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Tuesday, November 25, 2014



As 2014 winds down it is once again time to review what the motley crew of authors, reviewers, and editors thought fit to consign to print in their various esteemed journals this year.


I.  Myeloma Redefined

Perhaps the manuscript with the greatest impact in the years to come may be the one just published by Vincent Rajkumar et al (Lancet Oncology 2014;15:e538-548) in the waning months of the year, which lays out the International Myeloma Working Group (IMWG) consensus to update the disease definition of multiple myeloma to include validated biomarkers in addition to existing requirements of end-organ dysfunction.


The rationale for updating the diagnostic criteria is that currently the definition of myeloma needs a clinical manifestation of serious end-organ damage before the diagnosis can be made. This definition prevents patients from getting early therapy to prevent organ damage from occurring in the first place. However, with the availability of less toxic and more effective treatment options, some of which have data to show a possible improvement with early intervention at a stage when patients are currently diagnosed to have smoldering myeloma, it is felt that a revision of the definition is warranted. Also, advances in laboratory and imaging techniques have meant that an update on diagnostic criteria is due.


The IMWG reached a consensus that if reliable biomarkers could be identified for patients with smoldering myeloma that predicted for 80 percent probability of progression to myeloma within two years, then such patients should be redefined as having multiple myeloma and be offered therapy.


With this goal in mind, the panel after data mining and reviewing published data came up with the following recommendations/modifications:

  1. Diagnostic for M-protein as part of diagnostic criteria is not mandatory; 
  2. Clonal bone marrow plasma cells ≥ 10% should be established by showing kappa/lambda restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen and in case of disparity between the aspirated core biopsy, the highest value should be used; 
  3. Renal insufficiency should be defined as a creatinine clearance < 40 mL/minute or a creatinine of > 2 mg/dL; and 
  4. Bone lesions should be defined as one or more osteolytic lesions seen not only on skeletal survey, but also if detected by CT or CT PET scanning.

In addition, the definition of multiple myeloma has been modified to include one or more of the following biomarkers of malignancy:

  1. Clonal bone marrow plasmacytosis > 60%; 
  2. Involved to uninvolved serum free light chain ratio ≥ 100 (the involved free light chain must be ≥ 100 mg/L); and   
  3. More than one focal lesion on MRI studies with each being at least 5 mm or more in size. 

These diagnostic criteria remove the need for documented end-organ damage as a mandatory requirement for definition of malignancy. 


This redefinition is certainly going to mean that more patients with plasma cell dyscrasia are going to be treated now instead of being observed as smoldering myeloma. Hopefully, this will cut down on the situations where previous recommendations to wait and watch led to the occasional patient ending up with acute renal failure or other adverse consequence, which subsequently led one to regret the decision to have adopted a wait and watch policy. 


It is likely that there will be situations in the immediate future where one may be hesitant to use the expanded definition to treat a totally asymptomatic patient now newly classified as having myeloma based on CT/PET and MRI or serum free light ratio value. However, as these more expanded criteria are adopted as entry criteria into clinical trials it is likely that with the passage of time conformity will ensue.


II. Randomized Phase III Trials with Conventional Therapy

Lotfi Benboubker et al (NEJM 2014:371:906-917) published results of the FIRST trial, which randomly assigned 1,623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression, the same combination for 72 weeks or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks. The primary end-point was comparison of progression-free survival with continuous lenalidomide and dexamethasone versus MPT. 


The median progression-free survival was 25.5 months with continuous lenalidomide and dexamethasone, 20.7 months with 18 cycles of lenalidomide and dexamethasone, and 21.2 months with MPT (p < 0.001 for both comparisons). Overall survival at four years was 59 percent with continuous lenalidomide and dexamethasone, which was statistically significantly improved compared with the 51 percent with MPT, but not when compared with the 56 percent with 18 cycles of lenalidomide and dexamethasone. Grade 3-4 adverse events were somewhat less frequent with lenalidomide and dexamethasone than with MPT (70% versus 78%).


Though this trial is likely to have little practice-changing impact here in the United States, it is hoped that it will lead to the approval of lenalidomide and dexamethasone for front-line therapy, which could be important in other areas of the world like Europe where the use of Revlimid and dexamethasone is still restricted to patients with relapsed and refractory disease. 


