Online First/Online Only
Articles/items published ahead of print or only online.
Tuesday, August 04, 2015
BY MARY BROPHY MARCUS
This is the fifth in a series of profiles of oncologists discussing how they unwind during the summer months -- check out the entire series here -- From traveling to music festivals and hidden oases to growing organic gardens and cycling to raise research funds, the profiles show the rich and diverse interests and unique experiences cancer experts have beyond their clinic and lab doors. Share your own summer vacation stories and photos with us on Twitter! Use #OTSummerVaca and we'll retweet.
Beti Thompson, PhD
Bo Jungmayer/Fred Hutchinson Cancer Research Center
Last year, cancer researcher Beti Thompson hopped back on a bike for the first time in 25 years.
"The last big bike trip I had done was in 1989, a long while ago. I literally did not touch my bike for years," says Thompson, PhD, Associate Director of Minority Health and Health Disparities at Fred Hutchinson Cancer Research Center in Seattle.
The 70-year-old cancer researcher says Obliteride was her motivation. It's an annual bicycle fundraising event sponsored by her employer with the mission to obliterate cancer forever. Riders of all ability can participate and choose from a variety of courses that range in distances and difficulty level.
She had heard about Obliteride and its aim to defeat cancer. "I had a son who died of colon cancer at a young age and I wondered if I could still ride my bike. I knew that at age 69 to get back on a bike and ride for 29 miles would be a challenge, but at least I had the good sense to know I couldn't do this without training. I started training in late April 2014 for the August 2014 ride."
Thompson says the first time back on her bike was "pure agony," but she just kept at it. She'd step away from her lab for a bicycle break between 1 and 2 pm each day to train.
"I'd go ride around the lake and I did this two or three times a week. Before, I was pretty sedentary, so this was quit an adventure for me. I thoroughly enjoyed it and I got to the point where I could ride further and faster. I got to the point where it went from agony to being able to do it in about 45 minutes."
Thompson says Obliteride 2014 turned out to be the hottest day of the year, steamier than normal for Seattle.
"They changed the course and made it a little less hilly. It was 29 miles, but I did it. We actually raised a substantial amount of money, close to $50,000, for our team. I was part of a team called ‘Closing the Gap’”--the idea being the gap in health disparities in cancer, her research area, she explains.
After the success of the first ride, Thompson says she thought to herself, “I did it when I was 69, bet I could do it at 70.'"
This summer's ride is this coming weekend, August 9th. A grandmother of four and very family-focused, Thompson says this year's ride will be even more special because she has recruited her daughter and son-in-law and their 8-year-old son (who'll be riding a tandem bike with his mother) to ride Obliteride with her.
"I feel a lot stronger and I have a lot more energy and endurance," Thompson says about taking up cycling again. "And it just makes me feel so good. That combination of biking and spending time with my grandkids--it keeps me balanced with my work life."
Friday, July 31, 2015
BY MARK L. FUERST
A common side effect of radiation treatment for prostate cancer can be reduced by factoring in anatomy and the dose of therapy into a new treatment formula, according to the results of a large population-based study.
Men with prostate cancer who have shorter rectums and those who receive intermediate to high doses of radiation are at higher risk of late rectal bleeding, and should receive tailored treatments to prevent the complication, according to a study presented at the American Association of Physicists in Medicine Annual Meeting (Abstract TH-AB-304-1).
“The risk of late rectal bleeding increases with increasing rectal volume receiving even mild dose spillover, above about 65 percent of the typical prescription dose,” the study’s senior author, Joseph Deasy, PhD, Chair of the Department of Medical Physics at Memorial Sloan Kettering Cancer Center (MSKCC), explained in an interview.
“Patients with shorter rectums have a larger risk, all other factors being equal, of late rectal bleeding. By reducing the dose to the edge of the area being irradiated in men with shorter rectums, possibly using better treatment image guidance, we can significantly reduce the risk of late-stage rectal bleeding.”
Confirms the Importance of Dose
Asked for his perspective for this article, Howard Sandler, MD, Professor and Chair of the Department of Radiation Oncology at Cedars-Sinai Medical Center in Los Angeles, said the study confirms that dose is important for late rectal bleeding. “The model might be useful to practicing radiation oncologists as a tool to guide their plan to reduce the risk of late rectal bleeding.”
