, 13%). Findings indicated that pain interference and fear of injury constrained participation in daily and recreational activities, reflecting low self-efficacy for activity engagement (16, 18). Satisfaction with surgical outcomes was captured in six studies (n = 6/16, 40%). Three studies indicated high overall satisfaction with limb salvage surgical results (26, 27, 29). Two studies reported most patients as satisfied with choosing limb salvage over amputation (17, 38). Despite this, one study revealed that fewer than two-thirds of amputees felt they had adequately understood the functional consequences prior to surgery but following surgery most felt their prostheses allowed engagement in desired activities (23). One study evaluated cognition (n = 1/16, 6%), which was found to be lower in patients aged 8–15 years compared to healthy controls, though not statistically significant (15). 3.6 Caregiver Outcomes Four studies assessed caregiver outcomes (15%), involving 126 parents (with incomplete reporting in two studies) (Table 1). Outcomes were self-reported by caregivers (n = 34; 75%) or reported by patients about their caregivers (n = 1/4, 25%). Across these studies, six different PROMs were used. Emotional functioning was the most frequently studied caregiver domain, reported in three studies (n = 3/4, 75%). One longitudinal study documented increasing parental anxiety and depression symptoms three years after their child’s surgery (39). Qualitative interviews revealed that parents often expressed denial of the diagnosis, fears about terminal outcomes, and distress about their own inability to cope (23, 25). Caregiver self-efficacy was reported in one study (n = 1/4, 25%), where parents present in the operating room described feeling better prepared to support their child post-surgery (25). Satisfaction with surgery was measured in one study (n = 1/4, 25%), in which parents reported more positivity when their child’s amputation appeared less severe than anticipated (25). Financial health as an outcome was reported in one study (n = 1/4, 25%) showing that 57% of parents experienced limits on insurance coverage for child prostheses and 38% reporting having paid out-of-pocket for prostheses (24). Family functioning was addressed in one study (n = 1/4, 3.7%), where patients described changes in parental behavior post-surgery, including becoming more protective or submissive (23). No studies assessed caregiver physical health outcomes. 4. DISCUSSION This review synthesizes three decades of patient- and caregiver-reported outcomes following limb salvage or amputation for pediatric bone and soft-tissue sarcomas. Physical functioning was generally moderate to good with small or inconsistent differences between procedures. Pain, including phantom pain, often persisted and affected participation. Psychosocial outcomes varied, with some children and survivors reporting acceptance and others noting body-image concerns and activity limits. Caregiver distress and financial strain were evident but infrequently measured. Evidence gaps remaining include heterogeneous PROM use, limited assessment of priority domains, and minimal attention to caregivers—restricting comparability and impeding family-centered care. Our findings highlight the functional and QOL-related impacts of both limb salvage and amputation. Results further suggest that rehabilitation, symptom control, and environmental accommodations at home, school, and in the community, may influence heavily on lived experience. This aligns with biopsychosocial models of disability in which impairments, activity limitations, and participation restrictions are shaped by contextual facilitators and barriers ( 52 ). It also underscores the importance of anticipatory preoperative guidance that maintains a focus on realistic post-surgical expectations for mobility, stamina, and participation—regardless of procedure ( 53 ). Several areas for improving family-centered care were identified. Pain management requires sustained attention across the surgical continuum. Early identification of phantom limb and neuropathic pain, education about pain triggers, and timely referral to interdisciplinary services may reduce constraints on participation post-surgery. Evidence from long-term survivors indicates that upwards of 41% report chronic pain decades after diagnosis, with one-quarter experiencing severe interference with activities of daily living—and that history of amputation or limb sparing surgery increase the odds of daily pain interference ( 41 , 42 ). School and recreation re-integration also requires structured planning, including graded return to physical education and close coordination with teachers and coaches ( 43 – 45 ). Addressing body image and visible differences through strategies including scar normalization and peer education may ease social discomfort ( 46 , 47 ). Finally, families could benefit from financial and system navigation support, particularly around prosthesis costs and insurance access barriers. A wide range of PROMs were used, often without justification for domain selection or consideration of psychometric suitability for pediatric oncology or survivorship. Tools were applied to assess function, general health, and symptom burden, making comparison and synthesis difficult. Key domains identified by children, adolescents, survivors, parents, and clinicians as research priorities (e.g., mental health, participation, educational and employment engagement, financial strain, and caregiver outcomes) ( 54 ) were only inconsistently assessed, and spiritual well-being was not evaluated at all. These gaps suggest the need for a measurement agenda in this area. First, efforts should coalesce around a core outcome set anchored to the World Health Organization (WHO)-endorsed International Classification of Functioning, Disability and Health (ICF) ( 48 ) and co-designed with patients, survivors and caregivers. Second, the core outcome set should include symptoms, activity, participation, physical, financial and social environments, and factors such as body image and self-efficacy. Longitudinal assessment timepoints should also be mapped to the surgical and overall cancer treatment journey to understand predictors of child and family outcomes, outcome trajectories, and supportive care needs. Third, PRO self-reporting should be encouraged whenever possible, with proxy reports used thoughtfully given tendencies for caregivers to overestimate children’s cancer symptoms and underestimate function ( 49 ). Fourth, transparent reporting of participant disease and demographic characteristics will enable equity-oriented analyses. At present, signals in the current literature (e.g., lower physical QOL among females, insurance barriers) warrant confirmation and targeted response. The family caregiver literature is notably thin given parents’ central roles in decision-making, clinical care, and advocacy. Where measured, anxiety and depressive symptoms were identified and preparedness for child limb surgery appeared to shape care confidence. Additional research is needed to understand caregiver-reported outcomes and support needs over time, and to examine the efficacy of caregiver-centered wellness interventions ( 50 ). Findings have direct clinical implications. In alignment with clinical practice guidelines ( 51 ), PRO collection should be embedded into routine practice to enable supportive care provision and to determine the effectiveness of administered interventions. Rehabilitation pathways should include early goal-directed mobility training, progressive return-to-activities, and coordination with schools. Pain care should include anticipatory management, timely treatment, and ongoing assessment. Psychosocial care should continue to focus on peer support, child self-esteem, family mental health, and resource navigation. Parent and survivor involvement strengthened this review by ensuring the research questions, outcomes of interest, and data interpretation reflected real-world experiences of limb surgery. Parent and survivor contributions directed the assessment of PROs in domains often missed in the literature, such as school participation, family impacts, and long-term psychosocial concerns, which directly shaped our synthesis. A key lesson learned was the value of dedicating time and structure for meaningful engagement, including clear communication about review methods. Future work should prioritize partner representation and supportive processes to enable contribution to emotionally sensitive topics. Additional review strengths include that we captured both patient and caregiver outcomes, allowing for a family-centered understanding of the surgical experience. Our inclusion of both physical and psychosocial outcomes provides a more holistic understanding of the impact of limb surgery across these groups, which is crucial to direct clinical care. Considering limitations, our synthesis is narrative and dependent on what studies chose to measure and report. Although no language limits were applied, practical constraints including our search strategy may still have favoured English-language publications, and grey literature was not systematically searched. This review highlights the need to report the experiences and needs of childhood cancer amputees and their family caregivers. Future research should prioritize prospective, longitudinal, multi-site studies that adopt common data elements and core PRO sets to enable causal inferences and pooled analyses. Mixed methods studies integrating child, survivor, and caregiver perspectives narratives with longitudinal assessments will clarify mechanisms and contextual modifiers of outcomes. Finally, interventional and implementation studies are needed to ensure that improvements in child survival are matched by improvements in QOL and participation. Collaborations led by those with lived experience, researchers, and clinicians will be valuable in fulfilling research gaps and developing interventions that improve outcomes for both childhood cancer patients and their family caregivers. Declarations Funding: This project was supported by the Operating Grant: SPOR – Guidelines and Systematic Reviews: The Evidence Alliance, grant number (154442). Author contributions: L.D. conceptualized this study. L.J. and L.D. drafted the study protocol. All authors participated in data collection, interpretation, manuscript drafting and revision. All authors reviewed the manuscript, approve of its contents, and agree to be accountable for the work. References Geiger EJ, Liu W, Srivastava DK, Bernthal NM, Weil BR, Yasui Y, et al. What Are Risk Factors for and Outcomes of Late Amputation After Treatment for Lower Extremity Sarcoma: A Childhood Cancer Survivor Study Report. Clin Orthop. 