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Hypofractionated radiation reduces toxic effects for women with early-stage breast cancer

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September 15, 2015

Hypofractionated whole-breast irradiation yielded lower rates of acute and short-term toxic effects compared with conventionally fractionated radiotherapy for patients with breast cancer, according to results from a pair of studies published in JAMA Oncology.

“Our clinical trial illustrates the benefits to women of receiving a shorter course of whole-breast irradiation delivered over 4 weeks in comparison to what had been our standard of delivering whole-breast irradiation over 6 weeks,” study researcher Benjamin D. Smith, MD, associate professor and research director in the department of radiation oncology at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “Our findings of less acute side effects during radiation and better energy and ability for care for family members 6 months after radiation are some of the first to note a real benefit to patients of receiving a shorter course of whole-breast irradiation (WBI).”

Benjamin Smith

Benjamin D. Smith

Conventionally fractionated radiation therapy — or treatment in smaller doses over a longer time — has historically been the standard for the management of breast cancer in the U.S. Previous studies that evaluated hypofractionated radiation — or higher doses over a shorter time — did not demonstrate benefit.

“Those studies were done with now-antiquated technologies,” Simona Shaitelman, MD, assistant professor of radiation oncology at MD Anderson, said in a press release. “Since then, with advances in technology, randomized studies in the United Kingdom and Canada have shown equal rates of recurrence in both groups, as well as equal survival. Yet our radiation oncology community has been slow to adopt the practice.”

Appropriate dosing

Shaitelman, Smith and colleagues assessed acute and 6-month toxic effects as well as quality of life in a cohort of 287 patients (median age, 60 years) — enrolled regardless of BMI or central axis separation — with ductal carcinoma in situ or invasive breast cancer who underwent breast-conserving surgery. Researchers randomly assigned 149 patients to conventionally fractionated WBI and 138 to hypofractionated WBI.

Baseline characteristics were comparable between the arms, including the Functional Assessment of Cancer Therapy for Patients with Breast Cancer total score (hypofractionated, 120.1; conventionally fractionated, 118.8). Equal proportions of women in each arm reported having somewhat or more lack of energy (38% vs. 39%) and somewhat or more trouble meeting family needs (10% vs. 14%) at baseline.

Overall, physician-reported results indicated hypofractionated irradiation resulted in fewer accounts of acute dermatitis (36% vs. 69%; P < .001), pruritus (54% vs. 81%; P < .001), breast pain (55% vs. 74%; P = .001), hyperpigmentation (9% vs. 20%; P = .002), fatigue (9% vs. 17%; P = .02) and overall grade 2 or higher acute toxic effects (47% vs. 78%; P ˂ .001) than conventionally fractionated WBI during treatment.

Six months following the treatment, physicians reported improved toxicity profiles for hypofractionated vs. conventionally fractionated WBI regarding fatigue (0% vs. 6%; P = .01), lack of energy (23% vs. 39%; P < .001) and trouble meeting family needs (3% vs. 9%; P = .01).

“I think our findings nicely complement those from other trials with longer follow-up,” Smith said. “Taken together, I believe that the available literature now indicates that these shorter courses of whole breast irradiation should be preferred for the vast majority of patients.

“In my own practice, I now consider 40 Gy in 15 fractions with a 10 Gy in 5 fraction boost the standard for patients who require whole-breast irradiation plus a boost,” Smith added. “This is a huge advance for our patients and also confers added value to the health care system.”

Patient-reported outcomes

In a second study, Reshma Jagsi, MD, DPhil, associate professor in the department of radiation oncology at University of Michigan Health System, and colleagues prospectively evaluated data on acute toxic effects and patient-reported outcomes in a large cohort of women treated with a variety of fractionation approaches in the Michigan Radiation Oncology Quality Consortium.

Reshma Jagsi, MD, DPhil

Reshma Jagsi

The analysis included 2,309 patients who received adjuvant WBI — 578 of whom received hypofractionated WBI — following a lumpectomy for unilateral breast cancer between 2011 and 2014. Patients reported toxic effects at baseline, weekly during treatment, and at follow-up.