Jesus San-Miguel et al (Lancet Oncology 2014;15:1195-1206) published results of the PANORAMA-1 study.  This multicenter randomized double-blind Phase III study of panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed and refractory multiple myeloma randomized patients to receive 21-day cycles of placebo or panobinostat, both in combination with bortezomib and dexamethasone. 


768 patients were enrolled. The median progression-free survival was significantly lower in the panobinostat group (11.99 months) than in the placebo group (8.08 months) (p< 0.0001). Median overall survival was 33.64 months for the panobinostat group and 30.39 months for the placebo group (p = 0.26).


Serious adverse events were recorded in 60 percent of patients in the panobinostat group and 42 percent in the placebo group. Common grade 3/4 laboratory abnormalities included thrombocytopenia (67% in the panobinostat group versus 31% in the placebo group); lymphopenia (53% versus 40%); diarrhea (36% versus 8%); ischemia or fatigue (24% versus 12%); and peripheral neuropathy (18% versus 15%). 


On November 6 the Oncologic Drugs Advisory Committee (ODAC) of the FDA voted 5 to 2 against recommending approval of the drug, as they felt that the benefits of panobinostat as potential treatment for myeloma outweighed its risks. A final FDA decision on the application for approval of panobinostat based on this trial is still pending.


III. Autologous Stem Cell Transplantation for Multiple Myeloma

Antonio Palumbo et al (NEJM 2014;371:895-905) reported on an open-label randomized Phase III study comparing melphalan at a dose of 200 mg/m² plus autologous stem cell transplantation with melphalan, prednisone, and lenalidomide and compared lenalidomide maintenance therapy with no maintenance therapy in patients with newly diagnosed multiple myeloma. 


273 patients 65 years of age of younger, were randomized to high-dose melphalan plus stem cell transplantation on melphalan, prednisone, and lenalidomide consolidation after induction and 251 patients to lenalidomide maintenance therapy or no maintenance therapy. The primary end-point was progression-free survival.


After a median follow up of 51.2 months, both progression-free and overall survival were significantly longer with high-dose melphalan plus stem cell transplantation than with melphalan, prednisone, and lenalidomide--43 months versus 22.4 months (p < 0.001) and four-year overall survival--81.6 percent versus 65.3 percent (p value =0.002). 


Median progression-free survival was significantly longer with lenalidomide maintenance than with no maintenance, 41.9 versus 21.6 months (p < 0.001).  However, three-year overall survival was not significantly prolonged 88 versus 79.2 percent (p = 0.14). 


This trial once again reaffirmed the role of autologous stem cell transplantation for patients with myeloma even in the era of novel drugs. 


Gordon Cook et al (Lancet Oncology 2014;15:874-885) reported on the first randomized open-label Phase III trial to study the role of high-dose chemotherapy with autologous stem cell transplantation in patients with relapse multiple myeloma after a previous autologous stem cell transplant (NCRI myeloma X relapse intensive trial). 


This multicenter trial recruited patients who had needed treatment for first progressive or relapse disease at least 18 months after previous autologous stem cell transplantation from 51 centers across the United Kingdom.  Before randomization patients received bortezomib, doxorubicin, and dexamethasone induction, and eligible patients were randomized 1:1 to either high-dose melphalan 200 mg/m² with salvage ASCT or oral cyclophosphamide (400 mg/m² per week for 12 weeks). 


Between April 2008 and November 2012, a total of 297 patients were registered, of whom 293 received induction therapy; 174 patients were randomized to ASCT or cyclophosphamide. 


After a median follow-up of 31 months, the median time to progression was significantly longer in the salvage ASCT cohort (19 months) than in the cyclophosphamide group (11 months) (p < 0.0001). 


Though the choice of therapy in the control arm could be questioned, this study provides evidence for the efficacy of high-dose melphalan and salvage ASCT in the management of patients with relapsed multiple myeloma eligible for intensive therapy.


IV. ‘Next-gen Duo’

2014 saw additional publications on pomalidomide and carfilzomib for patients with relapsed disease: 


Paul Richardson et al (Blood 2014;123:1461-1469) reported on the results of the MM-002 randomized Phase II study of pomalidomide alone or in combination with low-dose dexamethasone in relapsed of relapsed/refractory multiple myeloma. The primary endpoint was progression-free survival.


A total of 221 patients were randomized with a median follow-up of 14.2 months. The median progression-free survival was 4.2 and 2.7 months (p = 0.003), and overall response rates were 33 and 18 percent (p = 0.013). The median response duration was 8.3 and 10.7 months, and the median overall survival was 16.5 and 13.6 months, respectively. Refractoriness to lenalidomide or the resistance to both lenalidomide and bortezomib did not affect outcomes with pomalidomide and dexamethasone.