2023;481(3):526–38. Belayneh R, Fourman MS, Bhogal S, Weiss KR. 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Supplementary Files Appendix.docx Appendix4FullExtractionTable.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 25 Feb, 2026 Reviews received at journal 15 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviews received at journal 03 Feb, 2026 Reviewers agreed at journal 03 Feb, 2026 Reviews received at journal 31 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers invited by journal 21 Jan, 2026 Editor assigned by journal 16 Jan, 2026 Submission checks completed at journal 07 Jan, 2026 First submitted to journal 16 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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09:56:52","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8143,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/a20ce4b078f3c9dccfbfd134.png"},{"id":101206490,"identity":"3d5fd160-60f4-450c-a6ae-7e6812781fe9","added_by":"auto","created_at":"2026-01-27 09:56:23","extension":"png","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":5608,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/6e79ea5d38b3859c4fa2b88f.png"},{"id":101170782,"identity":"38a177aa-0f7b-4cb2-9cc4-75715667d91a","added_by":"auto","created_at":"2026-01-27 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09:56:16","extension":"xml","order_by":26,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":267715,"visible":true,"origin":"","legend":"","description":"","filename":"cc8dea59e20e43f09f85ac113bbeecaf1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/447adebead97a0378396a1e5.xml"},{"id":101170781,"identity":"fe0a2af0-3013-4b6b-a09c-66c3b227cc3e","added_by":"auto","created_at":"2026-01-27 00:04:57","extension":"html","order_by":27,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":285203,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/1122ec2c287601c6f32b40c1.html"},{"id":101170757,"identity":"0e52ff67-9d07-4814-8c17-de18e556afe0","added_by":"auto","created_at":"2026-01-27 00:04:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":257075,"visible":true,"origin":"","legend":"\u003cp\u003eStudy identification process.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/229bb39c11955062f85008ca.png"},{"id":101170766,"identity":"cf4d3e8c-4001-4314-a6f4-c1db7914101c","added_by":"auto","created_at":"2026-01-27 00:04:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":145468,"visible":true,"origin":"","legend":"\u003cp\u003eStudy publications over time\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/c983c7c6ff4b96cd92310791.png"},{"id":102294791,"identity":"472bdbe7-f82d-4ff5-844d-f0f2dba3cbc1","added_by":"auto","created_at":"2026-02-10 09:57:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1926597,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/cbd8180e-2360-4620-9a98-5f4b74165403.pdf"},{"id":101207127,"identity":"5f076a88-4b99-4fef-960c-05425e4a4402","added_by":"auto","created_at":"2026-01-27 09:57:39","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":39756,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/89871e6def5fa44754dad8d2.docx"},{"id":101206383,"identity":"9b2dc1a1-3221-4d01-a16c-70ded01f8d29","added_by":"auto","created_at":"2026-01-27 09:56:07","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":62976,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix4FullExtractionTable.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8379832/v1/3a24c115dd094d9a8a652394.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Patient- and Caregiver-Reported Outcomes After Limb Salvage or Amputation for Pediatric Bone and Soft Tissue Sarcomas: A Scoping Review","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eChildhood bone tumors and soft tissue sarcomas\u0026mdash;most commonly osteosarcoma and Ewing sarcoma\u0026mdash;require multimodal therapy that often includes limb-directed surgery. Over the last decades, advances in chemotherapy protocols, prosthetic technology, and surgical techniques, have expanded the use of limb salvage procedures, with amputation remaining necessary in certain clinical contexts (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). These approaches aim to maximize survival but inevitably shape the daily functioning and quality of life (QOL) of patients and survivors\u0026mdash;affecting mobility, independence, pain, participation at school and in recreation, body image, social relationships, and long-term wellbeing (\u003cspan additionalcitationids=\"CR4 CR5\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Understanding impacts across surgery type from the perspectives of children, survivors, and their family caregivers is essential. Patient-reported outcomes (PROs) capture how health status and treatment effects are experienced in everyday life, while reports from caregivers\u0026mdash;who provide practical, emotional, and advocacy support\u0026mdash;can illuminate needs that clinician reports and medical record may miss (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eStill, despite the critical importance of understanding child function and participation, evidence is dispersed across disciplines and study designs. Outcomes beyond physical function, including psychosocial health, schooling and employment, and caregiver perspectives, are inconsistently assessed and reported. The fields of pediatric surgical oncology care and research lack consensus on which PRO measures (PROMs) are practical to administer and which capture the domains that matter most to children and families. A comprehensive map of what has been studied, how it has been measured, and where the gaps remain is required to inform practice and guide research, including by directing PRO measure selection and administration, as well as family-centered supports. By charting the nature of research in this area and identified child-, survivor-, and caregiver-reported post-surgical outcomes, a coherent agenda for interdisciplinary clinicians and researchers working at the intersection of pediatric oncology, surgery, and rehabilitation can be developed.\u003c/p\u003e \u003cp\u003eThis review was guided by the following research questions: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) What health outcomes, reported by children diagnosed with bone tumors or soft tissue sarcomas, survivors of such cancers, and their family caregivers, are associated with having undergone limb salvage surgery or cancer-related amputation? (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) What gaps exist in the evidence related to measuring PROs in these groups that might limit current clinical care efforts or future evidence generation?