1. What data in particular will be shared?
   Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
   


2. What additional supporting information will be shared?
   Response -  Study Protocol
   
   
3. Who will be able to view these files?
   Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
   


4. For what types of analyses will this data be available?
   Response - Any purpose.
   


5. By what mechanism will data be made available?
   Response - Proposals should be directed to [samprasdsouza3000@gmail.com].
   


6. For how long will this data be available start date provided 16-12-2025 and end date provided 16-12-2027?
   Response - Immediately following publication. No end date.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - nil

Introduction    

   Lung and breast cancers are two of the most common regions of cancer occurrences in men and women respectively. If considered globally, among women, breast cancer ranks as foremost cause of death from cancer. In India, one in every nine individuals could develop cancer in their lifetime  and breast cancer accounts for over 50 to 60 percent of all cancers among the female population.

       Treatment of breast cancers depend on the stage of the disease. Stage 0, also known as ductal carcinoma in situ can be treated with lumpectomy (surgical excision of the tumor) and radiation or with mastectomy (surgical removal of the entire lung). Non-metastatic breast cancers (Stages I-III) can be conservatively managed with chemoradiation therapy (CRT), immunotherapy, endocrine therapies or treated using surgery. While stage IV, being metastatic is treatable with chemoradiation therapy, but is not curable. CRT has helped achieve good survival rates in cancer patients, but there are multiple short and long-term adverse effects that have been associated to it. Patients who undergo chemoradiation therapy have experienced significant reduction in their muscle mass (loss of muscle fibers), muscle strength (leading to weakness) and physical performance which in part fulfills the criteria for the diagnosis of a condition called sarcopenia as defined by EWGSOP (European Working Group on Sarcopenia in older people).

       Sarcopenia is a progressive, age-related, generalized loss of skeletal muscle mass, strength or function. In conditions like obesity and various other malignant diseases it is considered a poor prognostic factor. This is so especially among cancer patients undergoing chemoradiation therapy as they are shown to develop greater CRT toxicity, had a higher risk of mortality (33%) and progression/relapse of disease (29%), compared to individuals not having sarcopenia.

       A study that was conducted internationally, involving older adults (aged 65 years and above) from eight different countries, demonstrated sarcopenia prevalence rates in geriatric Indian population (17.5%) to be greater than their peers from other countries that were included in the study.  Hence  it may be so that due to a higher sarcopenia prevalence, a dearth  of allied health services among Indian hospitals and a lack of awareness among these people, Indian women with breast cancer may be at a much greater risk of developing sarcopenia and related adverse effects compared to the patients in countries more developed than our own. It therefore becomes necessary that these patients are monitored closely for early detection of signs of sarcopenia which would immensely help in improving survival as well as the quality of life among women with breast cancer.

       By implementing the EWGSOP2 criteria before the commencement, during and after the completion of chemoradiotherapy therapy, a clear picture may be obtained about the occurrence of sarcopenia among these individuals.

PROCEDURE

The ethical clearance will be obtained from the Father Muller Institutional Ethics Committee. A pilot study will first be conducted following which the actual study will be conducted. Written informed consent will be obtained from the patients/caregivers/family members after which the study will be explained to them in detail. Subjects with breast cancer admitted to FMMC will be screened based on the inclusion and exclusion criteria. The demographic data of the patient will be collected. In the week, before the commencement of CRT, patient will be screened for probable sarcopenia using SARC-F. This involves answering the 5 questions under the 5 categories of – muscle strength, assistance in walking, rising from a chair, stair climbing and history of falls. This will be followed by the measurement of hand grip strength using hand-held dynamometer, muscle mass measurement by bioelectric impedance machine while physical performance physical performance is measured using Timed-Up and Go (TUG) Test.

To measure the hand grip strength, the patient will be given the dynamometer which the patient will hold in their hand and squeeze with as much effort as possible. The force that the patient produces will be the measure of their grip strength in kgs. To measure the total muscle mass, the patient will be asked to step barefoot onto the platform of the bioelectrical impedance machine and hold the handle and lift the arms up at 90-degree angle to the body. The machine measures the total skeletal muscle mass and displays it on the screen of the device in percentage. EWGSOP defines muscle mass cutoff point in kgs. Therefore, the percentage will be calculated using the formula: (skeletal muscle mass % x total body weight)/100. To perform TUG, test the patient begins from a seated position on a chair with armrest. Patient wears their regular footwear and can have a walking aid nearby if they need one while walking. The patient stands up on the therapist’s command (the therapist starts the stopwatch), walks three meters, and after turning around, walks back towards the chair and end the test by sitting on the chair. The watch is stopped when the patient returns to seated position. Time taken is noted by the therapist.

The same procedure will be followed in the 3^rd week and the 7^th week wherein the patient will be approached and the 5-item questionnaire SARC-F will be administered after which their hand grip strength using a hand-held dynamometer, muscle mass using bioelectric impedance machine and physical performance using Timed-Up and Go (TUG) Test will be measured. The cutoff points as defined by the EWGSOP are provided in the Table 1. The data obtained will be compiled on a Microsoft excel sheet for further analysis.

STATISTICAL ANALYSIS

The data will be described by frequency and percentages for categorical variables and Mean and Standard Deviation or Median and Inter-Quartile Range for numerical variables.

Paired t-test will be used to check for differences between the pre-and post-intervention scores.

Repeated measures ANOVA will be used to study changes in scores across all 3 time points.

If data is found to deviate from normality, non-parametric alternatives of the above-mentioned tests will be used.

p-value <0.05 will be considered to be statistically significant.

IMPLICATIONS

Sarcopenia is essentially a loss of muscle mass, which if present in breast cancer patients would lead to complications that may otherwise be preventable through early intervention or timely treatment. By studying its occurrence and/or progression due to breast cancer treatment (chemoradiation therapy) will help to put into place various measures to prevent or treat the condition along with ongoing cancer treatment. This can be achieved prehabilitation, resistance training, nutritional supplementation, multimodal exercise programs and blood flow restriction training etc. to improve muscle mass, muscle strength and physical performance in these patients.