Nikoletta Lendvai et al (Blood 2014;124:899-906) reported on a Phase II single-center study of carfilzomib given at an escalated dose of 56 mg/m² with or without low-dose dexamethasone in relapsed multiple myeloma. At time of enrollment, all patients had received prior bortezomib and immunomodulatory drugs with a median of five prior regimens. Of the 42 response-evaluable patients, 55 percent achieved at least a partial response.


Median duration of response and progression-free and overall survival were 11.7, 4.1, and 20.3 months, respectively. Of six patients who responded, progressed, and had dexamethasone added, four achieved at least stable disease. Grade 3/4 adverse events possibly related to carfilzomib included lymphopenia (43%), thrombocytopenia (32%), hypertension (25%), pneumonia (18%), and heart failure (11%). Seven patients (16%) discontinued treatment due to adverse events.


This dose of carfilzomib is being compared head to head to bortezomib in the randomized Phase III ENDEAVOR trial. 


V.  Coming Down the Pike: Ixazomib 

The year saw the publication of several Phase I/II studies of ixazomib, an orally bioavailable small molecule inhibitor of the 20S proteasome. Ixazomib has been shown to have similar selectivity and potency to bortezomib, but a shorter disassociation half-life. Ixazomib has been shown to have preclinical activity and antitumeric activity in xenograft models of myeloma, some of which were bortezomib resistant.


Shaji Kumar et al (Blood 2014;124:1047-1055) reported on a Phase I study of weekly dosing with ixazomib in relapsed and refractory multiple myeloma. The maximum tolerated dose (MTD) was determined to be 2.97 mg/m². Dose-limiting toxicities were grade 3 nausea, vomiting, and diarrhea in two patients and grade 3 skin rash in one patient. Common drug-related adverse events were thrombocytopenia (43%), diarrhea (38%), nausea (38%), fatigue (37%), and vomiting (35%). Peripheral neuropathy was seen in 20 percent of patients, with only one grade 3 event reported. The overall response rates were 18 percent and 27 percent at the MTD.


Richardson et al (Blood 2014;124:1038-1046) reported Phase I study of twice-weekly ixazomib in relapsed/refractory multiple myeloma patients. The MTD was 2 mg/m² with dose-limiting toxicities (grade 3 rash and grade 4 thrombocytopenia). Adverse events included nausea (42%), thrombocytopenia (42%), fatigue (40%), and rash (40%). Grade 1/2 drug-related peripheral neuropathy occurred in 12 percent of patients, and no neuropathy of grade 3 or higher was seen. Fifteen percent of patients achieved a partial response or better. 


Based on these two Phase I studies, it was decided to pursue once-weekly dosing of ixazomib for future development. 


Kumar et al (Lancet Oncology 2014;15:1503-1512) reported the results of an open-label Phase I/II study on the safety and tolerability of ixazomib in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma. The MTD of ixazomib was established at 2.79 mg/m², which was converted to a 4 mg fixed dose based on population pharmacokinetics.


Grade 3 or higher events included skin rash (17%), neutropenia (12%), thrombocytopenia (8%), and peripheral neuropathy (6%). A very good partial response rate or better was seen in 58 percent of patients. 


This three-drug combination has now moved into a pivotal Phase III randomized clinical trial, where the three-drug combination will be compared with lenalidomide and dexamethasone.


VI. Minimal Residual Disease (MRD) Monitoring

Minimal residual disease monitoring is emerging as a difficult topic as we aim for deeper responses in multiple myeloma made possible by the incorporation of immunomodulating drugs and proteasome inhibitors. To date, most of the literature in this arena lately has been based on multi-perimeter flow cytometry to define MRD. 


Joaquin Martinez-Lopez et al (Blood 2014;123:3073-3079) reported on a next generation sequencing-based platform to define the value of MRD. 


A total of 133 multiple myeloma patients in at least very good partial response after front-line therapy were identified and MRD was assessed using IGH-VDJH, IGH-DJH, and IGK assays. The results were contrasted with those of multi-perimeter flow cytometry (MFC) and specific eukaryotic type polymerase chain reaction (ASO-PCR). Concordance between sequencing and MFC and ASO-PCR was 83 percent and 85 percent, respectively.