Deasy said that as many as 10 percent of men who have radiation therapy for prostate cancer suffer from rectal bleeding that can occur several months after the treatment, and about five to 20 percent of prostate cancer patients have late rectal bleeding even years after treatment.
“Chronic late bleeding occurs over an extended time years after radiation therapy. It can be treated, but it can be painful, uncomfortable, and reduces quality of life of patients. We can change treatments to reduce the risk of bleeding.”
1,001 Men from 5 Institutions
At the AAPM meeting, Maria Thor, PhD, a post-doctoral fellow at MSKCC, presented the results of the study from five institutions that analyzed 1,001 men who received various types of radiation therapy for prostate cancer. Rectal cross-sectional area, length, and volume were compared between patients who did and did not have late rectal bleeding.
Patients with the late effect were found to have had significantly smaller and shorter rectums than non-late rectal bleeding patients, and a larger volume of the rectum was exposed to a medium to high dose of radiation.
“We found that for patients with a larger cross-sectional area on imaging showing the rectum and prostate in square centimeters, those with smaller rectums had a higher risk of having this complication,” Deasy said.
“We also found the relative volume of rectum exposed at about 45 Gy was at increased risk--This is a new result because it was thought that only the very highest doses of radiation increased the risk of complications.”
The probability of bleeding was able to be predicted using a mathematical formula during treatment planning to minimize the risk. “This formula potentially could be put into treatment planning systems that are routinely used,” Deasy said.
If the model continues to hold up to the criticism of peer-review as part of publication, “then we need to work with the treatment-planning company vendors, and possibly the FDA as well, to put the model into the clinical environment as a decision support tool for planners and physicians.”
Radiation technique matters as well, he continued. In comparing three-dimensional conformal radiotherapy versus more modern intensity-modulated radiotherapy (IMRT), the team found a larger rectal volume of radiation among those receiving intermediate-high doses in 3D-conformal radiotherapy.
“Newer technology, IMRT, is effective at reducing this problem. We don’t have a complete picture of why that is the case, although we know it is related to a reduced high dose to the rectum.”
Affirmation for IMRT
Sandler agreed that the study is another affirmation of the use of IMRT. “The principle is that the more radiation a normal structure gets, the more likely the patient will have side effects. We have worked hard over the last 20 years to improve the therapeutic ratio of radiation, to continue to provide radiation to the tumor and less radiation to normal tissues. But this is still complex.
“We have developed useful metrics about the risks of side effects based on the shape of radiation dose curves. But sometimes there is a tradeoff. We may give a large dose to a small area, or a low dose to a large volume of area.”
There are also individual patient factors to consider. “We can give the same treatment and one patient has complications, and another one does not,” he said.
The group at Memorial Sloan Kettering Cancer Center has taken a different approach to accurately assessing the risk of complications, Sandler continued: “They were able to able to predict the risk of late rectal bleeding in about 15 percent of patients. The sample size of the study is good, and there are a good number of events,” Sandler noted.
Improving Dose Distribution
The results are similar to previous studies in that more radiation and a larger volume of the dose led to a higher risk of side effects. “The utility of the information is that a practicing physician could potentially use their formula to predict the risk of late rectal bleeding,” Sandler said. “If the risk is above an acceptable threshold, the radiation oncology team could improve the plan to get a lesser dose to the rectum. For patients with a short rectum, we can work harder to make up for that by improving the dose distribution of radiation.”
Sandler added: “When I plan a case, I mostly focus on the high doses to the rectum. I usually don’t emphasize instructions on low doses, but with this observation, I might consider low doses as important as well.”
Deasy said: “We can potentially modify the details of dose distributions as they are now generated by using treatment plan optimization. This optimization is performed by the computer using mathematical algorithms, to find the best treatment plan that has the desired dose characteristics as translated into mathematical terms.”
