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Articles/items published ahead of print or only online.
Monday, April 27, 2015
BY KURT SAMSON
The tyrosine kinase inhibitor sunitinib appears to offer a small improvement in progression-free survival in patients receiving chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC), according to a small, placebo-controlled study by the Alliance for Clinical Trials in Oncology.
Prior studies have indicated that sunitinib may block vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR). VEGF plays a key role in tumorigenesis and VEGFR serve as the molecular bridges between cells that promote VEGF’s action in cell growth and transcription, the researchers explained.
Prior small trials in patients with ES-SCLC have yielded mixed results, with some studies reporting slight gains in progression-free survival (PFS) and others not, but all have found significant toxicity in treated patients.
Sunitinib has been approved for other cancers, including gastrointestinal stromal tumors in patients who do not response to or who are unable to tolerate imatinib, as well as in advanced renal cell carcinoma and pancreatic neuroendocrine tumors.
In the new trial, available online ahead of print in the Journal of Clinical Oncology (doi:10.1200/JCO.2014.57.3105), progression-free patients who had received chemotherapy were randomly assigned to maintenance therapy with either placebo or sunitinib at 37.5 mg per day until progression. Cross-over into the treatment arm was allowed if there was disease progression in the placebo group.
The primary endpoint was PFS assessed using a test the investigators determined had 89 percent power. The trial enrolled 144 patients, 138 of whom had received chemotherapy. Among them, 85 received maintenance therapy–44 with sunitinib and 41 with placebo.
Prophylactic cranial irradiation (PCI) was offered to all patients who had a complete or partial response to chemotherapy, beginning approximately four to six weeks after the final cycle. Among those who chose radiation, sunitinib was withheld for at least two days before, during, and after radiotherapy.
There was some evidence of single-agent activity in the sunitinib arm, the researchers reported. Three patients, or 6.8 percent, converted to having a complete response after maintenance therapy compared with none in the placebo group. A total of 34 of 78 patients who achieved stable disease, or partial or complete response, were included. Although the data were balanced for patients receiving PCI, there was no significant difference in PFS in PCI recipients or non-recipients treated with sunitinib, the results showed.
“I think that our study and others have concluded that sunitinib inhibits VEGF in general,” said the lead author, Neal E. Ready, MD, PhD, Associate Professor of Oncology at Duke University School of Medicine. “In the immediate group, three patients had a complete response and a fourth had a partial response.”
In the placebo group, the median PFS was 2.1 months versus 3.7 months for those given sunitinib, for a hazard ratio of 1.62. Median overall survival from random assignment was 6.9 months for patients on placebo and 9.0 months for those receiving sunitinib. A total of 10 out of 13 patients evaluated after the crossover phase had stable disease, ranging from six to 27 weeks.
Toxicity and adverse events were reported in 53.5 percent of patients who received immediate sunitinib. Grade 3 adverse events included fatigue in 19 percent of patients, decreased neutrophils in 14 percent, and decreased leukocytes or decreased platelets in seven percent.
Grade 4 adverse events included GI hemorrhage in one patient, as well as pancreatitis, hypocalcemia, and elevated lipase levels, all in the same patient. In the placebo group fatigue was reported in 10 percent, and one patient each had thrombocytopenia and hypernatremia.
“I would consider this dramatic, and the findings support more study of maintenance therapy and research on novel therapeutics to reduce toxicity,” Ready said, adding that it also indicates that it is possible to safely study maintenance therapy even among crossover patients for whom sunitinib had a positive effect.
Earlier trials used either higher or lower doses of the drug, which resulted in higher rates of toxicity or efficacy, and were smaller and not randomized, he noted.
Accompanying Editorial: Time for Phase III?
In an accompanying editorial (JCO doi:10.1200/JCO.2014.60.1815), Natasha B. Leighl, MD, MMSC, a member of the Lung Disease Site Group of the National Cancer Institute of Canada’s Clinical Trials Group, who is Associate Professor at the University of Toronto and a medical oncologist at Princess Margaret Cancer Centre, asked whether the time has come to consider a larger Phase III study of sunitinib rather than a larger Phase II trial.
Therapeutic progress in treating SCLC has been disappointing despite rapid development of targeted therapy in non-small-cell lung cancer, especially those with extensive disease, she said. And even though new alternatives have been developed, for both limited and extensive SCLC, etoposide-platinum (EP) therapy remains the standard systemic treatment--“Standard treatment of SCLC has not changed in decades.”
