Journal of Clinical Oncology (JCO) Podcast

This JCO Podcast provides observations and commentary on the JCO article "Therapy-Related Cardiac Risk in Childhood Cancer Survivors: An Analysis of the Childhood Cancer Survivor Study" by Bates et al. My name is Joseph Carver, and I am the Chief of Staff at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, Pennsylvania. My specialty is cardio-oncology. It is universally accepted that therapeutic radiotherapy and/or anthracycline-based chemotherapy have a significant impact on the heart resulting in cardiac morbidity and mortality. High risk groups are now defined on the basis of a doxorubicin-equivalent anthracycline dose of ≥250 mg/m2 and/or total radiation dose of ≥30 Gy when the heart is in the treatment field. It is universally accepted that therapeutic radiotherapy and/or anthracycline-based chemotherapy have a significant impact on the heart resulting in cardiac morbidity and mortality. High risk groups are now defined on the basis of a doxorubicin-equivalent anthracycline dose of ≥250 mg/m2 and/or total radiation dose of ≥30 Gy when the heart is in the treatment field. Total dose delivered does not reflect specific cardiac exposure. This has led to report the mean heart dose that is the percent cardiac volume within the radiation fields. For most treated patients, discovery of anthracycline cumulative dosing is easily abstracted and straightforward. For modern therapeutic radiation, however, historical mean heart dose or other cardiac dosimetric parameters have not been traditionally reported and may be more difficult to obtain. This has led to a lack of consensus about the cardiovascular risk when the total dose is In the article that accompanies this podcast, Bates et al1 enhance our understanding of the association between cardiac volume exposure to different radiation therapy doses and rates of serious cardiac conditions among long term survivors of pediatric cancer and reaffirms the association of cumulative anthracycline dose and subsequent risk for cardiomyopathy. With data from the Childhood Cancer Survivorship Study, they determined the rates of self-reported grade 3-5 cardiac conditions as defined by Common Terminology Criteria for Adverse Events v4.03 in 24,214 >5-year survivors who were treated for a variety of cancers at a median age of 7 years. Evaluation occurred at a median follow-up of 20.3 years with a median attained age of 27.5 years. Late cardiac risk was compared to 5,046 untreated siblings. For each survivor, radiation fields were reconstructed on age-specific phantoms to calculate estimated mean heart dose and the percent of heart volume receiving at least 5 Gy (low dose) and 20 Gy (higher dose). Doxorubicin-equivalent doses were similarly abstracted. Toxicity parameters were any cardiac disease, coronary artery disease and heart failure. They found a cumulative incidence of cardiac disease, 30 years from diagnosis of 4.8% (95% CI 4.3-5.2). There was a dose relationship between mean heart dose and all parameters. Both low-moderate doses (5-19.9 Gy) to a large volume of the heart (>50%) and higher doses (≥20Gy) to small cardiac volumes (0.1-29.9%) were associated with an increased risk of cardiac disease. Heart failure drove the risk of high doses to small volumes while CAD drove the risk of low doses to large volumes. Similarly, they reconfirm the relationship between cumulative anthracycline dosing and any cardiac disease with an increased risk for those treated at a younger age (≤ 13 years of age). An increased relative risk for any cardiac disease was also present with any anthracycline exposure (0.1- This study shows that low-moderate dose RT to a large volume of the heart and higher-dose RT to a small volume of the heart increase the risk of late cardiac disease. It also reconfirms the association of cumulative anthracycline dosing and cardiac risk, especially in patients who were treated at What are the take-home points of this study? In spite of modern techniques to deliver therapeutic radiation and avoid the heart, a "safe" cardiac dose has not been well-defined. Two large retrospective, phantom-based studies have shown an increased risk of coronary heart disease of 7.4% per 1 Gy MHD in breast cancer and lymphoma patients. These studies have not only alerted radiation oncologists to the potential risk of even "low" radiation doses to the heart but have also driven them to push RT planning algorithms to optimize one parameter, mean heart dose. The problem with this single metric is that two treatment plans with vastly different dose maps can have the same mean heart dose: 1) low dose spread out to a large volume such as in an intensity modulated radiotherapy plan; or 2) high dose to a small volume (that may include the left anterior coronary artery) with almost no dose to the rest of the heart such as in breast tangents or a proton therapy plan. Even with current image-driven treatment planning algorithms that prioritize a low mean heart dos

This JCO Podcast provides observations and commentary on the JCO article Durable Tumor Regression and Overall Survival in Patients with Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy by Paul Nghiem, MD, PhD et al. My name is Reed Drews, and I am a member of the Cutaneous Oncology Program at Beth Israel Deaconess Medical Center in Boston, MA. My oncologic specialty is non-melanoma skin cancers. Merkel cell carcinoma is a rare, aggressive neuroendocrine skin malignancy with high propensity for local recurrence and regional lymph node and systemic metastases. Its incidence rises exponentially with aging and is 10-fold higher in chronically immunosuppressed patients. When Merkel cell carcinoma is advanced and/or unresectable, historical 5-year overall survival rates are low, from 14 to 27%. Cytotoxic chemotherapies, like platinum plus etoposide used in other high-grade neuroendocrine malignancies, have not yielded durable response rates. The cutaneous cell (or cells) of origin in Merkel cell carcinoma remains controversial. Nevertheless, scientists have identified 2 pathogenetic pathways leading to Merkel cell carcinoma. In 80% of cases, clonal integration of a polyomavirus leads to Merkel cell polyoma virus-positive Merkel cell carcinoma. In the other 20% of cases, ultraviolet light-induced DNA damage leads to polyoma virus-negative Merkel cell carcinoma. Polyoma virus-negative Merkel cell tumors display predominant cytosine to thymine transitions, a signature of DNA damage from UV light, and they have a 100-fold greater mutational burden than virus-positive Merkel cell cancers. For both subtypes, loss of immune surveillance, as with aging or chronic immunosuppression, contributes to Merkel cell carcinoma development, with diminished non-self-antigen recognition of UV-induced neo-antigens in virus-negative tumors and viral oncoproteins in Merkel cell polyoma virus-positive tumors. Given these factors, investigators have recently studied whether immune checkpoint inhibitors might hold promise for managing advanced Merkel cell carcinoma. To date, 3 antibody inhibitors of the programmed cell death-1 pathway (abbreviated PD-1), including anti-PD-ligand-1 avelumab, anti-PD-1 nivolumab and anti-PD-1 pembrolizumab, have been tested in patients with chemotherapy-refractory and/or treatment naïve Merkel cell carcinoma. The 62% objective response rate from avelumab in treatment-naïve Merkel cell carcinoma was nearly twice that observed in chemotherapy-refractory disease. In 2017 avelumab became the first immune checkpoint inhibitor approved by the FDA for advanced Merkel cell carcinoma. Nivolumab yielded similar results, as did pembrolizumab according to a 2016 report from Nghiem and colleagues of a multicenter, phase 2, non-controlled study with 26 patients. As reported in this JCO publication, Nghiem and colleagues have now increased their cohort to 50 patients through the multicenter expanded phase 2, Cancer Immunotherapy Trials Network-09/Keynote-017 trial. They administered pembrolizumab 2 mg/kg intravenously every 3 weeks for up to 2 years. Median follow-up time was 14.9 months, with a range from 0.4 to 36.4 months. This represents the longest follow-up to date of any anti-PD-1 pathway inhibitor for first-line treatment of advanced Merkel cell carcinoma. The 50-patient cohort included 43 patients with (stage IV) distant metastatic disease and 7 with stage IIIB recurrent locoregional disease not amenable to definitive surgery or radiation therapy. All patients had normal organ and bone marrow function and an Eastern Cooperative Oncology Group performance status of 0 to 1. Key exclusion criteria were previous systemic therapy for unresectable Merkel cell carcinoma, immunodeficiency or systemic immunosuppressive therapy, active autoimmune disease, concurrent second cancer, and active central nervous system metastases. The median age of enrolled patients was 70.5 years, with 80% age 65 or older. 64% of patients had Merkel cell polyoma virus-positive tumors. For previous management of their primary Merkel cell carcinoma, 42 patients had had surgery, and 35 patients had had radiation treatment. While no patient had previously received systemic therapy for advanced Merkel cell carcinoma, 3 patients had received adjuvant chemotherapy greater than 6 months prior to study enrollment. Patients received a median of 10.5 doses of pembrolizumab – range 1 to 35 doses—and the median treatment duration was 6.6 months – range 1 day to 23.6 months. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors, version 1.1. Responses were generally rapid and durable with 2.8 months as the median time to response – range 1.5 to 9.7 months. The objective response rate to pembrolizumab was 56%, with complete and partial responses of 24% and 32%, respectively; 10% had stable disease; and 32% had progressive disease. At time of data analysis, 20 of 28 responses were on-going,