Patients who were MRD-negative by sequencing had significantly longer time to progression (median 81 versus 31 months; p <0.0001) and overall survival (median not reached versus 81 months; p = 0.02) compared with patients who were MRD-positive. 


In complete response patients, the time to progression remained significantly longer for MRD-negative compared with MRD-positive patients (131 vs. 35 months; p = 0.0009). 


The next generation sequencing-based assay has a sensitivity of 1 in 10-6 and is currently offered as the ClonoSIGHT assay by Sequenta, Inc. 


Going forth, we now have two competing technologies for assessment of minimal residual disease. This adds to the urgency of reaching a consensus around the definition of minimal residual disease. Publications looking at flow cytometry to date have used a variety of assays, from four-color to eight-color assays for the sensitivity of about one cell in 10-4. This assay can be affected by the number of events studied and the threshold used to define MRD positivity. 


VII. Genomics

The genetic heterogeneity of multiple myeloma was confirmed in two high-profile publications using next- generation sequencing technology to sequence large cohorts of patients.


Jens Lohr et al (Cancer Cell 2014;25:91-101) reported on massive barrow sequencing of paired/normal samples from 200 multiple myeloma patients. Frequent mutations in KRAS, NRAS, BRAF, FAM46C, TP53, and DIS3 were observed. Mutations were often present in subclonal populations, and multiple mutations within the same pathway were observed in the same patient. 


Niccolò Bolli et al (Nature Communications 2014;5:2997) used whole exome sequencing, copy number profiling, and cytogenetics to analyze 84 multiple myeloma samples. Most cases were found to have a complex subclonal structure with clusters of subclonal variants including subclonal driver mutations. Serial sampling revealed diverse patterns of clonal evolution including linear evolution, differential clonal response, and branching evolution. There was heterogeneity in the mutational spectrum across samples with few recurrent genes. 


Both of these publications complement earlier reports using next-gen sequencing technologies that have made it difficult to identify “targets” for those of us wishing to give up AK-47s and become snipers. 


These publications are testament to the fact that basic science researchers and clinical trialists continue to successfully chip away at this edifice and hope that those from the dawning age of personalized and precision medicine will help in the future to deliver a fatal blow.

RAVI VIJ, MD, is Associate Professor of Medicine at Washington University School of Medicine in the Section of Stem Cell Transplant and Leukemia, Division of Medical Oncology, in St. Louis, Missouri.

Monday, November 24, 2014

                                                     Robert C. Young, MD

Being Mortal, the latest in the steady stream of illuminating books on medical subjects penned by the remarkable surgeon-author Atul Gawande, addresses the problems of aging and end-of -life care. As someone who is solidly on the right side of life’s bell-shaped curve, this reviewer found Being Mortal enlightening, instructive, and humanizing.


Dr. Gawande begins with the perspective of a young medical student. Medical students come to the field because of their compassion and empathy. What they don’t come with is the knowledge of how to treat and how to cure illness. Their medical education begins a transformation that shifts the physician’s focus to that of treatment and away from the more encompassing concept of aid.


Before concentrating on the central theme of his book, Gawande explores the human desire for independence. In modern societies, this has resulted in a natural evolution toward the separation of families. As he says, “Global economic development has changed opportunities for the young dramatically. Prosperity depends upon escaping the shackles of family expectation to follow their own path.” This is true for both children and parents. Parents want “intimacy at a distance.” This has led to an entirely new model of how contemporary families live their lives.


He then throws the aging process into this equation, showing how, for many, the gradual and inevitable deterioration of function dramatically alters this dynamic when the adults in the family can no longer be independent. Unlike Gawande’s grandfather, who simply aged at home, continuing his role of family patriarch while being cared for by a large and loving family, modern families face a more complex and harder truth: What do we do with Dad?


Gawande then chronicles the development of care centers for aging patients, taking us through the history of poor houses, hospitals, nursing homes, assisted living facilities and retirement communities. Finally he describes some of the really novel new facilities that actually address the elderly’s needs for a life with independence and with meaning.


The examples are both instructive and encouraging. But these contemporary care centers face two major obstacles: Regulations, which place legal constraints on them to insure safety, and the constant intervention from medicine’s desire to fix. In Gawande’s view, “Medical professionals concentrate on repair of health, not sustenance of the soul.”