Also asked for her opinion, Colleen A. F. Lawton, MD, a former President of the American Society for Radiation Oncology, who is Professor and Vice Chair of the Department of Radiation Oncology at Medical College of Wisconsin, said: “The data says we need to pay attention to mid-range doses of radiation and the length of the patient’s rectum. We always knew that on the high-dose end we needed to be careful in the rectum. Here’s some science that proves that this is the right thing to do in using a mid-range dose of radiation in addition to the high dose.
“This is the first information I have seen about shorter rectums, and it makes sense,” she continued. “If a rectum has a smaller volume with shorter length, there is a higher risk of complications than a rectum with larger volume due to the longer length.”
Lawton agreed that this new formula could be very helpful for radiation oncologists in the community. “The simple thing would be to plug the formula into the planning system on the front side of the radiation plan. If a patient has a risk of rectal bleeding at a certain level, it will tell you what the V50 should be.”
Or a radiation oncologist could use the formula on the backside of the plan. “Based on the plan generated, if the patient has a certain risk of late rectal bleeding, then you could use the formula to get the V50 down.”
Lawton added: “We all want our patients to avoid late complications. This data helps us in planning to reduce significant late rectal bleeding.”
Deasy said that as more comprehensive datasets and analyses are brought forward, “we can expect some updating of well-accepted dose-volume tolerance guidelines.”
Friday, July 31, 2015
BY MARY BROPHY MARCUS
This is the fourth in a series of profiles of oncologists discussing how they unwind during the summer months -- check out the entire series here -- From traveling to music festivals and hidden oases to growing organic gardens and cycling to raise research funds, the profiles show the rich and diverse interests and unique experiences cancer experts have beyond their clinic and lab doors. Share your own summer vacation stories and photos with us on Twitter! Use #OTSummerVaca and we'll retweet.
East Coast born and raised, pediatric oncologist Patrick Zweidler-McKay didn't know a jot about horses before he moved to Texas a decade ago. Now, he spends every weekend all summer long on his horse ranch in the hill country just outside of Houston.
"It's basically our weekend home; 17 acres of wooded land and three horses, one for each family member, my wife, myself, and our 11-year-old son. We go out there every weekend and try to ride three or four times while we're there," says Zweidler-McKay, MD, PhD, Section Chief for Pediatric Leukemia and Lymphoma at the University of Texas MD Anderson Cancer Center, in Houston.
Zweidler-McKay grew up in the Philadelphia area, where he also attended college and medical school, and spent his residency years in Boston. In 2005, MD Anderson recruited him, and he and his wife and baby son made the move to Houston.
"Houston is like any large city. It has a symphony and a ballet and a zoo and museums, so we felt pretty much at home down here. But then one April we went driving outside of the city during blue bonnet season. In this area, you take your child, your baby, in blue bonnet season and set them down amongst the flowers and take pictures. We hadn't been outside Houston at that time and when we got out into the hill country we fell in love with the rolling hills and the pastures and flowers," he said.
Soon after, they bought property in the area, and learned that it was located in the heart of an equestrian community. "So, having no experience, we started taking lessons. Even my son, who was three-years-old at the time, started taking lessons on a little pony."
They fell in love with riding and horses and bought three quarter horses. Zweidler-McKay says he's even learned how to give his steeds "pedicures" to keep their hooves in good health.
Early in their marriage, Zweidler-McKay says he and his wife, who also works full-time, agreed that regular family time was important to them. The ranch, he says, nurtures that.
"I have trouble making personal time when I am in the city because I both see patients and I have a laboratory, and being so close, I have difficulty not coming in on weekends. Before the ranch, I had gotten into a pattern where I'd spend Saturday and Sunday working in the lab or hospital, so we decided the best thing was for me not to be in Houston," he explains.
He still takes his laptop and cell phone along so that he can check email and stay in touch with staff in case an emergency arises, but there's no phone at the ranch. "I'll limit my work on the computer to when my son and wife are resting in the afternoon."
Zweidler-McKay says it's been especially rewarding to see the ranch's influence on his preteen son.
“During the week he's on his electronics and doesn't want to play with me, but on the weekends he seeks me out to ride or be together. He has a tree house and a zip line."
Zweidler-McKay shared one more summer vacation milestone with OT: He recently visited his sister in Switzerland for several weeks (he is a dual Swiss-American citizen) and for the first time in his 10 years, he turned off his work cell phone for an entire vacation.
