An Interventional Study To Assess The Dosimetric Feasibility Of A One-week Adjuvant Hypofractionated Radiotherapy Schedule In Patients With Carcinoma Breast

Breast cancer is the most commonly diagnosed malignancy in females and the second most common cause of cancer mortality worldwide (Globocan data, 2022).

It is treated with a multimodality approach that includes surgery, Chemotherapy, Radiotherapy, and Immunotherapy. Radiotherapy is used in the treatment of breast cancer in early, locally advanced, and metastatic stages in both curative and palliative intent. Adjuvant RT reduces the 10-year risk of recurrences (locoregional and distant) from 35% to 19.3% (Absolute reduction 15.7%,95% CI, p<0.00001). (EBCTCG Meta-analysis).

The standard radiotherapy dose used in our setting for treating breast cancer is 50 Gy/25#/2Gy per fraction or 40 Gy/15#/3week/2.66 Gy per fraction. However, response to radiation therapy depends upon the α/β ratio. Tumour with a low α/β ratio responds to higher dose per fraction. Breast cancer is one of them. Healthy tissue of the breast and ribcage also has α/β ratio of 2.8 (low). Several studies on hypo-fractionating the dose have taken place worldwide showing satisfactory results (like FAST Forward trial, UK). Still, till now it is not the standard of care in breast cancer management. With ultra-hypofractionation, the major concern is for late normal tissue effects and whether the tight normal tissue constraints provided in the Fast-forward trial is achievable in our setting. This hypofractionation also has economic and logistic advantages in low-resource settings where the patient load is high and adequate radiotherapy facilities are not available.But before implementing such ultra-hypofractionated regimens universally, robust evidence is warranted which is lacking especially in resource-limited setting.

In this study we will try to prove that The 26 Gy in 5 fraction schedule(Ultra Hypofractionation)of adjuvant radiotherapy delivered in once daily fractions over 1 week in Breast Cancer patients is feasible in terms of radiation dose received by Organs at risk(Heart, lung, esophagus) and in terms of preventing the short-term and long-term radiation toxicities.

It is an interventional single-arm prospective study.

Study population will include breast cancer patients coming to the OPD of Radiation Oncology, AIIMS Mangalagiri, with complete microscopic resection of invasive breast cancer post breast conservation surgery or mastectomy for whom local or locoregional radiotherapy is recommended.

Sample size is calculated to be 35(conveninent sampling method will be used).Patients will be screened for inclusion and exclusion criterias. Patients satisfying the inclusion criteria after scheduled pre-radiotherapy investigations will be prescribed 26.0 Gy in 5 fractions over 1 week to chest wall or whole breast +/-regional lymph nodal irradiation +/- boost to tumor bed (10Gyin 5 fractions over 1 week). A clinical assessment will be conducted with close monitoring for acute toxicities of radiotherapy based on CTCAE Version 5, and a QoL questionnaire will be administered before and after RT. Clinical follow-up after 1 month and 2DECHO, PFT after 3 months, then clinical follow-up and QoL questionnaire and Thyroid Function test months after radiotherapy will be done for each patient to assess the acute or long-term toxicities(According to CTCAE guidelines it will be graded and managed accordingly if occurs)and locoregional recurrence.

The Continuous variables like age of patients, EORTC QLQ C-30 and B-23score, will be summarized as mean and standard deviation or median and interquartile range. The categorical variables like CTCAE grading,type of cancer, ER/ PR positivity, HER 2 positivity will be summarized as frequency and proportion. The association between continuous variables will be analysed using the t-test. The association between categorical variables will be analysed using Chi-square test. The change in quality of life and CAE grading over the time of observation will be analyzed by paired t-test and McNemar chi-square test. The p-value less than 0.05 will be considered statistically significant. The data analysis will be done using IBM SPSS version 26.

Our study may provide important insights into the feasibility and tolerance of ultra-hypofractionated adjuvant breast radiotherapy in resource-limited settings.