\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Framework\u003c/h2\u003e \u003cp\u003eThe scoping review followed the framework developed by Levac et al. (2010), encompassing inc question formation, study identification and selection, data charting, and synthesis (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Reporting adhered to the PRISMA Extension for Scoping Reviews and the PRISMA Extension for Searching guidelines (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) (\u003cb\u003eAppendix 1\u003c/b\u003e). The review protocol was pre-published on Open Science Framework (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://osf.io/f8a94\u003c/span\u003e\u003cspan address=\"https://osf.io/f8a94\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Study Identification\u003c/h2\u003e \u003cp\u003eA health sciences librarian developed and executed \u003cem\u003ede novo\u003c/em\u003e searches on June 26, 2024, across Ovid MEDLINE, CINAHL, APA PsycInfo, Cochrane CENTRAL, Social Services Abstracts, and ASSIA, using tailored subject headings and keywords without filters or limits. The MEDLINE strategy was peer reviewed using PRESS (Peer Review of Electronic Search Strategies) guidelines (\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e) before translation to other databases. Search completeness was assessed through retrieval of known studies and dual screening the first 200 records per database. Reference lists of included studies and relevant reviews were also screened. Search strategies are presented in \u003cb\u003eAppendix 2\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Eligibility Criteria\u003c/h2\u003e \u003cp\u003eEligibility was defined using the PCC (Population, Concept, Context) framework. The \u003cem\u003epopulation\u003c/em\u003e was children and adolescents (\u0026le;\u0026thinsp;18 years at surgery) who underwent limb salvage or amputation for bone or soft-tissue cancers, and their family caregivers (individuals providing primary parental care but not necessarily biological parents). The \u003cem\u003econcept\u003c/em\u003e was studies of childhood bone tumors and soft tissue sarcomas, as classified in the International Classification of Childhood Cancer (3rd edition) reporting PROs (defined as health information coming directly from patients or caregivers) and needs (subjective states prompting use of medical or other resources). The \u003cem\u003econtext\u003c/em\u003e was all healthcare settings and qualitative or quantitative study designs, excluding single case reports (\u0026lt;\u0026thinsp;10 participants), commentaries, protocols, discussion papers, book chapters and conference abstracts. No restrictions were applied by data or language; for non-English studies, translation was planned. Studies without explicit age ranges were included if the mean plus SD was \u0026le;\u0026thinsp;18.9 years.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Study Screening\u003c/h2\u003e \u003cp\u003eRecords were managed in Covidence. Duplicate were removed and titles, abstracts, and full texts were independently screened by two reviewers, with disagreements resolved by a third reviewer.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Data Abstraction and Charting\u003c/h2\u003e \u003cp\u003eA standardized Excel abstraction form with an embedded coding manual was piloted on five studies and revised iteratively. Two reviewers independently abstracted data, with disagreements resolved by consensus. Study authors were contacted for clarification where necessary. Extracted data items were publication metadata, study design data, and participant characteristics. Health outcomes were coded with details on measurement tools and reported results.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Data Synthesis and Reporting\u003c/h2\u003e \u003cp\u003eQuantitative data were summarized descriptively. Qualitative data were synthesized descriptively and organized in a matrix of outcomes and needs by participant type and domain. Given heterogeneity in study design, results were synthesized narratively with subgroup patterns explored where data permitted.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.8 Patient and Public Involvement\u003c/h2\u003e \u003cp\u003eThis review was initiated by a patient and public partner (LD) and funded by the Strategy for Patient-Oriented Research\u0026ndash;Evidence Alliance (SPOR-EA), which is jointly supported by the Canadian Institutes of Health Research (CIHR) and 41 public and not-for-profit partners across Canada (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The SPOR-EA invited public submissions of research questions to guide literature reviews and the topic of PROs in the context of pediatric oncological surgery was proposed by LD based on her experience of as mother of a child with a cancer-related amputation (ED) and the need to improve access to high-quality evidence.\u003c/p\u003e \u003cp\u003eThe project was co-led LD and LJ with contributions from ED. Partners were full team members, providing input across every review phase \u0026ndash; such as the creation of the search strategy, study screening, data interpretation, and dissemination of findings. Patient and public partner contributions are reported using the Guidance for Reporting Involvement of Patient and the Public (GRIPP)-2 short form (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) (\u003cb\u003eAppendix 3\u003c/b\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003e3.1 Study Characteristics\u003c/h2\u003e\n \u003cp\u003eThe search identified 11,403 records, of which 27 were included (Fig.\u0026nbsp;1). Studies were published between 1989 and 2023 (Fig.\u0026nbsp;2) and conducted in North America (United States, Canada), Europe (Netherlands, United Kingdom, Italy, France, Spain, Germany), Asia (China, Turkey, Iran), South America (Brazil, Peru), and Australia. Study details are summarized in Table\u0026nbsp;1, with extracted data presented in \u003cstrong\u003eAppendix 4\u003c/strong\u003e. Designs varied considerably, with cross-sectional (n = 11; 41%) (14–24) and retrospective (n = 8; 30%) studies most common (25–32). Three studies (11%) were prospective or longitudinal cohorts (33–35), two (7.4%) were descriptive (7.4%) (38, 40), one was a case-control (4%) (36), and two were randomized controlled trials (7%) (34, 37). Sample sizes ranged from 11 to 181 participants (median: 37; IQR: 20-72.5).\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eCharacteristics of Included Studies and Population\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eStudy Characteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003ePatient Characteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCaregiver Characteristics\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOutcome Measure\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAuthor and Year\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy Design\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample Size\u0026nbsp;\u0026amp;\u003c/p\u003e\n \u003cp\u003eSex/Gender\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge at Surgery in Years (Mean, SD)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDiagnosis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSurgery Type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSurgery Location\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample Size \u0026amp; Sex/Gender\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTools Used\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBekkering et al., 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNetherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCross-sectional, multi center\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 33\u003c/p\u003e\n \u003cp\u003e(17M, 16F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.5 (SD = 2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 26, Ewing Sarcoma: n = 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 23, amputation n = 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTACQOL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBekkering et al., 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNetherlands\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCross-sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 82\u003c/p\u003e\n \u003cp\u003e(41M, 41F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.2 (SD = 4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 67, Ewing's Sarcoma n = 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 55, amputation n = 27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTESS and Baecke Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCooper et al., 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCross-sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 30\u003c/p\u003e\n \u003cp\u003e(14M, 16F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.97 (SD = 2.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 17, Ewing Sarcoma n = 7, Chondrosarcoma n = 1, Soft Tissue Sarcoma n = 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePROMIS Short Form v1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEiser et al., 1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnited Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCross-sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 41\u003c/p\u003e\n \u003cp\u003e(24M, 17F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalignant Primary Bone Tumor n = 41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSF-36 and interviews\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eForni et al., 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDescriptive quali-quanitative study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 20\u003c/p\u003e\n \u003cp\u003e(12M, 8F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSF-36 and interviews\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGinsberg et al., 2007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProspective multi-site study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 91\u003c/p\u003e\n \u003cp\u003e(48M, 43F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.52 (SD = 4.