So what do the elderly actually want in the portion of their life that is physically compromised but when death is not imminent? Gawande says: ”They ask only to be permitted, insofar as possible, to keep shaping the story of their life in the world--to make choices, and sustain connections to others according to their own priorities.”


In the later two chapters—“Letting Go” and “Hard Conversations”—Gawande comes to grips with the central theme of the book. Because being honest about prognosis is so difficult and emotionally charged, and because doctors don’t want to dismantle hope, we continually use terms like “regression” and “response,” which are technically correct but don’t address the fundamental reality of the patient’s illness.


This is unrealistic but understandable. But it is also unfair and unprofessional. In a study in British Medical Journal of 500 terminally ill patients, 63 percent of doctors overestimated survival, and only 17 percent underestimated it. Of note, the better the doctor knew the patient, the more likely the estimate was to be incorrect (Christakis and Lamont: BMJ 2000:320:469-473).    


One of His Most Effective & Endearing Qualities…

One of Gawande’s most effective and endearing qualities is his use of his own shortcomings to illustrate his points. For example, when caring for a patient with thyroid and lung cancer, a partial response to her thyroid cancer led Gawande to suggest that “perhaps experimental therapy could work against both of her cancers”--which he realized was sheer fantasy. He implores us to be honest with patients and with ourselves about the critical distinction between cure and care.


Once that distinction is made and discussed openly, it allows possibilities for a whole new approach to patient care. One can then integrate hospice and/or palliative care with conventional treatments. He quotes what is now a well-known New England Journal of Medicine study on Stage IV lung cancer patients, where half of them received usual care and the other half had usual care plus parallel visits with a palliative care specialist. Those who saw the palliative care specialist, entered hospice earlier, stopped chemotherapy earlier, experienced less suffering and they lived 25 percent longer (Temel et al: NEJM 2010;363:733-742).


Gawande devotes substantial portions of the book to conversations between doctors and patients at the end of life. Here, as he says, words matter. You don’t ask, “What do you want at the end of your life?” You ask, “If time is short, what is most important to you?” These are difficult but critical questions that enable doctors to deliver what the patient desires and not just what is possible or convenient.


Patients or family members often want the doctor to continue until there is nothing more that can be done. But rarely is there nothing more that doctors can do. We must resist the desire to try to fix something when a different sort of care is required.


Gawande is a master at using his own personal observations and experiences and, as noted, often his own failures to illustrate important lessons. He writes beautifully but succinctly. He seamlessly couples scientific information with personal illustrations. This book should be required reading for anyone entering the field of Oncology. Absorbing his message will make them a better oncologist and a more satisfied doctor.


Gawande leaves us with this thought: “The simple view is that medicine exists to fight death, and that is, of course its most basic task. Death is the enemy. But the enemy has superior forces. Eventually it wins. And in a war you cannot win, you do not want a general who fights to the point of annihilation. You don’t want a Custer. You want a Robert E. Lee, someone who knows how to fight for territory that can be won and how to surrender it when it can’t.”




2014, Metropolitan Books, ISBN 0805095152, available in hardcover, paperback, Kindle, and audio editions.

Monday, November 24, 2014

Past studies have linked two mutant proteins, inisocitrate dehydrogenase 1 (IDH1) and IDH2, among the most common genetic differences in patients with intrahepatic cholangiocarcinoma (IHCC), but new research has identified why. In genetically engineered mouse models of adult livers, the expression of those IDH1 and IDH2 mutations impaired liver cell development and liver regeneration, and increased the number of cells, leading to tumor formation, according to the data published earlier this year in Nature (2014:513;110-114).


“iCCA is resistant to standard treatments like chemotherapy and radiation,” study coauthor Josep Maria Llovet, MD,  Director of the Liver Cancer Program, Division of Medicine, Icahn School of Medicine at Mount Sinai, said in a news release. “Understanding the molecular mechanism of the disease is the key to finding a treatment that works.”




Previous research has shown mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity, resulting in alterations in cell differentiation, survival, and extracellular matrix maturation, according to the study. The data from this research showed that in the mouse models, IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2-hydroxyglutarate (2HG) and suppression of the master transcriptional regulator of hepatocyte differentiation, HNF-4α. The mouse models expressing mutant IDH in the adult liver also showed an abnormal response to hepatic injury, characterized by HNF-4α silencing, impaired hepatocyte differentiation, and “markedly” elevated levels of cell proliferation, according to the study.


