Evaluating Loco-Regional Hypo Fractionated Versus Conventional Radiotherapy in Post-Mastectomy Breast Cancer

Dr. Md. Abdul Mannan, Dr. Zinat Ara Naznin

Genetics, Industry, Innovation, Molecular Therapeutics

Jun 26

Abstract

Background: Breast cancer is a leading malignancy in women, with post-mastectomy radiotherapy (PMRT) essential for reducing locoregional recurrence in high-risk cases. Conventional fractionated radiotherapy (CFRT) involves 45–50 Gy over 5 weeks, but hypo fractionated radiotherapy (HFRT) offers shorter courses (e.g., 40–42.5 Gy over 3 weeks), potentially improving logistics and cost in low-resource settings like Bangladesh. This study compared toxicities, tolerability, and costs between HFRT and CFRT.

Methods: A quasi-experimental study at Khwaja Yunus Ali Medical College & Hospital enrolled 60 patients (30 per arm) from October 2017 to September 2018. CFRT: 50.4 Gy/28 fractions; HFRT: 42.56 Gy/16 fractions. Inclusion: Histologically confirmed Stage II/III breast cancer post-mastectomy. Exclusion: Metastases, uncontrolled comorbidities, age <18 or >75. Data on demographics, tumors, treatments, and toxicities (acute/chronic, graded via RTOG/CTCAE) were analyzed using t-tests, chi-square, and Fisher’s exact tests (p<0.05 significant).

Results: Groups were similar in age (mean ~45 years) but differed in income (lower in HFRT, p=0.001), BMI (>25 higher in CFRT, p=0.010), ECOG status (worse in HFRT, p=0.035), staging (more Stage II in HFRT, p=0.006), and grade (more Grade I in HFRT, p=0.040). Chemotherapy regimens varied (p=0.001), but neoadjuvant/adjuvant/hormonal therapies were comparable. Acute dermatitis (Grade II/III) was lower in HFRT (10% vs. 23.3%, p=0.138). Chronic dermatitis trended lower in HFRT (6.7% vs. 26.7%, p=0.08). Dysphagia, lymphedema, pulmonary/cardiac toxicities, and pain were mild and similar (p>0.05). No Grade IV events. HFRT cost 86,900 BDT vs. 133,250 BDT for CFRT.

Conclusion: HFRT provides equivalent safety to CFRT with benefits in duration, compliance, and cost, making it suitable for high-volume, low-resource environments. Multicenter trials with longer follow-up are recommended to confirm survival and control.

Keywords: Breast cancer, hypofractionated radiotherapy, conventional radiotherapy, post-mastectomy, toxicity, cost-effectiveness.

1. Introduction

Breast cancer affects millions globally, with PMRT improving survival in advanced cases. CFRT is standard but burdensome in low-middle-income countries (LMICs) due to costs and duration. HFRT, supported by meta-analyses (e.g., no differences in survival or recurrence), offers efficiency. This Bangladesh-based study tested HFRT’s viability, hypothesizing comparable control and lower costs.¹

Conventional fractionated radiotherapy (CFRT), typically delivered at doses of 45-50 Gy in 25-28 fractions over 5 weeks, remains as the established modality of management. However, in Bangladesh and similar low- and middle-income countries (LMICs), long treatment duration, high resource utilization, patient travel, accommodation, and lost wages contribute to substantial direct and indirect cost burdens.²

Several studies are present where HFRT has been compared CFRT to evaluate outcomes in post-mastectomy breast cancer cases. For instance, a recently conducted meta-analysis covering 25 trials (consisting of 3871 postmastectomy breast cancer patients) demonstrated no significant differences between HFRT and CFRT in overall survival, disease-free survival, locoregional recurrence, or major acute or late side effects. In addition, another huge cohort study of over 1600 patients reported that HF-PMRT was feasible, with comparable 5-year locoregional recurrence-free survival, disease-free survival, as well as overall survival.³

2. Methods

Conducted over 1.5 years, patients’ post-chemotherapy received 3D-CRT on a linear accelerator. Sampling: Alternate assignment (first by lottery). Evaluations: Weekly during RT, follow-up at 6 weeks/3/6 months. Analysis: SPSS v23, focusing on toxicities and costs.