In Japan, irinotecan-platinum (IP) is now an accepted alternative, and prophylactic cranial irradiation in responding patients helped improve survival in most studies. Further, a recent study indicated that thoracic irradiation in responding ES-SCLC patients might also prolong survival.
Leighl said that although the current study had challenges, notably the inability to combine sunitinib with concurrent EP chemotherapy, the researchers did demonstrate better PFS than with placebo, and the data confirmed single-agent activity with a complete response rate of seven percent.
Nonetheless, SCLC is known to be associated with multiple genomic variables, she said, and because there has been so little progress in treating SCLC there has been “a lack of investment and enthusiasm” in studying newer targeted approaches, especially in patients with extensive disease. Moreover, most patients become too ill to participate in trials.
“Should we move forward with a sufficiently powered Phase III study to definitively answer the question of whether maintenance sunitinib improves survival?” she asked. “Should only ES-SCLC be studied, where the bar for success is lower, or should both limited and extensive stage be included, increasing the relevant population for study and accelerating accrual?”
Because half of the sunitinib subjects in the Ready et al study required dose reduction, she also asked if the next trial should use 25 mg daily instead of 37.5 mg, although lower doses of drugs for other diseases have resulted in decreased effectiveness and the same might prove true for sunitinib.
The editorial also asked if such a study should also include other possible targets of sunitinib. Because the new study did not report activity in other biomarkers, she said she wondered if subjects selected for a Phase III trial should be exclusively chosen for VEGF or if other protein expression, genomic alterations, or other potential predictors of sunitinib benefit, such as genetic polymorphisms or tumor microRNA levels, should be also included.
“These researchers have successfully completed a challenging Phase II trial, demonstrating a clear signal of benefit with sunitinib. Should they proceed to a larger study? The chance of a successful Phase III trial based on positive Phase II results has been estimated at 28 percent. Will sunitinib be the next advance in the treatment of SCLC or just another blind alley? There is only one way to find out,” Leighl concluded.
David Spigel: Phase III Trial Might Be Premature Due to Toxicity Concerns
Also asked for his perspective for this article, David R. Spigel, MD, Director of Lung Cancer Research at Sarah Cannon Research Institute in Nashville, Tennessee, said that conducting a Phase III study at this time could well be premature: “I’m a little biased because Dr. Ready and I conducted similar studies, but we stopped ours [Lung Cancer 2012, 77:359-364] because the toxicity levels with sunitinib were too high.”
In addition, he said, although the new study suggests that sunitinib may increase progression-free survival, this may not translate in a larger Phase III trial: “I am very much in favor of exploring anti-angiogenesis agents and the data so far has been encouraging, but we saw this a few years ago with thalidomide, which also initially showed promise against SCLC tumors but was later found in a larger study to provide no benefit while increasing the risk of blood clots and other serious adverse events.”
Search for Biomarkers
Spigel also emphasized that researchers have yet to identify a biomarker for angiogenesis in tumors and, historically, SCLC trials have generally been negative and selecting a sizeable study population for a larger study would be difficult. Moreover, there is no way to know if the new findings will translate into better overall survival rates over time.
“If a Phase III trial is to be conducted at this point, I think it will take a tremendous leap of faith to do so. We probably need better efficacy data upfront, and there has not been enough of this data in the Phase II studies conducted thus far.”
Several researchers are looking at other potential angiogenesis inhibitors that may prove to be better candidates for trials in these patients, he added: “The full story is far from done yet, but we could be getting closer to finding an actual biomarker for these cancers. I am also excited about some of the advances being made in immunotherapy to treat these patients. I personally think that we will have better strategies in the future.”
Saturday, April 25, 2015
BY MEERI KIM, PHD
A new prospective, observational study of the frequency, magnitude, and factors associated with benign thyroid nodule growth during the first five years after diagnosis shows that any transition to thyroid cancer in such patients is rare.
The study, in the March 3rd issue of the Journal of the American Medical Association (2015;313:926-935), looked at 992 patients with one or more asymptomatic, sonographically or cytologically benign thyroid nodules from eight hospital-based thyroid-disease referral centers in Italy. Nodules were assessed for changes with yearly thyroid ultrasound examinations that reported overall size, baseline factors associated with growth, new nodule appearances, and thyroid cancer diagnosis.
The majority of nodules, 69 percent, remained stable in size throughout follow-up and exhibited no significant growth or shrinkage throughout follow-up. Even for those nodules that did grow bigger, the rate of size increase was extremely slow and had no bearing on whether they became malignant or not. Thyroid cancer was detected in only 0.3 percent of the original nodules.
