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Wednesday, September 17, 2014




SAN FRANCISCO – Elderly lung cancer patients with severe co-morbidities can undergo successful treatment  using stereotactic body radiation therapy without late toxicities or loss of tumor control, researchers reported here at the American Society for Radiation Oncology Annual Meeting (Abstract 56).


In an update of the RTOG 0236 study, primary tumor recurrence was a remarkable seven percent after five years of follow-up in a group of patients whose health was compromised by emphysema, heart disease, or stroke and were not eligible for surgery, said Robert Timmerman, MD, Professor and Vice Chair of the Department of Radiation Oncology at the University of Texas Southwestern Medical Center.


Of the original cohort of 59 frail patients with medically inoperable Stage 1 non-small-cell lung cancer (NSCLC), the 60-month overall survival was 40 percent, and about 26 percent of this patient population achieved disease-free survival at 60 months.


But the key message, he said, was the lack of late complications: “The really exciting news was that there really wasn’t any significant difference in the toxicity with longer follow-up, which was something many people thought was going to happen,” he said in an ASTRO news conference. “In fact, toxicities were nearly the same as in the initial report. In that report, 17 patients experienced high-grade toxicity that was mostly pulmonary-related. That was the same in this report.


“The trial included frail patients who had so many serious medical problems that they could not withstand standard treatment for early-stage lung cancer, which is surgery,” Timmerman said. “Patients like this are typically not allowed in clinical trials because their health is so bad, but these were exactly the patients we selected for RTOG 0236.”


The RTOG 0236 results with a follow-up of two to three years were first presented at the 2009 American Society of Clinical Oncology Annual Meeting. “The results at that time were frankly astounding with nearly perfect local control at the treated site,” he said. “There was skepticism, however, and that led to incomplete market penetration at cancer centers due to concern about late toxicity that might occur with longer follow-up or additional recurrences.


“So the results of this trial with a median follow-up of four years with patients having follow-up of over seven years show that indeed the irradiated tumors are very well controlled, with a five-year primary tumor recurrence rate of only seven percent – which is on par with surgery.”



Timmerman predicted that these updated results will re-energize the uptake of stereotactic body radiation therapy for patients who have no other options or who decline surgery. “These results, I think, will change the dynamic of people using stereotactic body radiation therapy. There were many people who wanted to hold back on its use for fear of terrible late side effects. That’s probably the biggest message from this long-term results: we do not see those horrible side effects.


“Even though we had only 59 patients in this study, I do believe it will drive practice because it was done through the cooperative group, which has a lot more credibility than single centers. This was practice changing when we first presented this study in 2009, and this report will make it more practice changing,” he suggested.


Insight into Emerging Role of SMRT’

Benjamin Movsas, MD, Chair of Radiation Oncology at Henry Ford Hospital in Detroit, who was the moderator of the news conference, said, “This study provides insight into the emerging role for stereotactic body radiation therapy in patients with lung cancer. At our hospital, we find this technology to be a very promising approach. We are offering very precise accurate treatment, which for the most part is extremely well tolerated.


“I just saw a patient last week who we treated three years ago with stereotactic body radiation therapy for medically inoperable non-small-cell lung cancer when he was 85. He said at the time that he wanted to continue to be able to play golf, and I can tell you that three years later, he’s playing golf, he’s doing well, and his lung cancer is in control. This is a patient who never would have been able to have surgery based on his other medical conditions.


“We mainly use stereotactic body radiation therapy for the medically inoperable, but there are also patients who for their own reasons decline surgery so we tell those patients that if they decline surgery this is a secondary alternative. All these cases are first presented at a multidisciplinary tumor board where we have surgeons, thoracic surgeons, medical oncologists, and radiation oncologists sitting around the table discussing the case before we treat any patients. These decisions are made as part of the multidisciplinary team approach.”


Timmerman said that survival of the patients in RTOG 0236 continues to decline, as would be expected in a cohort of frail patients due to competing causes of death. However, “survival is still very impressive at five years, at 40 percent with a median survival of 48 months.”


A number of recurrences emerged that were not part of the original treatment, including seven patients who had regional failure very late – sometimes after five years after treatment, he said. “There were only two patients in the previous report. Overall, combining local recurrence and regional recurrence, the rate was 38 percent.”


