Researchers at The University of Texas MD Anderson Cancer Center say they’ve determined that women with early stage breast cancer who receive shorter courses of whole breast radiation therapy experience lower toxicity and improved quality of life compared to counterparts who undergo longer courses radiation treatment.
In an original investigation paper published online first in the journal JAMA Oncology, the scientists say these findings should be communicated to women as part of the shared decision-making dialog between breast cancer patients and their physician.
The paper, entitled “Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation, A Randomized Clinical Trial“ (JAMA Oncol. Published online August 06, 2015. doi:10.1001/jamaoncol.2015.2666), is coauthored by Simona F. Shaitelman, MD, MEd; Pamela J. Schlembach, MD, Isidora Arzu, MD, PhD, Elizabeth S. Bloom, MD, George H. Perkins, MD, MBA, Valerie Reed, MD; Shalin Shah, MD; Michael C. Stauder, MD; Eric A. Strom, MD; Thomas A. Buchholz, MD, Welela Tereffe, MD; Wendy A. Woodward, MD, PhD, Benjamin D. Smith, MD, Gregory M. Chronowski, MD, Diana Amaya, RN, Tanisha Davis, RN, William Guerra, BA, Lois Hamblin, RN, of The University of Texas MD Anderson Cancer Center, Houston; Matthew Ballo, MD, of The University of Tennessee Health Science Center, Memphis; Daniel Buchholz, MD, Tomas Dvorak, MD, and Patrick Kelly, MD, PhD, of the University of Florida Health Cancer Center, Orlando Health, Orlando; Emily Grade, MD, of the Banner MD Anderson Cancer Center at Gilbert, Arizona; Michelle Ludwig, MD, PhD of the Baylor College of Medicine, Houston, Texas — all in the respective Departments of Radiation Oncology at those five institutions; along with Joe Ensor, PhD of the Houston Methodist Research Institute at Methodist Hospital, Houston; Donald Baumann, MD of the Department of Plastic Surgery at the MD Anderson Center; Alastair M. Thompson, MD and Kelly K. Hunt, MD, of the MD Anderson Center Department of Surgical Oncology; and Gabriel Hortobagyi, MD of the MD Anderson Center Department of Breast Medical Oncology, who say the most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain, noting that historically in the management of breast cancer in the U.S., radiation treatment has been given in smaller doses over a longer period of time, using a method called conventionally fractionated whole breast irradiation (CF-WBI), rather than with higher doses over a shorter period of time, or hypofractionated whole breast irradiation (HF-WBI).
The researchers report that in an unblinded randomized trial (Trial Registration http://clinicaltrials.gov Identifier: NCT01266642) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended. Seventy-six percent of study participants were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of six months. Of note, previous studies with HF-WBI excluded patients with a larger body mass index (BMI), despite obesity being a strong associated risk factor for the disease. Also, the MD Anderson study included a boost dose as part of the treatment, and the researchers note that previous HF-WBI studies did not systematically look at this practice of giving additional treatment to target the tumor bed with a higher dose.
The investigators note that the treatment arms were well-matched for both baseline quality of life and treatment characteristics, and cites both physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B) questionnaire designed to assess quality of life of breast cancer patients. Participants self-reported their overall well-being prior to treatment and six months after completing their therapy, and Physicians assessed patient toxicities weekly during treatment and six months after completing radiation.
Based on data collected, the researchers found that treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy, and that these findings should be communicated to patients as part of shared decision-making.
“Decades ago, the U.S. radiation oncology community looked at abbreviating treatment time with disappointing results,” explains MD Anderson assistant professor Radiation Oncology Simona Shaitelman, M.D.
“Those studies were done with now-antiquated technologies,” says Dr. Shaitelman, the study’s first author, in an MD Anderson 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.”
Indeed, the MD Anderson research team notes that only one-third of patients for whom HF-WBI is currently recommended as appropriate treatment by the American Society of Radiation Oncology (ASTRO) actually receive the shorter course of therapy. Consequently, the operative question becomes, “with modern technology, and knowing that the survival and recurrence outcomes are equal, can we offer patients a better option?” and it was considered essential that the investigators look at how they were giving therapy and if that therapy impacted patients’ quality of life, both acutely during treatment and in the short-term after treatment.
The researchers found that compared to the CF-WBI cohort, those randomized to HF-WBI experienced less acute toxicity during treatment, including: breast pain, dermatitis, skin darkening and fatigue. At six month follow up, toxicities were generally similar between the HF-WBI and CF-WBI patients, although the HF-WBI patients were noted to have less fatigue, and better ability to care for their family, compared to those treated with CF-WBI.
Patients who received the shorter course reported less difficulty in caring for their families’ needs. “This is a major priority for women undergoing breast cancer radiation,” says Dr. Shaitelman. “Most are busy working mothers, working inside or outside the home, and are juggling a number of priorities. It’s paramount that we address this need.”
“The findings provide some of the first data to show a benefit with the shorter course of treatment not just an alternative for patients,” says Benjamin Smith, M.D. , associate professor, Radiation Oncology, at MD Anderson. “This study fills in a missing piece in the literature,” says Dr. Smith, the study’s corresponding author. “No longer do I regard the shorter course of treatment as just an option for patients, but rather the preferred starting point for discussion with patients if they need whole breast radiation.”
The MD Anderson Center researchers report that control outcomes continue to be followed, and to date no meaningful difference in survival rates has been observed. Also, data like this and other studies are substantive enough that Dr. Smith believes it would be worthwhile for organizations like ASTRO and NCCN to consider expanding recommendations for patients to receive HF-WBI.