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEwing Sarcoma n = 14, Osteosarcoma n = 77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 69, amputation n = 22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTESS and SF-36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHan et al., 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCross-sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 120\u003c/p\u003e\n \u003cp\u003e(79M, 41F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.1 (SD = 4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 94, Ewing sarcoma n = 26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSF-36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHenderson et al., 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetrospective, descriptive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 15\u003c/p\u003e\n \u003cp\u003e(8M, 7F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.6 (range, 4–15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary bone sarcoma n = 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePODCI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHenderson et al., 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetrospective review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 38\u003c/p\u003e\n \u003cp\u003e(19M, 19F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.4 (range, 4–15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 31, Ewing sarcoma n = 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePODCI and MSTS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHopyan et al., 2006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAustralia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetrospective cohort study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity osteosarcoma and Ewing sarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSF-36 and TESS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJamshidi et al., 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 43\u003c/p\u003e\n \u003cp\u003e(19M, 24F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEwing Sarcoma n = 43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 19, upper limb n = 26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMSTS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJaraway et al., 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetrospective exploratory descriptive study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 13\u003c/p\u003e\n \u003cp\u003e(3M, 10F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRange: 6–16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBone cancer n = 23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 22\u003c/p\u003e\n \u003cp\u003e(9M, 13F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5-scale Likert and open-ended interview\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMeng et al., 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObservation Cohort Study, Longitudinal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 56\u003c/p\u003e\n \u003cp\u003e(37M, 19F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.0 (SD=\u003c/p\u003e\n \u003cp\u003e3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 38, Amputation n = 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower limb n = 52, Unspecified n = 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 104\u003c/p\u003e\n \u003cp\u003e(49M, 55F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHADS-A and HADS-D\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePiscione et al., 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eU.S.A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed Methods; Cross Sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 21\u003c/p\u003e\n \u003cp\u003e(11 M, 10 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 16,\u003c/p\u003e\n \u003cp\u003eEwing sarcoma n = 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 18\u003c/p\u003e\n \u003cp\u003eAmputation = 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eASKp\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePiscione et al., 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed Methods: Longitudinal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 181\u003c/p\u003e\n \u003cp\u003e(44 M,110 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 57, Ewing sarcoma n = 28, Other n = 8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage: n = 86, Amputation n = 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 154, Upper extremity n = 27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003epTESS- Leg, pTESS-Arm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSainsbury et al., 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed Method; Retrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10 (Range = 1.5–17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 9, Ewing sarcoma n = 8, Adamantinoma n = 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTelephone survey (including components of SF-12 and PedsQL), Gillette Functional Assessment Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmith et al., 1995\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative, Retrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmputation n = 67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatient medical records and physician notes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStevenson et al., 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnited Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative, Retrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEwing Sarcoma n = 6, Osteosarcoma n = 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUpper limb n = 11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTESS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTabone et al., 2005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative, Observational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 37 (25 M, 12 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 19, Ewing sarcoma. N = 18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 15, Amputation n = 2, Not specified n = 17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCHQ\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTacyildiz et al., 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative; Retrospective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 39 (24 M, 15 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 34, Amputation n = 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnspecified Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTebbi et al., 1989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed Method; Cross-sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 33 (16 M, 17 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.9 (SD = 2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmputation n = 33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInterview\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTran et al., 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative; Secondary analysis of a multicenter, blinded RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 150\u003c/p\u003e\n \u003cp\u003e(98 M, 52 F)\u003c/p\u003e\n \u003cp\u003e(total study: n = 597)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary bone sarcoma n = 146, Giant cell tumor n = 3, Soft-tissue sarcoma n = 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTESS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTunn et al., 2004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative; Cross sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmputation n = 44, Limb salvage n = 34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower Extremity n = 78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTESS-LE and\u003c/p\u003e\n \u003cp\u003eUnspecified Questionnaire\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVasquez et al., 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePeru\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative; Cross sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 19 (8 M, 11 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 17, Ewing sarcoma n = 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb salvage n = 15, Amputation n = 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSF-36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTirado et al., 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative; Cross sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 17 (8 M, 9 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 13, Ewing sarcoma n = 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmputation n = 19, Limb salvage n = 12 *Some patients had multiple surgeries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSF-36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWang et al., 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative, Prospective RCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 45 (23 M, 22 F)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTreatment Group Mean 14.3 (SD = 2.8), Placebo Mean 13.9 (SD = 2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOsteosarcoma n = 41, Ewing sarcoma n = 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmputation n = 45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLower extremity n = 45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVisual Analog Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeir et al., 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuantitative; Cross sectional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003en = 28 (16 M, 12 F) (total study: n = 123)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmputation n = 28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimb Loss Parent Survey\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eASKp, Activities Scale for Kids – Performance Version; CCSS, Childhood Cancer Survivor Study; CHQ, Child Health Questionnaire; F, Female; HADS-A, Hospital Anxiety and Depression Scale–Anxiety; HADS-D, Hospital Anxiety and Depression Scale–Depression; M, Male; MSTS, Musculoskeletal Tumor Society; NA, Not applicable; NR, Not reported; PedsQL, Pediatric Quality of Life Inventory; PODCI, Pediatric Outcomes Data Collection Instrument; PROMIS, Patient-Reported Outcomes Measurement Information System; pTESS, Parent Toronto Extremity Salvage Score; SF-12, 12-Item Short Form Health Survey; SF-36, 36-Item Short Form Health Survey; TACQOL, Children’s Quality of Life Questionnaire; TESS, Toronto Extremity Salvage Score; TESS-LE, Toronto Extremity Salvage Score – Lower Extremity; USA, United States of America\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003e3.2 Patient and Survivor Characteristics\u003c/h2\u003e\n \u003cp\u003eCharacteristics are shown in Table\u0026nbsp;1. Osteosarcoma (20 studies; 71%) and Ewing sarcoma (15 studies; 54%) were most frequently represented. Where reported, mean age at surgery ranged from 10 to 15 years (15, 33, 39). Limb salvage was described in 22 studies (82%), particularly in more recent cohorts (16, 37). Amputation was described in 16 studies (59%), with older studies focusing exclusively on this approach (23, 31). Lower extremity resections were reported in 20 studies (74%) (14, 15, 17–23, 25–29, 33, 34, 36–39). Upper extremity procedures were examined in three studies (11%), within mixed-site populations (30, 35, 36). Four studies did not report surgical site (15%) (24, 31, 32, 40).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003e3.3 Caregiver Characteristics\u003c/h2\u003e\n \u003cp\u003eCaregivers were included in four studies (15%) (23–25, 39). In all cases, caregivers were mothers or fathers.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003e3.4 Outcome Measures\u003c/h2\u003e\n \u003cp\u003eOutcome measures were heterogeneous (Table\u0026nbsp;1). Multi-dimensional QOL or functional tools included the: Toronto Extremity Salvage Score (TESS) and parent-proxy TESS (pTESS), used in seven studies (26%) (15, 20, 28, 30, 33, 35, 37); Short Form Health Surveys (SF-12 or SF-36) used in seven studies (26%) (17, 19, 21, 22, 28, 33, 38); Musculoskeletal Tumor Society (MSTS) tool, used in eight studies (30%) (20, 22, 28, 29, 33, 36, 36, 37); and Pediatric Outcomes Data Collection Instrument (PODCI), used in two studies (7%) (26, 29). Other validated instruments less frequently used included the PROMIS short forms (16), the Child Health Questionnaire (CHQ)(40), and the Pediatric Quality of Life Inventory (PedsQL) (27). Psychological or symptom-specific measures were also used to measure PROs, such as the Hospital Anxiety and Depression Scale (HADS) (39) and the pain intensity Visual Analog Scale (34). Eight studies (30%) incorporated qualitative or mixed methods, including interviews, open-ended questionnaires, and telephone surveys (15, 17, 18, 23, 25, 27, 35, 38). One study used medical records and physician notes to source PRO data (31).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003e3.5 Patient and Survivor Outcomes\u003c/h2\u003e\n \u003cp\u003eTwenty-five studies (93%) reported patient or survivor outcomes (Table\u0026nbsp;2). Outcomes were primarily self-reported (n = 18/25; 72%), with fewer joint patient-caregiver reports (n = 5/25; 20%) or caregivers-only reports (n = 3/25; 12%). Thirty-six distinct PROMs were used, most commonly the TESS (n = 8/25; 32%), SF-36 (n = 7/25; 28%), PODCI (n = 3/25; 12%), and semi-structured interviews (n = 3/25; 12%). Reporting of respondent type (child vs. proxy) was inconsistent and discrepancies between reporters were seldom analyzed. Timing also varied widely; longitudinal outcome trajectories were uncommon, limiting insight into critical windows such as pre-operative period, early rehabilitation, return to school, or transition to survivorship.\u003c/p\u003e\n \u003cdiv\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eOutcomes Measured Across Studies\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003ePhysical Functioning\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eEmotional Functioning\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eSocial and Occupational Functioning\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGeneral Health\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMobility and Function\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIndependence\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSelf-Image \u0026amp; Esteem\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMental Health\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSatisfaction with Surgery\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCognition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSelf-Efficacy\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRecreational Ability\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSocial \u0026amp; Relational\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFinancial\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEducational \u0026amp; Occupational\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSpiritual\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAcceptance by Others\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"16\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBekkering et al, 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBekkering et al., 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCooper at al., 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEiser et al., 1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eForni et al., 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGingsberg et al., 2007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHan et al., 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHenderson et al., 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHenderson et al,, 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHopyan et al., 2006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJamshidi et al., 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePiscione et al., 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePiscione et al., 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSainsbury et al., 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmith et al., 1995\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStevenson et al., 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTabone et al., 2005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTacyilidiz et al., 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTebbi et al., 1989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTran et al., 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTunn et al., 2004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVasquez et al., 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTirado et al., 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWang et al., 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeir et al., 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"16\"\u003e\n \u003cp\u003e\u003cstrong\u003eCaregiver Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJaraway et al., 2013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMeng et al., 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTebbi et al., 1989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeir et al., 2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv id=\"Sec16\"\u003e\n \u003ch2\u003e3.5.1 Physical Functioning\u003c/h2\u003e\n \u003cp\u003ePhysical functioning was the most evaluated domain, assessed in 23 studies (85%). Within the domain, the most assessed aspects were mobility/function (n = 17/23; 74%), independence (n = 17/23; 74%), and pain (n = 13/23; 56%).\u003c/p\u003e\n \u003cp\u003eFemales reported lower physical QOL and general health than males in two studies (21, 22), while no functional differences were observed between limb salvage and amputation groups (15). Survivors generally reported lower health-related QOL (HRQOL) than healthy controls (15, 32). Many patients described being unable to run, having trouble climbing stairs, or struggling to sit on the floor (17, 18). One study found that the physical functioning and pain significantly improved from surgery to 6- and 12-months post-surgery, with overall HRQOL being lower in bone tumor patients than the general population (21).\u003c/p\u003e\n \u003cp\u003ePatient and survivor functional independence in was evaluated through general indicators (e.g., need for assistive devices) and specific tasks such as housework, childcare, and physically navigating different terrains. Three longitudinal studies documented improvements in independence over time (21, 23, 37), with others noting that independence was closely linked to mobility aid use (15, 23, 27).\u003c/p\u003e\n \u003cp\u003ePain was common and persisted months or years post-surgery (23, 32). Pain was described both as continuous and episodic (e.g., occurring after physical exertion or in cold weather) (17). Limb-sparing procedures were associated with pain, hypersensitivity, numbness, and stiffness (18). Three investigations explicitly assessed phantom limb pain (23, 31, 34). One study found that pediatric cancer amputees were four times more likely to report phantom limb pain than those with trauma-related amputations, especially amongst those exposed to chemotherapy (31). Another study found that gabapentin was effective in preventing acute post-operative phantom limb pain (34).