He also said more distant metastases appeared in the updated report: “There were 15 such patients, or 31 percent in our five-year results while there were only 11 in the previous report. The local-regional failure did increase up to 39 percent after five years, indicating that our staging at the time of diagnosis was incorrect and that there were micrometastases. It did take a long time for many of these to appear, and most of them did appear outside of the treated area.”


In an interview, he noted that some of the recurrences may have been influenced by patients who continued to smoke cigarettes despite being treated for lung cancer: “We strongly encourage our patients to stop smoking, and use the opportunity to raise the stakes for them and give them whatever options for support that we can,” he said. “But honestly, many patients continue to smoke. It’s hard to believe, but they do. I don’t have specific information on recurrences, but half the patients in the study continued to smoke while on the trial.”






Tuesday, September 16, 2014



By Robert H. Carlson


HOUSTON – There are different kinds of cancer pain and not all of them require opioids – for example, pain management might at various times mean management of suffering, rehabilitation, function counseling, or other maneuvers.


“Pain is always a multidimensional construct; it is never just electrical activity going through the dorsal horn,” said Eduardo Bruera, MD, Professor and Chair of the Department of Palliative Care and Rehabilitation Medicine at the University of Texas MD Anderson Cancer Center, speaking here in an introductory lecture at the 18th Annual Interdisciplinary Conference on Supportive Care, Hospice, and Palliative Medicine, sponsored by MD Anderson. “We need to be cautious with the interpretation that the word pain always means more opioid.”


He said attempting to measure pain on a scale of intensity as a nociceptive equivalent is an error: “We cannot measure the production of pain. If we could, we would have our problem solved; we could titrate our opioid the same way a diabetic titrates insulin. A number such as 8 out of 10 does not tell us where the pain comes from, as there is a wide variation in production of pain, in perception of pain, and in the way we express the pain.”


If, however, it were possible to determine the origin of pain for a patient who scores pain as 8/10, and 85 percent of that was from nociception, that patient's pain will respond to opioids, Bruera said.


But a patient with only 30 percent of the pain due to nociception and the rest due to somatization, tolerance, incidental pain, or chemical coping, will not. “Do not react reflexively and 'throw the drugstore' at the patient in pain. Instead, figure out where the contributing factor is,” he said. “Opioids are ‘stupid’ drugs--they do not know which pathway to take, and it is not possible to target only the nociceptor pathway.”


Coping Chemically

Bruera said opioid agents are problematic in about 20 percent of cancer patients receiving them, because 20 percent of people who develop a cancer have a history of coping with their problems chemically, either with alcohol or drugs.


“These patients pose a considerable challenge to the interdisciplinary team,” he said. “We have to recognize that we are not doing such a great job at early diagnosis [of chemical coping], and so we frequently find ourselves with patients who have great difficulty.”


He advised oncologists to carefully screen patients who are going to be starting on a strong opioid for risk of alcoholism or drug abuse.


“Of course these patients will need opioids too, because they have pain, but be careful with opioid dose titration,” he said. “Use the help of palliative care colleagues in those patients who screen positive for a history of alcohol or drug abuse because the treatment of those patients will be more complex for their opioid management.”


CAGE-AID Questionnaire Simple, Effective

Prospective assessment of chemical dependence is not always accurate, Bruera said, and screening is necessary to identify the individual who is coping chemically.


A “chemical coper” is a person who uses medications in non-prescribed ways to cope with distress from anguish, suffering, or despair.


“And opioids do alleviate that suffering,” Bruera said.


Problematic alcohol use predicts for opioid chemical coping, he said, and he called the four-question CAGE-AID questionnaire a wonderful screening tool for both inpatient and outpatient practice. “If a patient scores negative, the likelihood that there will be a problem is never zero but is way lower” than for patients who answer yes to one or more of the questions.


The CAGE-AID questionnaire was originally related to alcohol use – CAGE is an acronym for its four questions -- and questions were later added regarding drug use (Adapted to Include Drugs):

·    Have you ever felt you should Cut down on your drinking or drug use?

·    Have people Annoyed you by criticizing your drinking or drug use?

·    Have you ever felt bad or Guilty about drinking or drug use?

·    Have you ever had a drink or used drugs first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover?