Patients were enrolled at MD Anderson’s Houston area locations, Orlando Health (formerly MD Anderson Orlando) in Orlando, Florida, and Banner MD Anderson in Gilbert, Arizona. The study was funded by a Career Development Aware grant from the Conquer Cancer Foundation of the American Society of Clinical Oncology, the Breast Cancer Research Foundation, grant RP140020 from the Cancer Prevention and Research Institute of Texas, the Center for Radiation Oncology Research at The University of Texas MD Anderson Cancer Center, a philanthropic gift from Ann and Clarence Cazalot, and grant P30CA016672 form the National Cancer Institute at the National Institutes of Health funding of the Biostatistics Resource Group. Neither Dr. Shaitelman nor Dr. Smith report any related conflicts.
Another new original Investigation paper published in JAMA Oncology, entitled “Differences in the Acute Toxic Effects of Breast Radiotherapy by Fractionation Schedule Comparative Analysis of Physician-Assessed and Patient-Reported Outcomes in a Large Multicenter Cohort“ (JAMA Oncol. Published online August 06, 2015,hypo-fractionation doi:10.1001/jamaoncol.2015.2605), observes that randomized trials have established the long-term safety and efficacy of hypofractionated whole-breast radiotherapy, but little is known about the acute toxic effects experienced by patients treated with hypo-fractionation as compared with conventional fractionation, particularly in real-world settings and from the patients own perspective.
The objective of the Open Source study, which is coauthored by Reshma Jagsi, MD, DPhil, Jean M. Moran, PhD, and Lori J. Pierce, MD, of the University of Michigan Department of Radiation Oncology at Ann Arbor (Dr. Jagsi is also associated with the Center for Bioethics and Social Science in Medicine, Ann Arbor; Kent A. Griffith, MS of the Center for Cancer Biostatistics at the University of Michigan School of Public Health; Thomas P. Boike, MD of McLaren Northern Michigan, Petoskey; Eleanor Walker, MD of Henry Ford Hospital, Detroit, Michigan; Teamour Nurushev, PhD of 21st Century Oncology, Detroit, Inga S. Grills, MD of Beaumont Health System, Royal Oak, Michigan; was to evaluate prospectively collected data on acute toxic effects and patient-reported outcomes in a cohort treated with varying radiation fractionation schemes in practices collaborating in the Michigan Radiation Oncology Quality Consortium (MROQC) — a multicenter, prospective collaboration through which detailed clinical, sociodemographic, treatment, dosimetric, and outcomes data are collected for patients receiving adjuvant radiotherapy after lumpectomy at 18 centers in the state of Michigan.
The MROQC is funded by Blue Cross Blue Shield of Michigan, but data are collected on all eligible patients within participating practices, regardless of insurance type. Because MROQC includes physician-assessed and patient-reported toxicity information from a large cohort of patients treated with varying fractionation schedules outside the context of selective and controlled clinical trials settings, it provides a unique opportunity to document in detail the acute toxic effects experienced by patients receiving breast radiotherapy in modern practice. It also allows for an evaluation of the comparative effectiveness of hypofractionated regimens as compared with conventional fractionation schedules in terms of the frequency and severity of acute toxic effects that commonly occur during adjuvant whole-breast radiotherapy.
The investigators compared toxic effects in patients receiving hypo-fractionation (HF) vs conventional fractionation (CF) during treatment (through 7 days after treatment) and in follow-up (post-treatment days 8-210), after adjustment for sociodemographic, clinical, and treatment characteristics. The MROQC includes academic and community radiation oncology practices across Michigan. All 2604 patients who received adjuvant whole-breast radiotherapy after lumpectomy for unilateral breast cancer at MROQC participating sites from October 2011 through June 2014 were registered, and the researchers analyzed 2309 for whom there was a comprehensive physician toxicity evaluation within one week of completion of radiotherapy and at least one weekly toxicity evaluation during treatment.
In comparing exposures to Hypo-fractionation vs CF, respectively, side-effects reported by physicians included dermatitis, pain, fatigue, and other common toxic effects associated with breast radiotherapy at baseline, weekly during radiotherapy, and in follow-up. Patients who consented also rated their own experiences, including breast pain, fatigue, and being bothered by symptoms.
Of the 2309 evaluable patients, 578 received HF. During treatment, after adjustment for sociodemographic, clinical, and treatment factors, patients receiving CF had significantly higher maximum physician-assessed skin reaction, self-reported pain, swelling bother, and fatigue, but slightly greater absence of skin induration in follow-up. No significant differences were observed in any other measured outcomes during follow-up extending through six months.
Based on their findings, the researchers summarize that Hypo-fractionation not only improves convenience but also may reduce acute pain, fatigue, and the extent to which patients are bothered by dermatitis in patients with breast cancer undergoing whole-breast radiotherapy, noting that their study provides information about the frequency and nature of acute toxic effects during whole-breast hypofractionated radiotherapy highly relevant to women considering this treatment and absent from the literature to date. They observe that given the importance of patient-reported outcomes and generalizable evidence of comparative effectiveness from patients treated outside the context of clinical trials, it provides a complement to the findings of randomized trials and encourages enthusiasm for this innovative approach.
The entire Open Source article can be accessed here:
The University of Texas MD Anderson Cancer Center
The University of Texas MD Anderson Cancer Center