\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec17\"\u003e\n \u003ch2\u003e3.5.2 Social and Occupational Functioning\u003c/h2\u003e\n \u003cp\u003eSixteen studies (59%) evaluated patient or survivor social and occupational functioning. The outcomes most frequently examined were in the social or relational domains (n = 11/16; 69%), which included family involvement, peer relationships, and social activities. Social functioning improved following surgery, particularly among males treated with limb-sparing procedures (21, 22, 29, 32). Social confidants were primarily identified as mothers, with peers described as being helpful, fearful, avoidant, and pitying after surgery (23). Survivors also described social discomfort, noting that others appeared uneasy discussing their illness (23).\u003c/p\u003e\n \u003cp\u003eEducational and occupational outcomes were reported in seven studies (n = 7/16, 44%). School challenges included learning difficulties, absenteeism, and repeating grades (15, 17). Compared to non-amputees and healthy siblings, amputees were less likely to graduate high school or college (32). School absences among amputees were commonly attributed to fear of injury or difficulties using stairs (17, 24). Employment outcomes, assessed in three studies (n = 3/16, 19%), indicated lower employment rates among survivors relative to siblings (17, 23, 32). Although one study found no overt hiring discrimination, survivors reported job loss due to their surgery or restricted mobility (23). While many survivors reported their opportunities as constrained, some described their experiences as influencing career choices, particularly toward health and social sciences (17).\u003c/p\u003e\n \u003cp\u003eRecreational ability was measured in five studies (n = 5/16, 31%), with children often reporting minimal difficulties with activities of daily living such as bathing or dressing (27). However, significant restrictions were reported for high-demand tasks such as sports and physical recreation, often accompanied by regret and frustration (15, 17, 18, 27).\u003c/p\u003e\n \u003cp\u003eFinancial impacts were described in one study (n = 1/16, 6%) with survivors describing prostheses as expensive to purchase and maintain (23). No studies assessed spiritual outcomes.\u003c/p\u003e\n \u003c/div\u003e\n \u003cdiv id=\"Sec18\"\u003e\n \u003ch2\u003e3.5.3 Emotional Functioning\u003c/h2\u003e\n \u003cp\u003eEmotional functioning was assessed in 15 studies (58%). Mental health outcomes were assessed in 13 studies (n = 13/15, 87%). One study reported that survivors sought psychiatric help to address intense fears of disease recurrence (17), with one showing improvement in mental health outcomes with time post-surgery (10).\u003c/p\u003e\n \u003cp\u003eSelf-image and self-esteem were examined in eight studies (n = 8/15, 53%). Findings included dissatisfaction with physical appearance, prostheses, or scars, alongside challenges with maturation. While many patients were satisfied with their physical appearance overall, perceptions of body image varied widely (26). Attitudes toward scars varied and included embarrassment, indifference, and pride (17, 27, 38). Three studies highlighted clothing restrictions and embarrassment in specific contexts such as swimming (17, 23, 38). Two studies suggested that self-acceptance was initially difficult but improved with age (26, 38). Self-esteem was generally comparable across ages and genders, with slightly higher ratings among patients without internally implanted devices (i.e., endoprostheses) (26, 40).\u003c/p\u003e\n \u003cp\u003eSelf-efficacy was examined in two studies (n = 2/15, 13%). Findings indicated that pain interference and fear of injury constrained participation in daily and recreational activities, reflecting low self-efficacy for activity engagement (16, 18). Satisfaction with surgical outcomes was captured in six studies (n = 6/16, 40%). Three studies indicated high overall satisfaction with limb salvage surgical results (26, 27, 29). Two studies reported most patients as satisfied with choosing limb salvage over amputation (17, 38). Despite this, one study revealed that fewer than two-thirds of amputees felt they had adequately understood the functional consequences prior to surgery but following surgery most felt their prostheses allowed engagement in desired activities (23). One study evaluated cognition (n = 1/16, 6%), which was found to be lower in patients aged 8–15 years compared to healthy controls, though not statistically significant (15).\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec19\"\u003e\n \u003ch2\u003e3.6 Caregiver Outcomes\u003c/h2\u003e\n \u003cp\u003eFour studies assessed caregiver outcomes (15%), involving 126 parents (with incomplete reporting in two studies) (Table\u0026nbsp;1). Outcomes were self-reported by caregivers (n = 34; 75%) or reported by patients about their caregivers (n = 1/4, 25%). Across these studies, six different PROMs were used.\u003c/p\u003e\n \u003cp\u003eEmotional functioning was the most frequently studied caregiver domain, reported in three studies (n = 3/4, 75%). One longitudinal study documented increasing parental anxiety and depression symptoms three years after their child’s surgery (39). Qualitative interviews revealed that parents often expressed denial of the diagnosis, fears about terminal outcomes, and distress about their own inability to cope (23, 25). Caregiver self-efficacy was reported in one study (n = 1/4, 25%), where parents present in the operating room described feeling better prepared to support their child post-surgery (25). Satisfaction with surgery was measured in one study (n = 1/4, 25%), in which parents reported more positivity when their child’s amputation appeared less severe than anticipated (25).\u003c/p\u003e\n \u003cp\u003eFinancial health as an outcome was reported in one study (n = 1/4, 25%) showing that 57% of parents experienced limits on insurance coverage for child prostheses and 38% reporting having paid out-of-pocket for prostheses (24). Family functioning was addressed in one study (n = 1/4, 3.7%), where patients described changes in parental behavior post-surgery, including becoming more protective or submissive (23). No studies assessed caregiver physical health outcomes.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eThis review synthesizes three decades of patient- and caregiver-reported outcomes following limb salvage or amputation for pediatric bone and soft-tissue sarcomas. Physical functioning was generally moderate to good with small or inconsistent differences between procedures. Pain, including phantom pain, often persisted and affected participation. Psychosocial outcomes varied, with some children and survivors reporting acceptance and others noting body-image concerns and activity limits. Caregiver distress and financial strain were evident but infrequently measured. Evidence gaps remaining include heterogeneous PROM use, limited assessment of priority domains, and minimal attention to caregivers\u0026mdash;restricting comparability and impeding family-centered care.\u003c/p\u003e \u003cp\u003eOur findings highlight the functional and QOL-related impacts of both limb salvage and amputation. Results further suggest that rehabilitation, symptom control, and environmental accommodations at home, school, and in the community, may influence heavily on lived experience. This aligns with biopsychosocial models of disability in which impairments, activity limitations, and participation restrictions are shaped by contextual facilitators and barriers (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e). It also underscores the importance of anticipatory preoperative guidance that maintains a focus on realistic post-surgical expectations for mobility, stamina, and participation\u0026mdash;regardless of procedure (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral areas for improving family-centered care were identified. Pain management requires sustained attention across the surgical continuum. Early identification of phantom limb and neuropathic pain, education about pain triggers, and timely referral to interdisciplinary services may reduce constraints on participation post-surgery. Evidence from long-term survivors indicates that upwards of 41% report chronic pain decades after diagnosis, with one-quarter experiencing severe interference with activities of daily living\u0026mdash;and that history of amputation or limb sparing surgery increase the odds of daily pain interference (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). School and recreation re-integration also requires structured planning, including graded return to physical education and close coordination with teachers and coaches (\u003cspan additionalcitationids=\"CR44\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Addressing body image and visible differences through strategies including scar normalization and peer education may ease social discomfort (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). Finally, families could benefit from financial and system navigation support, particularly around prosthesis costs and insurance access barriers.