Hypofractionation Reduces Whole-Breast Irradiation Acute Toxicity In Early Breast Cancer

Acute toxicity benefits of hypofractionated whole-breast irradiation shown in a randomised clinical trial and a cohort study

medwireNews: Physician- and patient-reported outcomes of two studies reported in JAMA Oncology support the use of hypofractionated whole-breast irradiation (HF-WBI) for early breast cancer, demonstrating reduced rates of acute toxicity compared with conventionally fractionated (CF)-WBI.

“These findings should be communicated to patients as part of shared decision making regarding election of radiotherapy regimen and are relevant to the ongoing discussion regarding the most appropriate standard of care for WBI dose fractionation”, say Benjamin Smith, from the University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.

Their randomised trial included 287 patients aged at least 40 years who underwent WBI following breast-conserving surgery, the majority (76%) of whom were overweight or obese.

Patients who received HF-WBI (42.56 Gy over 16 fractions plus boost) were significantly less likely to experience grade 2 or higher acute effects than those given CF-WBI (50.00 Gy over 25 fractions plus boost), at 47% versus 78%.

This included significantly fewer reports of maximum physician-assessed acute dermatitis (36 vs 69%), Pruritus (54 vs 81%), breast pain (55 vs 74%), hyperpigmentation (9 vs 20%) and fatigue (9 vs 17%) during irradiation.

And 6 months after treatment was completed, patients who received HF-WBI were significantly less likely to report having a lack of energy or trouble meeting family needs, with significant odds ratios of 0.39 and 0.34 after adjusting for confounding factors.

“Strikingly, our multivariable analysis found that the negative impact of CF-WBI on both energy and ability to meet family needs was comparable to or greater than the effect of adjuvant chemotherapy on these end points”, Benjamin Smith et al emphasise.

Further support for HF-WBI use was provided by the Michigan Radiation Oncology Quality Consortium multicentre cohort study of 2309 patients given adjuvant radiotherapy after lumpectomy.

The 1731 patients in this study who received CF-WBI had significantly higher maximum physician-assessed skin reactions during treatment than the 578 women who underwent HF-WBI, for both moist desquamation (28.5 vs 6.6%) and grade 2 or more severe dermatitis (62.6 vs 27.4%).

CF-WBI was also associated with significantly higher rates of self-reported moderate or severe pain (41.1 vs 24.2%), often or always experiencing a sensation of burning or stinging (38.7 vs 15.7%) and hurting bother (33.5 vs 16.0%) during radiotherapy.

There were also trends towards more reports of swelling bother (29.6 vs 15.7%) and fatigue (29.7% vs 18.9%) with CF-WBI than HF-WBI, although 6 months after treatment was completed patients who received CF-WBI were more likely to report absence of skin induration (84.5 vs 81.2%).

“It is critical to recognize that hypofractionation not only provides equivalent long-term tumor control in selected patients at considerably lower cost and greater convenience, but it may also represent a more tolerably administered approach”, say Reshma Jagsi, from the University of Michigan in Ann Arbor, USA, and co-authors of the cohort study. 

Shyam Tanguturi and Jennifer Bellon, from Harvard Medical School in Boston, Massachusetts, USA, in an accompanying comment “applaud” the authors of the two “highly complementary” studies for incorporating quality of life measures as a primary endpoint. 

While acknowledging that the studies lack adequate data to rule out the possibility that the peak of acute events may occur after treatment, they nevertheless emphasise: “With comparable tumor control, lower costs and reduced morbidity, hypofractionation should be strongly considered for the majority of patients with early-stage disease.”

References

Shaitelman SF, Schlembach PJ, Arzu I,et al. Acute and short-term toxic effects of conventionally fractionated vs hypofractionated whole-breast irradiation. A randomized clinical trial. JAMA Oncol 2015; Advance online publication 6 August. doi:10.1001/jamaoncol.2015.2666

Jagsi R, Griffith KA, Boike TP,etal. Differences in the acute toxic effects of breast radiotherapy by fractionation schedule. Comparative analysis of physician-assessed and patient-reported outcomes in a large multicentre cohort. JAMA Oncol 2015; Advance online publication 6 August. doi:10.1001/jamaoncol.2015.2590

Tanguturi SK, Bellon JR. Hypofractionation for early-stage breast cancer. No more excuses. JAMA Oncol 2015; Advance online publication 6 August. doi:10.1001/jamaoncol.2015.2605

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