To compare the efficacy and toxicity of hypofractionated radiotherapy versus conventional fractionated radiotherapy in postmastectomy breast cancer using meta-analysis. The PubMed, EMbase, Cochrane Library, Google Scholar, Wan Fang and CNKI databases were searched to identify controlled clinical trials comparing hypofractionated radiotherapy versus conventional fractionated radiotherapy in postmastectomy breast cancer. Overall survival (OS) was the primary endpoint, and disease-free survival (DFS), locoregional recurrence (LRR), distant metastasis (DM), acute skin toxicity, acute lung toxicity, late skin toxicity, lymphedema,, shoulder restriction, and late cardiac related toxicity were the secondary endpoints. Twenty-five controlled clinical trials involving 3871 postmastectomy breast cancer patients were included in this meta-analysis according to the selection criteria. The meta-analysis revealed that there were no significant differences in OS (OR = 1.08, 95% CI = 0.87~1.33, P = 0.49), DFS (OR = 1.13, 95% CI = 0.91~1.40, P = 0.28), LRR (OR = 1.01, 95% CI = 0.76~1.33, P = 0.96), DM (OR = 1.16, 95% CI = 0.85~1.58, P = 0.34), acute skin toxicity (OR = 0.94, 95% CI = 0.67~1.32, P = 0.72), acute lung toxicity (OR = 0.94, 95% CI = 0.74~1.20, P = 0.62), late skin toxicity (OR = 0.98, 95% CI = 0.75~1.27, P = 0.88), lymphedema (OR = 0.99, 95% CI = 0.77~1.28, P = 0.94), shoulder restriction (OR = 0.75, 95% CI = 0.43~1.31, P = 0.31), or late cardiac related toxicity (OR = 1.17, 95% CI = 0.82~1.65, P = 0.39) between the two groups. The results of this study show that compared to conventional fractionated radiotherapy, hypofractionated radiotherapy is not significantly different with respect to efficacy or toxicity in postmastectomy breast cancer. Additional large randomized clinical trials are needed to further confirm this conclusion.

/pdf/comparing-hypofractionated-to-conventional-fractionated-5d4l6adrb0.pdf

Comparing hypofractionated to conventional fractionated radiotherapy in postmastectomy breast cancer: a meta-analysis and systematic review.

Purpose The associations among radiation fractionation, body mass index (BMI), and acute skin toxicity with adjuvant radiation for breast cancer is of increasing interest. This study evaluated the rate of grade ≥2 dermatitis and moist desquamation (MD) in patients with a high BMI who were treated to the breast or chest wall to understand the role of radiation target, fractionation regimen, and BMI. Methods and materials We retrospectively evaluated 280 patients treated with adjuvant radiation for breast cancer after up-front surgery. We collected information on patient demographics, disease and treatment characteristics, and acute skin toxicities. Multiple logistic regression models were used to evaluate for predictors of grade ≥2 dermatitis and MD. Results Patients undergoing post-mastectomy radiation therapy (PMRT) had the highest rate of MD (24%). The rate was lower (8.7%) among lumpectomy patients, but those receiving conventional fractionation had a higher rate of MD (10.9%) compared with hypofractionated therapy (1.8%; P = .05). Among lumpectomy patients, chemotherapy use (odds ratio, 3.74; P = .04) and regional nodal irradiation (odds ratio, 3.29; P = .03) were also significant predictors of MD. Despite an elevated average BMI among lumpectomy patients, hypofractionated therapy resulted in lower rates of skin toxicity. Conclusions We identified multiple risk factors for acute skin toxicity, including the use of PMRT and conventionally fractionated regimens. Elevated BMI, regional nodal irradiation, and chemotherapy use were associated with an increased risk of MD. Our findings highlight the need to explore the use of less toxic hypofractionated regimens in patients who are at the highest risk of acute skin toxicity, including those with a higher BMI and those receiving PMRT.

Predictors of radiation-induced acute skin toxicity in breast cancer at a single institution: Role of fractionation and treatment volume.

Purpose Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen. Methods and Materials Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non–reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications. Results After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%. Conclusions This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.

5-Year Update of a Multi-Institution, Prospective Phase 2 Hypofractionated Postmastectomy Radiation Therapy Trial.