Despite the fact that thyroid nodules are common in adults, the amount of evidence to guide long-term management--particularly those that appear benign upon initial evaluation--has been largely insufficient. For instance, current guidelines recommend reassessment of cytology if significant growth is observed, despite there being a previously untested connection between growing nodules and risk of malignancy.
These new results suggest that guidelines like these for benign thyroid nodule surveillance should be updated and reconsidered.
An unexpected side effect of improvements in medical imaging has been the detection of asymptomatic thyroid nodules during radiological evaluations that include the neck. In adult populations, the prevalence of thyroid nodules has been estimated to be 40 to 50 percent.
“What we now observe is an epidemic of thyroid nodules, especially in females,” said the study’s senior author, Sebastiano Filetti, MD, Professor of Internal Medicine at Sapienza University of Rome. “This is due mainly to the technique of detection—i.e., incidental findings--by using diagnostic imaging like CT scan and Doppler.”
Once nodules are discovered, a fine-needle aspiration biopsy for larger or sonographically suspicious nodules can separate out the benign from the malignant lesions. While the protocol for a malignant lesion is clear, the next steps are less obvious for those patients with a cytologically benign or sonographically nonsuspicious thyroid nodule. Current guidelines lack both precision and a strong basis of clinical evidence for how physicians should proceed in terms of follow-up, Filetti said.
Even though more than 90 percent of the detected nodules turn out to be clinically insignificant benign lesions, they can still incite anxiety in patients, particularly in light of repeated visits and testing.
Asked for her perspective, Louise Davies, MD, MS, Associate Professor of Surgery at the Geisel Medical School at Dartmouth, said: “One is the big issues is how do you follow these people, how much do you follow up, and when is it okay to stop looking? Previous guidelines have always seemed to me unsatisfying, that even a benign thyroid nodule should continue to be followed--it brings people into the medical system in a way that is not necessarily justified.”
The American Thyroid Association guidelines—available at Thyroid 2009;19:1167-1214--advise repeating thyroid ultrasonography after six to 18 months and if nodule size is stable, every three to five years. However, if significant growth has been observed, then the physician should reassess the nodule's cytology using fine-needle aspiration.
But some experts are not convinced that such follow-up is necessary.
“What do I do with this nodule? It’s benign, but how many times in the next 10 years do I have to check--every six months? Every three?” Filetti said. “This was the motivation, to find out both for the patient and the physician in order to make strong points in the guidelines if nodules are benign.”
Filetti and his colleagues studied a total of 1,567 nodules from patients recruited between 2006 and 2008, who had an average age of 52.4, and 82 percent of whom were female. A significant growth/shrinkage consisted of at least a 20 percent increase or decrease (with a minimum of two millimeters in magnitude) in two or more nodule diameters.
For 184 of 992 patients (18.5%), a nodule shrank in size. In 153 out of 992 patients (15%), growth was seen in 174 nodules (11%) and was associated with the presence of multiple nodules, main nodule volumes larger than 0.2 mL, and being male.
“For the 15 percent for whom we found growth, does that mean it’s dangerous? he asked. “No: the growth was really small, and the growing does not mean it’s malignant,” he said. Growth of benign nodules was slow enough not to be detectable clinically, only by imaging. For example, the average largest diameter increase reported in the study was 4.9 mm over the five years.
Of the five original nodules later found to be cancerous (0.3%), only two had expanded in size during follow-up. All were first discovered by ultrasound, which suggests that surveillance could focus on this method of detection rather than performing a repeat fine-needle biopsy. In addition, new nodules were detected during follow-up in 93 patients (9.3%), including one cancerous lesion.
Summing up, Filetti said that that when a nodule is classified as benign, nothing more than a “soft follow-up” is called for. In other words, physicians can administer a second ultrasound examination one year later, and in the absence of changes, perform a reassessment after five years.
In an accompanying editorial, Anne Cappola, MD, ScM, Associate Professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism at the Perelman School of Medicine at the University of Pennsylvania, outlined the importance of the study for shaping future guidelines on the follow-up of thyroid nodules. She said that in particular, she hopes the findings will reduce unnecessary expense and resources dedicated to frequent follow-up for the vast majority of benign lesions that do not require that.
“It’s really a matter of being more efficient in finding the ones you need to monitor closely and letting the ones go that you don’t need to worry about,” she said in an interview.
