Reporter’s Notebook: ASTRO 2013
Vol. 14 No. 12 P. 24
Editor’s Note: This article was prepared from press materials released at the American Society for Radiation Oncology (ASTRO) annual meeting this fall in Chicago.
Avoiding Certain Areas Preserves Memory in Whole-Brain RT
Limiting the amount of radiation absorbed in the hippocampal portion of the brain during whole-brain radiotherapy (WBRT) for brain metastases preserves memory function in patients for up to six months after treatment, according to research presented at ASTRO’s recent annual meeting.
The single-arm, phase 2 study was a multi-institutional, international clinical trial in the United States and Canada, conducted through the Radiation Therapy Oncology Group (RTOG). Researchers compared the study group with a historical control group of patients who had received WBRT without hippocampal avoidance.
This study enrolled 113 adult patients from 2011 through 2013 who had a measurable brain metastasis outside of a 5-mm margin around the hippocampus. Of those patients, 100 were analyzable, and 76% were categorized as recursive partitioning analysis (RPA) class 2. All of the patients received hippocampal avoidance WBRT (HA-WBRT) to 30 Gy in 10 fractions.
In all analyzable patients, the dose received by the entirety of the hippocampus did not exceed 10 Gy, and the maximum dose did not exceed 17 Gy. Patients were assessed at baseline and posttreatment at two-, four-, and six-month intervals. The primary end point of the trial was the Hopkins Verbal Learning Test-Delayed Recall (HVLT-DR) at four months.
Results showed that the 42 patients who were analyzed at four months postradiotherapy had a 7% decline in HVLT-DR from baseline to four months (95% confidence interval [CI]: -4.7% to 18.7%). This is statistically significant when compared with the historical control group (p = 0.0003), which demonstrated a 30% decline in HVLT-DR at four months. Six months after treatment, the 29 patients who were analyzed had a 2% decline in HVLT-DR from baseline (95% CI: -9.2% to 13.1%).
“Radiotherapy to the brain is known to impact the memory function of cancer survivors,” said Vinai Gondi, MD, the study’s lead author; the codirector of the Cadence Brain Tumor Center and associate director of research at the Cadence Proton Center in Warrenville, Illinois; and a clinical assistant professor at the University of Wisconsin School of Medicine and Public Health in Madison. “A compartment of neural stem cells located in the hippocampus, sensitive to radiotherapy and important for memory function, is thought to be central to these effects. Our research group developed advanced radiotherapy techniques that spare this hippocampal neural stem cell compartment from significant radiation doses. The study results were statistically better than historical data of whole-brain radiotherapy without hippocampal sparing and present a number of opportunities to introduce hippocampal sparing in other contexts of radiotherapy to the brain. The RTOG is currently developing phase 3 trials to explore these other contexts and to validate these results.”
Source abstract: “Memory Preservation With Conformal Avoidance of the Hippocampus During Whole-Brain Radiotherapy (WBRT) for Patients With Brain Metastases: Primary Endpoint Results of RTOG 0933”
Shorter Hormonal Therapy Equally Effective in Many Prostate Cases
Long-term hormonal therapy after radiation therapy for intermediate-risk prostate cancer provided no additional benefits than short-term hormonal therapy, according to an analysis of the Radiation Therapy Oncology Group (RTOG) 9202 prostate cancer trial.
Men with advanced prostate cancer typically receive hormonal therapy to reduce the level of androgens in their bodies. Although hormone therapy alone will not cure prostate cancer, lowering androgen levels can reduce the size of prostate tumors or stall their growth.
Researchers reviewed all patients enrolled in RTOG 9202 categorized with intermediate-risk prostate cancer with T2 disease, a prostate-specific antigen (PSA) of 10 or lower, and a Gleason Score of 7; or who were immediate-risk prostate cancer patients with T2 disease, a PSA level of 10 to 20, and a Gleason Score lower than 7.
A total of 133 patients were analyzed. The long-term adjuvant androgen deprivation group consisted of 59 patients, and the short-term androgen deprivation therapy group consisted of 74 patients. Statistical analysis was used to determine overall survival (OS), disease-specific survival (DSS), and PSA failure rates.
“Most clinicians have felt that more was better when it came to blocking testosterone in prostate cancer patients: however, results for the specific end points we focused on, OS and DSS, indicate that this was clearly not the case,” said Amin Mirhadi, MD, the study’s lead author and a radiation oncologist at Cedars-Sinai Medical Center in Los Angeles. “This data supports administering less treatment, which will result in fewer side effects and reduce patients’ overall health care costs.”
