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Blood & Cancer

Author: MDedge Hematology & Oncology

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Interview-style hematology/oncology podcast from MDedge Hematology-Oncology. The show is hosted by Dr. David Henry with Pearls from Dr. Ilana Yurkiewicz for clinical hematology and oncology health care professionals. The information in this podcast is provided for informational and educational purposes only.
27 Episodes
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  David Cella, PhD, of Northwestern University in Chicago, joins Blood & Cancer as the guest host for a conversation on patient-reported outcomes and how to apply them in oncology clinical practice with Ethan Basch, MD, of the University of North Carolina, Chapel Hill. In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about invisible illness and what it’s like for a patient to be dying but appear outwardly healthy. Show notes By Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia  Patients understand how they are doing better than clinicians do. Subjective patient outcomes (pain, fatigue, myalgias) are difficult for clinicians to classify and are often discordant with patient reports. In routine practice and clinical trials, the clinician reporting of adverse events/patient symptomatic side effects is inconsistent and incomplete. Physicians may not know about symptoms and side effects of patients undergoing treatment because: Patients are scared their dose will be reduced or discontinued. Patients don’t want to let their doctors down. Patients think feeling ill after chemo is “normal.” Questionnaires produce more accurate reports of patient symptoms than conversations with providers. CTCAE = Common Terminology Criteria for Adverse Events (provider version). PRO-CTCAE = Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events. It is a library of individual items asking patients directly about symptomatic events. It is used in many clinical trials to monitor patient-reported adverse events. Monitoring patient-reported outcomes (PROs) systematically during visits decreases rates of emergency department visits and hospitalizations. Nurses and patient advocates often alert providers to PROs.   Resources: CTCAE PRO-CTCAE Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) consortium    For more MDedge Podcasts go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc
James C. Reynolds, MD, of the University of Pennsylvania, Philadelphia, joins Blood & Cancer host David H. Henry, MD, also of the University of Pennsylvania, to discuss the ins and outs of constipation among cancer patients: how to recognize it, how to treat it, and why you need to ask about it. Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University talks about those tough phone calls. You can interact with the show on Twitter: @DavidHenryMd @IlanaYurkiewicz @MDedgeHemOnc Show notes By Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia  Stool dysmotility is defined by a both objective imaging and the Bristol stool scale. Narcotics, mechanical issues (anastomoses), nausea, lack of exercise, and low-liquid or low-fiber diet contribute to constipation. There is a placebo effect of up to 40% for drugs given for constipation. Reglan (metoclopramide) in low doses, used sporadically, is relatively safe. However, it has been associated with Parkinsonian-type movement disorders and depression. Gastric emptying tests (and stomach function) are influenced by stress, mood, nausea, side effects, and hormones. They are not efficacious to evaluate gastric motility in the inpatient setting. Anal pain and fecal incontinence can occur during acute therapy (including radiation proctitis). It is important for clinicians to ask patients about constipation as it may be paradoxical and manifest as diarrhea. Fecal incontinence and sphincter dysfunction following therapy is multifactorial. Flat plate, proctosigmoidoscopy, and anal manometry can give a detailed description of anal function and compliance. It is important for clinicians to ask patients about constipation and fecal incontinence. Further reading: Managing constipation in adults with cancer (J Adv Pract Oncol. 2017 Mar;8[2]:149-61). Bristol Stool Chart   For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc
In this bonus edition, MDedge Postcasts voice Nick Andrews brings an interview from our sister show, the Postcall Podcast with Ilana Yurkiewicz, MD.  You can learn more about the Postcall Podcast by clicking here. Ilana Yurkiewicz, MD, is a hem/onc fellow at Stanford. She writes the Hard Questions Column for MDedge Hematology/Oncology and writes/records/produces the Clinical Correlation segment of Blood & Cancer, the official podcast of MDedge Hematology/Oncology.   Dr. Yurkiewicz's 's articles: Doctor will you please lie to me? Should doctors disclose primary results?   A complete list of Dr. Yurkiewicz's column, Hard Questions is available here, and you can check out Blood & Cancer here. Links from the interview: Ted Chiang Story of Your Life Exhalation Arrival  
Cancer-related fatigue