This JCO Podcast provides observations and commentary on the JCO article Gonadal Functioning and Perceptions of Infertility Risk among Adult Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study by Lehmann et al. My name is Leslie Schover, and I am retired from the faculty of MD Anderson Cancer Center and currently Founder of Will2Love.com a digital health company in Houston, Texas. My oncologic specialty is cancer-related problems with reproductive health, i.e. sexual function and fertility. Damaged fertility is unfortunately quite common in survivors of childhood cancer. A variety of chemotherapy drugs, as well as surgery affecting parts of the reproductive system or radiation therapy focused on the pelvis or brain, can damage spermatogenesis, reduce ovarian reserve, or interfere with uterine function. In general, males are more at risk than females for cancer-related infertility. Some survivors do not undergo puberty without hormonal support. For others, fertility may recover over time. However, many young women who have menstrual cycles in their teens or twenties are at risk for premature ovarian failure, leaving a narrowed window of time to become pregnant. Men do not know whether they have normal sperm counts, motility, or form unless they have had a recent semen analysis. People diagnosed with cancer before puberty may never have been counseled about fertility. Even survivors treated as teens or young adults typically do not know their fertility status unless they have consulted an expert in reproductive endocrinology or andrology. Surveys of young survivors suggest that the majority want to have children, particularly those who are childless. A number of studies have documented markers of infertility or reduced rates of offspring in survivors of cancer, but little has been known about their perceptions of their fertility status. In the paper that accompanies this podcast, Lehmann and colleagues present novel data about the risk perceptions for infertility compared to indicators of actual gonadal function in over a thousand long-term survivors of childhood cancer participating in the St. Jude Lifetime Cohort. None of the participants already had children or a previous pregnancy. The mean age of the sample was 29, with a mean follow-up of 22 years since cancer diagnosis. 85% were white and 32% had at least a 4-year college degree. 52% were married or in a relationship. Only 10% of men and 16% of women had been tested for infertility outside of the study. Gonadal function was measured by a semen analysis in 56% of men and by a panel of hormones in the others. In women under age 40, status as fertile vs. sub-fertile was assigned by chart review based on menstruation, diagnosed premature ovarian failure, or hormonal assays. Perception of risk for infertility was based on one question with a Likert scale of 5 response options, comparing one's own fertility to that of peers who had not had cancer. Answers were dichotomized into two categories: perceived at risk for fertility or perceived normal fertility. 62% did perceive themselves as at risk for infertility. Those who perceived their fertility as damaged had characteristics that would indicate potentially more knowledge about cancer and fertility, including being older, white, in a relationship, having a college education, a history of gonadotoxic treatment, having tried unsuccessfully to conceive, or having sexual dysfunction. In actuality, 24% of women and 56% of men had evidence of impaired gonadal function. However, actual medical status had no significant relationship to perceptions of risk. The most common discordance was that the survivor believed him or herself to have damaged fertility when medical tests appeared normal. This included 20% of men and 44% of women. Inaccurate perceptions were more common in respondents who were white, had more education, had more gonadotoxic cancer therapy, were very concerned about their fertility, and had sexual dysfunction. In contrast only 16% of men and 5% of women overestimated their fertility potential. In terms of clinical implications, it is common for young survivors to overestimate their risk of infertility. Such beliefs can diminish quality of life. A young person who feels like "damaged goods" may be distressed about the future and perhaps reluctant to date or to enter into a committed relationship. For women, risky drinking was another factor associated with overestimating fertility risk. Risky drinking, and the notion that pregnancy is impossible, may contribute to findings in other studies of excess rates of unintended pregnancies and failure to use consistent contraception in young adult female survivors. Those unaware of their damaged fertility maybe in for distress and disappointment if they try for a pregnancy. Clearly a greater effort should be made to inform young survivors about risks to fertility and to refer them for testing at intervals of fertility status. It ap