Source abstract: “Effect of Long-Term Hormonal Therapy (vs. Short-Term Hormonal Therapy): A Secondary Analysis of Intermediate Risk Prostate Cancer Patients Treated on RTOG 9202”
ASTRO Releases Its Choosing Wisely List
ASTRO has released its list of five radiation oncology treatments that are commonly ordered but may not always be appropriate. The list is part of the national Choosing Wisely campaign, an initiative of the American Board of Internal Medicine Foundation. The ASTRO list identifies five targeted treatment options for which the organization recommends detailed patient-physician discussion before being prescribed.
The five recommendations are as follows:
• Don’t initiate whole-breast radiotherapy as part of breast conservation therapy in women aged 50 and older with early-stage invasive breast cancer without considering shorter treatment schedules. Whole-breast radiotherapy decreases local recurrence and improves survival for women with invasive breast cancer treated with breast conservation therapy. Most studies have utilized “conventionally fractionated” schedules that deliver therapy over five to six weeks, often followed by one to two weeks of boost therapy. Recent studies, however, have demonstrated equivalent tumor control and cosmetic outcome in specific patient populations with shorter courses of therapy (approximately four weeks).
• Don’t initiate management of low-risk prostate cancer without discussing active surveillance. Patients with prostate cancer have numerous reasonable management options, including surgery and radiation as well as conservative monitoring without therapy in appropriate patients. Shared decision making between the patient and physician can lead to better alignment of patient goals with treatment and more efficient care delivery.
• Don’t routinely use extended fractionation schemes (more than 10 fractions) for palliation of bone metastases. Studies suggest equivalent pain relief following 30 Gy in 10 fractions, 20 Gy in five fractions, or a single 8-Gy fraction. A single treatment is more convenient but may be associated with a slightly higher rate of retreatment to the same site. Strong consideration should be given to a single 8-Gy fraction for patients with a limited prognosis or transportation difficulties.
• Don’t routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry. There is no clear evidence that proton beam therapy for prostate cancer offers any clinical advantage over other forms of definitive radiation therapy. Clinical trials are necessary to establish a possible advantage of this expensive therapy.
• Don’t routinely use intensity-modulated radiation therapy (IMRT) to deliver whole-breast radiotherapy as part of breast conservation therapy. Clinical trials have suggested lower rates of skin toxicity after using modern 3D conformal techniques relative to older methods of 2D planning. In these trials, the term IMRT generally has been applied to describe methods that are more accurately defined as field-in-field 3D conformal radiotherapy. While IMRT may be of benefit in select cases where the anatomy is unusual, its routine use has not been demonstrated to provide significant clinical advantage.
To date, more than 80 national and state medical specialty societies, regional health collaboratives, and consumer partners have joined the Choosing Wisely campaign to promote conversations about appropriate care. With the release of this new list, the campaign will have covered more than 250 tests and procedures that the specialty society partners say are potentially overused and inappropriate, and that physicians and patients should discuss further.
Shorter TAS Therapy Aids Results With Fewer Side Effects
A shorter course of androgen-suppression therapy prior to radiation therapy, when compared with a longer course of androgen-suppression therapy, yields favorable outcomes and fewer adverse effects for intermediate-risk prostate cancer patients, according to research presented at ASTRO’s 2013 annual meeting. The study confirmed a disease-specific survival rate of 95% when patients received fewer weeks of neoadjuvant (NEO) total androgen suppression (TAS).
The multi-institutional phase 3 trial, Radiation Therapy Oncology Group 9910, evaluated 1,490 intermediate-risk prostate cancer patients from 152 institutions in the United States and Canada.
“Sometimes, preliminary research leads us to assume that more treatment is better, but this study serves as a strong cautionary note to put the promising treatment to the test,” said Thomas Pisansky, MD, the study’s lead author and a professor of radiation oncology at the Mayo Clinic in Rochester, Minnesota. “Overall, both groups had very good outcomes, but patients assigned to group 2 had more side effects from androgen suppression than group 1, who received only eight weeks of NEO TAS. Now, investigators know the upper boundary of how much androgen suppression is needed in this group of patients. The results have substantial importance because they can alter the research strategy to one in which investigation can now concentrate on ways to simplify the treatment and further reduce side effects.”
Source abstract: “Radiation Therapy Oncology Group 9910: Phase III Trial to Evaluate the Duration of Neoadjuvant (NEO) Total Androgen Suppression (TAS) and Radiation Therapy (RT) in Intermediate-Risk Prostate Cancer (PCa)”
SRS May Help Avoid Whole-Brain Therapy
Stereotactic radiosurgery (SRS) without accompanying whole-brain radiotherapy (WBRT) improved mean survival without a greater risk of new brain metastases in brain cancer patients aged 50 and younger, according to research presented at ASTRO’s 2013 annual meeting.