\u003c/p\u003e \u003cp\u003eA wide range of PROMs were used, often without justification for domain selection or consideration of psychometric suitability for pediatric oncology or survivorship. Tools were applied to assess function, general health, and symptom burden, making comparison and synthesis difficult. Key domains identified by children, adolescents, survivors, parents, and clinicians as research priorities (e.g., mental health, participation, educational and employment engagement, financial strain, and caregiver outcomes) (\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e) were only inconsistently assessed, and spiritual well-being was not evaluated at all.\u003c/p\u003e \u003cp\u003eThese gaps suggest the need for a measurement agenda in this area. First, efforts should coalesce around a core outcome set anchored to the World Health Organization (WHO)-endorsed International Classification of Functioning, Disability and Health (ICF) (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e) and co-designed with patients, survivors and caregivers. Second, the core outcome set should include symptoms, activity, participation, physical, financial and social environments, and factors such as body image and self-efficacy. Longitudinal assessment timepoints should also be mapped to the surgical and overall cancer treatment journey to understand predictors of child and family outcomes, outcome trajectories, and supportive care needs. Third, PRO self-reporting should be encouraged whenever possible, with proxy reports used thoughtfully given tendencies for caregivers to overestimate children\u0026rsquo;s cancer symptoms and underestimate function (\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e). Fourth, transparent reporting of participant disease and demographic characteristics will enable equity-oriented analyses. At present, signals in the current literature (e.g., lower physical QOL among females, insurance barriers) warrant confirmation and targeted response.\u003c/p\u003e \u003cp\u003eThe family caregiver literature is notably thin given parents\u0026rsquo; central roles in decision-making, clinical care, and advocacy. Where measured, anxiety and depressive symptoms were identified and preparedness for child limb surgery appeared to shape care confidence. Additional research is needed to understand caregiver-reported outcomes and support needs over time, and to examine the efficacy of caregiver-centered wellness interventions (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFindings have direct clinical implications. In alignment with clinical practice guidelines (\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e), PRO collection should be embedded into routine practice to enable supportive care provision and to determine the effectiveness of administered interventions. Rehabilitation pathways should include early goal-directed mobility training, progressive return-to-activities, and coordination with schools. Pain care should include anticipatory management, timely treatment, and ongoing assessment. Psychosocial care should continue to focus on peer support, child self-esteem, family mental health, and resource navigation.\u003c/p\u003e \u003cp\u003eParent and survivor involvement strengthened this review by ensuring the research questions, outcomes of interest, and data interpretation reflected real-world experiences of limb surgery. Parent and survivor contributions directed the assessment of PROs in domains often missed in the literature, such as school participation, family impacts, and long-term psychosocial concerns, which directly shaped our synthesis. A key lesson learned was the value of dedicating time and structure for meaningful engagement, including clear communication about review methods. Future work should prioritize partner representation and supportive processes to enable contribution to emotionally sensitive topics.\u003c/p\u003e \u003cp\u003eAdditional review strengths include that we captured both patient and caregiver outcomes, allowing for a family-centered understanding of the surgical experience. Our inclusion of both physical and psychosocial outcomes provides a more holistic understanding of the impact of limb surgery across these groups, which is crucial to direct clinical care. Considering limitations, our synthesis is narrative and dependent on what studies chose to measure and report. Although no language limits were applied, practical constraints including our search strategy may still have favoured English-language publications, and grey literature was not systematically searched.\u003c/p\u003e \u003cp\u003eThis review highlights the need to report the experiences and needs of childhood cancer amputees and their family caregivers. Future research should prioritize prospective, longitudinal, multi-site studies that adopt common data elements and core PRO sets to enable causal inferences and pooled analyses. Mixed methods studies integrating child, survivor, and caregiver perspectives narratives with longitudinal assessments will clarify mechanisms and contextual modifiers of outcomes. Finally, interventional and implementation studies are needed to ensure that improvements in child survival are matched by improvements in QOL and participation. Collaborations led by those with lived experience, researchers, and clinicians will be valuable in fulfilling research gaps and developing interventions that improve outcomes for both childhood cancer patients and their family caregivers.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis project was supported by the Operating Grant: SPOR \u0026ndash; Guidelines and Systematic Reviews: The Evidence Alliance, grant number (154442).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e L.D. conceptualized this study. L.J. and L.D. drafted the study protocol. All authors participated in data collection, interpretation, manuscript drafting and revision. All authors reviewed the manuscript, \u0026nbsp;approve of its contents, and agree to be accountable for the work.\u0026nbsp;\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGeiger EJ, Liu W, Srivastava DK, Bernthal NM, Weil BR, Yasui Y, et al. What Are Risk Factors for and Outcomes of Late Amputation After Treatment for Lower Extremity Sarcoma: A Childhood Cancer Survivor Study Report. Clin Orthop. 2023;481(3):526\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBelayneh R, Fourman MS, Bhogal S, Weiss KR. Update on Osteosarcoma. Curr Oncol Rep. 2021;23(6):71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGeenen MM, Cardous-Ubbink MC, Kremer LCM, van den Bos C, van der Pal HJH, Heinen RC, et al. Medical Assessment of Adverse Health Outcomes in Long-term Survivors of Childhood Cancer. JAMA. 2007 June 27;297(24):2705\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlessa M, Alkhalaf HA, Alwabari SS, Alwabari NJ, Alkhalaf H, Alwayel Z, et al. The Psychosocial Impact of Lower Limb Amputation on Patients and Caregivers. Cureus. 2022;14(11):e31248.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcQuerry J, Gammon L, Carpiaux A, Talwalkar V, Iwinski H, Walker J, et al. Effect of Amputation Level on Quality of Life and Subjective Function in Children. J Pediatr Orthop. 2019;39(7):e524\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobert RS, Ottaviani G, Huh WW, Palla S, Jaffe N. Psychosocial and functional outcomes in long-term survivors of osteosarcoma: A comparison of limb-salvage surgery and amputation. 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Effects of paediatric limb loss on healthcare utilisation, schooling and parental labour supply. Disabil Rehabil. 2010;32(24):2046\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJaraway D, Perry S, Phillips M, Ziegler P, Wolgemuth A, Scott SD. Preparing parents to help support their child post-amputation for bone cancer. ORNAC J. 2013;31(4):13\u0026ndash;9, 24\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenderson ER, Pepper AM, Marulanda GA, Millard JD, Letson DG. What is the Emotional Acceptance After Limb Salvage with an Expandable Prosthesis? Clin Orthop. 2010;468(11):2933\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSainsbury DCG, Liu EH, Alvarez-Veronesi MC, Ho ES, Hopyan S, Zuker RM, et al. Long-Term Outcomes following Lower Extremity Sarcoma Resection and Reconstruction with Vascularized Fibula Flaps in Children. Plast Reconstr Surg. 2014;134(4):808\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHopyan S, Tan JW, Graham HK, Torode IP. Function and Upright Time Following Limb Salvage, Amputation, and Rotationplasty for Pediatric Sarcoma of Bone. J Pediatr Orthop. 2006;26(3):405\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenderson ER, Pepper AM, Marulanda G, Binitie OT, Cheong D, Letson GD. Outcome of Lower-Limb Preservation with an Expandable Endoprosthesis After Bone Tumor Resection in Children. J Bone Jt Surg. 2012;94(6):537\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStevenson JD, Doxey R, Abudu A, Parry M, Evans S, Peart F, et al. Vascularized fibular epiphyseal transfer for proximal humeral reconstruction in children with a primary sarcoma of bone. Bone Jt J. 2018;100-B(4):535\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith J, Thompson JM. 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Gabapentin as an Adjuvant Therapy for Prevention of Acute Phantom-Limb Pain in Pediatric Patients Undergoing Amputation for Malignant Bone Tumors: A Prospective Double-Blind Randomized Controlled Trial. J Pain Symptom Manage. 