This JCO podcast provides observations and commentaries on the JCO article entitled "Indeterminate Pulmonary Nodules at diagnosis in Rhabdomyosarcoma: Are they clinically significant?" A report from the European Pediatric Soft Tissue Sarcoma Study Group by Bas Vaarwerk, MD et al. My name is Alberto Pappo and I am the head of the division of solid tumors at St Jude Children's Research Hospital in Memphis, TN. My oncology specialty is pediatric oncology. In this report, Bas Vaarwerk, and investigators from the European Pediatric Soft Tissue Sarcoma Study Group evaluated the significance of indeterminate pulmonary nodules at diagnosis in children with rhabdomyosarcoma defined as the presence of less than 5 pulmonary nodules measuring less than 5mm or 1 pulmonary nodule that measured between 5 and 9 millimeters. This analysis included 316 patients who were enrolled on the EpSSG RMS 2005 study for non-metastatic rhabdomyosarcoma from September 2005 through December 2013 and for whom chest computed tomography scans were obtained at diagnosis and were available for review. Treatment in the EpSSG RMS 2005 study was stratified according to risk group, pathology, post-surgical stage, site, nodal involvement, size and age. All patients received multi agent chemotherapy with ifosfamide (except for low risk patients), vincristine and actinomycin D (IVA chemotherapy). High risk patients were randomized to IVA or IVA with doxorubicin and after 9 courses if in complete remission, were eligible for a second randomization between end of therapy and additional maintenance therapy with 6 courses of vinorelbine and cyclophosphamide Local control was determined by risk group, tumor site, age and response to therapy and radiotherapy was given at week 13 in doses ranging from 36 to 51.4Gy. All chest computed tomography scans were reviewed by the local radiologist at the treating center. Data was obtained and recorded using case report forms. All computed tomography scans were performed with minimum slice thickness of 3 to 5 mm. The median age at diagnosis for the 316 eligible patients was 5.4 years and the median follow up time for the cohort was 75 months. There were 249 (78%) patients who did not have a pulmonary nodule and 67 (21%) who had at least one indeterminate pulmonary nodule. Patient and treatment characteristics were similar between the 2 groups; 80% of the patients presented with Group III unresectable disease, 54% had high risk disease, and 71% had favorable histology tumors such as embryonal histology tumors. Twenty four percent of patients received maintenance chemotherapy and 77% were treated with local radiotherapy A total of 100 nodules were identified in the 67 patients. Nodules ranged in size from 1 to 8 mm. 69% of the patients presented with one pulmonary nodule, 92% of the patients had nodules that measured less than 5 mm 85% of the nodules were unilateral. The 5-year event-free survival for patients with indeterminate pulmonary nodules was 77% and for those without nodules 73.2%. These differences were not statistically significant with a p value of 0.68. The 5-year overall survival rates were 82% for patients with indeterminate pulmonary nodules and 80.8% for those without nodules. The differences between these 2 groups were not statistically significant with a p value of 0.76. There were no significant differences in outcomes based on the number or size of the nodules. Similarly, there were no differences in clinical outcome based on histology, fusion status, age and type of chemotherapy received. Lung metastases developed in 3% of patients with indeterminate pulmonary nodules and in 1.6% of patients without nodules a value that was not statistically significant. The authors conclude that the presence of indeterminate pulmonary nodules in newly diagnosed children with rhabdomyosarcoma as defined in this report does not adversely affect the outcome of these patients and these children can be adequately treated with non-metastatic risk-based clinical protocols. This report highlights the challenges of assigning risk and therapy based on the presence of a limited number of small pulmonary nodules in children with newly diagnosed rhabdomyosarcoma when they are detected using newer imaging modalities such as thin cut computed tomography of the chest. The authors have successfully demonstrated in this retrospective study that newly diagnosed patients with rhabdomyosarcoma who present with indeterminate oligometastatic disease to the lung which in this study was defined as the presence of 4 or fewer pulmonary nodules measuring less than 5 mm or one nodule that measures 5 to 9 mm, have similar outcomes to patients who present without pulmonary nodules. More importantly, these patients can be treated with less intense trials that may include the use whole lung irradiation which is known to significantly increase the risk of breast cancer in childhood cancer survivors. The authors have implemented a standardized de

This JCO Podcast provides observations and commentary on the JCO article "Tamoxifen pharmacogenetics and metabolism: Results from the prospective CYPTAM study" by Sanchez-Spitman et al. My name is Vered Stearns, and I am a Professor of Oncology and Co-Director of the Breast and Ovarian Cancer Program at the Kimmel Cancer Center at Johns Hopkins in Baltimore, Maryland. My oncologic specialty is medical oncology. In the paper that accompanies this podcast, the authors report results of a prospective clinical study designated CYPTAM, which was designed to correlate endoxifen serum concentrations and outcomes of women prescribed adjuvant tamoxifen. The investigators enrolled 667 women with breast cancer who were initiating tamoxifen or who have been on tamoxifen for fewer than 12 months. The investigators obtained blood samples for CYP2D6 genotyping using the Amplichip CYP450 Test, and measured steady state concentrations of endoxifen with a high-performance liquid chromatography-tandem mass spectrometry. Co-primary endpoints included association of recurrence-free survival with endoxifen concentrations and with CYP2D6 genotypes. The patients were censored at the time of tamoxifen-discontinuation in case of a transition to an aromatase inhibitor. Several additional endpoints included disease-free survival, complete relapse-free survival, complete disease-free survival and overall survival. The statistical analysis plan was designed as a gate-keeper analysis for the co-primary objectives. Only if an association was found with a p-value below 0.05, were the remaining objectives considered. The authors were not able to demonstrate an association between endoxifen concentrations and recurrence-free survival on tamoxifen. They also were not able to demonstrate an association either when exploring endoxifen concentrations in quartiles or when considering other thresholds. Likewise, there was no association between CYP2D6 genotypes and recurrence-free survival. Almost two decades ago, researchers recognized that the absence or inhibition of the CYP2D6 enzyme is associated with very low concentrations of endoxifen, a potent and abundant anti-estrogen metabolite of tamoxifen. Whether low concentrations of endoxifen predict an inferior survival outcome has not been definitively determined. Multiple retrospective and small prospective studies evaluated CYP2D6 genotypes and survival outcomes and have provided mixed evidence. Clinicians have, therefore, wondered whether CYP2D6 genotype testing or endoxifen monitoring will assist in treatment recommendations. The CYPTAM investigators attempted to prospectively correlate endoxifen serum concentrations and outcomes for women taking tamoxifen. The CYPTAM study is associated with several limitations, and, therefore, it does not provide a definitive answer to the controversy. For example, women were enrolled in the study either before starting tamoxifen or up to 12 months after initiation of the drug. This strategy could have led to incomplete baseline data and to the exclusion of individuals with early recurrences. In addition, about two-thirds of study participants transitioned to aromatase inhibitors following a short course of tamoxifen. The sequential administration of tamoxifen and aromatase inhibitors is superior to tamoxifen alone. Some of the patients who transitioned to aromatase inhibitors could have suffered a recurrence had they have stayed on tamoxifen alone. Furthermore, the authors did not have information regarding concomitant CYP2D6 inhibitor use. CYP2D6 inhibitors are commonly co-administered with tamoxifen and can contribute to misclassification of the CYP2D6 phenotype. The challenge moving forward is that single agent adjuvant tamoxifen is rarely used. Most postmenopausal women with hormone receptor-positive breast cancer are recommended an aromatase inhibitor instead of, or in sequence with, tamoxifen. Premenopausal women with high risk hormone receptor-positive tumors are recommended ovarian suppression with tamoxifen or an aromatase inhibitor. Women prescribed tamoxifen alone are usually at extremely low risk of recurrence, and a prospective study in this group of women will require a large number of participants to demonstrate differences between phenotypes. Given current practice, it may not be feasible to fully determine the role of endoxifen concentrations and CYP2D6 genotypes as predictors of tamoxifen efficacy. Retrospective analyses that used samples obtained through large prospective studies, such as the Arimidex, Tamoxifen, Alone or in Combination and the Breast International Group 1-98, failed to demonstrate an association between CYP2D6 phenotypes and survival outcomes. Taken together, the data at present are insufficient to recommend CYP2D6 testing or analysis of metabolic profile in women for whom tamoxifen is considered. Indeed, clinical guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network do

