December 2011

ASTRO Reporter’s Notebook
Radiology Today
Vol. 12 No. 12 P. 28

Editor’s Note: This article is based on information presented at three press briefings at the American Society for Radiation Oncology (ASTRO) 53rd Annual Meeting in Miami Beach, Fla., in October.

Radiation for Prostate Cancer May Interfere With Cardiac Devices 
Prostate cancer patients undergoing intensity-modulated radiation therapy (IMRT) who have implanted cardiac devices for the treatment of heart problems have a 25% chance that the device will malfunction, according to information presented at the annual meeting. The findings are in contrast to previous reports suggesting that unsafe interactions with cardiac pacemakers and cardiac defibrillators and IMRT therapy are rare.

“The study results will hopefully encourage closer monitoring of cardiac devices by both the radiation oncologist and the cardiologist, as many clinicians are unaware of this relatively common interaction,” said Steven DiBiase, MD, a radiation oncologist at the Robert Wood Johnson School of Medicine in Camden, N.J. “Such close monitoring could provide rapid intervention to prevent any clinical cardiac problems when IMRT is administered.”

Since many patients undergoing pelvic IMRT for the treatment of prostate cancer have cardiac pacemakers and cardiac defibrillators, investigators sought to determine the influence of IMRT on the functioning of such devices.

 The retrospective study examined 505 men with localized prostate cancer who were treated with IMRT from 2009 to 2011. Of this patient group, 24 patients had cardiac devices and were closely monitored before and after treatment for any interaction with their cardiac device.  The study shows that six patients (25%) with cardiac devices experienced a mechanical malfunction as a result of their IMRT treatments, causing the device to reset to the manufacturer’s designated default settings. None of the patients developed clinical cardiac problems, yet two men required pacemaker replacements.

“This cardiac device interaction is not fully understood,” DiBiase said. “It is not clear whether this cardiac device interaction is unique to IMRT treatments or related to more sensitive cardiac devices to ionizing radiation in recent years. However, the association does exist and must be taken into account when these patients undergo IMRT.” ■


Shorter Prostate Radiation Course Provides Similar Results
A shorter course of radiation treatment that delivers higher doses of radiation per day is as effective for decreasing intermediate to high-risk prostate cancer from returning as conventional radiation therapy at five years after treatment, according to a randomized trial presented at the annual meeting.

The hypofractionation approach used was given in a shorter period of time with higher doses per day and was expected to be equivalent to four extra treatments using conventional fractionation. While the hypofractionation treatment was hypothesized to be superior, the same tumor control rates were observed. The conventionally fractionated patients had better outcomes than expected. The benefit of the hypofractionation method was that comparable results were achieved with 2 1/2 fewer weeks of treatment.

“This long-term study confirms that hypofractionated radiation that shortens treatment by about 2 1/2 weeks is a practical approach to effectively controlling prostate cancer, as compared to the more standard treatment for men with intermediate to high-risk prostate cancer,” said Alan Pollack, MD, chairman of radiation oncology at the University of Miami Miller School of Medicine.

Using hypofractionation to compress treatment schedules is based on years of studies indicating that there could be a radiobiologic advantage to this approach. Prior research has suggested that the increased dose from hypofractionated treatments would kill tumor cells to a greater degree than the potentially damaging effects of increased dose on the surrounding normal tissues, namely the rectum, penile structures affecting erections, and bladder. Using newer intensity-modulated radiation therapy (IMRT) techniques further limits dose to the normal tissues. IMRT has proven value in limiting side effects in the treatment of prostate cancer with external beam radiotherapy.

The study involved 303 men with intermediate to high-risk prostate cancer who were randomized to receive either hypofractionated IMRT or conventionally fractionated IMRT between 2002 and 2006. High-risk patients in the study also received a form of hormone therapy for two years. The patients were followed for more than five years to find out whether their cancer returned by monitoring prostate-specific antigen, an established indicator of prostate cancer recurrence when increasing levels are seen.

"We are still learning how best to apply hypofractionation, and the results in this trial show that the technique is very effective," Pollack said.

In terms of side effects, the rates were relatively low for both methods. There were identical long-term rates of bowel/rectal reactions and the frequency of unsatisfactory erections. There was, however, significantly higher bladder control in the conventionally fractionated patients.

