Conventional vs hypofractionated radiotherapy: a comparison of clinical-pathological characteristics, dosimetric parameters and toxicity in post-mastectomy patients at Ocean Road Cancer Institute December 2019 to March 2020

Abstract

ABSTRACT Background: According to GLOBOCAN 2018, breast cancer amongst females is the most commonly diagnosed malignancy and the leading cause of cancer deaths. In Tanzania, just as in most other sub-Saharan countries, this number is only second to cervical cancer. Radiotherapy, an essential component in the adjuvant management of breast cancer, has traditionally been delivered using standard or conventional fractionation, consisting of a total dose of 50 Gy delivered at 1.8 to 2Gy daily fractions over 5-6 weeks. However, studies have demonstrated that hypofractionation schemes, utilizing lower total doses such as 40 Gy or 42.5 Gy, delivered at more than 2 Gy daily fractions over about 3 weeks offer the same therapeutic benefit and safety profile as standard fractionation. This benefit has mostly been studied post-breast conserving surgery. Hypofractionation in the post mastectomy setting is slowly being adopted across the world, including Tanzania, where the recent arrival of linear accelerators has facilitated its utilization at Ocean Road Cancer Institute. Despite the foregoing, no data has as yet been published on how post-mastectomy hypofractionation compares to conventional fractionation, with regard to dosimetric parameters and acute toxicities amongst breast cancer patients in Tanzania. Objective: The aim of this study was to compare the dosimetric parameters and acute toxicities of conventional radiotherapy with hypofractionated radiation therapy in post mastectomy patients with indications for radiotherapy at Ocean Road Cancer Institute. Methods: This was a prospective comparative study between hypofractionated (HFRT) and conventional (CFRT) schemes of radiotherapy (RT) from December 2019 through March 2020. A total of 74 post-mastectomy patients undergoing adjuvant radiotherapy were conveniently sampled and recruited into the two study groups, with 37 patients in each of the two arms; conventional fractionation (50 Gy in 25 Fractions, 2 Gy/day over 5 to 6 weeks) or hypofractionation (42.5Gy in 16 Fractions, 2.67 Gy/day over 3 weeks). All patients were treated using the linear accelerator, with the 3D conformal technique. Patient demographics, tumour characteristics, management and dosimetric parameters were collected prior to radiotherapy. Evaluation for acute toxicities was conducted immediately upon completion of treatment and within 90 days as per the RTOG radiation toxicity grading system. Data analysis was done using SPSS and presented in the form of tables and graphs. Independent t test was used to test the mean differences between these two groups and a p value <0.05 was considered statistically significant. Results: This study recruited 74 post mastectomy patients who were on treatment at Ocean Road Cancer Institute between December 2019 and March 2020. Both HFRT and CFRT were allocated 37 patients each, with fairly equal distribution of social demographic and clinical features. The mean participant age was 51±12 years, with the majority within the age range 41-50. The mean BSA and BMI were 1.7±0.2 and 24.8±7.6 respectively. All participants had a diagnosis of invasive ductal carcinoma. The most common stage was IIIB (27%) and IIIA (29.7%) and grade was III (18.9%) and II (18.9%) in CFRT and HFRT respectively. One third (33%) of all participants had ER positive tumours, while ER-, PR+, HER2+ and HER2- status was documented in 40%,26%,23% and 51% respectively. The maximum dose to the chest wall PTV, as indicated by D2%, was higher with CFRT (mean=55.20 Gy) than with HFRT (mean=47.15Gy). The near minimum dose to the chest wall PTV (D98%) was lower with HFRT (mean=37.61Gy) than with CFRT (39.94%). The mean V95% of the chest wall PTV was 90.19%, in CFRT, and slightly higher at 92.58% in HFRT, a difference that was statistically significant (p=0.001). A statistically significant lower ipsilateral lung V35Gy, V40Gy and mean dose was noted with hypofractionation. Immediately post treatment, no statistically significant difference was noted in the proportions of grade 0 skin toxicities (51.4% in CFRT and 48.6% in HFRT) and grade 1 skin toxicities (48.6% in CFRT and 51.4 in HFRT). No grade 2 or 3 skin toxicities were noted immediately post treatment. Toxicity grade appeared to change at subsequent follow up within 90 days of treatment, with grade 2 and 3 toxicities being noted, respectively, in 43.25% and 10.8% of patients in CFRT, and 45.9% and 8.1% of patients in HFRT. Conclusion: This study demonstrated that hypofractionation and conventional fractionation regimens have comparable acute skin toxicity profiles, with grade 2 toxicity being the most common and that hypofractionation results in a lower dose to the heart, lung and spinal cord.