The baseline ultrasound should be used to guide future surveillance of benign nodules on a case-by-case basis. If a worrisome sonographic feature is present—for example, hypoechogenicity, irregular margins, taller-than-wide shape, intranodular vascularity, or microcalcifications--then the patient may be followed more closely. If the baseline ultrasound is nonsuspicious, however, repeated and strict follow-up is likely inappropriate.
“It’s an issue in terms of cost and inconvenience, but the big issue is patient worry,” Cappola said. “Patients don’t understand how they could have this thing in their neck and not have it be a cancer.”
The data support the validity of a benign cytology result obtained by ultrasound-guided fine-needle aspiration, she continued. The test in this study had an extremely low false-negative rate of just 1.1 percent.
‘Hard Evidence to Present to Patients’
Davies said she applauds the researchers for giving her hard evidence that she can present to her patients with benign thyroid nodules, particularly the ones worried about thyroid cancer.
“It was the low rate of cancer identification that really struck me most as a relief. Also, the fact that size increase was not a harbinger of malignancy, especially if the nodule wasn’t sonographically suspicious--that’s very reassuring. These are real things that you can take to your patients and say, 'The likelihood that we’re missing a cancer here is really low.'”
She also notes that the American Thyroid Association is in the midst of an overhaul of its guidelines, although it isn't clear whether these new results will be taken into account.
Overtesting by physicians, although often originating from a place of good intentions, can drive both heightened costs and patient anxiety. For instance, through her own research, Davies has discovered that physicians order multiple tests at once--such as inappropriate thyroid ultrasounds when all that was needed for the particular patient was a thyroid-stimulating hormone blood test (Laryngoscope 2010;120:2446-2451).
“Among my patients who are in other forms of cancer surveillance, even cancer survivors, they describe to me not being able to sleep well for days and weeks before their appointments, due to the anxiety that comes up with the waiting and the wondering. I think that’s something we physicians underestimate.”
Also, she stressed that because thyroid nodules are so common, it may not be practical from a workforce standpoint to closely watch over that many individuals when the vast majority of nodules will remain benign.
Friday, April 24, 2015
BY KURT SAMSON
A frailty scoring system created by the International Myeloma Working Group (IMWG)--the research arm of the International Myeloma Foundation, made up of approximately 160 myeloma researchers around the world—appears to make possible better assessment of the risk of mortality and toxicity in elderly patients with newly diagnosed multiple myeloma.
The research team, led by Antonio Palumbo, MD, Chief of the Myeloma Unit at the University of Torino in Italy, evaluated pooled data from three prospective trials on 869 newly diagnosed elderly patients. A geriatric assessment was performed in each patient at the time of diagnosis and a scoring system of 0 to 5 was used based on age, comorbidities, and cognitive condition. The findings were published in the March 26 issue of Blood (2015;125:2068-2074).
Patients were classified into three groups:
· Fit (score of 1, 39 percent of patients);
· Intermediate (score of 2, 31 percent of patients); and
· Frail (score lower than 2, 30 percent of patients).
With a median 18 months of follow-up, the three-year overall survival rates were 84 percent in fit patients, 76 percent in the intermediate group, and 57 percent in frail individuals. The cumulative incidence of grade 3 or higher nonhematologic adverse events at 12 months was 22.2 percent in fit patients, 26.4 percent in the intermediate-fitness category, and 34.0 percent in frail subjects.
The cumulative incidence of treatment discontinuation at one year was 16.5 percent for fit subjects, 20.8 percent for those in the intermediate-fitness category, and 31.2 percent in frail patients. The frailty scores were still associated with overall survival regardless of staging and type of treatment regimen, the study showed.
Three Instead of Two Categories
“Until now we had young and elderly; now we have young, elderly fit, and elderly frail--basically three categories instead of two,” Palumbo said in an interview.
“Age and comorbidities are not always the first issues considered before treatment. This should be the case, but it is not always. More education on this issue is very badly needed. To deliver a full dose of chemotherapy in a frail patient exposes them to a significant greater risk of comorbidities, and this often results in discontinuation of therapy.”
Because the system better predicted mortality, toxicity, and the likelihood of treatment discontinuation, the IMWG B, which sponsored the study, proposed using frailty scoring system in designing future clinical trials of blood cancer treatments, Palumbo noted.
“Simply relying on age, physical performance, and a doctor’s clinical judgment are insufficient to properly assess risk in elderly patients who are diagnosed with melanoma. This assessment tool is a more sensitive predictor of clinical outcomes, and the proposed score may be adopted as a valid new standard to evaluate patient frailty.”