"Late urinary symptoms were higher with hypofractionation but were low overall, particularly when the incidence of persistent urinary symptoms—less than 10% at five years—was analyzed, rather than just as an isolated event," Pollack said. “Hypofractionation is rapidly gaining momentum for many types of cancers. The results presented here bring us much closer to effectively treating prostate cancer in a shorter period of time, with acceptable side effects.”■


IMRT Has Fewer Harmful Side Effects Than 3D-CRT for Prostate
Men with localized prostate cancer treated with intensity-modulated radiation therapy (IMRT) have 26% fewer late bowel and rectal side effects and a statistically improved lower dose of radiation to the bladder and rectum compared with those who undergo 3D conformal radiation therapy (3D-CRT), according to a randomized study presented at the meeting. Findings also show there is a significant 15% increase in rectal side effects in white men compared with other races, regardless of the radiation treatment.

“The racial differences were definitely surprising, and we are still unsure as to why this exists,” said Jeff Michalski, MD, a radiation oncologist at Washington University Medical Center in St. Louis. “While it could be a real difference in the tolerance to treatment, it could also represent cultural differences in reporting side effects and physician interpretation of patient descriptions. This will be the topic of further investigation.”

IMRT is a newer, specialized form of 3D-CRT that allows radiation to be more exactly shaped to fit a tumor and further limits the amount of radiation received by healthy tissue near the tumor. This may safely allow a higher dose of radiation to be delivered to the tumor, potentially increasing the chance of a cure.  This study is a preliminary analysis of acute and late toxicity in men receiving high-dose radiation therapy in a phase 3 Radiation Therapy Oncology Group dose-escalation trial.

Researchers sought to compare the toxicity rates of high-dose radiation therapy with standard-dose radiation treatment using IMRT and 3D-CRT. The toxicities were scored from the grade of 0 (no toxicity) to 4 (severe toxicity). The study also examined what patient characteristics may be associated with toxicity.

The study involved 748 men who were randomized to the high-dose arm of the trial. Of this group, 491 were treated with 3D-CRT and 257 with IMRT. Findings showed that IMRT is associated with a statistically significant decrease in acute Grade 2+ rectal/bowel and urinary toxicity. There was also a trend for a 26% reduction in Grade 2+ late rectal and bowel side effects.

“This study supports the continued use of IMRT in the management of prostate cancer. It is a safe and very well-tolerated therapy with fewer complications than 3D-CRT,” Michalski said. ■


Most Cancer Physicians Reach Out to Bereaved Family, Caregivers
While 70% of surveyed cancer care physicians initiate contact with the bereaved family and caregivers of their patients who have died, more than two-thirds believe they have not received adequate training in this area during their residency or fellowship, according to a study presented at the annual meeting.

“In particular with cancer, there has been a movement to encourage physician involvement throughout the course of disease, including after a patient’s passing,” explained Aaron S. Kusano, MD, a radiation oncology resident at the University of Washington School of Medicine in Seattle. “The empathy in physicians dedicated to cancer care doesn’t translate into an inherent ability to lead difficult conversations or comfortably express grief.”

Only recently studies have begun to look at physician practices following a patient’s death.

The primary goal of this prospective study was to examine the frequency and nature of bereavement practices among cancer care and palliative care physicians in the northwest United States. Researchers wanted to identify factors and barriers associated with bereavement follow-up and determine whether there were differences in practices by medical specialty.

An anonymous online pilot survey was completed by 162 attending radiation oncologists, medical oncologists, surgical oncologists, and palliative care physicians who were directly involved in patient care in the fall of 2010.

The study found that 70% of cancer care physicians were routinely engaged in at least one bereavement activity they initiated and that sending a condolence letter was by far the most common form of follow-up. Other physician-initiated activities included making a telephone call to families or attending a funeral service following a patient’s death.

For those who did not initiate bereavement follow-up, findings indicated that 90% of respondents would routinely be available for phone conversations if called by a patient’s family.

There were several factors that made an individual more likely to perform active follow-up, including being a medical oncologist (compared with a radiation oncologist and a palliative care physician), having access to a palliative care program, and feeling the responsibility to write a condolence letter. The most commonly perceived barriers to bereavement follow-up were lack of time and uncertainty as to which family member to contact. In addition, feeling uncomfortable about what to say and a lack of bereavement support resources made follow-up less likely.