This JCO Podcast provides observations and commentary on the JCO article "Impact of Surveillance Imaging Modality on Survival After Recurrence in Patients with Favorable Histology Wilms Tumor: A Report from the Children's Oncology Group" by Mullen et al. My name is Dr. Meredith Irwin, and I am an oncologist and Professor at the Hospital for Sick Children and University of Toronto in Toronto, Canada. My oncologic specialty is pediatric solid tumors. Wilms tumor is the most common pediatric kidney tumor. With current therapies, the 5-year overall survival for newly diagnosed patients is 90%. For the 15% who relapse, most commonly in the lung or abdomen, the cure rates still often exceed 50%. The likelihood for cure is based on a number of risk factors, including histology, stage and previous therapies. Thus, similar to many pediatric cancer patients, those with Wilms undergo surveillance imaging during and following completion of upfront therapy in order to potentially discover recurrences sooner with the hope that early identification of lower disease burden will translate to higher salvage rates. However, to date, several small studies have failed to demonstrate that early detection of recurrence by surveillance imaging is associated with better prognosis for pediatric cancers including medulloblastoma, lymphoma and neuroblastoma. Moreover, with increasing awareness of the potential risks from imaging-associated ionizing radiation exposures and associated financial costs, there is significant interest in generating evidence to determine optimal surveillance strategies and limit cumulative exposures. To address these issues for Wilms tumor, the study by Mullen et al was designed to determine whether, compared to relapses detected by surveillance with chest x-ray and ultrasound, those detected with cross-sectional CT imaging were associated with improved survival rates. To do this, four authors retrospectively reviewed flowsheets and imaging reports for patients who recurred on the 5th National Wilms Tumor Study (NWTS-5) between 1995 and 2002 to determine whether their relapses were identified by signs/symptoms or scheduled surveillance imaging. If by imaging, they recorded the modality- CT, ultrasound and/or chest x-ray. The study cohort included the 281 patients who recurred following initial diagnosis of favorable histology unilateral Wilms. All patients underwent imaging at specified time intervals, but the modalities varied. The 5-year overall survival for this cohort post-relapse was 67%, which is similar to other studies. 48% of recurrences were detected with routine surveillance by chest x-ray or ultrasound, 25% by surveillance with CT, and 25% presented with symptoms between scheduled imaging, most commonly pain or abdominal mass. Certain characteristics differed among these groups. The CT-detected patients were more likely to be stage 4, and in the symptoms group, more relapses were extrapulmonary and occurred post-treatment. The authors asked whether the specific method of detection of relapse impacted prognosis. Although recurrences detected by symptoms were associated with an inferior 5-year survival of 55%, versus 76% for the imaging-detected group, there were no differences in survival for patients based on the imaging modality used for detection at any point during or following therapy. There was also no significant advantage to CT over u/s or x-ray for abdominal and chest relapses, respectively. Although a higher number of foci detected at recurrence and larger relapse size correlated with inferior outcomes, analyses failed to find a significant advantage for CT use in the subgroups of lung-only relapses or advanced-stage patients. The authors also examined financial burden and radiation exposures. To determine the economic impact, the authors predicted costs based on US Medicaid/Medicare reimbursement rates. For patients with stage III disease, more than 200 imaging studies (with estimated costs between $20,000 and $45,000) were required to identify one relapse. For stage IV, between 158 and 190 studies costing more than $15,000 were needed. Estimated radiation exposures from these surveillance protocols varied between 9.4 and 83 mSv, depending on the total number of CTs. Although it is difficult to quantify how cumulative radiation doses may impact future cancer risks, expert groups have estimated that there is a 1 in 1,000 increased risk of future cancer deaths for every 10mSv exposure at age 10, and these risks are higher for patients exposed at younger ages. Other potential negative consequences of surveillance imaging not examined by these authors include the associated psychological stress for families, which is termed "scanxiety," and possible adverse neurological effects of anesthetic agents for young children. The significance of this report is that it is the first study to compare the utility and cost of different imaging methods for the identification of Wilms tumor recurrences. I

This JCO Podcast provides observations and commentary on the JCO article, "Impact of Baseline Steroids on Efficacy of PD-(L)1 Blockade in Patients With NSCLC" by Arbour et al. My name is Deepa Rangachari, and I am an Assistant Professor of Medicine at the Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts, USA. My oncologic specialty is thoracic cancers. For decades, the management of advanced non-small-cell lung cancer has relied on use of cytotoxic chemotherapies with a median overall survival not exceeding one year. As this longstanding therapeutic approach has been limited by modest efficacy, finite durability, and significant treatment-associated toxicity, evolving better tailored, more effective, and less toxic care strategies has long been an unmet need. Beginning in the mid-2000s with the identification of actionable oncogenic driver mutations in the epidermal growth factor receptor, the landscape for personalized care in advanced non-small-cell lung cancer has been permanently transformed. Today, the evidence-based standard of care for upfront therapeutic stratification in all patients with advanced stage disease relies on mandatory genomic and immunologic profiling, with emphasis on identifying subsets of patients who will experience better outcomes and less toxicity through the use of disease-specific therapies. It is in this landscape that the use of immune checkpoint inhibitors has flourished for patients with lung cancer. Since 2015, 3 different immune checkpoint inhibitors—Nivolumab, Pembrolizumab, and Atezolizumab—have all gained approval from regulatory agencies for management of patients with advanced stage non-small-cell lung cancer on the basis of phase III studies showing improved overall survival with more durable responses, less toxicity, and better quality of life with checkpoint inhibitors when compared with chemotherapy.[1-5] This benefit has been seen in both previously treated patients regardless of tumor programmed death ligand 1 (hereafter referred to simply as "PD-L1") status and in upfront management of patients with high tumor PD-L1, defined by a tumor proportion score >/= 50%. Combined chemoimmunotherapy for patients with non-squamous disease regardless of tumor PD-L1 status is also now a vetted approach.[6] With widespread use of immune checkpoint inhibitors now the standard of care for many patients with this disease, important pragmatic concerns regarding concurrent use of checkpoint inhibitors and corticosteroids have emerged. Specifically, as many patients will present with refractory anorexia, nausea, fatigue, pain, brain metastases, and/or dyspnea for which corticosteroids are often used as helpful adjuncts to cancer-directed therapy for symptomatic palliation, what if any are the consequences of concurrent use? How do we balance these symptomatic issues against the need for delivering effective cancer therapy? Due to concerns for the immunomodulatory effects of corticosteroids on T-cell activity and function, nearly all clinical trials leading to approval of these agents have excluded patients requiring the equivalent of Prednisone 10-20mg daily or more prior to initiation of checkpoint inhibitor therapy. In contrast, there is now an emerging body of evidence suggesting the safety of subsequent corticosteroid use, once checkpoint inhibitors have been started, for management of immune-related adverse events , without jeopardizing any previously achieved therapeutic benefit.[7, 8] But what about those patients being newly initiated on checkpoint inhibitors who have been previously maintained on palliative corticosteroids? In the article that accompanies this podcast, Arbour and colleagues present important insights into this question. This is a retrospective analysis of 640 patients with advanced non-small-cell lung cancer with immunotherapy-naïve disease treated with checkpoint inhibitors at the Memorial Sloan Kettering and Goustave Roussy Cancer Centers from 2011-2017. Data regarding steroid dose, mode of administration, and indications for use were collected along with efficacy of checkpoint inhibitors as assessed by an independent team of radiologists using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. At the time of checkpoint inhibitor initiation, 90/640 (14%) of patients were receiving the equivalent of Prednisone 10mg/day or more; an additional 17 patients (or 3% of the total study population) were receiving The most common indications for steroid use reflect those seen in routine clinical practice: dyspnea/respiratory symptoms (33%), fatigue (21%), and brain metastases (19%). Clinicopathologic characteristics between the steroid and no steroid groups were generally well balanced. As might be expected, however, there were more patients with poor performance status and history of brain metastases in the steroid group. Amongst the Sloan Kettering cohort, steroid use of >/= 10mg/day was associated wit

