bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyponatremia and cancer: Results of a retrospective analysis of 45 patients treated with a short course of low-dose tolvapan.
Authors: Cervera-Grau JM , Esquerdo Gaspar , Barrajon Enrique , Peiro Rafael , Santos Ortega Manuel , Rodriguez Villalva Silvia , De Piaggio Marina , Espinoza Venegas Macarena Paz , Montiel Rayo Ana Belen
Published: March 2020

e20705

Background: Hyponatremia in the cancer patient is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH). Other factors may cause hypovolemic hyponatremia, diarrhea, and vomiting. It’s present in 47% of cancer admissions. Introduction of vaptans acting as V2-receptor antagonists considerably improved the unconvincing results of conventional treatment consisting of fluid restriction potentially combined with sodium supplementation and/or demeclocycline therapy. Methods: We present a retrospective analysis of hyponatremic cancer patients treated with Tolvaptan. 45 patients, [31 men 14 women], median age 69 years old. 31.1 % had lung cancer, 17,6% other tumors, 11,1% colorectal and 11,1% prostate cancer. Histology: 53,3% Adenocarinoma, 15,6% SCLC, 15,2% others and 5,6% Epidermoid.The mean of the lowest sodium level was associated with squamous histology (Na 118 mEq/L). Descriptively, older patients (>66 y) had lower levels of Na compared to those younger than 66y (Na 122 mEq/L vs Na124 mEq/L). Median of Na at diagnosis of hyponatremia was 124 mEq/L,"waiting period" days before starting treatment,1d (SD= 1,745). Duration treatment [ Sodium levels out of risk according to the doctor criteria]. Results: Participants improved significantly after treatment period (p=.000). There were no differences in TOLVAPTAN improvements between patients with ≤ 124 mEq/L vs >124 mEq/L (p=.142), but patients with Na ≤ 124 mEq/L tend to achieved higher levels of sodium at the end of treatment (p=.016). No significant differences between different histology, location, "waiting period", duration of treatment, or age. However, Men significantly improved after treatment with tolvaptan (p=.000) and women do not showed significant changes (p=.753) (women had significantly higher pretreatment sodium level than men (122.4 mEq/L vs. 126.2 mEq/L,(p= .05). Conclusions: Tolvaptan is effective in the treatment of hyponatremia in patients with differents histological cancers especially with levels lower than 124 mEq/L. Tolvaptan had good safety profile with no side effects. A short course of two days and low dose (15mg/p.o./d ) with Tolvaptan restored safe Sodium levels.
Evaluation of depression, anxiety, and stress in nonmetastatic locally advanced head neck cancer patients: Prospective study in a tertiary medical center of India.
Authors: Mazumder Koustav , Sarkar Shyamal Kumar , Ray Sudeshna , Mukherjee Anindya
Published: March 2020

e20707

Background: Head neck cancer is one of the prevalent cancers in India. The diagnosis, treatment and the treatment outcome affect various psychological issues of the patients. The aim of the study is to assess depression, anxiety and stress of locally advanced head neck cancer patients, receiving concurrent chemoradiation. Methods: It was a prospective study done in the department of Radiotherapy, Medical College & Hospital, Kolkata from July 2012 to January 2013. Depression Anxiety Stress Scale (DASS) was used to assess the Depression, Anxiety and Stress of the locally advanced non metastatic head neck carcinoma patients. The assessment of the psychological factors was done by the DASS questionnaire in Bengali Version. Each patient was assessed by this scale after 1) breaking bad news, 2) 3 wks after starting the concurrent chemoradiation, 3) on completion of the treatment and 4) 6 weeks after completion ,assessing the response. In each time it was compared with the baseline values using paired t test. Results: Study was carried out with 45 locally advanced non metastatic head neck carcinoma patients. Among them majority are male (77.78%). It was seen that after “breaking bad news” 68.89% of patient are significantly depressed (p < .05). Depression was more among Male population, having age less than 60 years. After 3 weeks of treatment and on completion - in both scenario depression decreased but anxiety and stress increased. There was a significant positive correlation between various toxicities (eg. Mucositis, Dysphagia) on Anxiety and Stress during the course of treatment. Depression after 6weeks on completion was significantly (p < .05) depends on the type of response. Conclusions: The psychological factors of the patients suffering from locally advanced head neck cancer should be taken in consideration right after diagnosis, assessed regularly during the course of management and appropriate care may be taken accordingly.
Palliative care in patients with advanced lung cancer in a network of health service research in integrative oncology.
Authors: Schad Friedemann , Axtner Jan , Happe Antje , Kroez Matthias , Matthes Burkhard , Grah Christian , Spahn Guenther , Matthes Harald
Published: March 2020

e20710

Background: Early palliative care was demonstrated to result in a superior survival and improvement of health related quality of live (HRQL) in patients with advanced lung cancer. Concepts of integrative oncology (IO) offer multimodal therapy strategies aiming to enhance patients’ salutogenic resources in addition to standard care. In the present study we analyzed patients with advanced lung cancer from a clinical registry in Germany. Methods: Data were collected by the Network Oncology, a clinical registry of hospitals and outpatients care specialized in Anthroposophic Medicine and integrative oncology. We analyzed 441 C34 patients of UICC stage IV that had at least one of the following additional therapies: Viscum album, embrocation, therapeutic unction’s, rhythmical massages, lymph drainage, physiotherapy, eurythmy therapy, music or drawing therapy, modeling, speech-, breathing and hyperthermia therapy. We calculated Kaplan-Meier survival based on right censored data and using Greenwoods 95% confidence intervals. Results: 43% of the patients were female and median age was 64 yr (min 32/ max 92). 84% received chemotherapy, 55% radiation and 40% surgery. Most frequent additional therapies were Viscum album (72%), embrocation (43%), therapeutic unction (42%), eurythmy therapy and physiotherapy (both 27%). Patients used combinations up to 9 different additional therapies (median ♀=3, median ♂=2) with significant difference between genders (Fisher’s exact test, < p=0.001). Median length of VA therapy was 6.4 months. Median OS was 1.05yr (95% CI: 0.83 - 1.32), 2 and 3 year survival was 31% and 20%, respectively. Conclusions: Integrative therapy concepts are of growing interest in cancer care. In this observational study patients received conventional and complementary interventions. A relevant number of lung cancer patient use IO when offered in palliative oncology. Median OS seems to be comparable to the palliative care group of Temel et al. 2010 (median OS=0.97yr, 95% CI: 0.53 – 1.41). Health service research in multimodal IO settings needs further evaluation in terms of HRQL measurement and effectiveness.
Prognosis disclosure to terminally ill cancer patients: A qualitative study among Japanese physicians.
Authors: Mori Masanori , Ogawa Miho , Nishimura Mashiho , Yamada Hirohide , Morita Tatsuya
Published: March 2020

e20717

Background: Prognosis disclosure could facilitate end-of-life discussions and advance care planning in advanced cancer patients. However, many Japanese and Japanese American patients do not wish to know of their own prognosis, and physicians infrequently disclose terminal prognosis in Japan. We aimed to investigate Japanese physicians’ practice and emotion regarding prognosis disclosure. Methods: We adopted a qualitative design based on semi-structured interviews and content analysis. Attending physicians in a local cancer center were eligible if they had disclosed terminal prognosis to their cancer patients and/or families more than three times in the past year. The sample size was justified by recruiting participants through consistent comparison analysis until data saturation occurred. Results: We conducted 11 face-to-face interviews and detected the following categories; [practice in disclosure], [reasons for/against disclosure], and [emotion regarding disclosure]. [Practice] indicated that some physicians have almost always disclosed prognosis to their patients, while others have almost never done so. It included various skills such as “having families/nurses attend the meeting,” “asking families how much prognostic information physicians should provide to patients,” “asking patients why they want to know,” and “answering with a range of estimation.” [Reasons for disclosure] included “to help patients deal with unfinished business” and “to support realistic hope.” [Reasons against disclosure] included “uncertain prognosis,” “physicians’ concern about hurting patients,” “lack of time and staff support for physicians,” and “insufficient training in communication skills.” Lastly, many physicians felt “sad,” “nervous,” and “difficult,” while few felt “fulfilled” when disclosing prognosis. Conclusions: Practice patterns, reasons and emotional experiences vary widely in prognosis disclosure among Japanese physicians. Team approach, physician training in communication skills, and understanding of families’ as well as patients’ preferences may contribute to better-quality individualized cancer care based on patients’ goals, not on physicians’ personal preferences.
Elderly patients and ovarian epithelial cancer (OEC) or primary peritoneal carcinoma (PPC): A retrospective analysis.
Authors: Mane Joan Manel , Lopez de Argumedo Gonzalo , Marrodan Ines , Muñoz Alberto , Ruiz de Lobera Abigail , Azkona Eider , Iruarrizaga Eluska , Arruti Mikel , Condori Elizabeth , Buque Aitziber , Lopez Escola Cristina , Carrera Sergio , Lopez-Vivanco Guillermo
Published: March 2020

e20718

Background: OEC frequency in elderly patients is increasing around the world and it’s expected to continue rising in the future. PPC is an entity with a similar behaviour. OEC is the most common cause of gynaecologic cancer-related death and it’s the fifth leading cause of cancer associated mortality among women; its relative risk is higher among elderly patients. In this study we try to identify clinical factors in elderly OEC and PPC patients in order to improve current medical management and to enhance clinical outcomes. Methods: From January 2007 to December 2011 a total of 53 elderly patients were included (≥65 years old). PPC: 11.3%; OEC: 88.7%. ECOG 0/1/2/3/4: 24.5/34/26.4/7.5/5.7%; 1.9% unknown. Stage at diagnosis: III (52.8%); IV (30.2%). Ca125 was increased in 79.2% of the cases; 64.2% of the patients underwent debulking surgery. The majority of patients (94.4%) received chemotherapy: monotherapy (13.2%) or polychemotherapy (86.8%). Results: Among 38 evaluable patients, partial response was observed in 45.4%, complete response in 27.2%, stable disease in 24.4% and progression in 3%; 18% of patients were retreated with the same schedule (platinum sensitivity) and 26.4% of the patients received more than one line of chemotherapy (range 2-5). Significant differences in overall survival (OS) were observed in multivariate analysis according to performance status (p=0.018). Median OS for all patients was 131 weeks. Conclusions: In our experience, results in elderly patients are comparable to those expected in younger patients. In this population, treatment options must be optimized.
CA184-240: A single-arm, open-label phase II study of vemurafenib followed by ipilimumab in patients with BRAF V600-mutated advanced melanoma (AM).
Authors: Hodi F. Stephen , Amin Asim , Saenger Yvonne M. , Pennock Gregory K. , Guthrie Troy H. , Salama April K. , Flaherty Lawrence E. , Koon Henry B. , Lawson David H. , Shaheen Montaser F. , Balogh Agnes , Konto Cyril , O'Day Steven
Published: March 2020

TPS9103

Background: Ipilimumab (Ipi), a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte antigen-4 expressed on T cells, and vemurafenib (Vem), a small molecule inhibitor of BRAF V600-mutated kinase, are both approved treatments for AM. Ipi has shown improved overall survival (OS) in two randomized phase III trials of patients with previously treated (3 mg/kg monotherapy) and previously untreated (10 mg/kg plus dacarbazine) AM. Vem has shown improved OS in a randomized phase III trial of patients that harbor the BRAF V600E mutation. The most common drug-related adverse events (AEs) with Ipi monotherapy were immune-related GI tract and skin toxicities, which were generally manageable using treatment guidelines. The most common AEs with Vem were arthralgia, rash, and fatigue. Vem can induce rapid and substantial responses, and resistance mechanisms are a focus of current investigation. This study will evaluate the safety of Vem lead-in followed by Ipi (prior to resistance) in patients with BRAF V600-mutated AM. Methods: An estimated 45 patients will be enrolled. Eligible patients include those ≥18 years old with previously untreated AM, a BRAF V600 mutation, and an ECOG PS of 0 or 1. Major exclusion criteria are primary ocular melanoma, active brain metastases, and autoimmune disease. Patients will initially receive Vem for 6 weeks (960 mg twice daily). After a washout period of 3-10 days (per protocol), patients will be initiated on Ipi at 10 mg/kg (every 3 wk for 4 doses, then once every 12 wk beginning at week 24, until disease progression or unacceptable toxicity). Vem will be restarted at the time of disease progression on Ipi (no minimum time to restart) or unacceptable toxicity on Ipi (restart minimum of 1 mo after the last dose of Ipi). Vem will be restarted at the last dose level tolerated at the end of the lead-in phase. Patients will be followed every 12 weeks for toxicity and/or disease progression, and subsequently will be followed every 12 weeks for survival. The objectives of this study are to estimate the incidence of grade 3-4 drug-related AEs. Exploratory objectives include the evaluation of efficacy (OS). Clinical trial information: NCT01673854.
Open-label, multicenter, single-arm, phase I, dose-dscalation with efficacy tail extension study of vemurafenib in pediatric patients with surgically incurable and unresectable stage IIIc or IV melanoma harboring BRAFV600 mutations (NCT01519323).
Authors: Navid Fariba , Chisholm Julia C. , Ferrari Andrea , Herzog Cynthia E. , Rodriguez-Galindo Carlos , Hauschild Axel , Krishnan Kartik , Pappo Alberto S.
Published: March 2020

TPS9104

Background: Although rare, melanoma is the most common form of skin cancer in children and the incidence is rising in the adolescent population. Similar to adults, the outcome for pediatric patients with advanced or recurrent melanoma is poor. Many adult studies of melanoma exclude patients under the age of 18 years. Approximately 50% of melanomas carry a mutation in the BRAF gene and the oral BRAF inhibitor vemurafenib (VEM) has demonstrated improved rates of overall and progression-free survival in adult melanoma patients who carry this mutation (Chapman et al; NEJM 2011). The current study is designed to determine the maximum tolerated dose (MTD)/recommended dose (RD), pharmacokinetics, safety, tolerability, and efficacy of VEM in pediatric patients with surgically incurable and unresectable stage IIIC/IV melanoma harboring BRAFV600mutations. Methods: Patients aged 12 through 17 years with newly diagnosed or previously treated measurable disease are eligible. Patients with radiographically stable, asymptomatic previously treated central nervous system lesions are also eligible. In the dose-escalation phase, patients will be enrolled sequentially to increasing dose cohorts of VEM following a 3+3 design. Dose-limiting toxicity will be assessed during the first cycle (defined as the first 28 days). The initial dose will be 720 mg BID (patients ≥45 kg) or 480 mg BID (patients <45 kg). Once the MTD/RD for the extension phase is defined based on the dose-escalation window, all patients will be eligible to receive the MTD/RD. The efficacy tail of the trial will enroll additional pediatric patients at the MTD/RD. Patients will receive VEM until disease progression, death, unacceptable tolerability, discontinuation from the study, or other protocol-specified criteria. The study aims to treat approximately 20 patients at the RD with 3-15 additional patients treated at other dose levels during the dose-escalation phase. This study is currently open at 18 sites in the USA, UK, Germany, Italy, and Australia. As of January 24, 2013, one patient has been enrolled. Clinical trial information: NCT01519323.
Multimodal therapy for the treatment of fatigue in patients with prostate cancer receiving androgen deprivation therapy and radiation.
Authors: Yennurajalingam Sriram , Carmack Cindy , Basen-Engquist Karen , Reuben James M. , Bruera Eduardo
Published: March 2020

TPS9650

Background: Cancer-related fatigue (CRF) is the most frequently reported symptom associated with cancer and its treatment. Unfortunately, there are limited treatment options to alleviate this distressing symptom. Preliminary data suggest that the combination of exercise, cognitive behavioral therapy (CBT), and methylphenidate (that is, multimodality therapy [MMT]) can play an important role in reducing CRF. The project’s objective is to explore the effects and safety of this MMT on CRF in prostate cancer patients scheduled to receive radiotherapy with androgen deprivation therapy. We hypothesizethat the MMT is capable of reducing CRF as measured by the FACIT-F subscale in prostate cancer patients scheduled to receive radiotherapy. Specific Aims:(1) Our primary aim is to obtain preliminary estimates of the effects of various treatments (exercise, CBT, and methylphenidate) and their combinations in reducing CRF in prostate cancer patients receiving radiotherapy, as measured by the change in patients’ FACIT-F subscale scores taken at baseline and on day 57 and the secondary objective is to determine the effects of the treatments and their combinations on anxiety and depressed mood (both measured by the Hospital Anxiety Depression Scale [HADS]); on physical activity and function (measured by an accelerometer and a handgrip dynamometer, respectively); on levels of inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-10) in serum and induced monocytes, before and after treatment Methods: For this study, we will use a randomized factorial design to assess 3 treatments (exercise, CBT, and methylphenidate) and their placebos in 8 replications. A total of 32 patients will receive each primary treatment and 32 will not. Patients will be studied for a 57-day period, during which they are scheduled undergo daily radiation treatments with androgen deprivation therapy. Fatigue, anxiety and depressed mood, and inflammatory cytokines will be determined at baseline and at 3 subsequent post-intervention assessments. After successful initiation so far 19/64 patients were enrolled. Accrual continues. Clinical trial information: NCT01410942.
Humanism in global oncology curricula: An emerging priority.
Authors: Giuliani Meredith Elana , Martimianakis Maria Athina (Tina) , Papadakos Janet , Broadhurst Michaela , Driessen Erik , Frambach Janneke
Published: March 2020

10505

Background: Training in humanism provides the skills to achieve shared decision making with patients and their families, to navigate systems level challenges and to function positively within the healthcare team. However, there is potentially a lack of attention to humanistic competencies in global oncology curricula due to the dominance of the biomedical model in curriculum design, the challenge of assessing humanistic competencies and global cultural considerations. The aims of this study were to explore to what extent humanistic competencies are included in global oncology curricula and the nature of the humanistic competencies included. Methods: Sixteen global oncology curricula identified in a prior systematic review were analysed. The curricula were coded using the Gold Foundation’s I.E.C.A.R.E.S (Integrity, Excellence, Collaboration & compassion, Altruism, Respect & Resilience, Empathy and Service) humanistic competency framework and the CanMEDS framework. Descriptive statistics were used to describe the proportion of items attributed to each aspect of the framework. Results: 7733 curricular items were identified in the 16 curricula and 729 (9%) aligned with the I.E.C.A.R.E.S framework. The proportion of humanistic items in individual curricula ranged from 2% to 26%. The proportion of humanistic items has been increasing from the curricula published in 1980-1989 (3%) to the curricula published in 2010-2017 with a mean of 11% (4 to 25%). There was a higher proportion of humanistic competencies in curricula from the European region (9%) than in other regions. Of the humanistic items 35% were under respect, 31% under compassion, 24% under empathy, 5% were under integrity, 2% under excellence, 1% under altruism, and 1% under service. The majority of the humanistic items also aligned with the professional (35%), medical expert (31%) or communicator (26%) CanMEDS domains. Conclusions: The proportion of humanistic competencies has been increasing in global oncology curricula over time however the overall proportion remains low. Humanism is largely represented by competencies of respect, compassion and empathy and there exists a conflation between humanism and professionalism. Future global curricular efforts may benefit from attention to incorporating all aspects of humanistic competencies.
Innovation, education, and research: A multidisciplinary survivorship care model.
Authors: Latif Hira , Martone Patrick , Shaw James Edward , Wisotzky Eric , Dilawari Asma Ali
Published: March 2020

10519

Background: Advances in early detection, therapeutics, and an aging population are expected to lead to an increase in the number of cancer survivors in the United States to 20 million by year 2026. The Institute of Medicine and Commission on Cancer recommends delivery of survivorship care plans on completion of curative treatment. While models exist for high-quality survivorship care, institutions encounter barriers such as lack of resources and limited training in survivorship. Our institution piloted a unique model combining fellows’ education with guideline-driven recommendations from a multidisciplinary team to provide consolidated survivorship care. Methods: A survey for self-reported competence and experience was conducted amongst the hematology and oncology fellows at the MedStar Washington Hospital Center. A bimonthly clinic staffed by a medical oncologist, oncology fellow and a cancer rehabilitation fellow was initiated in September 2018. Didactic lectures, curriculum syllabus and recommended assessments were established. Screening tools for distress, patients’ confidence in knowledge about survivorship and physical function via PROMIS 20a were administered; clinical assessments including the “6-minute walk test” were used to assess cardiovascular health. Results: Most fellows had not encountered a survivor of lung (16%), GU (0%) and head and neck cancer (33%). Majority of the fellows had never delivered a survivorship care plan. Scores were low in competence and experience in survivorship. By December 2018, 15 patients with 17 diagnoses of cancer were referred to the clinic. 10 were survivors of hematologic malignancies while 7 were of solid tumors. The no-show rate was 40%. Fellows conducted the assessments and were supervised by an oncology attending. Of the 9 patients seen, 4 were referred for physical therapy; additional referrals for psychology and cardiology were frequent. Conclusions: A comprehensive multidisciplinary survivorship clinic focusing on fellows’ education is a feasible model for delivery of survivorship care and aims to bridge the gap in experience and competence of fellows. Future goals include re-assessment of patient-reported outcomes, physical function, and competence of fellows.
Training of oncologists: Results of a global survey.
Authors: Jalan Divyanshi , Rubagumya Fidel , Hopman Wilma M. , Vanderpuye Verna D. , Lopes Gilberto , Seruga Bostjan , Booth Christopher M. , Berry Scott R. , Hammad Nazik
Published: March 2020

10526

Background: While several studies have highlighted the global shortages of oncologists and their workload, few have studied the characteristics of current oncology training. Methods: An online survey was distributed through a snowball method via national oncology societies and a pre-existing network of contacts to cancer care providing physicians in 57 countries. Countries were classified into low- or lower-middle-income countries (LMICs), upper-middle-income countries (UMICs), and high-income countries (HICs) based on World Bank criteria. Results: 273 physicians who trained in 57 different countries responded to the survey; 33% (90/273), 32% (87/273), and 35% (96/273) in LMICs, UMICs and HICs respectively. 60% of respondents were practicing physicians and 40% were in training. The proportion of trainees was higher in LMICs (51%; 45/89) and UMICs (42%; 37/84), than HICs (19%; 28/96; P = 0.013). A higher proportion of respondents from LMICs (37%; 27/73) self-fund their core oncology training compared to UMICs (13%; 10/77) and HICs (11%; 10/89; P < 0.001). Respondents from HICs were more likely to complete an accepted abstract, poster and publication from their research activities compared to respondents from UMICs and LMICs (abstract: 37/72 (51%) from HICs, 18/66 (27%) from UMICs, 24/65 (37%) from LMICs, P = 0.014; poster: (42/72 (58%) from HICs, 28/66 (42%) from UMICs, 13/65 (20%) from LMICs, P < 0.001; publication: 43/72 (60%) from HICs, 32/66 (49%) from UMICs, 24/65 (37%) from LMICs, P = 0.029). Respondents identified several barriers to effective training including skewed service to education ratio and burnout. With regards to preparedness for practice, mean scores on a 5-point Likert scale were low for professional tasks like supervision and mentoring of trainees, leadership and effective management of an oncology practice, and understanding of healthcare systems irrespective of country grouping. Conclusions: Investment in training by the public sector would be vital to decreasing the prevalence of self-funding in LMIC. Gaps in research training and enhancement of competencies in research dissemination in LMIC require attention. Instruction on cancer care systems and leadership need to be incorporated in training curricula in both LMICs and HICs.
Targeting B-cell malignancies: Impact of an educational curriculum on BTK inhibitors.
Authors: Willis Lauren , Tanzola Mindy , Caracio Richard , Lucero Katie S. , Shah Bijal D. , Woyach Jennifer Ann , Furman Richard R. , Wang Michael , Brown Jennifer R.
Published: March 2020

10531

Background: We sought to determine if a curriculum of online continuing medical education (CME) activities could improve hematologists/oncologists (hem/onc) knowledge and competence related to clinical decision making in the use of BTKi in patients with B-cell lymphomas. Methods: An expert panel identified knowledge/competence gaps related to the use of Bruton's tyrosine kinase inhibitors (BTKi) in B-cell lymphomas. A clinical practice assessment (CPA) survey was launched May 2018 to further assess baseline educational needs. Based on the needs identified, 7 activities were posted online between May-Dec 2018. Multiple-choice questions were asked before and after participation in each activity and were grouped into learning topics. Mean knowledge/competence was calculated for the CPA and across all 7 activities. The impact of education was examined using a pre/post design. Statistical significance was assessed using a chi-square statistic ( P < .05 level). Results: For all topics except foundational/differentiating BTKi, the audiences participating in the baseline CPA and the other 7 activities, were similar or lower at pre-test, suggesting that learning needs continued until our education addressed them. All changes from pre-to-post-test were significant ( P < .001). The largest relative percent change from pre- to post-test was seen with knowledge of resistance mechanisms for BTKi as well as knowledge/competence managing AE of BTKi. Post-test there was a high level of knowledge about the selectivity seen with 2nd generation BTKi. Conclusions: This analysis shows that online CME, utilizing many different formats (video, text, panel discussions) can significantly improve the knowledge and competence of hem/oncs in multiple areas surrounding the use of BTKi for the treatment of B-cell lymphomas. Results also suggest the following areas warrant further education: awareness of clinical trial safety and efficacy data for BTKi and mechanisms for resistance to BTKi. [Table: see text]
Online education about immunotherapy for melanoma: Outcomes over time.
Authors: Parikh Kinjal , Lucero Katie S. , Repetto Patti , Kadkhoda Haleh , Warren Charlotte , Gearhart Jacqueline , Weber Jeffrey S.
Published: March 2020

10533

Background: The indications and use of immune checkpoint inhibitors (ICIs) for the treatment of melanoma have grown since the first drug approval in 2011. The expanding evidence base and number of indications challenges clinicians to stay up to date with how best to integrate these agents into treatment pathways. The objective of this study was to assess trends over time in oncologists’ knowledge, competence, and confidence using ICIs in the treatment of melanoma. Methods: A series of online continuing medical education (CME) activities about the role of ICIs in the treatment of melanoma was launched in April 2014; 18 included multiple-choice knowledge/competence questions and a confidence question assessed on a 5-point Likert-type scale before and immediately after the activity. Activities that had at least 30 oncologists participate pre/post are included in this analysis. A pre-/post-assessment study design was used, and educational effect was assessed with Chi-square tests. Analyses were conducted to examine trends in knowledge, competence, and confidence over four years on a quarterly basis. Weighted averages in each of the outcomes were calculated by quarter. Results: A total of 92,373 learners participated from April 2014-March 2018, including 57,432 physicians, of whom 11,922 were oncologists. The average increases from pre- to post-test for knowledge- (12 activities), competence- (11 activities), and confidence-based (9 activities) questions were 21%, 15%, and 6%, respectively (P < 0.01 for all comparisons). The absolute increase in knowledge from pre-test in 2014 (48%) to post-test in 2018 (78%) was 30 percentage points; and for competence, 6% (from 62% in 2014 to 68% in 2018). The mean confidence rating pre-test in 2015 was 2.51 versus 3.37 post-test in 2018. Conclusions: Online CME improves oncologists’ knowledge, competence, and confidence using ICIs in the treatment of melanoma. As new data emerge and indications expand, new educational activities are necessary to reinforce existing knowledge, close persistent gaps, and increase oncologists’ confidence using ICIs in this clinical setting.
Non-oncologist physician knowledge of radiation therapy at an urban community hospital.
Authors: Siau Evan , Salazar Hernando , Klein Jonathan
Published: March 2020

10534

Background: Appropriate referral for radiation therapy (RT) is crucial for cancer care. Previous work suggests that many non-radiation oncologists who care for cancer patients are uncomfortable referring for RT. We surveyed physicians in a community hospital in Bronx, New York to assess their training in RT and understanding of RT. Methods: Invitations to complete an online questionnaire were sent to all faculty and resident physicians at St. Barnabas Hospital. The questionnaire asked about previous training in oncology, RT knowledge self-rating and an objective knowledge assessment of RT indications and effectiveness. Statistical analysis used Pearson chi-square and Fisher’s exact test for categorical variables and Student’s t-test and ANOVA for interval variables. Results: 247 participants received the invitation email, and 87 responded (35% response rate). Among responders, 19 were attending physicians (22%) and 66 (76%) were residents (2 failed to disclose). 51 respondents (59%) were from Internal Medicine (IM) and 20 (24%) from Emergency Medicine. 72% of respondents reported caring for > 5 cancer patients in the past month, but 45% (37% of IM respondents) never refer patients for RT. 71% of respondents stated they received no formal radiation oncology training in medical school, and 47% reported no oncology training at all. Pluralities believed themselves to be “somewhat knowledgeable” about RT indications (49%), benefits (53%), and side effects (55%). Objective assessment mean score was 6.2/12 (median 7) for all respondents. IM respondents scored higher than others (mean 7.7 vs 3.5; p < 0.001), but only 28% of IM respondents (0% of others) scored 10/12 or higher. Scores did not differ between attending and resident physicians (p = 0.75), resident PGY level (p = 0.43), or receiving oncology training in medical school (p = 0.54). Factors cited by > 50% as affecting RT referral decisions either “somewhat” or “a lot” were: type of cancer, patient wishes, family wishes, poor functional status, and life expectancy. Conclusions: Many physicians are unaware of RT effectiveness or indications, which may affect referral patterns. Previous oncology training was not associated with higher knowledge scores.
Believe the H.I.P.E.: Hematology-Oncology Inter Professional Education to improve provider collaboration at an inpatient tertiary medical center.
Authors: Martin Richard Lewis , Hux Anna , Miller Ryan , Davidson Mario , Horn Leora , Gilbert Jill
Published: March 2020

10538

Background: With projected provider shortages and increasing pharmaceutical complexity, Advanced Practice Providers (APPs) and Pharmacists are becoming increasingly utilized members of hematology/oncology teams. Despite significant interdependence in practice, inter-professional training remains rare. Medical IPE has been shown to improve learning satisfaction and attitudes, however, IPE has seldom incorporated inter-professionalism into content development nor has it been evaluated in terms of sustainability. Methods: We developed a pilot IPE curriculum consisting of six, 1-hour long, case-based sessions. A preparation phase required a lead APP, Fellow, and Pharmacist to collectively build a case around three teaching points; 1) diagnosis, 2) treatment, and 3) coordination of care. The APP and Pharmacist presented the case while the Fellow moderated to ensure active participation among all groups. Surveys on collaboration, interaction, interest, and connection, as well as open-ended comments on strengths and areas for improvement were collected after each session ( > 80% completion rate). Results: With 3 of 6 sessions completed (02/19), attendance was stable, averaging 10 of 18 (Fellow), 5 of 8 (APP), and 3 of 6 (Pharmacist). Sessions were rated an average of 4.6/5 on collaboration, 4.5/5 interactive, 4.7/5 application, 4.3/5 communication, and 4.2/5 professionalism. 69% of attendees reported being more likely to attend future conferences. 65% reported feeling more connected to the care team. The most common suggestion for improvement was giving more teaching opportunities to the APPs. Session leaders were initially recruited but quickly transitioned to eager volunteers. Conclusions: Our IPE curriculum shows promising initial sustainability with perceived high marks in collaboration and applicability. Incorporating inter-professionalism into content development and longitudinal delivery to providers in practice provides a novel approach to educating IP teams. Future steps include ensuring continued sustainability, conducting qualitative and quantitative analysis, and dissemination to other units.
Activity and safety of cabozantinib in patients with gastrointestinal stromal tumor after failure of imatinib and sunitinib: EORTC phase II trial 1317 CaboGIST.
Authors: Schoffski Patrick , Mir Olivier , Kasper Bernd , Papai Zsuzsanna , Blay Jean-Yves , Italiano Antoine , Benson Charlotte , Kopeckova Katerina , Ali Nasim , Dileo Palma , Le Cesne Axel , Menge Franka , Cousin Sophie , Charon-Barra Celine , Wozniak Agnieszka , Marreaud Sandrine , Litiere Saskia , Nzokirantevye Axelle , Gelderblom Hans
Published: March 2020

11006

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. Advanced GIST is treated with tyrosine kinase inhibitors (TKIs). Most patients (pts) develop resistance over time. We reported in 2013 (Van Looy CTOS) that cabozantinib (cabo), a TKI targeting KIT/MET/AXL/VEGFR, showed activity in GIST xenograft models through inhibition of tumor growth, proliferation and angiogenesis, both in imatinib-sensitive and -resistant tumors (Gebreyohannes Mol Cancer Ther 2016;15:2845-28). Cohen (Cancer Res 2015;75:2061-70) found that cabo can overcome compensatory MET signaling in GIST in vitro. EORTC 1317 assessed the safety and activity of cabo in pts who had progressed on imatinib and sunitinib. Methods: In this multi-center, open label, single arm Phase 2 study eligible metastatic GIST pts received 60 mg (freebase weight) cabo p.o./d. Primary endpoint was progression-free survival rate at wk 12, assessed by local investigator per RECIST 1.1. If at least 21 of 41 eligible and evaluable pts were progression-free at wk 12, the activity of cabo was sufficient to warrant further exploration (A’Hern one-stage design). Results: A total of 50 consenting pts were eligible and started treatment between 02/2017 and 08/2018, with 16 (32%) still continuing cabo at the database cut-off in 01/2019. The number of 3 wk treatment cycles ranges from 2-28+. Among the first 41 eligible and evaluable pts, 24 were progression-free at wk 12, satisfying the study decision rule. Among all 50 pts, 30 were progression-free at wk 12 (60%, 95% confidence interval (CI) 45-74%). A total of 7 pts achieved a confirmed partial response (PR) (14%, 95%CI 6-27%) and 33 had stable disease (SD) (66%, 95%CI 51-79%). Progression as best response was seen in 9 pts (18%, 95%CI 9-31%), one was not evaluable. Disease control (PR+SD) was achieved in 40 pts (80%, 95%CI 66-90%). Median progression-free survival was 6.0 mo (95%CI 3.6-7.7). The most common cabo-related grade ≥3 adverse events were diarrhea (74%), hand-foot syndrome (58%), fatigue (46%), hypertension (46%), weight loss (38%) and oral mucositis (28%), with 33 (66%) pts requiring dose reductions, 25 (50%) treatment interruptions and no cabo-related deaths. Conclusions: EORTC 1317 met its primary endpoint, with 24/41 pts (58.5%) being progression-free at wk 12. Results of this trial confirm preclinical data and warrant further exploration of cabo in GIST. Clinical trial information: NCT02216578.
Exploration of tumor genetic alterations and associations with clinical outcomes: Retrospective genomic analysis of archived liposarcoma (LPS) and leiomyosarcoma (LMS) samples from phase III trial of trabectedin (T) versus dacarbazine (D).
Authors: Thomas Shibu , Joshi Shilpy , Shen Dong , Knoblauch Roland Elmar , Gormley Michael , Wang George C. , Ricci Deborah S. , Motley Clifford , Maki Robert G. , von Mehren Margaret , Patel Shreyaskumar , Demetri George D.
Published: March 2020

11019

Background: To explore tumor genomic associations with response/resistance as potential predictive or prognostic biomarkers for T and D in metastatic LMS and LPS tumor samples. Methods: Genomic alterations [single nucleotide variants (SNVs) or gene copy number variations (CNVs)] were identified using whole exome sequencing (WES) of archived tumor samples from NCT01343277. Association of tumor-subtype or genetic alterations with clinical outcomes including maximum tumor volume reduction (MTVR), overall survival (OS), progression free survival (PFS) and treatment cycles received was assessed using multivariate Cox proportional hazard models. Results: A total of 178 uterine LMS (uLMS), 121 non-uterine LMS (non-uLMS), 60 de-differentiated LPS (ddLPS), 40 myxoid LPS (mLPS) and 14 pleomorphic LPS (pLPS) tumors underwent WES. Homozygous deletions (HD) were observed at relatively high frequency in 4 genes -AC092821.1 (36.4%), LCE3B (35.4%), LCE3C (32.1%), HEATR4 (24.4%) across all sarcoma subtypes. These genes are involved in cell proliferation, innate immune response and differentiation. HD in any of these genes was associated with improved OS in the T treatment arm. Tumors with MDM2 amplifications showed worse clinical outcome in the T treatment arm in terms of PFS and OS consistent with T-mediated induction of p-53 dependent apoptosis (Table). Conclusions: HD in any of 4 genes was associated with longer OS in patients treated with T. This molecular signature, which covers 40% of total sarcoma and 0.4% of overall solid tumors population, warrants further prospective validation. Novel genetic alterations and clinical associations. [Table: see text]
Multi-institutional analysis of outcomes in patients with dedifferentiated chondrosarcoma (DDCS).
Authors: Bui Nam , Dietz Hilary , Hirbe Angela C. , Ganjoo Kristen N. , Van Tine Brian Andrew , Keedy Vicki Leigh , Davis Elizabeth J.
Published: March 2020

11028

Background: DDCS is a rare bone tumor with a poor prognosis. While no standard therapy exists, NCCN guidelines recommend osteosarcoma regimens (ORs). Methods: We performed a retrospective review (January 1, 2007-June 1, 2018) at three sarcoma centers and identified 46 patients (pts) with DDCS to evaluate treatments and outcomes. Results: Median age was 62.5 years (23-83); 61% were male. Median tumor size was 10.5cm (2-34). Most pts had localized disease at diagnosis (dx) (80%), extremity primary (76%), and did not receive neo/adjuvant chemotherapy (70%) or radiotherapy (69%). Local and distant recurrences were frequent (35% and 57%, respectively) and rapid (6.6 months (m) and 5.4 m, respectively). Twenty-eight pts received chemotherapy, 9 neo/adjuvant and 19 for metastasis (met) (Table). Response rate to first line ORs was poor (53% progressed). Notably, 11% had a partial response (D/I). Tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) led to stable disease. Median overall survival was 22.8 m and 7.2 m; 5-year survival rates were 30% and 0% in localized and metastatic disease, respectively. Median follow-up was 12.5 m (1.4-120). A multivariate cox proportional hazards model (age, sex, location, met at dx) identified met at dx as the only risk factor for worse prognosis (HR 2.8, p=0.026). Conclusions: DDCS is an aggressive malignancy with a poor prognosis. Despite guidelines to treat with ORs, the benefit is unclear, illustrating the need for randomized trials comparing standard regimens to novel agents. [Table: see text]
Italian survey of second tumors in patients with diagnosis of GIST (gastrointestinal stromal tumor).
Authors: Gasperoni Silvia , Messerini Luca , Fumagalli Elena , Manglaviti Sara , Vincenzi Bruno , Mazzocca Alessandro , Pantaleo Maria A. , Nannini Margherita , Badalamenti Giuseppe , Incorvaia Lorena , Ottaviano Margaret , Palmieri Giovannella , Grignani Giovanni , D'Ambrosio Lorenzo , Meoni Giulia , Paderi Agnese , Fancelli Sara , Caliman Enrico , Tofani Lorenzo , Mini Enrico
Published: March 2020

11032

Background: GISTs are the most common mesenchymal tumors of the digestive tract. As of recent, new links are being made between GISTS and secondary malignancies. However, whether the coexistence of GISTs with other tumors is stochastic, or the result of related pathogenetic mechanisms is still unknown. Methods: We retrospectively reviewed clinical and molecular features from all GIST patients with second tumors treated in seven Italian GIST reference centers. Qualitative variables were compared using the Fisher exact test. Results: Clinical data of 184 patients with diagnosis of GIST were evaluated. Median age at diagnosis was 66 years, KIT exon 11 resulted the most frequent mutation (73%) while seven patients (3.8%) had a genetic syndrome. The most common primary GIST localizations were stomach (54%) and small intestine (33%). Second tumors arose mostly from gastrointestinal and genitourinary tract. Fourtythree patients had two primary tumors other than GIST and five patients had three other primary malignancies. According to Miettinen criteria, 45% of non-metastatic patients at diagnosis belong to low or very low-risk classes. We highlighted a significant correlation (P=0.002) between risk class and second/third tumor localization, with considerably high percentage of GI second malignancies in low/very low risk GISTs (table). Conclusions: The high frequency of second/third tumors reported in low and very low GIST calls for a careful follow-up also in these patients. Furthermore, this population requires further genetic investigation, NGS analysis is ongoing. [Table: see text]
Determinants of secondary alterations in WWTR1-CAMTA1 fusion epithelioid hemangioendothelioma.
Authors: Seligson Nathan David , Awasthi Achal , Millis Sherri Z. , Liebner David A. , Hays John L. , Chen James Lin
Published: March 2020

11045

Background: Epithelioid hemangioendothelioma (EHE) is a rare vascular sarcoma characterized by the WWTR1- CAMTA1 fusion ( WC-F) in a majority of cases. EHE demonstrates a biphasic clinical course; remaining indolent for many years before suddenly demonstrating aggressive progression. Cell cycle mutations have been previously noted to account for some secondary alterations; however, little is known regarding the chronicity of these secondary alterations or their clinical implications. Here we present the largest assessment of secondary genomic variants and their clinical import. Methods: Comprehensive genomic profiling from 45 WC-F positive EHE patients (pts) were provided by Foundation Medicine (FMI). 8 of these 45 pts were treated at The Ohio State University (OSU) and were evaluated retrospectively through chart review. Known deleterious alterations, variants of unknown significance (VUS), and genomic copy quantification for the WC-F was included in our analysis. Targetable gene variants were defined by OncoKB. Chi-square and student’s t-tests were used as appropriate. Results: Genomic copy number of the WC-F best fit a log-normal distribution (range: 13-2,131 copies). 20 pts (44%) did not exhibit any secondary genomic variants. The most commonly altered genes included: CDKN2A/B (7 variants), RB1 (3 variants), and ATRX (3 variants). Commonly identified pathways included: cell cycle (9 pts, 20.0%), epigenetic modulators (7 pts, 15.6%), and DNA damage repair (7 pts, 15.6%). Eight pts exhibited targetable gene variants (18%) as defined by OncoKB. Subjects ≥50 years of age exhibited a greater proportion of clinically targetable variants (27.6% vs 0%; p = 0.02). Pts with a secondary genomic variant exhibited elevated WC-F copy numbers (p < 0.001). OSU pts with aggressive EHE were more likely to have a second genomic variant (80% vs 0%; p = 0.03) when compared to indolent EHE, with trends toward higher WC-F copy numbers (809±315 vs 207±147; p = 0.2) and older age at diagnosis (59.5±5.5 vs 36.7±8.8; p = 0.1). Conclusions: In this study, secondary genomic variants in WC-F driven EHE are more common in older patients ( > 50 yo). Further, the presence of secondary genomic variants is associated with an aggressive phenotype and may drive poor prognosis. Prospective research is needed to confirm these findings.