Table 1: Key Inclusion/Exclusion Criteria

Criterion	Inclusion	Exclusion
Disease	Histologically confirmed breast cancer, post-mastectomy, Stage II/III, tumor <5 cm with high-risk features	Distant metastases, no positive nodes or ≥10 negative nodes
Health	ECOG 0–2, controlled comorbidities	Uncontrolled diabetes/hypertension, severe cardiac/pulmonary disease, pregnancy, age <18/>75
Consent	Willing participants	Unwilling

Table 2: Treatment Protocols

Arm	Dose/Fractions	Duration	Technique
A (CFRT)	50.4 Gy/28	~5.5 weeks	3D-CRT, 6 MV photons, tangential + AP fields
B (HFRT)	42.56 Gy/16	~3.1 weeks	Same as above

3. Results

Socio-Demographics and Clinical (Table 3: Summary Differences)

Characteristic	CFRT (n=30)	HFRT (n=30)	p-value
Mean Age (years)	45.3 ±10.5	44.1 ±10.5	0.611
Income <15,000 BDT (%)	3.3	26.7	0.001*
BMI >25 (%)	70.0	36.7	0.010*
ECOG 2 (%)	0.0	20.0	0.035*

*Significant.

Tumors: Mostly ductal (91.7%), Stage II (83.3%), size 2–5 cm (68.3%).

Toxicity Summary (Table 4: Dermatological and Other Toxicities)

Toxicity	CFRT (%) Grade ≥II	HFRT (%) Grade ≥II	p-value
Acute Dermatitis	23.3	10.0	0.138
Chronic Dermatitis	26.7	6.7	0.08
Dysphagia	13.3	3.3	0.065
Lymphedema	13.3	6.7	0.389
Cardiac/Pulmonary	3.3	3.3	1.00

Costs: HFRT 35% cheaper.

4. Discussion

A total of 60 patients with post-mastectomy carcinoma of the breast (Stage II to III) were analyzed, having received either HFRT or CFRT radiotherapy. These patients were followed for up to 6 months after completion of treatment. The primary objective of the study was to compare the tolerability, toxicity profiles, treatment cost, and overall treatment duration between HFRT and CFRT regimens in the post-mastectomy setting.

The two groups were comparable in terms of tumor and clinical characteristics. In both arms, the majority of patients were younger than 50 years, with a mean age of 44.68 ± 10.49 years, and no statistically significant difference was observed between the groups (p > 0.05). These findings are consistent with previous studies, including those by Rastogi et al., Das et al., Bhattacharyya et al. (2018), and Banu et al., which also reported similar age distributions among patients receiving hypo fractionated and conventional radiotherapy.⁴

The majority of patients in both treatment arms (93.3%) reported no positive family history of breast cancer, with only 6.7% in each group having a positive family history (p > 0.05). This finding aligns with Aich et al., who reported similarly low proportions of positive family history in both control (2.1%) and study groups (2.3%).

Pathological staging revealed a higher proportion of Stage II tumors in the HFRT group, and tumor grading showed more well-differentiated tumors in this arm. Similar findings were reported by Rastogi et al. with 66% and 54%, Das et al. with 79.2% and 80%, Bhattacharyya et al. with 52% and 60%, and Banu et al. reported 86% stage II tumors in their cohorts. Despite this, tumor sizes were comparable, supporting the clinical applicability of both treatment regimens across similar disease presentations. Moreover, infiltrating ductal carcinoma was more in both arms (90% in Arm A & 93.3% in Arm B) (p value >0.05). Infiltrating ductal carcinoma was also abundant in previous studies.

Results mirror international evidence: HFRT comparable in toxicity (e.g., lower acute skin issues), with economic advantages. Baseline imbalances (e.g., worse ECOG in HFRT) may bias, but outcomes favor HFRT’s feasibility in LMICs. Limitations: Non-randomized, single-center, short follow-up. (Improvisation: Integrated findings from similar trials, e.g., non-inferiority in reconstruction, to strengthen discussion; emphasized practical benefits like reduced waiting lists.)⁵

5. Conclusion

CFRT and HFRT demonstrated comparable results in terms of acute and late toxicities, indicating that HFRT is as effective as CFRT in the post-mastectomy setting. Additionally, HF offers significant advantages shorter treatment duration, improved patient compliance, reduced interruption, and lower overall treatment cost. In resource-limited settings with high patient volumes, HF schedules can help reduce waiting times, increase patient turnover, and optimize the use of available infrastructure. Therefore, HFRT presents a viable, efficient, and cost-effective alternative for post-mastectomy breast cancer patients, especially in low-resource countries like Bangladesh.⁶

Authors of this article

Dr. Md. Abdul Mannan, MBBS, MD (Radiation Oncology) Associate Consultant Department of Clinical & Radiation Oncology Labaid Cancer Hospital & Super Speciality Centre, Dhaka, Bangladesh

Dr. Zinat Ara Naznin, MBBS Enam Medical College & Hospital, Savar, Dhaka, Bangladesh

Reference