Cancer-related fatigue

2019-05-3000:33:15

  David Cella, PhD, and Lisa Wu, PhD, both of Northwestern University in Chicago, discuss fatigue and sleep disturbance related to cancer – its prevalence and possible treatments -- in this episode of Blood & Cancer.   In Clinical Correlation (29:45), Ilana Yurkiewicz, MD, of Stanford (Calif.) University, shares a case that highlights the resilience that patients show in the face of cancer, and asks: Can a positive attitude improve outcomes?   Show notes By Hitomi Hosoya, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia  Cancer-related fatigue is prevalent in cancer patients and cancer survivors. Sleep disturbance also is prevalent in this population and can be related to fatigue. In breast cancer patients, for instance, fatigue during treatment can be as high as 80%. Even after 7-9 years of treatment, more than 50% of breast cancer patients reported sleep disturbances, according to one study. Cancer-related fatigue is different from usual daily fatigue; it is more severe, more distressing, and not relieved by rest. Cancer-related fatigue and sleep disturbance are thought to be related to pro-inflammatory cytokines, endocrine dysfunction, and possibly to circadian rhythm. Cancer-related fatigue should be evaluated from treatment regimen perspectives, metabolic perspectives, or other underlying medical problems. If the above conditions are ruled out, psychosocial therapy (exercise, cognitive behavioral therapy) should be considered. Recently, light therapy using broad-spectrum bright light to correct circadian rhythm has been studied. The gold standard treatment for sleep issues in cancer is cognitive behavioral therapy for insomnia.  
Hazard ratio? P value?

Hazard ratio? P value?