This meta-analysis was conducted using the individual patient data from three randomized clinical trials from North America, Europe, and Asia with the aim to evaluate the results of SRS alone, compared with WBRT and SRS, for patients with one to four brain metastases.
A total of 364 patients from the three trials were evaluated. Of those, 51% had been treated with SRS alone, and 49% received both WBRT and SRS. Nineteen percent of patients in the study were aged 50 or younger, and 60% had a single brain metastasis. Twenty-one percent of all patients had local brain failure, defined as the occurrence of the progression of previously treated brain metastases, and 44% had distant brain failure, or the occurrence of new brain metastases in areas of the brain outside the primary tumor site(s). Eighty-six percent of the patients died during follow-up.
The analysis revealed that patients who received only SRS had a median of 10 months of survival time after treatment as opposed to 8.2 months for patients who underwent WBRT and SRS. Overall, local brain failure occurred earlier in patients who received only SRS (6.6 months posttreatment) as opposed to patients who underwent WBRT and SRS (7.4 months posttreatment). Distant brain failure also was found earlier overall in patients who received only SRS, occurring at 4.5 months posttreatment, compared with 6.5 months posttreatment for patients who received both WBRT and SRS.
“We expected to see a survival advantage favoring combined therapy, given the additional benefits of whole-brain radiation, particularly with respect to increasing local control and reducing the risk of new brain metastases,” said Arjun Sahgal, MD, the study’s lead author and an associate professor of radiation oncology at the University of Toronto in Canada. “Our study indicates, however, a survival advantage for SRS alone in younger patients who also interestingly were observed to have no greater risk of new brain metastases despite the omission of whole-brain radiation. This implies that WBRT may not be required for all patients with brain metastases, particularly younger patients, and SRS alone should be considered as the favored first-line therapeutic option. The implications are significant, as it has been shown in other studies that WBRT is detrimental to short-term memory function and negatively impacts some aspects of patients’ quality of life.”
Source abstract: “Individual Patient Data (IPD) Meta-Analysis of Randomized Controlled Trials (RCT) Comparing Stereotactic Radiosurgery (SRS) Alone to SRS Plus Whole Brain Radiotherapy (WBRT) in Patients With Brain Metastasis”
XRT in Breast-Conserving Therapy Doesn’t Increase Future Chest Problems
Early-stage breast cancer patients who receive external beam radiation therapy (XRT) don’t have a higher risk of serious long-term side effects in the chest area, including an increase in death from cardiac disease and secondary malignancies, according to research presented at ASTRO’s recent annual meeting.
The study utilized patient information from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. It evaluated women identified as having primary stage T1aN0 breast cancer (tumor of 5 mm or less that has not spread to the lymph nodes) who received surgery with or without postoperative radiation therapy between 1990 and 1997. The analysis was done to determine whether XRT was associated with increased mortality due to breast cancer, secondary cancer in the chest area, or cardiac conditions for these patients; only patients with breast cancer identified as the first malignancy were included.
The women had a median age of 55 to 59 and were divided into two groups: 2,397 who received XRT after surgery and 2,988 who did not receive XRT after surgery.
At 10 years posttreatment, overall survival rates were 91.6% for the XRT patients and 87% for the non-XRT group. Breast cancer survival rates were 97% for the XRT patients and 95.7% for the non-XRT group. Cardiac cause-specific survival was 96.7% for the XRT patients and 92.7% for the non-XRT group.
Analysis of the data further demonstrates that, with a median follow-up of 14 years, there was no statistically significant difference in deaths from subsequent nonbreast cancers in the chest area, the majority of which were lung cancers. The number of deaths from cardiac causes was not significantly higher for those patients treated with XRT for left-sided breast cancer compared with those with right-sided breast cancer among the patient sample and time period reviewed. More women from the non-XRT group died from all causes, including cardiac causes, suggesting that those patients had worse general health conditions than the women who received radiation therapy.
“Breast-conserving therapy, consisting of lumpectomy and XRT, has been an excellent approach to early breast cancer treatment, offering equivalent disease control and better cosmetic results compared to mastectomy as demonstrated by multiple randomized controlled trials in the past,” said Jason Ye, MD, the study’s presenting author and a second-year resident in radiation oncology at Weill Cornell Medical College in New York. “Our study’s results suggest that serious long-term side effects of radiation therapy, such as increase in deaths from cardiac disease and secondary malignancies, are rare. Radiation therapy is an integral part of early-stage breast cancer treatment for those who choose to have a lumpectomy instead of a mastectomy, with its benefits likely far outweighing the potential risks in majority of the cases…”
Source abstract: “Breast Cancer (BC), Second Cancer, and Cardiac Mortality in Stage T1aN0 BC Patients With or Without External Beam Radiation Therapy (XRT): NCI SEER Study”