Background and Rationale

Patient reported outcome measure (PROM) is a valid objective method to evaluate and report pain and functional ability of a patient eliminating the biases of the treatment provider(1). Limb salvage surgery is the standard of care for treatment of benign and malignant extremity tumors. Over 90% of patients undergo limb salvage as standard of care. The functional outcome varies widely based on the anatomical structures resected and reconstruction feasibility. As of now, physician reported outcome measures are widely used, MSTS (Musculoskeletal tumor society staging) being the most widely adopted. There are obvious limitations and biases to this approach.  Objective evaluation of the success of these procedures is better done using a PROM compared to traditionally used physician reported measures like MSTS(2).  Such a score has not been validated for use in the Indian context and languages. The Toronto Extremity Salvage score (TESS) is a reliable method to evaluate functional disability in patients undergoing treatment for extremity sarcoma. It was developed in English and has been translated and validated in 6 languages (Japanese, Korean, Chinese, Danish, Portuguese, Dutch)(3–5). It has 30 items about limitations of activity in daily life with regards to movement of body part. mobility, self-care, activities of daily routine. Each is scored from 0 (impossible) to 5(without restriction). The individual components are added together ranging from 0-100, higher the score, better the function. It is open source for further translation ad adaptation to regional languages.  The goal of this study is to translate, culturally adapt TESS for both upper and lower extremities into Hindi/Marathi and validate the translated version in patients who have undergone surgical treatment for benign and malignant tumors of the extremity. This shall pave way for objective assessment of function across this cohort for the Indian subcontinent and allow easier translation and validation into regional languages. This shall allow a uniform comparable objective patient empowered standard for multi-institutional comparative or collaborative studies.

Aims:

Translation, cultural adaptation and validation of TESS for extremity tumors in English, Hindi, Marathi.

Instrument for validation

The TESS score is a self-administered questionnaire. It has 30 items about limitations of activity in daily life with regards to movement of body part. mobility, self-care, activities of daily routine. Each is scored from 0 (impossible) to 5(without restriction). The individual components are added together ranging from 0-100, higher the score, better the function.  

MSTS (physician administered score) has been used widely in musculoskeletal oncology literature ,shall be used  for validity. (3,5)

Details of both scores is attached in the appendix below.

Population and setting

Adult patients treated surgically at Bone and soft tissue DMG, Tata memorial Hospital, for an extremity bone or soft tissue tumor (benign or malignant) with a curative intent shall be included in this study.

Inclusion criteria

1.     Age >18 years  

2.     treated surgically with curative intent for an extremity bone or soft tissue tumor (benign or malignant) with a minimum 3 months follow up

3.     Ability to communicate in English/Hindi/Marathi.

4.     Ability to give a valid written informed consent.  

Exclusion criteria

1.     Patients with impaired or challenged communication or inability to complete the questionnaire without external help

2.     Patients with unstable medical, oncologic or other emergencies

3.     Patients being treated with palliative intent or best supportive care

4.     Patients presenting with local or systemic recurrence

Study Design

This is a single center prospective observational cohort study

Study Procedure

Adult patients matching the inclusion criteria shall be given a detailed patient information sheet, after concerns are allayed, if they so choose to participate in the study, they shall be requested to fill the self- administered TESS score in their preferred language. Age, gender, diagnosis, site, primary diagnosis shall be recorded on the given case record form by the patient or an unbiased interviewer. A second score shall be filled a week later in person or returned by post/email/messaging service as per patient preference. If a messaging application is chosen, it shall be encrypted, the message shall not be disseminated across any groups and will be restricted to one competent member under direct supervision of the PI. Privacy shall be protected throughout such a transfer.

Outcome measures

Well published criteria for cross cultural adaptation by Beaton et al(6) and Guillemin et al (7) shall be employed.  The upper and lower extremity scores would be adapted separately. The steps of the study shall include,

1.     face validity,

2.     translation,

3.     concurrent validity,

4.     construct validity and

5.     reliability.

6.     Confirmatory factor analysis

The forward translation in each language would be performed by 3 bilingual translators, one of whom would be naive about the issues addressed in TESS and outside of medical background. Two other independent bilingual translators outside of medical background shall perform the respective language translation back into English. A final expert group including the principal investigators, translators shall review the versions and individual components in detail to reach a consensus based final translation for clinical use. After an initial pilot of 12 patients to assess the face validity, sequential accrual for the remaining patients shall be performed for the validation process.

Assessment sequence

The patient would be provided a score on paper to be filled on the day of outpatient visit. A second score is provided to be filled a week later and returned by post or in person. The pair is coded to allow test-retest analyses. Patient identification data shall not be paired to the questionnaire to allow anonymity.