And the findings showed that mutant IDH worked with the KRAS gene—known to be essential in cancer development—to drive the expansion of liver progenitor cells, development of premalignant biliary lesions, and progression to metastatic IHCC.   


The findings provide new insights about the development of iCCA, which could inform novel treatment options, Llovet added. Phase I trials are currently ongoing for patients with iCCA with specific IDH1/2 mutations.


This study was conducted through partnerships with Massachusetts General Hospital Cancer Center; the Department of Medical Oncology at Dana-Farber Cancer Institute; the Department of Medicine at Harvard Medical School; HCC Translational Research Laboratory of Barcelona-Clínic Liver Cancer Group of the Liver Unit at Institut d'Investigacions Biomèdiques August Pi i Sunyer; Hospital Clínic at University of Barcelona; the Gastrointestinal Surgery and Liver Transplantation Unit of the National Cancer Institute; the Department of Experimental Oncology in Milan, Italy; the Department of Pharmacology, Toxicology and Therapeutics at the University of Kansas Medical Center; the University of Rochester Medical Center; Agios Pharmaceuticals; Institució Catalana de Recerca i Estudis Avançats; and the University of Barcelona.

Monday, November 24, 2014

After identifying in earlier research that patients with prostate cancer had severe gaps in comprehension of basic prostate health terms, a team of researchers developed a video-based tool that they have found improved prostate health literacy. The research is published online ahead of print in the journal Cancer (DOI: 10.1002/cncr.29101).


“[The research] shows that video tools can help patients understand these critical prostate health terms in a meaningful way,” senior author Viraj A. Master, MD, PhD, FACS, Winship urologist and Director of Clinical Research in the Department of Urology at Emory University, said in a news release.



Previous research has shown that both in patients in underserved areas, as well as patients attending specialty urology and radiation oncology clinics (the latter findings being research conducted by Master and his colleagues) misunderstanding of common prostate cancer terms was prevalent and severe, the authors noted in the study. Fewer than 50 percent of the men in the research from Master’s group understood the term “impotence,” 15 percent understood the term “incontinence,” and less than a third understood the term “urinary function” and “bowel habits.”


The researchers developed a video-based educational tool with narrated animations depicting 26 terms that doctors and medical staff routinely use in conversations with patients with prostate cancer. Fifty-six men from two low-income safety net clinics—six having been previously diagnosed with prostate cancer, five of whom had received treatment—viewed  the video tool and completed interviews with the researchers to evaluate their understanding of terms related to prostate cancer both before and after the intervention.


Patients’ comprehension of the terminology significantly improved for the majority of the terms, according to the researchers’ findings. Specifically:

·         Comprehension improved significantly for 13 of the 32 total terms tested—however many of the terms that did not exhibit significant improvements were very well understood even before the video intervention, the study noted;

·         Comprehension of the term “incontinence” improved from 14% understanding the term before the intervention to 50% afterward;

·         Comprehension of the term “urinary control” improved from 55% pre-intervention to 93% post-intervention;

·         Comprehension of “bowels” improved from 14% pre-intervention to 46% post-intervention;

·         Comprehension of “impotence” improved from 58% pre-intervention to 84% post-intervention; and

·         Understanding of the function of the prostate improved from 11% pre-intervention to 30% post-intervention.


This study is one of the first to examine the efficacy of a video-based educational tool with language specifically tailored to low-literacy populations in improving patient comprehension of key medical terminology related to prostate cancer treatment and the associated adverse effects, the study notes.


“The ultimate goal is to give patients a vocabulary toolkit to further enable them to make shared and informed decisions about their treatment options,” Master added.  “Our next goal is to improve the tool further, and study this tool at different centers.”

Sunday, November 23, 2014



A new survey shows discrepancies between how oncologists and nurses perceive their teamwork and collaboration in hospital settings where cancer patients are treated. The results suggest that cancer team members would benefit from programs and training that promote better communication between medical team members, the researchers concluded.


"The results of the study were not surprising, but emphasize the need for structures to facilitate communication and teamwork among inpatient care providers," said the first author, A. Charlotta Weaver, MD, Assistant Professor of Medicine in the Division of Hospital Medicine at Northwestern University Feinberg School of Medicine.