Read the related article "First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2–Positive and Hormone Receptor–Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial" by Rimawi et al on JCO.org. Transcript: This JCO Podcast provides observations and commentary on the JCO article 'First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in HER2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial' by Rimawi et al. My name is Sara Tolaney and I am Assistant Professor of Medicine at Harvard Medical School and Senior Physician at Dana-Farber Cancer Institute in Boston, Massachusetts. My oncologic specialty is breast cancer. Since the seminal report of the benefits of adding trastuzumab to chemotherapy, we have seen an improvement in survival for patients with metastatic HER2-positive disease from approximately two years to now almost 5 years. This dramatic improvement in outcomes can be attributed to the use of continued anti-HER2 therapy beyond progression as well as the introduction of new HER2-directed therapies. The largest improvement in survival has come from the addition of pertuzumab to a taxane and trastuzumab as seen within the CLEOPATRA study. This resulted in an impressive almost 16-month improvement in overall survival and established this regimen as a first line standard in the metastatic setting. While chemotherapy and dual anti-HER2 therapy is the current first line treatment approach, we are now left with the question about how best to optimize therapies available to us, and whether or not there are other first line approaches we could consider in order to lessen toxicity. One potential alternative approach for patients with hormone-receptor positive, HER2-positive disease could be to consider the use of hormonal therapy. There has been some concern that hormone-receptor positive tumors that are also HER2-positive may be relatively resistant to hormonal therapy. One reason for this may be that activation of HER2 can result in direct phosphorylation and activation of the estrogen receptor. This potential HER2 and ER bidirectional cross-talk has provided justification for combinatorial therapy targeting both of these pathways concurrently. There have been at least three trials that have examined the addition of single agent HER2-targeted therapy to hormonal therapy. The TAnDEM trial randomized a little over 200 patients with hormone-receptor positive, HER2-positive breast cancer to either anastrozole alone or in combination with trastuzumab as first line therapy and found a 2.4-month improvement in progression free survival, but no difference in overall survival. The dual EGFR/HER2 tyrosine kinase inhibitor, lapatinib, has also been investigated in combination with hormonal therapy. A phase 3 study in the first line metastatic setting found that adding lapatinib to letrozole improved progression free survival from 3.0 to 8.2 months, and another trial that looked at adding lapatinib to fulvestrant found an improvement in progression free survival from 3.3 to 5.9 months. These three studies suggest that single agent HER2-targeted therapy adds modestly to endocrine therapy, and there has therefore been interest to see if dual HER2 targeted therapy added to hormonal therapy would result in a more significant improvement in outcomes. Since data from CLEOPATRA had suggested that the addition of pertuzumab and trastuzumab to chemotherapy led to significant improvements in disease-free and overall-survival, In the article that accompanies this podcast, Rimawi and colleagues were interested in exploring if adding pertuzumab to trastuzumab and hormonal therapy could offer additional benefits. The PERTAIN study was a multicenter phase 2 trial that enrolled 258 patients with locally-advanced or metastatic hormone-receptor positive, HER2-positive breast cancer who had not previously received systemic therapy in the advanced disease setting, outside of endocrine therapy, and randomized them to receive trastuzumab plus an aromatase inhibitor or trastuzumab plus pertuzumab and an aromatase inhibitor. Patients were allowed to receive induction chemotherapy with a taxane for 18-24 weeks in combination with trastuzumab (with or without pertuzumab) at the treating investigator's discretion; this was decided prior to randomization and patients were stratified by whether or not they had received induction chemotherapy. The trial demonstrated an improvement in progression free survival from 15.8 months to 18.89 months with the addition of pertuzumab to an aromatase inhibitor and trastuzumab, meeting its primary endpoint. This improvement in progression free survival was not associated with a significant improvement in objective response rate (63.3 vs 55.7%). It is important to note that 57% of patie