Statistical considerations for outcome measures and sample size calculation

Sample size:

The TESS score has 30 items, considering 3-4 patients per item for validation per language, we need 100 patients. The estimated sample size for 3 languages, English, Hindi, Marathi is thus 300 patients. Considering for some attrition, data loss, we shall set the sample size at 400.

Reliability, Validity and confirmatory factor analysis

Spearman rank correlation coefficient would be used to measure convergent validity against validated MSTS summary scores. All analyses would be performed by R version 3.2.0. and SPSS.  Test- retest reliability would be examined using intra class coefficient. The intra-class-coefficient would be considered strong (>=0.7), moderate (0.5-0.7), and weak if <0.5. Significance would be 2 tailed and set at <0.05.

A Cronbach’s alpha of >0.70(9) would be considered adequate for measuring internal consistency. Intra-class coefficients would be estimated between 2 sets of responses to assess test-retest variability. Bland-Altman plots would be used to see the absolute differences between the 2 scores, against the mean, to show limits of agreement.

Confirmatory Factor analysis for each factor loaded on its subscale and model fit using root mean square error of approximation RMSEA (not more than0.08), comparative fit index and normed fit index (not less than 0.9) shall be performed.

Analyses

If 80% or more were answered as Not applicable, the score would be excluded from analyses. For discrepancy of scores with difficult answers the first response shall be considered. Floor and ceiling effects shall be measured to ascertain discrimination, the acceptable standards vary from 5-15%.

Data management

All study records will be kept with confidentiality in the investigators’ office or clinical research unit. Periodic audits will be performed by the investigators to ensure completeness and quality of data. Access to study documents will be available to the investigators and the Data Monitoring Committee.

Ethical aspects

The study will be conducted strictly as per International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines and the principles of the Declaration of Helsinki. An informed consent in the language of patient’s choice shall be administered.

Risk Benefit

This study does not add or impose any risk to the participants. Validation of the score will empower our patients and us to make better decisions for optimizing their functional well-being.

Feasibility

The annual outpatient load in the BST DMG is in the 1000s, we have 2 out-patient clinics per week, assuming a recruitment of 10 patients per week or 5 patients per out-patient clinic, we expect to complete recruitment within 1 year.

Significance

The validation of this outcome measure shall pave way for objective functional assessment and benchmark comparative studies for the sarcoma and non-sarcoma benign and malignant extremity tumor patient population across the subcontinent.

Conflict of Interest

The investigators declare no present or potential conflicts of interest in the conduct or outcome of this study.

Budget and funding

Funding yet to be applied for.

References 

1.         Black N. Patient reported outcome measures could help transform healthcare. BMJ [Internet]. 2013 Jan 28 [cited 2020 Jul 25];346. Available from: https://www.bmj.com/content/346/bmj.f167

2.         Enneking WF, Spanier SS, Goodman MA. A System for the Surgical Staging of Musculoskeletal Sarcoma. Clinical Orthopaedics and Related Research®. 1980 Dec;153:106–120.

3.         Ogura K, Uehara K, Akiyama T, Iwata S, Shinoda Y, Kobayashi E, et al. Cross-cultural adaptation and validation of the Japanese version of the Toronto Extremity Salvage Score (TESS) for patients with malignant musculoskeletal tumors in the lower extremities. Journal of Orthopaedic Science. 2015 Nov 1;20(6):1098–105.

4.         Xu L, Sun M, Sun W, Qin X, Zhu Z, Wang S. Cross-cultural adaptation and validation of the Chinese version of Toronto Extremity Salvage Score for patients with extremity sarcoma. SpringerPlus. 2016 Jul 19;5(1):1118.

5.         Kim H-S, Yun J, Kang S, Han I. Cross-cultural adaptation and validation of the Korean Toronto Extremity Salvage Score for extremity sarcoma. Journal of Surgical Oncology. 2015;112(1):93–7.

6.         Beaton DE, Bombardier C, Guillemin F, Ferraz MB. Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures. Spine. 2000 Dec 15;25(24):3186–3191.

7.         Guillemin F, Bombardier C, Beaton D. Cross-cultural adaptation of health-related quality of life measures: Literature review and proposed guidelines. Journal of Clinical Epidemiology. 1993 Dec 1;46(12):1417–32.

8.         Sinha R, van den Heuvel WJA, Arokiasamy P. Validity and Reliability of MOS Short Form Health Survey (SF-36) for Use in India. Indian J Community Med. 2013;38(1):22–6.

9.         Cronbach LJ. Coefficient alpha and the internal structure of tests. Psychometrika. 1951 Sep 1;16(3):297–334.