We evaluated the long-term outcomes and late toxicity of conventional fractionated (CF) and hypofractionated (HF) postmastectomy radiotherapy (PMRT) in terms of locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and late toxicity. A cohort of 1640 of breast cancer patients receiving PMRT between January 2004 and December 2014 were enrolled. Nine hundred eighty patients were treated with HF-PMRT: 2.65 Gy/fraction to a total of 42.4–53 Gy and 660 patients were treated with CF-PMRT: 2 Gy/fraction to a total of 50–60 Gy. The median follow-up time was 71.8 months (range 41.5–115.9 months). No significant difference was found in the rates of 5-year LRRFS, DFS, and OS of HF-PMRT vs CF-PMRT; 96% vs. 94% (p = 0.373), 70% vs. 72% (p = 0.849), and 73% vs. 74% (p = 0.463), respectively. We identified a cohort of 937 eligible breast cancer patients who could receive late toxicities assessment. With a median follow-up time of this patient cohort of 106.3 months (range 76–134 months), there was a significant higher incidence of grade 2 or more late skin (4% vs 1%) and subcutaneous (7% vs 2%) toxicity in patients treated with HF-PMRT vs CF-PMRT. Patients who received additional radiation boost were significantly higher in the HF-PMRT group. Grade 2 or more late RTOG/EORTC lung toxicity was significant lesser in HF-PMRT vs CF-PMRT (9% vs 16%). Grade 1 brachial plexopathy was also significant lesser in HF-PMRT vs CF-PMRT (2% vs 8%). Heart toxicity and lymphedema were similar in both groups. HF-PMRT is feasible to deliver with comparable long-term efficacy to CF-PMRT. HF-PMRT had higher grade 2 or more skin and subcutaneous toxicity but less lung and brachial plexus toxicity.

/pdf/conventional-versus-hypofractionated-postmastectomy-3lyxj5nf4a.pdf

Conventional versus hypofractionated postmastectomy radiotherapy: a report on long-term outcomes and late toxicity

Introduction

The most recent clinical practice guidelines released by Cancer Australia draw attention to unanswered questions concerning the health economic considerations associated with hypofractionated radiotherapy. This study aimed to quantify and compare the healthcare costs at a regional Australian radiotherapy institute with respect to conventionally fractionated post-mastectomy radiotherapy (Cf-PMRT) versus hypofractionated post-mastectomy radiotherapy (Hf-PMRT) administration.



Methods

Medical records of 196 patients treated with post-mastectomy radiotherapy at the NSW North Coast Cancer Institute from February 2008 to June 2014 were retrospectively reviewed. Australian Medicare item numbers billed for patients receiving either Cf-PMRT of 50 Gy in 25 daily fractions or Hf-PMRT of 40.05 Gy in 15 daily fractions were calculated. Decision tree analysis was used to model costs. Independent-samples t-tests and Mann–Whitney U-tests were used to compare crude average costs for Cf-PMRT and Hf-PMRT and determine which treatment components accounted for any differences.



Results

Hf-PMRT, with or without irradiation to the regional lymph nodes, was associated with significantly reduced Medicare costs ($5613 AUD per patient for Hf-PMRT vs $8272 AUD per patient for Cf-PMRT; P < 0.001). Savings associated with Hf-PMRT ranged from $1353 (22.1%) for patients receiving no regional irradiation to $2898 (32.0%) for patients receiving both axillary and supraclavicular therapy.



Conclusions

Hf-PMRT results in a significant reduction in the financial costs associated with treating breast cancer patients in a regional Australian setting when compared with Cf-PMRT.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/1754-9485.12405

Use of hypofractionated post-mastectomy radiotherapy reduces health costs by over $2000 per patient: An Australian perspective

BACKGROUND The conventional radiotherapy (CRT) in postmastectomy breast cancer is 1.8-2.0 Gy daily for 25 fractions, while hypofractionated radiotherapy (HFRT) delivered dose in fewer fractions with larger radiation intensity. The present study compares the efficacy of HFRT and CRT. MATERIAL AND METHOD From 2004 to 2006, 215 patients were retrospectively reviewed. Sixty seven patients received CRT and 148 patients received HFRT (2.65 Gy in 16-18 fractions). Five-year locoregional control (LRC), disease free survival (DFS), overall survival (OS) and toxicities were analyzed. RESULTS Median follow-up was 39 months. Five-year LRC was 86.6% in CRT and 85.8% in HFRT (p = 0.852). Five-year DFS was 62.7% and 69.6% (p = 0.136) in CRTand HFRT respectively. Patients who received HFRT had significant increase in 5-year OS (62.7% and 73.0% (p = 0.048). No difference of toxicities including changes in chest wall appearance, skin fibrosis, brachial plexopathy, arm edema, pulmonary fibrosis, rib fractures and cardiovascular events was found between two groups. CONCLUSION HFRT is as effective as CRT in postmastectomy breast cancer.

A retrospective study comparing hypofractionated radiotherapy and conventional radiotherapy in postmastectomy breast cancer.

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A retrospective study comparing hypofractionated radiotherapy and conventional radiotherapy in postmastectomy breast cancer.