Read the related article "Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group" on JCO.org This JCO podcast provides observations and commentary on the JCO article "addition of vincristine, irinotecan to vincristine, dactinomycin and cyclophosphamide does not improve outcome for intermediate risk rhabdomyosarcoma a report from the Children's Oncology Group by Hawkins, et al." My name is Alberto Pappo and I am a pediatric oncologist and Head of the Division of Solid Tumors at St Jude Children's Research Hospital in Memphis, Tennessee. Investigators of the Children's Oncology Group (COG) developed a prospective randomized study to improve the outcome of patients with intermediate risk rhabdomyosarcoma by comparing the addition of the doublet vincristine and irinotecan (which will be called the irinotecan arm) to standard vincristine actinomycin D and cyclophosphamide (which will be called the VAC arm) to VAC chemotherapy only. Intermediate risk disease comprises the largest subgroup of patients with rhabdomyosarcoma and comprises patients with embryonal histology who present with tumors that are non-metastatic and unresected and arise in unfavorable sites as well as patients who present with non-metastatic alveolar histology tumors. The authors nicely review prior failed strategies that were aimed at increasing the outcome of this group of patients including dose intensification of active agents as well as the addition of novel agents such as ifosfamide, etoposide and topotecan. 1-3 Irinotecan is a prodrug that is converted to its active metabolite SN38 and inhibits topoisomerase I. In a front-line trial for patients with metastatic rhabdomyosarcoma demonstrated a high level of activity with a 70% early response rate and an 8% disease progression rate.4 Based strong preclinical and clinical data, this agent was incorporated into an upfront randomized trial for rhabdomyosarcoma testing the benefit of adding vincristine and irinotecan to standard VAC in intermediate risk rhabdomyosarcoma. Eligibility criteria included patients with embryonal rhabdomyosarcoma who had stage II and III clinical Group 3 disease and any alveolar rhabdomyosarcoma without evidence of distant metastases. During the first 12 weeks the two treatments were identical in duration of schedule with the exception of the substitution of irinotecan for dactinomycin and cyclophosphamide at week 4 and for cyclophosphamide at week 7 and 10 in the irinotecan arm. During the next 30 weeks irinotecan replaced actinomycin D and cyclophosphamide at weeks 16, 19, 25, 31 and 37 in irinotecan arm. Patients were evaluated for response at week 15, 30 and at the end of therapy. Radiation therapy unlike the prior COG D9803 trial started early at week 4 instead of 12 and the dose was determined by the clinical group and histology with doses ranging to 36 Gy for those with clinical group I and II to 50.4Gy for those with Group III disease. The study was designed with an 80% power to detect an overall increase in the long term event-free survival from 65% with VAC chemotherapy to 76% with the doublet VAC VI with a sample size of 486 patients. Between December 2006 and December 2012 there were 481 patients enrolled on the study of whom 33 were ineligible. Of the remaining 448 eligible patients 222 were randomized to VAC and 226 were randomized to the irinotecan arm. The patient's characteristics were similar between both arms and to other COG trials. There was a slight predominance of males, 61% of patients were between 1 and 10 years of age and 71% were Caucasian. Embryonal rhabdomyosarcoma was the predominant histology seen in 53% of the patients and 86% had clinical Group III disease. The most common primary site was parameningeal followed by bladder prostate, extremity and retroperitoneum. With a median followup for surviving patients of 4.8 years the estimated 4 year event-free survival was 63% for the VAC arm and 59% for the irinotecan arm. The estimated 4 year overall survival rates was 73% for the VAC arm and 72% for the irinotecan arm. There were no differences in radiographic response among clinical Group III patients as assessed by institutional report by week 15 and no evidence of differences in outcome by treatment arm in the histologic subgroup analysis. When compared to the previous trial D9083 which had slightly different eligibility criteria, there were no differences in event and overall survival for patients with alveolar rhabdomyosarcoma. However, patients with embryonal tumors had an inferior 4 year event-free survival in this trial when compared to patients in D9803 although the 4 year overall survival rates were similar. The vast majority of treatment failures were due to tumor progression or recurrence. The 4 year local failure rate was 22.4%, the 4 year regional lymph node failure rate was 5.7% a

Intensifying therapy in children with pediatric B-ALL and IKZF1 deletions leads to improved survival. Read the related article "Intensifying Treatment of Childhood B-Lymphoblastic Leukemia With IKZF1 Deletion Reduces Relapse and Improves Overall Survival: Results of Malaysia-Singapore ALL 2010 Study" on JCO.org

Discussion of a recent study that evaluated prospectively psychosocial well being measures in breast cancer patients before and after receipt of CPM. Read the related article "Prospective Study of Psychosocial Outcomes of Having Contralateral Prophylactic Mastectomy Among Women With Nonhereditary Breast Cancer" on JCO.org

This podcast discusses the important risks and potential benefits of PD-1 immune checkpoint blockade in patients with thymic epithelial neoplasms. Read the related article "Pembrolizumab for Patients With Refractory or Relapsed Thymic Epithelial Tumor: An Open-Label Phase II Trial" on JCO.org

GRAALL-2005 study shows no overall benefit for cyclophosphamide intensification in older adults with ALL, despite a general improvement in outcomes for the younger adults. Read the associated article by Huguet et al on JCO.org.

Highlighting the importance of BCMA-CAR T therapy for patients with relapsed refractory multiple myeloma and discusses future avenues of clinical investigation. Read the related article "T Cells Genetically Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma" on JCO.org

This podcast includes commentary upon a large case control series that examined the incidence of cardiac injury in association with radiation dose to distinct segments of the left ventricle and coronary arteries. Read the associated article by Taylor et al on JCO.org.

This is an evaluation of PCI in stage III Non-Small-Cell Lung Cancer. While the incidence of symptomatic brain metastases is reduced, neurological toxicity is increased and no effect on survival is demonstrated. This trial reconfirms that routine administration of PCI is not a current standard of care. Read the associated article by De Ruysscher et al on JCO.org. This JCO Podcast provides observations and commentary on the JCO article 'Prophylactic Cranial Irradiation (PCI) Versus Observation in Radically Treated Stage III Non-Small-Cell Lung Cancer (NSCLC): A Randomized Phase III NVALT-11/ DLCRG-02 Study' by De Ruysscher et al. My name is Everett Vokes, and I am the Chairman and Professor of Medicine at the University of Chicago in Chicago, United States of America. My oncologic specialty is head and neck and lung cancer. De Ruysscher et al present a randomized trial evaluating the role of prophylactic cranial irradiation, referred to as PCI in this podcast, in patients with stage III non-small-cell lung cancer treated with curative intent. In doing so they have addressed an important issue. Brain metastases are a frequent site of treatment failure and can occur in isolation from additional system disease. It has been postulated that PCI could prolong survival and disease-free survival. In localized small-cell lung cancer, PCI has already been shown to decrease the incidence of brain metastases by about 50% with an impact on long-term survival. However, it is well established that PCI can lead to neurocognitive decline associated with reduced quality of life. Specifically, the authors initially staged patients with a contrast enhanced brain CT or MRI and randomized patients to observation or PCI after concurrent or sequential chemoradiotherapy with or without surgery. Patients were randomized 1:1; PCI was designated to start at a maximum of 6 weeks after the last chemoradiotherapy and could be given as 36 Gy in 18 fractions, 30 Gy in 12 fractions or 30 Gy in 10 fractions. Patients were then monitored for disease progression including symptomatic brain metastases within 24 months from the time of randomization as primary endpoint. Quality of life measurements were performed as well. Key symptoms were defined as signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures and focal neurological symptoms. MRI or CT was triggered by such symptoms. The initial goal was to randomize 300 patients. However, accrual was slow and was decreased to 175 randomized patients overall. Between 2009 and 2012, 195 patients were registered, 175 were randomized, 87 to PCI and 88 to observation. The proportion of patients developing symptomatic brain metastases two years after therapy was 7% in the PCI group and 27% in the control group. This compares to a historical average of approximately 30%. PCI thus did decrease the cumulative incidences of symptomatic brain metastases. However; neurological adverse events were also increased. In particular, grade I-II memory impairment and cognitive disturbance were significantly increased in the PCI arm. Non-neurologically events such as alopecia, fatigue and headache were also significantly more frequent in the PCI group. When evaluating patient reported adverse events, headache was reported to occur significantly more frequently in the PCI arm. Of interest, neurological side effects tended to increase over time after PCI whereas non-neurological adverse events were highest during PCI and decreased over time. Overall survival at median follow-up of 51 months was not improved, with a hazard ratio of 0.9. PCI did significantly increase time to develop brain metastases, and the median progression-free survival was slightly longer at 12.3 versus 11.5 months in the PCI group, but again this was not statistically significant.. Overall, this study does demonstrate that PCI can significantly reduce the incidence of symptomatic brain metastases in patients with stage III non-small cell lung cancer. However, this comes at the cost of increased neurological adverse events even though most of these were mild in nature. Furthermore, an impact on overall survival was not demonstrated. It could be argued that this study was somewhat small and that a larger study could have shown a more pronounced effect, especially on progression-free survival, which did show a trend favoring PCI. On the other hand, symptomatic brain metastases nowadays can be treated at the time of recurrence with SBRT and other modern radiotherapy techniques. In addition, the recent durvalumab trial (PACIFIC) demonstrating that consolidation durvalumab can increase progression-free survival also demonstrated a reduction in brain metastases in durvalumab treated patients, suggesting that improved systemic therapy may emerge as a better approach to tackling the clinical problem of brain metastases in stage III NSCLC. So is PCI a recommended standard of care for patients with s