“This study highlights the needs to more clearly define the physicians’ role in bereavement activities and address bereavement activities in provider’s postgraduate training as we work to improve the multidisciplinary treatment of cancer patients and their families,” Kusano said. ■


Chemo Plus Radiation Before Surgery Boosts Tumor Response for Rectal Cancer
Rectal cancer patients who use a new combination of the chemotherapy called capecitabine together with five weeks of radiation (50 Gy) before surgery have an 88% chance of surviving the cancer three years after treatment, according to research presented at the annual meeting.

“The results of the trial allow us to recommend a new preoperative treatment, the ‘Cap50’ regimen, in locally advanced rectal cancer,” said Jean Pierre Gerard, MD, a radiation oncologist at Centre Antoine-Lacassagne in Nice, France. “It’s safe and reduces the risk of the cancer coming back to less than 5%.”

The primary treatment for rectal cancer is surgery. However, there is a risk of cancer regrowth within the bowel and surrounding tissues. Not only is this recurrence incurable in the majority of patients, but it can cause negative side effects. Depending on the location and stage of the cancer, doctors usually recommend radiation therapy and chemotherapy before surgery. The optimal regimen has not been determined.

The ACCORD 12 trial involved 598 patients with locally advanced rectal cancer who were diagnosed and treated in 50 hospitals in France between 2005 and 2008. Researchers wanted to find the most effective and safe preoperative treatment for rectal cancer by comparing a combination of two different chemotherapies and two different radiation doses. Patients were randomized to receive either CAP45 (chemotherapy, capecitabine, and radiation treatment at 45 Gy) or Capox50 (chemotherapies, capecitabine and oxaliplatin, along with radiation at 50 Gy).

At three years after treatment, the Capox50 regimen did not significantly increase the chance of the cancer returning or surviving the disease compared with the Cap45 treatment. Oxaliplatin, given as part of the Capox50 treatment, was shown to immediately increase side effects, with some cases of severe diarrhea, and was not effective in increasing the chance of local tumor sterilization.

However, the increase of radiation dose from 45 to 50 Gy in five weeks was effective, well tolerated, and did not extend the duration of treatment.

“The results of this trial, when analyzed together with the Italian STAR01 and the American NSABP R04 randomized trials, bring solid scientific evidence that a Cap50 regimen should be the standard treatment for locally advanced rectal cancer,” Gerard said. “Using capecitabine avoids the intravenous injection of fluorouracil, while a radiation dose of 50 Gy in 25 fractions over five weeks increases the chance of tumor sterilization and limits the risk of local recurrence to 5% or less.” ■


Vitamin D Deficiency in Cancer Patients Predicts Advanced Disease
More than three-quarters of cancer patients have insufficient levels of vitamin D and having the lowest levels is associated with more advanced cancer, according to a study presented at the annual meeting.

“Until recently, studies have not investigated whether vitamin D has an impact on the prognosis or course of cancer. Researchers are just starting to examine how vitamin D may impact specific features of cancer, such as the stage or extent of tumor spread, prognosis, recurrence or relapse of disease, and even sub-types of cancer,” said Thomas Churilla, lead study author and a medical student at Commonwealth Medical College in Scranton, Pa.

Researchers sought to determine the vitamin D levels of patients at Northeast Radiation Oncology Center in Dunmore, Pa., a community oncology practice, and to see whether vitamin D levels were related to any specific aspects of cancer. The study involved 160 patients with a median age of 64 and a 1:1 ratio of men to women. The five most common primary diagnoses were breast, prostate, lung, thyroid, and colorectal cancer. A total of 77% of patients had vitamin D concentrations either deficient (less than 20 ng/mL) or suboptimal (20 to 30 ng/mL). The median serum vitamin D level was 23.5 ng/mL. Regardless of the age or sex of the patient, levels of vitamin D were below the median predicted for advanced stage disease in the patient group.

Patients who were found to be vitamin D deficient were administered replacement therapy, increasing serum D levels by an average of 14.9 ng/mL. Investigators will be analyzing whether vitamin D supplementation had an impact on aspects of treatment or survival in the long term.

“The benefits of vitamin D outside of improving bone health are controversial, yet there are various levels of evidence to support that vitamin D has a role in either the prevention or the prediction of outcome of cancer,” Churilla said. “Further study is needed to continue to understand the relationship between vitamin D and cancer.” ■