2019-05-2300:27:05

Episode 17: David L. Streiner, PhD, of McMaster University, Hamilton, Ont., and the University of Toronto, joins Blood & Cancer host David Henry, MD, of Pennsylvania Hospital, Philadelphia, to talk hazard ratios and P values as they examine the clinical relevance of findings from a phase 3 trial.   In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about how to balance family versus patient preferences.   Show notes By Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia  A phase 3 trial is a randomized, controlled trial testing a new intervention against placebo or treatment as usual. Randomization maximizes the chances that the groups are equivalent but does not guarantee it. With randomization, you also are accounting for variables that are unknown and/or cannot be controlled for.  Phase 3 trial discussed by Dr. Henry and Dr. Streiner: AURELIA trial: Bevacizumab plus chemotherapy vs. chemotherapy alone for platinum-resistant ovarian cancer. Inclusion criteria: Ovarian cancer that has progressed on a platinum-based therapy. Randomization: 361 patients randomized 1:1 to receive bevacizumab plus chemotherapy versus chemotherapy alone. Primary endpoint: Progression-free survival (PFS). Main outcome: PFS had a hazard ratio 0.48 (95% confidence interval, 0.38-0.60). A hazard ratio of 0.48 means that patients in the experimental group had half the risk of experiencing a bad outcome (progression) than patients in the comparison group did. The hazard ratio includes a confidence interval (CI) at the end of the value because it is an estimate. The CI represents where the true hazard will fall 95% of the time. If 1.0 is included in the range, then the result is not statistically significant, and the events could have happened by chance. An ad hoc analysis is conducted at the end of the study. It is not a prespecified statistical idea. It is thought provoking and hypothesis generating but not conclusive. Reference: AURELIA trial: J Clin Oncol. 2014;32(13):1302-8.
Howard “Skip” Burris, MD, the chief medical officer of Sarah Cannon Cancer Institute in Nashville, Tenn., joins the podcast as the guest host for a discussion of PD1 and PDL1 in the treatment of lung cancer. Dr. Burris interviews Melissa Johnson, MD, the associate director of lung cancer research at Sarah Cannon. Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University dives into the financial realities of cancer care.   Show notes By Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia   Programmed death ligand (PDL1) is a protein that is expressed by the tumor to escape detection by the immune system. T-cells produce PD1; when PD1 binds to PDL1, cancer can remain undetected. By blocking the binding of PD1 to PDL1, the immune system is able to recognize a tumor as foreign. Tumors with a high mutational burden typically have the most robust response to PD1 and PDL1 therapy. Treatment of patients with lung cancer with high mutational burden or high PDL1 score greater than 50% could likely be treated with monotherapy PDL1. Treatment of patients with lung cancer with low mutational burden or low PDL1 score consists of chemotherapy plus immunotherapy. In the field of lung cancer, tumor mutation burden is lower because lung cancer is typically driven by a single oncogene (EGFR, ALK, etc.). About 20% of lung cancer patients have a long and durable toxicity-free durable course when treated with PD1 and PDL1 inhibitors. Immunotherapy takes longer than chemotherapy to manifest a positive or beneficial change in patients. Monotherapy with PD1 and PDL1 inhibitors can cause autoimmune toxicity which may be recurrent. Upfront testing of PD1 and PDL1 in patients in clinics could lead to the early identification of patients who may benefit from immunotherapy.   Additional reading: ESMO biomarker fact sheet for immunotherapy. J Immunother Cancer. 2018 Jan 23;6(1):8. doi: 10.1186/s40425-018-0316-z. You can contact the show at podcasts@mdedge.com and you can interact with us on Twitter at @MDedgeHemOnc To subscribe to this and other MDedge podcasts, go to www.mdedge.com/podcasts.    
Episode 15   Host David Henry, MD, welcomes David J. Kuter, MD, of Harvard and Massachusetts General Hospital to talk about idiopathic thrombocytopenic purpura. He answers questions like: what are the causes? When do you treat? In Clinical Correlation this week, Ilana Yurkiewicz, MD, explores pregnant patients.    Show notes By Hitomi Hosoya, MD, PhD, resident in the department of internal medicine, Pennsylvania Hospital of the University of Pennsylvania Health System, Philadelphia   Causes of idiopathic thrombocytopenic purpura : Secondary causes include chronic lymphocytic leukemia, lymphoma, and autoimmune conditions and account for 30%-50% of ITP. Idiopathic ITP is associated with pregnancy, post-viral infection, and vaccination and accounts for 50%-75% of ITP.   Pathophysiology: Antibodies attach to platelets, which are cleared by the liver or spleen (increased consumption). T cells or B cells attack bone marrow (reduced production).   When to treat: Major bleeding. Platelet count less than 20 x 109/L.   Initial treatment: Corticosteroids (dexamethasone or prednisone). These drugs should not be used for more than 6 weeks. Intravenous immunoglobulin is appropriate with major bleeding or when a patient requires immediate surgery.   Subsequent treatment: Platelet count less than 20 x 109/L during steroid taper. Rituximab (50%-70% response rate). Thrombopoietin receptor agonist (90% response rate); eltrombopag (oral) or romiplostim (subcutaneous).
  Howard “Skip” Burris, MD, the chief medical officer at Sarah Cannon Cancer Institute in Nashville, Tenn., joins the podcast as a guest host for a discussion on chimeric antigen receptor (CAR) T-cell therapy with Helen Heslop, MD, of Baylor College of Medicine, Houston. Dr. Heslop, who has been a leader in CAR T-cell therapy research, recently received a Lifetime Achievement Award from the American Society for Blood and Marrow Transplantation.   Contact the show: podcasts@mdedge.com or follow us on Twitter at @MDedgeHemOnc.   EP 14 Show Notes: By Emily Bryer, DO, is a resident in the department of internal medicine, University of Pennsylvania, Philadelphia. Checkpoint inhibition is the main immunotherapy used in oncology; this allows endogenous T cells to react against targeted antigens on tumor cells. CAR T-cell therapy: Autologous product (T cells collected from recipient) are expanded ex vivo, genetically modified with chimeric antigen receptor, and then are reinfused into the patient. While antibody treatment can be used for multiple patients, CAR T-cell therapy is currently patient specific and autologous. Current candidates for CAR-T therapy: Acute lymphoblastic leukemia (ALL) in children and young adults. CD19 diffuse large B-cell lymphoma. There is a 40% response rate plateau at 2 years with CAR-T therapy, with lymphoma response rates lower than those of pediatric ALL. CAR T-cell therapies likely will continue to be done on an inpatient basis because of significant side effects: Cytokine release syndrome and neurotoxicity. Future directions for CAR-T therapy: Continue ongoing studies in mantle cell lymphoma and chronic lymphocytic leukemia. Investigate the potential to replace autologous transplant with CAR T-cell therapy. Maintain and enhance activity of CAR by promoting immune response with multiple antigens, such as CD19 + CD22. Reduce complications associated with CAR-T therapy. Study CAR-T therapy earlier in the disease process. Image credit: Caron A. Jacobson and Jerome Ritz/Wikimedia Commons/Public Domain References: Image: Leukemia & Lymphoma Society June CH. Chimeric antigen receptor therapy. N Engl J Med. 2018 Jul 5;379(1):64-73.  
ASCO GI 2019