"I've been with MD Anderson for 10 years and I've never turned off my Blackberry... until this vacation to Switzerland. We have so many pictures of me on vacation where I'm sitting in a beautiful place and I have the Blackberry. So I turned it off. It was a little bit hard," said Zweidler-McKay, who did check email about once a day.
"One of my patients relapsed while I was away on vacation and I spent a serious amount of time on emails just coordinating the care of that patient. But that's the life I committed to. It's a lifelong commitment. Other doctors do it [take time off] better than me but it's been a challenge for me. But I survived it. I'd certainly recommend it to other oncologists, to turn off their paging devices, while they're on vacation. For mental health."
Wednesday, July 29, 2015
BY MEERI KIM, PHD
For clinical trials designed to test new cancer therapies, the outcome of overall survival had long been regarded as the gold-standard primary endpoint. But the results of a new study suggest that may be inappropriate as an outcome measure for the evaluation of treatments for chronic myeloid leukemia (CML). Instead, the likelihood of survival appears to be influenced more by patients’ existing comorbidities than by the disease itself.
The study, published in the July 2 issue of Blood (2015;126:42-49), included 1,519 patients diagnosed with CML who were recruited for the large German CML Study IV, from July 2002 to March 2012. At diagnosis, comorbidities for each subject were identified and used to calculate an age-adjusted index. Common comorbidities included diabetes, nonactive cancer, and chronic pulmonary disease.
In multivariate analysis, the comorbidity index proved to be the most powerful predictor of overall survival. However, these comorbidities had no effect on responses to therapies, remission rates, or progression to advances phases of CML. “It seems that in CML trials, a lot of patients die due to other reasons than their disease, and that death is not related to CML itself,” the first author, Susanne Saussele, MD, a hematologist and oncologist at Medizinische Fakultät Mannheim der Universität Heidelberg, said in an interview. “It is not clear if analyses differentiating between CML-related and non-related deaths are really free of bias. We tried to find a way to exclude this bias as we investigated the impact of comorbidities at the time point of diagnosis of CML on survival.”
Effects of TKI Therapy
Long-term survival rates for patients with CML have risen dramatically with the tyrosine kinase inhibitors (TKIs), changing CML into a chronic disease that although requiring long-term treatment, can be successfully managed. With regular TKI therapy, patients diagnosed with the disease today can expect to live about as long as a member of the general population, she said.
“Survival may no longer be the best endpoint for CML trials because any improvement in outcomes achieved with a new therapy will be difficult to detect when most of the deaths are not going to be related to the leukemia,” said the author of an accompanying editorial, Timothy Hughes, MBBS, MD, FRACP, FRCPA, Head of Translational Leukaemia Research at the South Australian Health & Medical Research Institute (SAHMRI), Head of the Department of Haematology at SA Pathology, and Consultant Haematologist at the Royal Adelaide Hospital.
“Getting a clear signal of disease benefit above the noise of the non-CML deaths will be very difficult.”
Saussele and her colleagues reported 511 comorbidities in the 1,519 CML patients at diagnosis who were participants in CML Study IV, a randomized five-arm trial designed to optimize TKI therapy with imatinib. The most commonly noted conditions were as follows:
- Diabetes mellitus (n = 106)
- Nonactive cancer (n = 102)
- Chronic pulmonary disease (n = 74)
- Moderate to severe renal insufficiency (n = 47)
- Myocardial infarction (n = 38)
The severity of comorbidities, along with patient age, was used to calculate the Charlson Comorbidity Index (CCI) for each subject. Based on their score, patients were then classified in CCI groups (higher score means increased likelihood of death):
- CCI Group 2 (n = 589);
- CCI Group 3-4 (n = 599);
- CCI Group 5-6 (n = 229); and
- CCI Group 6+ (n = 102).
“This study is a timely reminder that the greatest danger for most patients with CML is their preexisting conditions rather than the leukemia itself,” Hughes said. “This is an important study looking at a large number of CML patients all receiving the same backbone of treatment with imatinib for their CML.”