The researchers found that even subjects in the intermediate fitness category experienced a slightly higher risk of grade 3 or higher non-hematologic adverse events, while the risk in frail patients was significantly greater. Grade 3 or higher non-hematologic adverse events occurred in 18 percent of fit subjects, 22 percent in the intermediate patients, and 30 percent of frail individuals.
Over the length of the study, the researchers reported that 17 percent of fit patients discontinued drug treatment for any cause, excluding death or disease progression, while 22 percent of the intermediate category discontinued treatment as did 25 percent of the frail subjects.
“The relationship between fitness and discontinuation of treatment is difficult to clearly define,” Palumbo said. “Frailty and discontinuation are major factors that reduce outcome, and are both equally important. But frailty appears to increase toxicity, and that is a major cause of therapy discontinuation.”
Combining frailty scores with the International Staging System (ISS), the three-year overall survival rate was 55 percent in the frail-ISS 3 patients but 94 percent for fit-ISS 1 individuals, the researchers found.
“The combination of these two independent parameters significantly improved the prognostic value of the single ones. This is therefore an important strategy in the future for predicting outcome. The scoring system could be used in everyday clinical practice as well as in the context of research to ensure an adequate representation of elderly patients and to allow more precise cross-trial comparisons,” the authors noted.
Palumbo said that the major limitation of the findings was that the study was retrospective—unfortunately, though, it is difficult to perform prospective studies in this setting, and the group is not planning any additional studies of the scoring system at this time.
At Ohio State University’s Wexner Medical Center, Ashley Rosko, PhD, Assistant Professor in the Division of Hematology is hoping to incorporate biomarkers into a fitness staging prognosis.
She was awarded a $150,000 new investigator grant from the National Comprehensive Cancer Network last year to conduct a study on comprehensive geriatric assessment and biomarkers of aging investigation among seniors with myeloma.
She is now conducting a pilot trial studying an electronic comprehensive geriatric assessment to measure fitness in pre-autologous hematopoietic stem cell transplantation (AHSCT) in older myeloma patients and determine the ability of molecular biomarkers, especially p16 expression in peripheral blood T- lymphocytes, to measure patient fitness and predict return to function after AHSCT.
She noted in an interview that the researchers have enrolled some 80 patients to date with a target of 100 subjects, and the hope is to present preliminary findings at the American Society of Hematology Annual Meeting in December.
“With the aging of the population, the need for such research has become more pressing,” Rosko said. “We are looking at multiple occult assessment factors. Generally these patients’ frailty is determined by their gait, how well they can rise from a chair, and cognitive factors, but geriatric assessment is more than just those factors.
“In addition to cognitive assessment and these issues, we also inquire about social support, nutrition, and a history of falling. It is very important to know how these patients are functioning at home and how they were doing before their cancer diagnosis.”
She commended the Italian study for including such a large number of subjects, which is difficult. “We are learning that functional and cognitive performance assessment is not enough. All of the patients included in the analysis were from clinical trials, and with trials the inclusion criteria is pretty stringent. But Dr. Palumbo and his colleagues were able to stratify them. The bottom line is that we need to redesign our approach to assessing such patients.
“In the studies used in this paper much of the data was subjective and came from self-reporting of things like gait, cognition, and balance. Using objective biomarkers might be a better tool and should be explored further.”
Molecular markers like p16 have never been explored before in these older multiple myeloma patients, with longer follow-up of toxicity, disease progression, and death.
In an accompanying editorial (Blood 2015;125:2014-2015), Ulf-Henrik Mellqvist, MD, PhD, Chairman of the Nordic Myeloma Study Group and a researcher in the Hematology Section at Gothenburg University and Sahlgrenska University Hospital in Sweden, said the stratification method reported by Palumbo et al might be a useful tool in identifying both it and frail elderly multiple myeloma patients: “Like most malignancies, multiple myeloma mainly affects elderly patients. Even so, in daily clinical practice, we usually consider only chronological age. It is quite obvious, however, that there is a huge difference between a 70-year-old fit patient and a frail patient above the age of 80.
The inferior survival rates found in older frail patients was most likely due to a greater frequency of treatment discontinuation and nonhematologic adverse events, and although a number of assessment and staging systems have been developed, not all have shown benefits, Mellqvist said.
“But so far they have not been able to provide information for adjusting the treatment of the individual patient. In this study, the authors show that their new system could produce information not possible to obtain by using standard performance status, ISS, or even biological data from chromosomal analyses, which we normally regard as very important prognostic tools.”
The study is also important because it has the potential to help guide individual treatment regimens, and by identifying frail patients, it could help clinicians choose well-tolerated, low-toxicity drug combinations and avoid harmful treatment regimens, Mellqvist wrote.