ASCO GI 2019

2019-04-2500:21:33

Daniel G. Haller, MD, of the University of Pennsylvania, Philadelphia, joins Blood & Cancer host David H. Henry, MD, also of the University of Pennsylvania, to review the top research presented at ASCO GI 2019. Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University shares the story of a patient who had no questions about the details of his treatment but needed answers about the “big picture.”   Show Notes By Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia   Phase 2 trial of pembrolizumab (Keytruda), chemotherapy, and trastuzumab (Herceptin) in gastric cancer: Patients had previously untreated HER2 IHC+ or FISH+ tumors. Patients received pembrolizumab, trastuzumab/CAPOX (capecitabine and oxaliplatin) or FOLFOX (folinic acid, fluorouracil, and oxaliplatin). Patients all had a 100% response rate, prompting an ongoing phase 3 trial (KEYNOTE-811).   Third-line therapy for gastric cancer – TAGS, a phase 3 trial: supportive care vs. trifluridine plus tipiracil (Lonsurf): Gastrectomy did not affect outcome, safety, or pharmacokinetics. Neutropenia, a major toxicity, is manageable. Trifluridine and tipiracil are now a National Comprehensive Cancer Network Level 1 guideline for third-line therapy in patients with gastric cancer.   Neoadjuvant chemotherapy in pancreatic cancer: Compared neoadjuvant gemcitabine and S1 (NAC-GS) with upfront surgery for patients with pancreatic ductal adenocarcinoma and planned resection. Saw a significant survival benefit (37 months) of NAC-GS over upfront surgery (26 months).   Circulating tumor cells (CTC) in colorectal cancer: Studied patients with planned colonoscopies for colorectal screening. Took blood at the time of the procedure. Identified an absolute correlation with CTC and an increased disease burden in patients with colon cancer.   Additional reading:   Lancet Oncol. 2018 Nov;19(11):1437-48.  Oncotarget. 2018 May 11;9(36):24561-71.
Statistics 101 for the oncologist   Episode 12: David L. Streiner, PhD, of McMaster University and the University of Toronto, joins Blood & Cancer host David Henry, MD, of Pennsylvania Hospital, Philadelphia, to break down the basic statistics knowledge that doctors need – but may not have – to understand and contextualize research findings. In Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University talks about reclaiming the term “sorry.” Dr. Yurkiewicz writes a regular column for Hematology News, which you can find by clicking here.   Show notes By Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia Statistics provide objective evidence for whether we are seeing a true effect of a medicine or intervention, or if that outcome occurs because of chance alone. Clinical trials include a selective population (usually from tertiary care hospitals) and tend to involve the most severe cases. When interpreting data reported from a trial, it is essential to ask how similar the population in the trial is to the population you see in your clinical practice.   Drug Approval Stages Phase 1: Assess drug efficacy and toxicity Phase 2: Identify correct dose; assess pharmacodynamics and pharmacokinetics Phase 3: Randomized, controlled trial necessary for confirming drug effectiveness and providing a comparison to current standard of care treatments How to design a trial Ensure that the surrogate endpoint is highly correlated to the outcome of interest     Additional reading by Dr. Streiner: Health Measurement Scales: A practical guide to their development and use (5th edition) PDQ Epidemiology (3rd edition)
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