Asked for his perspective for this article, Jay Yang, MD, Assistant Professor in the Division of Hematology/ Oncology at Wayne State University School of Medicine and the Barbara Ann Karmanos Cancer Institute, said: “CML-related deaths may theoretically be an ideal endpoint, but practically speaking, when someone dies it's often difficult to ascribe a cause of death.”
Hughes added that a focus on CML-related deaths could also mask a subtle increase in non-CML-related deaths induced by new therapies. This might have been the case with the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials) and DASISION (Dasatinib versus Imatinib Study in Treatment-Naive CML Patients) trials, where higher rates of infection and toxicity may explain the lack of overall survival differences despite a lower rate of progression seen with the newer agents.
“Another problem [with using CML-related death as an endpoint] is that it ignores the possibility that the treatment itself may increase the rate of non-CML deaths,” Hughes continued. “We see this with the second-generation TKIs where a reduced CML-related death rate is counterbalanced by an increase in non-CML deaths.”
While overall survival as a CML study outcome is still important and should not be forgotten about, Yang suggests that researchers should also use surrogate endpoints such as progression-free survival, complete cytogenetic remission, major molecular remission, and deep molecular response.
“Most patients with CML live a very long time and have an excellent prognosis,” Yang said. “When you're talking about these highly effective agents--imatinib and others--it's going to be nearly impossible nowadays to detect an overall survival benefit when you're doing these head-to-head trials.”
Wednesday, July 29, 2015
BY ED SUSMAN
PALM SPRINGS, California--Children with chronic pain appear to be able to switch from opioids to twice-daily oxycodone controlled-release tablets, researchers reported here at the American Pain Society Annual Scientific Meeting.
A total of 107 of the 155 patients aged six to 16 were assessed as being “very much” or “much” improved by their caregivers after being switched to oxycodone.
The study was sponsored by Purdue Pharma, with the company’s medical liaison, Stacy Baldridge, RN, MSN, reporting the results in a poster study.
Another 17 patients were judged to be minimally improved, and the caregivers said that the for the rest of the patients evaluated after four weeks of therapy there was no change in their condition, and in one child the treatment appeared to worsen the pain and in another two the pain was considered to be very much worse. About 25 percent of the children in the study had cancer-related pain, and the others had pain related to other conditions.
“Chronic pain in children is the result of biological, psychological, developmental, and sociocultural factors, and includes persistent and chronic pain,” Baldridge said. “Only a small number of analgesics have been studied in children. Data on oxycodone in children are limited, and the safety and efficacy of oxycodone hydrochloride controlled-release tablets have not been established in children below the age of 18.”
‘Effective & Reasonable Alternative to Morphine’
Asked for his perspective for this article, James Cleary, MBBS, Director of the Pain and Policy Studies Group at the University of Wisconsin, Madison, who was not involved with the study, said: “We know that there is a global under-treatment of children with cancer with pain. There are a number of reasons why, and one of those reasons is the formulation issue.
“In the U.S., we have treatment solutions available, but that is not the case in the rest of the world. This study shows that oxycodone is an effective and reasonable treatment for children instead of morphine for pain relief. Despite what has been said about the company in the media, I think the company is being reasonable in doing the appropriate studies in children.”
There have been very few studies looking at the pharmacokinetics and tolerability of these medicines in children, Cleary continued. “If we look at U.S. studies for pediatric pain relief, the guidelines recommend that we not use codeine, yet if you look at the most common medicine used in children it is actually codeine. The World Health Organization has taken codeine out of the guidelines for treatment of persistent pain in children.”
‘Need Pain-Registration Studies’
He said companies should be doing appropriate pain registration studies, looking at the specific kinetics in children. “In this study the researchers have taken children who were relatively tolerant of opioids and put them on twice-a-day Oxycontin. This is not to say we should be starting children on Oxycontin, but the study does discuss dosing by weight and appears to be following all the appropriate pharmacological guidelines.”
Cleary noted that in treating adults for persistent pain, doctors will often switch medicines, since at some point drugs may lose effectiveness. “It is beneficial to have the safety record of a new medicine for children--I think it is great to have this new information.”
He said that the pediatric cancer pain population is small, “but like any population we need to do more to relieve the suffering of this population.”