“Another potential important issue for a new robust frailty scoring system could be that elderly patients found fit could benefit from more intense treatment.”
Saturday, April 18, 2015
BY ROBERT H. CARLSON
A pharmacist-led medication assessment of geriatric cancer patients found a high prevalence of polypharmacy, excessive polypharmacy, and potentially inappropriate medication, according to the report online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2014.58.7550).
The researchers, from Thomas Jefferson University's Jefferson School of Pharmacy, reported that among 234 geriatric cancer patients:
· 41 percent were taking five to nine medications (including prescription, non-prescription, and complementary medications and supplements, but not cancer treatments);
· 43 percent were taking 10 or more medications, and
· 51 percent were taking potentially inappropriate medication.
The mean number of medications used by each patient in this study was 9.2; the mean age of patients was 80, and approximately two-thirds were female.
A comprehensive medication review is considered to be an integral part of the geriatric oncology assessment, but current guidelines do not state which health care professional should be performing the medication assessment, the researchers wrote.
“Physicians should be aware that a high percentage of patients are taking five or more concurrent medications, which increases the risk for adverse drug effects, drug-drug interactions, and non-adherence as a result of increased pill burden and regimen complexity,” the first author, Ginah Nightingale, PharmD, Assistant Professor in the Department of Pharmacy Practice at Jefferson, said in an e-mail exchange.
A comprehensive medication assessment should be done prior to anti-cancer therapy initiation and then periodically, she said. Because some senior adult oncology patients may have a poor prognosis or a diagnosis of terminal cancer, a comprehensive medication assessment is important to adjust or reduce the use of unnecessary medications.
“The focus of the assessment should be on prioritizing the patients’ goals of care, such as relieving symptoms and maintaining functionality.”
The most prevalent potentially inappropriate medications were benzodiazepines, gastrointestinal medications, NSAIDs, antiplatelet medications, and first-generation antihistamines.
Specific co-morbidities associated with those potentially inappropriate medications were cardiovascular, neurologic, and psychiatric conditions.
Nightingale said that including prescription, non-prescription, and complementary medications and supplements in the study did not overstate the problem of polypharmacy. Rather, “it provides a more transparent sneak peek of what’s in the 'medicine cabinet' of the cohort of senior adult oncology patients seen at our center, a sense of the landscape of their medication use.”
She noted that a patient can meet the criteria for excessive polypharmacy and not be on a potentially inappropriate medication, although the study did show that the more medications a patient takes the greater the potential for inappropriate medication use.
Potentially inappropriate medications were identified using the 2012 Beers Criteria, the Screening Tool of Older Person's Prescriptions (STOPP), and the Healthcare Effectiveness Data and Information Set (HEDIS). The researchers recommended the development of a medication assessment tool that integrates the 2012 Beers and STOPP criteria and said that clinicians should also consider cancer diagnosis, prognosis, and cancer-related therapy.
She noted that the 2012 Beers criteria are currently being updated by the American Geriatric Society, with the 2015 version scheduled to be released this summer.
She said her research team is awaiting this update, and is also evaluating the draft of the National Comprehensive Cancer Network update for the guidelines for treatment of older adults with cancer, which also address some of the limitations associated with the 2012 Beers criteria.
Nightingale and her coauthors acknowledged in the article that this single-institution study had a small sample size compared with previous studies and did not include any anticancer treatments or cancer-related therapies.
Also because medication use in this population changes continuously, especially for patients who will begin anticancer and/or supportive care-related therapies, follow-up data on the acceptance of pharmacist interventions would further strengthen the study findings, the paper stated.
“The literature shows that pharmacists are underused in the ambulatory oncology setting and have an opportunity to play a critical, long-term role in providing safe, effective, and affordable medication-related care,” Nightingale said.
‘We All Need to Be Geriatric Oncologists’
“All adult oncologists are now geriatric oncologists,” noted the author of an accompanying editorial (JCO: doi: 10.1200/JCO.2014.60.3548), Stuart M. Lichtman, MD, Attending Physician at Memorial Sloan Kettering Cancer Center and Professor of Medicine at Weill Cornell Medical College.
Geriatric oncology is no longer a niche field with only a few dedicated researchers. “Clinicians should not fear the words 'geriatric assessment.”
He elaborated in an e-mail exchange: “The fear of geriatric assessment is multiple: not enough time, not enough knowledge; and being uncertain how to use the information and not sure of its importance.”
Geriatric assessment should no longer be the purview of the geriatrician, but will need to be incorporated into daily practice in all oncology fields, he said.
“We all need to become well-educated geriatric oncologists,” he said, but he added that it's going to take time for physician education to catch up.
Standard medical practice now incorporates drug use as part of routine evaluation, but it is well established that the traditional oncology evaluation is not adequate, and will fail to uncover many specific problems. “But with minor modifications this can be made to focus on older patients,” he said.
Discontinuing unnecessary medication is the most important thing, Lichtman said, particularly drugs like statins to lower cholesterol. “Does an older patient with advanced cancer really need statins?”
Lichtman said the study by Nightingale and colleagues highlights an important aspect of geriatric assessment in patients with cancer: “Evaluating polypharmacy by using the accepted guidelines is one way clinicians can begin to feel comfortable with geriatric evaluation and make a tangible impact on patient care.”
Friday, April 10, 2015
BY HEATHER LINDSEY
Ten quality indicators identified by the American Academy of Hospice and Palliative Medicine (AAHPM) and the Hospice and Palliative Nurses Association (HPNA) may help patients receive the best possible palliative and end-of-life care, according to the initial recommendations of the organizations’ consensus project, Measuring What Matters (MWM), published in the April issue of the Journal of Pain and Symptom Management (2015;49:773-781). The measures were developed so they can be applied to a variety of specialties, but may also have a direct application to oncology.
“We embarked on this project because we recognized a need among patients and their families,” said Joseph D. Rotella, MD, MBA, HMDC, FAAHPM, Co-chair of the MWM Clinical User Panel and AAHPM’s Chief Medical Officer. While there are more than a hundred published measures related to palliative and hospice care quality, there is no consistency among programs across the country regarding which measures are being used, he explained. Consequently, making sense of a patient’s experience is difficult.
The 10 measures range from an assessment of physical, psychological, social, spiritual, and functional needs, to having patients’ treatment preferences followed.
“If we could get programs around the country using some of the same measures, then we could develop benchmarks and best practices,” he said. Using the same quality indicators could also help physicians to more easily share information, which could then lead to the development of the next generation of measures.
‘Reasonable Starting Point’
Robert M. Taylor, MD, FAAN, FAAHPM, Associate Professor and a pain and palliative medicine physician at Ohio State University Comprehensive Cancer Center—Arthur G James Cancer Hospital and Richard J Solove Research Institute, called the 10 measures a reasonable starting point for assessing palliative and hospice care--. “It’s a challenge to come up with measurements that matter.”
And while these indicators are a good initial effort, they do have several limitations for measuring palliative care in the oncology setting, noted James T. D'Olimpio, MD, FACP, FAAHPM, Director of Supportive/Palliative Oncology and the Cancer Pain and Symptom Control Service at North Shore University Hospital in New York.
For this consensus project, paper authors evaluated 75 scientifically validated measures and determined which 10 would be the most meaningful to patients and their families for managing their palliative and hospice care needs.
Rotella explained that the team looked for indicators that are actionable, meaning that they can be directly assessed and used to improve quality of care. The indicators are also balanced to include pain and symptom management, health care decision-making, and spiritual and emotional needs, and to reflect the National Consensus Project (NCP) Palliative Care Guidelines domains.
The researchers narrowed the list of 75 measures through a modified Delphi rating process. A technical advisory panel judged the strength of the indicators, while a clinical user panel determined which were most clinically relevant.
Overall, the measures are intended to help palliative care and hospice providers systematically evaluate the effectiveness of their programs and to develop strategies to keep improving practice, ensuring that patients and families get the very best care possible across settings, Rotella said.
The authors evaluated "a huge body of work from the past 30 years and found the measures that make the most sense and have the most meaning in the context of clinical care," said Charles von Gunten, MD, Vice President of Hospice and Palliative Care at OhioHealth. “They synthesized what can be used in routine practice.”
Applications to Oncology
While the study is a good first step toward developing indicators for palliative and hospice care, the general measures may be challenging to apply to oncology, D’Olimpio said. Palliative and hospice care need to be integrated into each area of medicine—approaches for oncology patients may be much different from those for congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) patients.
Patients with cancer have a more rapid trajectory of decline toward the last few months of life than those with CHF or COPD, which tend to be associated with a series of losses of function, he added. Ultimately, each medical specialty will likely have its own comprehensive set of palliative and hospice care indicators.
The set of initial 75 measures included some that were specific to cancer patients--for example, those endorsed by ASCO in its Quality Oncology Practice Initiative, Rotella noted. However, when narrowing the 75 to 10, “we had to choose measures that could be used more broadly. I agree that oncologists might want to have certain measures focused just on cancer patients, and many of those measure exist and are used in quality programs.”
Another limitation, D’Olimpio said, was that early referrals and outpatient palliative care management were not thoroughly addressed in this paper.
The authors did not discuss at length the clinical limitations of the measures, “and we’re not at the point where we can take this information and apply it to outpatient practice,” he said. The lack of outpatient quality metrics is the next big challenge in palliative care.
Rotella said that that many of the 10 measures can be applied to oncology patients, whether they are receiving palliative care in the outpatient setting, concurrently with other treatments that have the potential of cure, or at the end of life. For example, measure #2, screening for pain, shortness of breath, nausea, and constipation can be done across all points of cancer care.
Von Gunten agreed: “The measures are applicable all the way through cancer care,” and distinctions between outpatient palliative and end-of-life hospice care don’t make sense clinically when using these measures for oncology patients, he said. “Everyone who walks into an oncologist’s office has needs in the physical--like pain--spiritual, practical and psychological domains, and that’s what these measures assess.”
And while the indicators will be refined over time, using them immediately could help move cancer care forward, he added: “They match what patients and families tell us they’re looking for in cancer care. Comprehensive cancer care is about the person and his or her family and not just the cancer. These measures help to capture this principle.”
Additionally, said Eduardo Bruera, MD, FAAHPM, Founder, Department Chair, and Professor of Palliative Care and Rehabilitation Medicine at the University of Texas MD Anderson Cancer Center, the indicators help in personalizing palliative care for oncology patients: “We have developed exquisite genomic tools for the personalized care of a tumor. These measures are an attempt at personalizing the care of the patient who brings that tumor to the cancer center."
Bruera said that while it makes sense to document palliative care because it ensures that you are caring for patients according to their wishes, there is still the question of how to operationalize this process: “Do you have a way to score some factors of care as more important than others, or to rate an institution based on the presence of having all or some of these indicators present?”
Some of the measures could be established as threshold items that institutions would need to implement to be considered compliant, he said. “Regrettably, we still do not have a lot of research on many of these items.” However, from a patient and family perspective, discussion, screening and treatment of physical symptoms and addressing psychological needs are the most relevant to managing suffering at the end of life.
Next Steps for Measuring What Matters
The next step of the MWM project is to have providers of palliative and hospice care, no matter what setting, to apply two or three of the existing measures to their quality improvement programs. “We want them to experience trying them out and sharing what’s working and what’s not,” Rotella said.
He recommends that the measures be used just as they were designed. For example, half of the MWM measures come from the PEACE (“Prepare, Embrace, Attend, Communicate, Empower”) hospice and palliative care quality measure set; helpful tools and resources for those measures are available online at www.med.unc.edu/pcare/resources.
Using even just a few indicators can help institutions compare “apples to apples, rather than apples to oranges,” Taylor noted.
Rotella said that another future goal for the MWM group is to develop a way to identify patients who would benefit from palliative or hospice care. Many patients are not referred to this form of care or are referred for only a short amount of time before they die.
Additionally, the researchers found no appropriate measures for the important cultural and social domains of care, indicating another gap that needs to be addressed, he said. “Ultimately, we want to be sure that patients get the care that matters the most and that provides the best quality of life.”
10 Palliative and Hospice Care Measures
1. Palliative care and hospice patients receive a comprehensive assessment (physical, psychological, social, spiritual, and functional) soon after admission;
2. Seriously ill palliative care and hospice patients are screened for pain, shortness of breath, nausea, and constipation during admission;
3. Seriously ill palliative care and hospice patients who screen positive for at least moderate pain receive treatment within 24 hours;
4. Patients with advanced or life-threatening illness are screened for shortness of breath and, if positive to at least a moderate degree, have a plan to manage it;
5. Seriously ill palliative care and hospice patients have a documented discussion regarding emotional needs;
6. Hospice patients have a documented discussion of spiritual concerns or preference not to discuss them;
7. Seriously ill palliative care and hospice patients have documentation of the surrogate decision-maker’s name (such as the person who has health care power of attorney) and contact information, or absence of a surrogate;
8. Seriously ill palliative care and hospice patients have documentation of their preferences for life-sustaining treatments;
9. Vulnerable elders with documented preferences to withhold or withdraw life-sustaining treatments have their preferences followed; and
10. Palliative care and hospice patients or their families are asked about their experience of care using a relevant survey.