“Always screen with CAGE-AID, because the alcohol questions alone do not work,” Bruera said.


He said patients should not be warned about the CAGE questions beforehand--such as, “Now we're going to ask about alcohol use“--because that reduces the predictive value to “no more than flipping a coin.”


CAGE-identified patients are significantly more likely to have a history of tobacco use or active nicotine use, he said.


“Cancer patients should have a regular assessment of the CAGE history and meticulous follow-up, and the physician should avoid refilling medication without that assessment. When treatment is successful and the patient should be experiencing less pain and therefore reducing the opioids, CAGE positivity will be a barrier to that.”


‘Being Fired Is Okay’

When dealing with a chemical coper, emphasize function and ignore pain intensity as a benchmark, Bruera said. "And avoid the 'p' word [pain]” when speaking with the patient, he added.


A palliative care team would emphasize non-chemical coping—i.e., counseling, exercise, social activities, spirituality, and interdisciplinary care.


And don't be afraid to set limits on the relationship: “Being fired by the patient [who demands narcotics] is okay,” Bruera said. “Be careful not to prescribe out of your area of ethical comfort.”


Bruera said he used to make the mistake of saying, “Addiction isn't a problem if you have pain,” and “Because you have pain, the opioids are not going have the effect they have when you are not having pain.”


“We've learned a lot since then,” he said.


‘Pseudo-Addiction Not Common’

Bruera was asked from the audience about “pseudo-addition”--when a patient asks for higher doses of opioids and is suspected of drug seeking, but who is actually being under-treated. The pseudo-addicted patient's supposed aberrant behavior disappears when the appropriate dose is given.


Bruera said there are some patients in this condition, but he cautioned that they should be carefully screened with the CAGE-AID questionnaire before having their dose increased.


If it is a case of pseudo-addition, then the patient should stabilize and the behaviors disappear. But if the behaviors stop and soon reappear, it's a sign the patient is coping chemically.


Other signs pointing to aberrant opioid use include the following:

·        running out of drugs too early;

·        losing (or reported theft) of drugs;

·        arriving impaired;

·        double doctoring;

·        criminal activities;

·        demanding a particular type and dose of opioid; and

·        acting up (including threats) and excessive pain expression during encounter.


Not Much Use for Medical Marijuana

Bruera was asked in an interview if there is a place for medical marijuana in palliative care for cancer patients. He said there are endogenous ligands to the cannabinoids and so they probably do have a physiological role.


“Many years ago we did some work with a synthetic marijuana as an anti-emetic; it had effects on the patients' perceptions and it was an anti-emetic, but not a very potent one,” he said. “There might be mild effects on appetite, emesis, or pain, but these are not even comparable to standard treatments for those adverse events, and there are considerable side effects to marijuana.


“If you ask me if there is one situation where I would prescribe either medical marijuana or any of the synthetic cannabinoids, I cannot find one.”

Tuesday, September 16, 2014




SAN FRANCISCO – Patients with non-small-cell lung cancer (NSCLC) who present with Stage IV disease may be able to achieve long-term survival if they undergo aggressive treatment for oligometastases, researchers reported here at the American Society for Radiation Oncology Annual Meeting (Abstract 168).


In a review of the medical literature, scientists at Western Ontario University identified 757 patients with oligometastases who were treated for NSCLC at 20 international sites, and after five years, almost 30 percent of the patients were still alive.


“That is a better outcome than patients with Stage III non-small-cell lung cancer, who have a five-year overall survival of around 15 percent,” said Allison Ashworth, MD, now Assistant Professor of Radiation Oncology at Queen’s University in Kingston, Ontario.


In the meta-analysis, she and her colleagues reviewed the outcomes among patients diagnosed with oligometastatic non-small cell lung cancer and determined that a subgroup of patients had an improved outlook over the perceived outcomes for advanced NSCLC. Of the 146 patients designated as low-risk because of being younger and having metachronous metastases and better performance status, the five-year overall survival was about 48 percent, she reported.


That contrasted with the 184 patients who presented with synchronous oligometastases, who had a five-year overall survival rate of 36 percent. However, patients who presented with synchronous oligometastases and chest lymph node involvement – i.e., N1 or N2 – had a five-year overall survival rate of 13.8 percent, she said. presentation.


In an interview, though, she cautioned that the patients in the study were atypical of the patients who walk in the door with Stage IV NSCLC: “These were carefully selected patients. Most of the patients in the study had just a single metastasis.”


Most often that metastasis was in the brain – 269 of the 757 patients. Of the patients included in the study, 668 had just one metastatic lesion. The researchers found that 63 patients who were treated had two metastatic lesions, and the remaining 26 had three to five.


The second most common lesion site was in the lungs – 254 patients. The other common sites were in the adrenals – 98 metastases; bone – 64 metastases; and the liver and lymph nodes – 18 metastases in each location.


Of the 757 patients, 635 underwent surgery to remove the primary tumor, and 339 were treated with surgery to remove the metastases. When doctors performed radiation procedures, they most often utilized high-dose, stereotactic ablative radiotherapy, Ashworth said.


About 72 percent of the patients included in the meta-analysis were men, and the median age of the patients was 61. The median progression-free survival time was 11 months; and median overall survival was 26 months. When disease recurred, in half the patients the recurrence occurred within one year of treatment.


‘Select Minority’

“Our study finds that some stage IV non-small-cell lung cancer patients can achieve long-term survival after aggressive treatments,” Ashworth said. “However, it is important to note that the patients in this study are a very select minority of stage IV patients who are younger, more physically fit, with a lower tumor burden and slower pace of disease than the average stage IV patient.


“We hope our study’s results will help determine which stage IV non-small-cell lung cancer patients are most likely to benefit from aggressive treatments, and equally as important, help identify those patients most likely to fail, thus sparing them from futile and potentially harmful treatments,” she said.


“Our research, however, cannot answer the question of whether the longer survival is due to the treatments or simply because these patients have less aggressive disease,” she continued. “We must await the results of randomized clinical trials to answer this question. In the meantime, it is our hope that our study will help cancer specialists in making treatment decisions and in the development of clinical trials.”


Clinical Trial Controversial

Whether there will be a randomized trial comparing patients who are treated aggressively versus those receiving standard-of-care treatment is controversial, though: “I am doubtful that we could put together a randomized trial,” said Roy Decker, MD, PhD, Associate Professor of Therapeutic Radiology at Yale University School of Medicine, who was asked his opinion for this article.


“We are treating these patients now and the national guidelines suggest we treat these patients, so I think most of us would find it very hard to randomize patients to not treat them,” he said.


Ashworth said the meta-analysis was limited because of the retrospective nature of the study and because not all the papers and sites provided complete datasets. “We propose that the overall survival risk classification scheme be considered for clinical decision-making and to guide selection/stratification of patients for clinical trials of ablative treatment,” she said.


Decker added, “We all have patients who have metastatic non-small-cell lung cancer disease. The classic way of looking at these patients is to say, ‘Well, the horse is out of the barn.’ But we all have seen these patients who are young and they are healthy and we really want to give them the benefit of the doubt so we treat them aggressively. Rather than just giving them chemotherapy alone, we treat them with radiation and surgery.


“We have all seen patients who are long-term survivors. We don’t know if these patients are cured or they just haven’t recurred yet, but the literature is full of case reports of patients who have lived 10 or 15 years.”


He said the work by Ashworth and her team represents a “systematic analysis of a large database which very nicely puts together the experience and kind of shows us that the way we have been treating these patients is probably correct.


“One of the prognostic factors that they identified was metachronous disease – basically someone who has a primary and it is surgically removed and then a year later develops a single site of disease and that is removed. What we don’t know is whether these patients have curable disease of whether they have very slow-growing disease. We could just be selecting for patients with indolent disease.


“Most patients with Stage 4 non-small-cell lung cancer present with widespread disease; the average age for metastatic lung cancer is in the 70s. So this is a very young, healthy group of patients. This is for people who can undergo the local treatment,” he explained.


While the researchers identified patients who have a good risk and those with a poor risk, “even those with a poor risk have about a 13 percent long-term survival, which really is better than one would expect. I think that if you had a patient even with all those bad factors and told them they had a 13 percent chance of survival for at least five years, I think that most of them would jump at it.”


Tuesday, September 16, 2014



SAN FRANCISCO – Radiation therapy for treatment of patients with early-stage Hodgkin’s disease appears to have long-term survival benefits compared with patients not treated with radiation, researchers reported here at the American Society for Radiation Oncology Annual Meeting (Abstract CT-08).


In the study, after 10 years about 84 percent of patients who underwent radiation therapy at the start of their treatment regimen were alive compared with 76 percent of those who did not undergo the therapy, a difference that translates to a 49 percent relative risk reduction that was highly significant, said Rahul R. Parikh, MD, Director of Proton Beam Therapy at Mount Sinai Health System in New York.


Timing Also Key

The timing of the radiation therapy also appeared to make a significant difference in outcome as well, he said. At 10 years, 84 percent of patients who had been treated with radiation within 30 days of disease diagnosis were alive compared with 78 percent of patients who received radiation therapy more than 30 days after diagnosis.


In the study, “we have identified specific factors – socioeconomic differences, insurance status, and facility type – associated with underutilization of radiation therapy which may be targeted to improve access to care,” he said. “This is the largest contemporary dataset of patients with early-stage Hodgkin’s disease.”


The researchers accessed the National Cancer Data Base and identified 41,420 patients diagnosed with Stages I-II Hodgkin lymphoma from 1998 to 2011. The median follow-up was 6.4 years; the median age of the patients was 37, with a range of 18 to 90.


Of the patients in the study, 20,897 did not receive radiation therapy – about 51 percent of the patients. There were 20,523 patients who received radiation at a median dose of 30.6 Gy as part of the combined-modality therapy. The patient population was about evenly divided by sex; more than 80 percent of the population were white and about 10 percent were black. A little more than one-third of the population was age 30 or younger, and approximately 25 percent were over age 50.


“The standard of care for Stage I-II Hodgkin lymphoma has been combined-modality therapy of chemotherapy followed by consolidation radiation therapy,” Parikh said. “Multiple randomized trials have found that use of radiation has resulted in tumor control and progression-free survival. A meta-analysis that included 1,245 patients found a substantial survival benefit with radiation in reducing the risk of mortality by 60 percent; and a SEER study that included 12,247 patients found that combined-modality therapy resulted in a five-year overall survival benefit with radiation therapy in which 87 percent of patients receiving radiation survived, compared with 76 percent of patients who didn’t receive radiation.”


He said that despite these results, beginning in the 2004-2006 period there has been a declining use of radiation therapy to the point that less than half of Hodgkin patients receive radiation therapy. In 1998, 56 percent of patients with Hodgkin lymphoma underwent radiation therapy, but in 2011 the radiation utilization in these patients had dropped to 41 percent of the total.


“The main reason given for not using radiation was that radiation was not part of the planned initial treatment strategy,” Parikh said in his oral presentation.


Possible Reasons for the Decline in Use of RT

There may be several reasons for that decline in use, explained Karen Winkfield, MD, Director of Hematologic Radiation Oncology at Massachusetts General Hospital Cancer Center/Harvard Medical School. “There are already randomized clinical trials that show the benefit of using radiation therapy in early-stage Hodgkin lymphoma, but the hard thing with randomized controlled trials is that sometimes you might not have a long enough time to show a clear overall survival benefit. Additionally, the number of patients in the randomized controlled trial is often small.


“The issue has been that many of the large studies used very large radiation fields, which is really not what we are doing today, and in fact the survival curves crossed after 12 years because of some of the late toxicities of radiation therapy – at least that’s what they are saying,” she said.


Another problem perceived with randomized controlled trials is that they have a homogeneous population that may not, in fact, represent the population of patients seen in the clinic, she added. “This study, though, is the largest cohort of patients being looked at to actually show that radiation therapy does indeed provide not only progression-free survival, which everyone acknowledges but also overall survival.


The study provides additional evidence to support what we already know: That not only does radiation therapy improve progression-free survival but it actually supports the benefit in terms of overall survival.”


Socioeconomic Status, Education Level, & Other Non-Medical Factors

The study also indicated that socioeconomic status, education level, and other non-medical factors may influence which patients receive optimal treatment, Winkfield said. For example, the report showed that 24.3 percent of the population studied did not have medical insurance – and they represented just 17.2 percent of the patients who underwent radiation therapy. People with lower education attainment and lower levels of household income were also less likely to receive radiation therapy.


These differences, she said, “speak to the issue of access--“This is a snapshot of what happens in the real world. That is why this is, for me, a very compelling study: There are large numbers of patients; it represents more than 75 percent of the patients being treated in the United States and it shows what happens. I think this is a great study.


“I hope it will renew and re-invigorate the discussions among colleagues. For me, it highlights the need for radiation oncologists being at the table. At the Massachusetts General Hospital Cancer Center we have developed a multidisciplinary team for Hodgkin’s lymphoma,” she said. “It is critically important to have discussions between the medical oncologist and the radiation oncologist, and also to allow the patients to be involved in their care.”


Parikh said that when all the parameters and variables were scrutinized with an eye toward what determined an overall survival benefit he found a correlation with age – patients 40 or younger were likely to do better, and white race was likely to increase the overall survival benefit.


But when it came to treatment, the use of radiation oncology provided a 54 percent reduction in the risk of mortality; the timing of when to receive radiation therapy resulted in a significant 16 percent reduction in the risk of mortality if patients were treated within 30 days of diagnosis.

Tuesday, September 16, 2014


SAN FRANCISCO—The American Society for Radiation Oncology has released its second list of five radiation oncology-specific treatments that are commonly ordered but may not always be appropriate. Both lists are part of the American Board of Internal Medicine’s national Choosing Wisely campaign, and the new announcement was made here on Sunday at ASTRO’s Annual Meeting. ASTRO released its original Choosing Wisely list at last year’s Annual Meeting (OT 10/25/14 issue).



“We are a consumer-driven society of ‘more is more’—but we need to bring the message back to what is necessary and what is appropriate for the individual patient,” Carol A. Hahn, MD, MS—who is Chair of ASTRO’s Clinical Affairs and Quality Council, which spearheaded development of the list—said during the panel titled “Innovative Payment Models and The Future of Radiation Oncology—Impact on Quality, Payment Reform, and Patient Care” when the list was announced. Hahn is also Associate Professor of Radiation Oncology at Duke University Medical Center.




“We’re starting to see some change in practice,” ASTRO President Bruce G. Haffty, MD, MS, noted during a news briefing. “We believe the Choosing Wisely campaign really does have an impact in terms of reserving resources in health care.”


The new list was developed by an ASTRO work group convened in January to narrow down a list of 28 draft concepts to nine potential items for the final list. The group included representatives from ASTRO’s healthy policy, government relations, and clinical affairs and quality committees. In an anonymous survey, ASTRO members then provided feedback rating the value and relevancy of each item. Incorporating that survey feedback, the work group submitted a list of eight items to the ASTRO Board of Directors—and the Board chose the final five items on the list.


The working group looked for items that were within radiation oncology’s sphere of reimbursement, Hahn noted in an interview after the session. “We looked for items where radiation oncologists really owned the issue.”


And the group also looked for items that were commonly done, she added. “Obviously if it’s a very rare procedure, it’s not going to have a lot of impact.”


The five new recommendations from ASTRO are:

·         Don’t recommend radiation following hysterectomy for endometrial cancer patients with low-risk disease;

·         Don’t routinely offer radiation therapy for patients who have resected non-small cell lung cancer, negative margins, N0-1 disease;

·         Don’t initiate non-curative radiation therapy without defining the goals of treatment with the patient and considering palliative care referral;

·         Don’t routinely recommend follow-up mammograms more often than annually for women who have had radiotherapy following breast conserving surgery; and

·         Don’t routinely add adjuvant whole brain radiation therapy to stereotactic radiosurgery for limited brain metastases.


The new Choosing Wisely list is published online on the ASTRO website at:, and will be included on the  Consumer Reports site in the overall patient brochure of all the Choosing Wisely recommendations from the 60-plus specialty organizations  (


“We want to empower patients to go to their providers with this data in hand and be aware of these discussions,” Hahn noted during the session. “It’s a stronger effort if patients become engaged as well as the membership, and will help us improve quality and promote care that’s truly necessary—the right care for the right patient at the right time.”


ASTRO has also drafted a manuscript defining its process of developing its Choosing Wisely list, which was presented at a poster presentation at the meeting (Abstract 2966)—Hahn was the first author—and will also be published in an article later this year in Practical Radiation Oncology.