2018;55(3):721\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiscione J, Barden W, Barry J, Malkin A, Roy T, Sueyoshi T, et al. The Pediatric Toronto Extremity Salvage Score (pTESS): Validation of a Self-reported Functional Outcomes Tool for Children with Extremity Tumors. Clin Orthop. 2019 Sept;477(9):2127\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJamshidi K, Ramezan Shirazi M, Bagherifard A, Mirzaei A. Curettage, phenolization, and cementation in paediatric Ewing\u0026rsquo;s sarcoma with a complete radiological response to neoadjuvant chemotherapy. Int Orthop. 2019;43(2):467\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTran TH, Hayden JB, Gazendam AM, Ghert M, Gundle KR, Doung YC, et al. Pediatric and Adult Patients Have Similar Functional Improvement After Endoprosthetic Reconstruction of Lower-Extremity Tumors. J Bone Jt Surg. 2023 July 19;105(Suppl 1):22\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eForni C, Gaudenzi N, Zoli M, Manfrini M, Benedetti MG, Pignotti E, et al. Living with rotationplasty\u0026mdash;Quality of life in rotationplasty patients from childhood to adulthood. J Surg Oncol. 2012;105(4):331\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng J, Wu J, Zhang X, Guo L, Li H. A longitudinal evaluation on 3-year change of anxiety and depression, and their risk factors among parents of childhood and adolescence patients with resectable osteosarcoma: A cohort study. 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Cancer. 2021;127(10):1679\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaul V, Inhestern L, Sigmund D, Winzig J, Rutkowski S, Escherich G, et al. Addressing gaps and enhancing experiences in support services for families of pediatric cancer survivors. Pediatr Res. 2025 July;98(1):168\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurns MA, Fardell JE, Wakefield CE, Cohn RJ, Marshall GM, Lum A, et al. School and educational support programmes for paediatric oncology patients and survivors: A systematic review of evidence and recommendations for future research and practice. Psychooncology. 2021;\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eG\u0026ouml;tte M, Gau\u0026szlig; G, Dirksen U, Driever PH, Basu O, Baumann FT, et al. Multidisciplinary Network ActiveOncoKids guidelines for providing movement and exercise in pediatric oncology: Consensus-based recommendations. Pediatr Blood Cancer. 2022;69(11):e29953.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVani MF, Lucibello KM, Trinh L, Santa Mina D, Sabiston CM. Body image among adolescents and young adults diagnosed with cancer: A scoping review. Psychooncology. 2021;30(8):1278\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHendriks RTJ, van Eenbergen MCHJ, de Boer ML, Sleeman SHE, Boll D, Husson O, et al. \u0026ldquo;There is still a part of me that would love to be the old me again\u0026rdquo;, how do adolescents and young adults (AYA) experience cancer-related bodily changes: a phenomenological interview study. J Cancer Surviv Res Pract. 2025;19(5):1623\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarlsson E, Gustafsson J. Validation of the International Classification of Functioning, Disability and Health (ICF) core sets from 2001 to 2019 - a scoping review. Disabil Rehabil. 2022 July;44(14):3736\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMack JW, McFatrich M, Withycombe JS, Maurer SH, Jacobs SS, Lin L, et al. Agreement Between Child Self-report and Caregiver-Proxy Report for Symptoms and Functioning of Children Undergoing Cancer Treatment. JAMA Pediatr. 2020;174(11):e202861.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodin G, Malfitano C, Rydall A, Schimmer A, Marmar CM, Mah K, et al. Emotion And Symptom-focused Engagement (EASE): a randomized phase II trial of an integrated psychological and palliative care intervention for patients with acute leukemia. Support Care Cancer. 2020;28(1):163\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeyns A, Jacobs S, Negrini S, Patrini M, Rauch A, Kiekens C. Systematic Review of Clinical Practice Guidelines for Individuals With Amputation: Identification of Best Evidence for Rehabilitation to Develop the WHO\u0026rsquo;s Package of Interventions for Rehabilitation. Arch Phys Med Rehabil. 2021 June;102(6):1191\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAyers DC, Franklin PD, Ring DC. The role of emotional health in functional outcomes after orthopaedic surgery: extending the biopsychosocial model to orthopaedics: AOA critical issues. J Bone Joint Surg Am. 2013;95(21):e165.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMednick L, Chen C. Do children need to know? Clinical and ethical concerns with caregivers not telling children about surgery. J Pediatr Surg. 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAldiss S, Hollis R, Phillips B, Ball-Gamble A, Brownsdon A, Chisholm J, Crowther S, Dommett R, Gower J, Hall NJ, Hartley H, Hatton J, Henry L, Langton L, Maddock K, Malik S, McEvoy K, Morgan JE, Morris H, Parke S, et al. Research priorities for children's cancer: a James Lind Alliance Priority Setting Partnership in the UK. BMJ Open. 2023;13(12):e077387.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 guideline statement. J Clin Epidemiol. 2016;75:40\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pediatric oncology, Sarcoma, Limb salvage, Amputation, Patient-reported outcomes, Quality of life, Caregivers, Scoping review","lastPublishedDoi":"10.21203/rs.3.rs-8379832/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8379832/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eChildren diagnosed with bone tumors or soft tissue sarcomas often undergo limb salvage surgery or amputation, procedures that shape long-term functioning and quality of life (QOL). Patient- and caregiver-reported outcomes (PROs) provide essential insight into physical, psychosocial, and participation impacts, yet existing evidence is dispersed and methodologically heterogeneous. This scoping review mapped the PRO literature for children, survivors, and caregivers following limb surgery and identified gaps limiting clinical care and research advancement.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eSix databases were searched. Eligible studies included children with bone or soft-tissue sarcomas and their family caregivers that reported PROs or needs related to limb salvage or amputation. Two reviewers independently screened studies and charted data. Quantitative and qualitative findings were summarized descriptively and synthesized narratively across QOL domains.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eTwenty-seven studies fulfilled inclusion criteria. Physical functioning was the most assessed domain, with generally moderate-to-good outcomes and limited differences between limb salvage and amputation. Pain remained common months to years post-surgery. Psychosocial findings were mixed, reflecting peer acceptance but also body image, recreation, and school participation challenges. Only four studies included caregivers, who reported anxiety, depression, financial strain, and shifting family roles. Across studies, PRO measurement was highly heterogeneous, with inconsistent domains of assessment, measurement tool use, and timepoints.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eChildren and families experience complex functional and psychosocial impacts after limb surgery, underscoring needs for enhanced rehabilitation, pain care, school reintegration, and caregiver support. A coordinated measurement agenda\u0026mdash;including core PRO domains, longitudinal assessment, and family-centered approaches\u0026mdash;is essential to strengthen evidence and improve survivorship care.\u003c/p\u003e","manuscriptTitle":"Patient- and Caregiver-Reported Outcomes After Limb Salvage or Amputation for Pediatric Bone and Soft Tissue Sarcomas: A Scoping Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-27 00:04:51","doi":"10.21203/rs.3.rs-8379832/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-25T10:39:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-15T22:40:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"317636986892602355434164116745893688836","date":"2026-02-05T13:55:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-03T23:21:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"121416496916251493469247967629278535788","date":"2026-02-03T21:41:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-31T13:24:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"56856617511799694909412209468563921396","date":"2026-01-21T21:10:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-21T21:02:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-16T21:53:19+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-07T08:22:23+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2025-12-16T21:15:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c3219351-1430-489a-9154-d8c402c5c7fa","owner":[],"postedDate":"January 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-17T08:24:18+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-27 00:04:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8379832","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8379832","identity":"rs-8379832","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}