In the article, now online ahead of print in the Journal of Oncology Practice (DOI 10.1200/JOP.2014.001536), she and her colleagues surveyed nurses, residents, hospitalists, and oncologists in oncology units at a large urban teaching hospital over a three-month period, from September to November 2012. Sixty-seven percent (129 people) completed the survey, which asked respondents to rate the quality of collaboration they had experienced with other professionals, using a five-point scale (1 = very low quality; 5 = very high quality). Also rated were potential barriers to collaboration using a four-point scale (1 = not at all a barrier; 4 = a major barrier).


Nurses gave the lowest ratings for the teamwork they had, while residents gave the highest ratings. Ratings of collaboration with nurses were high across all types of professionals, yet ratings of collaboration with physicians varied significantly by professional type, with nurses reporting lower ratings of collaboration with all physician types.


Perceived barriers to collaboration differed by professional type, too. Nurses perceived negative attitudes regarding the importance of communication to be the biggest barrier. Oncologists did not perceive any of the listed options—including not knowing the names of other health care providers, difficulty reaching other providers, and not having physicians and nurses on the same paging and telephone systems—as major barriers to collaboration.


In-Patient Teamwork as Important as Out-Patient

 Asked for her opinion for this article, Patricia Ganz, MD, Distinguished Professor of Health Policy & Management and Medicine at UCLA Fielding School of Public Health and the David Geffen School of Medicine at UCLA and Director of Cancer Prevention & Control Research at UCLA’s Jonsson Comprehensive Cancer Center, said the findings are not all that different from what has also been shown in other inpatient settings.


Still, the study may not give a full picture, though, she said: "It was a nice piece of evidence showing there are misperceptions about communication and teamwork, and some barriers to communication, but this may not be the whole story.


It’s possible that a larger study, including more oncologists--only 15 of the 129 respondents in this study were oncologists, while 89 were nurses--might capture more information.


Nevertheless, she added, "I think it's informative in that the whole thrust of team-based care needs to be as strongly emphasized, or even more so, in in-patient settings as it does in outpatient settings because of the acuity of patients.


"It's good to shine a light on these issues because there's a lot at stake. These are seriously ill patients on an oncology unit and the stakes are high to get it right. Whatever we can do as professionals to ensure nothing falls through the cracks due to communication errors is very important."


Not Typically Included in Medical Education

Weaver noted that training in teamwork is traditionally lacking from formal physician medical education. "Given the results of the study, we have geographically localized our patients by care team, which we think has improved communication, engagement, and efficiency."


Her group is also actively involved the process of creating "interprofessional" rounds to address teamwork, collaboration, and patient safety, she said.


"We expect these interprofessional rounds to help bridge the power differential between nurses and physicians. However, these rounds are geared toward inpatient providers, and do not yet include outpatient physicians [oncologists]. Our next step is to develop robust communication structures that actively involve oncologists. We currently communicate with oncologists, but on an ad hoc basis, and the nurses are not involved in these conversations."


Also asked for her perspective, Bindu Danee, RN, MSN, Unit Director of Hematology/Transplant at UCLA Health System, said, "When physicians invest a lot of time and solicit nurses to come into the room and join them and they ask for their perspective and goals and plan—the next steps moving forward—nurses feel they have a better stake."


On her team at UCLA, the nurses have "a very low threshold" before they go to a provider with a concern about orders, or symptom management, or the patient plan, an approach benefits patients as well as the care team, she said.


Training and regular meetings help keep communication lines open, too, she said, noting that her medical director had organized a retreat earlier this year for all of the faculty physicians, the NP supervisor, and herself, among others.


"We had in-patient and out-patient personnel. We were really trying to articulate where there are inconsistencies in our program so we can deliver effective care to our patients. We’re coming to the table making sure we are all on the same page and understanding where our gaps are collaboratively. This is not just physician-directed. We started it this year. We had the retreat, and then we had a debriefing two months later to see where we are now, looping in issues discussed during the retreat.”




New NCI-ASCO Project Aims to Apply ‘Theoretical, Empirical, and Practical’ Evidence about Teamwork to Oncology Care

The American Society of Clinical Oncology and the National Cancer Institute, in collaboration with one of ASCO’s journals, the Journal of Oncology Practice (JOP), have launched a project to apply the science of team-based health care delivery to oncology clinical care. An article in ASCO’s Quality Care Symposium Daily News notes that the plan is for a working group of writing teams from NCI and ASCO to research and then write a paper for eventual submission to be presented at the next Quality Care Symposium, which will be held in 2016. The resulting feedback and discussion at the meeting will then be incorporated into a revised manuscript for JOP. The full article is available at