The public perception of medical marijuana has outpaced medical knowledge. Oncologists encounter an increasing number of patient questions and interest regarding its use. This study highlights the beliefs, attitudes and knowledge of medical oncologists regarding the therapeutic use of marijuana. View the related article Medical Oncologists' Beliefs, Practices, and Knowledge Regarding Marijuana Used Therapeutically: A Nationally Representative Survey Study by Braun et al on JCO.org. This JCO Podcast provides observations and commentary on the JCO article ''Medical Oncologists' Beliefs, Practices and Knowledge Regarding Marijuana Used Therapeutically: A Nationally-Representative Survey Study' by Braun and colleagues. My name is Kimberson Tanco, and I am an Assistant Professor at the University of Texas MD Anderson Cancer Center in Houston, Texas. I am a Palliative Medicine physician. Medical marijuana is one of the fastest growing medical issues nationwide, so much so it is now legal under certain conditions in more than half of the country, with additional limited indications in certain "non-legal" states for pediatric refractory epileptic conditions.1 Most of the current trials are directed towards non-cancer conditions. In contrast, in the article that accompanies this podcast, Braun and colleagues highlight a variety of key issues that face oncology practitioners regarding cannabis and its potential uses and toxicities. As healthcare professionals, it is inevitable that we will be asked by our patients and/or their caregivers about the use of medical marijuana, either in a legalized or a non-legalized state. This study does a good job of recording clinician beliefs and practices from different regions of the nation. It also points out a very important fact that the interest and curiosities about the use of medical marijuana far outpaces our knowledge base as demonstrated in their results. It was very interesting to know that up to 80% of oncologists conducted discussions and 46% recommended medical marijuana for clinical use as compared to only 30% feeling sufficiently knowledgeable enough to make informed recommendations. This is quite a change from 2010, when they cited that only 20% of family practitioner respondents in Colorado would recommend medical marijuana and The authors highlighted key points from the study including the need for expedited clinical trials exploring potential medicinal effect of marijuana in oncology, the need for educational programs about medical marijuana and policies to incentivize the training of clinicians on this issue. In the next few minutes, I would like to discuss these points. Their first point about the need for clinical trials is certainly a key step into understanding the pharmacology and effects of cannabis, which would help improve educational programs and open up federal, state and institutional policies. However, there are a variety of challenges faced in conducting medical marijuana research.2 In spite of changes in state policy and increasing prevalence of cannabis use, cannabis is still not legalized by the federal government and remains a Schedule I substance. Furthermore, an investigator must navigate through the National Institute on Drug Abuse or NIDA, Food and Drug Administration, Drug Enforcement Administration, state departments, state boards, institutional review boards, and funding sources among others. Additionally, supply of cannabis for research purposes is only available through NIDA and is sourced from the University of Mississippi, which has been the sole cultivator since 1968. An important point is that federal supplies of cannabis may also have been harvested earlier and stored in freezer, and may have lower potencies than those sold in state-regulated markets. Hence, investigator results may have to be taken with caution as they relate to appropriate dosing of cannabis products, particularly when they will be taken from state dispensaries. Additionally, there are drug delivery challenges in inhalation, vaporization or ingestion as well as what the author perfectly described as "entourage effects" in where the effect may be different after administering the whole plant vs. isolated cannabinoids. On the other hand, as a benefit of conducting more standardized trials, we can also compare through head-to-head trials the benefits and toxicities against currently available oral cannabinoids such as dronabinol and nabilone. The study also demonstrated that oncologists believed that medical marijuana can be beneficial for certain symptoms like anorexia, nausea, and anxiety. Standardized trials would allow us to discover and outline indications, dosages, mode of delivery and more for these symptoms that plague cancer patients. The second key point is about improving educational programs and is reflected by the results of the study showing only 30% of oncologists feel that they have sufficient knowledge regarding cannabis. In my personal experience,

This commentary summarizes findings from a study of racial disparities in medical financial hardship, identifies gaps in the current evidence base, and discusses health policy considerations for to reducing the risk of financial hardship. Read the related article "Financial Impact of Breast Cancer in Black Versus White Women" on JCO.org

This podcast discusses a phase II trial evaluating the combination of everolimus and fulvestrant compared to fulvestrant alone in pretreated hormone receptor-positive metastatic breast cancer in terms of context within the current hormone treatment environment and toxicity management. Read the related article Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102" on JCO.org

This podcast discusses a CCSS study of very late infection-related mortality in asplenic adult survivors childhood cancer, with risk increasing precipitously after age 40. Read the related article "Late Infection-Related Mortality in Asplenic Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study" on JCO.org

This podcast describes the extended follow-up of the large International phase II CheckMate 205 study of single-agent nivolumab for patients with relapsed/refractory classical Hodgkin lymphoma after failure from autologous stem cell transplant. Read the related article on JCO.org.

This podcast provides comment on the accompanying JCO article "ENGAGE: Evaluation of a streamlined oncologist-led BRCA mutation testing and counseling model for patients with ovarian cancer" by Nicoletta Colombo, et al and evaluates the need for new delivery models for genetic testing for oncology patients. Related Article: Evaluation of a Streamlined Oncologist-Led BRCA Mutation Testing and Counseling Model for Patients With Ovarian Cancer

This commentary examines whether patient-reported outcomes were substantially different in men given chemohormonal therapy versus hormone therapy in the CHAARTED randomized controlled trial. Related Article: Quality of Life During Treatment With Chemohormonal Therapy: Analysis of E3805 Chemohormonal Androgen Ablation Randomized Trial in Prostate Cancer

This podcast reflects upon a recent retrospective study of breast cancer patients with local regional recurrence, and whether imaging is needed for all such patients. Read the related article on JCO.org.