A significantly greater proportion of patients who received conventionally fractionated WBI experienced physician-assessed skin reaction (grade 2 or higher dermatitis, 62.6% vs. 27.4%; P < .001; moist desquamation, 28.5% vs. 6.6%; P < .001), self-reported moderate or severe pain (41.1% vs. 24.2%; P = .003); burning or stinging bother often or always (38.7% vs. 15.7%; P = .002), hurting bother (33.5% vs. 16%, P = .001), swelling bother (29.6% vs. 15.7%, P = .03) and fatigue (29.7% vs. 18.9%; P = .02).

Researchers observed no significant differences in outcome measures during 6-months follow-up.

“We observed substantial differences by fractionation schedule in both physician-assessed and patient-reported acute toxic effects … during radiation treatment, but similar experiences after treatment,” Jagsi and colleagues wrote. “This suggests that the selection of radiation fractionation schedule may affect the incidence of acute, treatment-related toxic effects of adjuvant whole-breast radiotherapy, which may compromise patients’ quality of life during this challenging period.”

Results of these two studies are “highly complementary” and support a shift in practice toward hypofractionated irradiation as a standard of care for patients with early-stage breast cancer, Shyam K. Tanguturi, MD, resident in the radiation oncology program at Harvard Radiation Oncology, and Jennifer R. Bellon, MD, assistant professor of radiation oncology at Harvard Medical School and a senior physician at Dana-Farber Cancer Institute, wrote in an accompanying editorial.

“At present, there are more limited data available on tumor control and toxic effects outcomes with hypofractionated irradiation for patients receiving regional nodal irradiation,” they wrote. “Nonetheless, the mounting evidence supporting hypofractionation can no longer be ignored. With comparable tumor control, lower costs and reduced morbidity, hypofractionation should be strongly considered for the majority of patients with early-stage disease.” – by Anthony SanFilippo

References:

Jagsi R, et al. JAMA Oncol. 2015;doi:10.1001/jamaoncol.2015.2590.

Shaitelman SF, et al. JAMA Oncol. 2015;doi:10.1001/jamaoncol.2015.2666.

Tanguturi SK and Bellon JR. JAMA Oncol. 2015;doi: 10.1001/jamaoncol.2015.2605.

For more information:

Benjamin D. Smith, MD, can be reached at MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email: BSmith3@mdanderson.org

Disclosure: Smith reports grant funding from Varian Medical Systems and a consultant/advisory role for MD Anderson Physicians’ Network. Jagsi, Tanguturi and Bellon report no relevant financial disclosures. Please see the full studies for a list of all other researchers’ relevant financial disclosures.

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PERSPECTIVE
Penny R. Anderson

Penny R. Anderson

These two articles are very important and the authors should be applauded for their efforts. These two studies address the relationship between fractionation schedules and acute/short term toxic effects from whole breast radiotherapy. Both studies demonstrated that hypofractionated whole-breast irradiation resulted in significantly lower rates of acute toxic effects than conventional whole-breast fractionation. Patients treated with hypofractionated whole-breast irradiation had lower rates of pruritus, breast pain, dermatitis, hyperpigmentation and fatigue than patients treated with conventional whole-breast fractionation.

These two JAMA Oncology articles contribute significantly to the growing body of evidence that supports the use of hypofractionation as an appropriate treatment regimen for a majority of patients with early-stage breast cancer.

These findings can be confirmed with our recent data from Fox Chase Cancer Center — scheduled for presentation at the ASTRO Annual Meeting in October — in which we compared patients treated with a course of hypofractionated whole-breast radiation with an incorporated tumor bed boost to patients treated with conventional whole-breast radiation with a sequential tumor bed boost. We demonstrated a significant decrease in grade 2 or higher acute side effects with the hypofractionated whole breast radiation regimen compared to the conventional whole breast fractionation regimen (18.7% vs. 47.7%; P < 0.01). Patient-reported cosmesis scores were similar between the two groups. We also demonstrated no difference in late side effects between the two fractionation schemes. In addition, and just as important, we demonstrated that long-term 8-year local control was not significantly different between the two treatment fractionation regimens (hypofractionation, 97.5% vs. conventional fractionation, 96.6%).

Penny R. Anderson, MD
Fox Chase Cancer Center

Disclosure: Anderson reports no relevant financial disclosures.