This podcast discusses whether the primary outcomes and study design for the reported trial were properly pre-specified and pre-registered prior to accruing participants. Related Article: Improving Breast Cancer Surgical Treatment Decision Making: The iCanDecide Randomized Clinical Trial

This podcast reviews the aims, methodology, and results of a population-level study that investigates the value of specialized pediatric palliative care services for children with cancer at the end of life, as well as discussing practical ways in which individuals and institutions can immediately apply study findings towards improvement of clinical care, education, and research initiatives. Related Article: Predictors of Specialized Pediatric Palliative Care Involvement and Impact on Patterns of End-of-Life Care in Children With Cancer

This podcast reviews the current evidence for using radiofrequency ablation or stereotactic body radiotherapy as primary treatment for nonsurgical management of early stage hepatocellular carcinoma. Related Article: Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Localized Hepatocellular Carcinoma in Nonsurgically Managed Patients: Analysis of the National Cancer Database

This podcast addresses the clinical implications of the high cost of the 21-gene assay in women with ER-positive, node-negative breast cancer. Related Article: Population-Based Study to Determine the Health System Costs of Using the 21-Gene Assay

Though opioid abuse is clearly an issue for cancer patients post-surgery, many other potential factors were not accounted for and should be included in a more in-depth study that goes beyond database analysis. Related Arcticle: New Persistent Opioid Use Among Patients With Cancer After Curative-Intent Surgery

The paper examines the cost-effectiveness of schedules of bone-modifying agents in patients with breast cancer and skeletal metastases and supports the 3-month administration of the generic zoledronic acid in terms of cost and efficacy. Read the accompanying article on JCO.org.

In this randomized trial, momelotinib was non-inferior to ruxolitinib for spleen response but was less effective in controlling symptoms. Related Article: SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor–Naïve Patients With Myelofibrosis

A Danish population based study of adults with acute myeloid leukemia is described, and the potential significance of educational level as a predictor of receipt of allogeneic transplant and overall survival is explored. Read the associated article on JCO.org.

With a large database analysis, the authors found an increase in hospice use among older patients with AML at the end of life, but this increase was largely driven by late enrollment. Read the associated article by Wang et al on JCO.org.

T-cell therapies targeting viral diseases have evolved from a patient-specific therapy, targeting a single virus, and requiring multiple months of specialized manufacturing, to readily-available cell banks capable of targeting multiple viruses for many individuals. Read the associated article by Tzannou et al on JCO.org.

This podcast examines the growing evidence to support the link between risk factors for cardiovascular disease and cancer. Related Article: Guideline-Based Statin Eligibility, Cancer Events, and Noncardiovascular Mortality in the Framingham Heart Study

Normalization of PET-CT is a strong predictor for progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM) Related Article: Prospective Evaluation of Magnetic Resonance Imaging and [18F]Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography at Diagnosis and Before Maintenance Therapy in Symptomatic Patients With Multiple Myeloma Included in the IFM/DFCI 2009 Trial: Results of the IMAJEM Study

Randomization to different methotrexate and steroid treatment strategies was not related to neuropsychological outcome in children treated for B-ALL, but age and insurance status were significant predictors. Read the associated article "Neurocognitive Functioning of Children Treated for High-Risk B-Acute Lymphoblastic Leukemia (HRALL) Randomized to Capizzi (CMTX) Versus High- Dose Methotrexate (HDMTX): A Report From the Children's Oncology Group (COG)" on JCO.org.

This podcast summarizes the study finding and discuss the clinical and policy implication of an article to appear in JCO that examined the impact of low-income subsidy on the utilization, adherence, and costs of oral immunomodulatory drugs among elderly myeloma patients. Read the article Subsidies for Oral Chemotherapy and Use of Immunomodulatory Drugs Among Medicare Beneficiaries with Myeloma by Olszewski et al.

In a unique approach to subsequent malignancy research, Teepen and colleagues report on subsequent solid cancer risk associated with chemotherapy exposure among survivors of childhood cancer, and emphasize the need for greater future collaborative survivorship research efforts. Related Article: Long-Term Risk of Subsequent Malignant Neoplasms After Treatment of Childhood Cancer in the DCOG LATER Study Cohort: Role of Chemotherapy

The SWORD study is one of the first randomized controlled trials targeting fear of cancer recurrence (FCR) and results support the efficacy of cognitive behavior therapy for the treatment of FCR, a prevalent and distressing concern among a significant proportion of cancer survivors. Related Article: Efficacy of Blended Cognitive Behavior Therapy for High Fear of Recurrence in Breast, Prostate and Colorectal Cancer Survivors; The SWORD- study, A Randomized Controlled Trial by van de Wal et al.

This podcast discusses the role of consolidation stem cell transplantation in patients with double-hit lymphoma who achieve a complete response to front-line therapy and also focuses on the benefit of intensive versus standard therapy for this disease. Related Article: Outcomes of Patients With Double-Hit Lymphoma Who Achieve First Complete Remission

This podcast summarizes and discusses the findings from a study by Guy and colleagues about the economic impact of chronic conditions in cancer survivors in the United States. Related Article: Economic Burden of Chronic Conditions Among Survivors of Cancer in the United States

This randomized controlled trial shows that Treatment Summary Survivorship Plans increase physician recommendation of needed care among breast cancer survivors but may not significantly impact patient adherence. Related Article: Randomized Controlled Trial of Survivorship Care Plans Among Low-Income, Predominantly Latina Breast Cancer Survivors

This podcast discusses the association between smoking and risk of death from pancreatic cancer.

Patients who had autologous reconstruction had higher satisfaction with breasts and well-being than patients who had implant-based reconstruction, but both groups experienced substantial physical morbidity.

This podcast describes the results and implications of the article published by Landier et al, describing the relationship between 6-MP ingestion habits and outcomes, as well as adherence, among children with acute lymphoblastic leukemia.

By Amanda Psyrri The findings of KEYNOTE-055 are summarized and compared to other immunotherapy studies in recurrent/metastatic head and neck squamous cell carcinoma. Related Article: Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study

Podcast re: 'Three-year Follow-up of an Alectinib Phase 1/2 Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP' by Tamura et al.

This podcast discusses the JCO article, "Late Relapse of classical Hodgkin Lymphoma: An Analysis of the German Hodgkin Study Group HD7-HD12 Trials" by Paul Jan Bröckelmann, et al. which demonstrates that late relapses are seen in a small fraction of early stage good risk Hodgkin lymphoma patients, which increase in incidence up to 20 years and do not appear to plateau, and examines the implications of these findings with respect to therapy and disease biology.

By Kenneth Bradstock This podcast describes a clinical trial of clofarabine in consolidation therapy for adults with acute myeloid leukemia. Related article: Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission