bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of palliative care patients WHO work.
Authors: Glare Paul A. , Alickaj Alberta , Blinder Victoria Susana , Nikolova Tanya , Ramirez Carey , Raghavan Vidya , Crowley Janeen , Frierson Ethel Linda
Published: March 2020

e20677

Background: There is an extensive literature on patients who return to work (RTW) after completing definitive cancer treatment. Much less is known about patients who work while on treatment. At a time of economic uncertainty as cancer becomes more of a chronic disease and palliative care is seen as offering much more than comfort care, issues affecting the working cancer patient needed to be explored. Methods: Cross sectional, anonymous survey completed once in two pain and palliative care clinics at a comprehensive cancer center by patients aged 25-65 who had been in paid employment prior to or during their treatment. Survey covered 37 items in three areas: cancer details (diagnosis, date of diagnosis, prior treatments, current disease status); occupation, work status and work ability; importance of work and factors interfering with work. Results: 97 surveys have been completed but up to 20% items missing responses. Cancer details: 54% females, median age 53, 79% working at diagnosis. Common primaries: Breast 26; CRC 14; lung 6; pancreas 4; prostate 2. 80% (67/84) reported having active disease, median 2 years since diagnosis, and 80% of them on treatment currently.Work status and attitudes of the 67 patients with active disease: 42% (29/68) are currently working, mostly full time, and typically will RTW after < 6 months off. 39% would like to work more hours. Work is important to 73% them, making 78% "feel normal", and 53% that they are “beating the cancer”. Fatigue interfered with work in 49%, pain in 38%, and side effects of pain medicines in 31%. Almost ¼ were anxious or depressed about their work situation. More than 20% experienced discrimination in the work place, but usually minor. Conclusions: Many of these patients with advanced cancer were trying to remain in the work force, even when they are on treatment and are sick enough to need to be followed in a Pain & Palliative Care clinic. Work is important to them and almost half would like to work more. Symptoms and side effects are interfering with their work ability. Some are experiencing discrimination in the work place. Interventions need to be developed to overcome some of these problems.
Predicting complications of chemotherapy-induced febrile neutropenia: A single-center experience.
Authors: Bhosale Bharatsinha Baburao , Patil Vijay , Muddu Vamshi , Singh Randeep , Dwivedi Pankaj , Noronha Vanita , Joshi Amit , Ghosh Jaya , Gupta Sudeep , Banavali Shripad , Prabhash Kumar
Published: March 2020

e20678

Background: Identifying the parameters associated with increased complications would help to formulate a cost-effective and rational therapy in patients with chemotherapy induced febrile neutropenia. Methods: We prospectively collected data from January 2007-December 2011 of consecutive episodes of neutropenic fever at our centre. Clinical features, laboratory characteristics and MASCC score were analysed to identify patients at higher risk for developing complications. Complications were defined as either of the following event: failure of first line antibiotics, organ failure, delay in next cycle of chemotherapy, inpatient admission and death. Results: Three hundred and eighty-eight febrile neutropenia (FN) episodes in 373 patients were included, 256 episodes of FN in hematolymphoid malignancies and 132 episodes of FN in solid tumours. The median age was 31 years (11-76 years). Two hundred and forty-four (65.4%) patients were male. One hundred forty-nine patients (39.94%) had FN during previous cycles, while primary GCSF prophylaxis was used for 205 (52.84%) cases. The median haemoglobin, nadir neutrophil count & median number of days with severe neutropenia (< 1X109/L) were 7.9 gm/dl, 0.04X109/L and 4 days respectively. A clinical focus of infection was present in 174 (44.8%) episodes, with gastrointestinal being the commonest in 70episodes (40.23%). High risk MASCC score (<21) was present in 156 episodes (40%). Complications were seen in 133(34%) instances. On Univariate analysis, age, type of malignancy, prophylactic growth factor use, clinical focus of infection, day of FN, MASCC score, nadir Hb and platelet count were significantly associated with complications. All predictive factors except age and nadir Hb could independently predict complication on multivariate analysis. Conclusions: Clinical and laboratory parameters in addition to MASCC score could help in identifying patients with FN who require hospitalisation and more intensive management strategies.
Are “Allow Natural Death” orders preferable to “Do Not Resuscitate” orders for patients with advanced cancer?
Authors: Emuron Dennis Omoding , Miljkovic Milos , Rhodes Lori , Abraham Joseph , Miller Kenneth David
Published: March 2020

e20685

Background: Over twenty years after the passage of the Patient Self-Determination Act, patients’ preferences regarding end-of-life (EOL) care are often unknown to physicians. The aim of this study was to assess the knowledge and attitudes of cancer patients regarding EOL care, and to compare “Do Not Resuscitate” (DNR) and “Allow Natural Death” (AND) orders. Methods: Adult patients with advanced cancer were invited to participate. The first 50 consenting patients were surveyed regarding their prognosis and attitudes about critical care and resuscitation. We presented them with hypothetical scenarios in which a decision on their code status had to be made if they had 1 year, 6 months or 1 month left to live. Twenty-five patients were given a choice between being “full code" and DNR, and then 25 patients had a choice between "full code" and AND. Results: Almost half the patients (49%) were not aware that their illness was terminal. Fifty percent reported having a living will. However, only 19% reported that their doctors knew their wishes regarding EOL care. In contrast, greater than 78% reported knowledge of intubation, tracheotomy, feeding tubes, and cardiopulmonary resuscitation (CPR). The proportions of participants choosing full resuscitation compared to the DNR or AND options did not differ significantly from 50% (p-values > 0.54). Their choices did not vary by age, sex, race, type of cancer, education or income level (p-values > 0.05). Patients' attitudes towards CPR, tracheostomy and feeding tubes were not significantly associated with their choice of "DNR" (p-values > 0.17), but those who wanted these interventions were significantly less likely to choose "AND" (p-values < 0.002). As many as 38% of the patients without a living will chose "DNR", while 11% opted for "AND" (p-values < 0.03). Conclusions: In this small sample of patients with advanced cancer many were unaware of their poor prognosis, and few informed their physicians of their EOL preferences. The wording of DNR and AND orders was not associated with patients' EOL preferences. Contrary to our expectation, the "Allow Natural Death" phrasing might be less acceptable to patients who view life-prolonging measures favorably.
Patterns of treatment (tx) with bone-modifying agents (BMA) in patients with bone metastases (mets).
Authors: Quigley Jane M , Hernandez Rohini Khorana , Cetin Karynsa , Pirolli Melissa A. , Quach David , Liede Alexander
Published: March 2020

e20690

Background: Bone mets can lead to serious and debilitating skeletal-related events (SREs: fracture, spinal cord compression, and surgery or radiation to bone). Three BMAs are approved in the US for prevention of SREs in cancer patients (pts) with bone mets: 2 intravenous bisphosphonates (IV BP) with recommended dosing every 3-4 weeks (pamidronate [PAM] and zoledronic acid [ZA]), and 1 RANK ligand inhibitor with subcutaneous injection every 4 weeks (denosumab). Monitoring real-world tx trends is important, particularly as low persistence has been linked to higher rates of SREs (Hatoum et al 2008). Methods: A retrospective cohort was defined from the Oncology Services Comprehensive Electronic Records (OSCER) database, which includes medical records from >500K pts treated at 76 US oncology practices. Adult solid tumor pts with bone mets who initiated tx with a BMA between Jan 2011 and Oct 2011 were included and followed for 12 mos after tx initiation. Pts were either naïve (no BMA in previous 6 mos) or transition (different BMA received in previous 6 mos). Results: The cohort was composed of 1445 denosumab pts (62% naïve) and 1807 IV BP pts (99% naïve). Pt characteristics were similar, although denosumab pts were somewhat more likely to have prostate cancer than IV BP pts (30% vs 25%). Denosumab pts were more likely to receive regular tx during follow-up and less likely to switch tx than IV BP pts (Table). Trends were consistent across tumor types and for naïve vs transition pts. Conclusions: This descriptive analysis reports on tx patterns for pts with bone mets since the availability of denosumab in Dec 2010. Denosumab represented almost half (44%) of pts initiating a BMA and one-third of pts naïve to tx. Uninterrupted tx was more common for denosumab pts than IV BP pts, regardless of tumor type. Trends, including reasons for and consequences of tx interruption, should be monitored as the pt experience develops. [Table: see text]
Role of bone scan in routine practice for early recognition of bisphosphonate-related osteonecrosis of the jaws (ONJ): Pro and con.
Authors: Fusco Vittorio , Tommasi Luigi , Muni Alfredo , Rouhanifar Hamed , Testori Ornella , Fasciolo Antonella , Benzi Luca , De Martino Iolanda , Randi Lorenza , Guglielmini Pamela Francesca , Pertino Antonella
Published: March 2020

e20694

Background: The literature on the role of 99mTc-MDP bone scan (BS) in the diagnosis and follow-up of bisphosphonate-related ONJ is limited and unconsistent. Following data are in favour: a) BS is an imaging technique with high sensitivity; b) sporadic cases of early jawbone (maxilla or mandible) uptake have been reported, occasionally even months or years before the clinical evidence of ONJ (bone exposure); c) the jaw BS uptakes can change on different stages of ONJ disease (acute/symptomatic or less); d) the BS is performed periodically in patients with skeletal metastases to check out the status of disease activity and the response to specific treatments; consequently the research of ONJ does not involve additional costs. Vice versa, some limitations include: a) BS is a technique with low specificity; bone traumatic, inflammatory, degenerative lesions can determine an uptake; b) a non-negligible proportion of patients (even without any tumor disease) shows jaw uptakes, due to dental diseases widely seen in the general population (abscesses, denture ulcers,periodontal disease,etc.); c) even in BP-related ONJ suspected cases, jaw uptake may be due to infections that are not necessarily connected to the osteomyelitis component of ONJ; d) bone necrosis (sequestrum) is usually not uptaking at the BS, but it can appear as a downtaking area surrounded by an uptaking area. Methods: We conducted a retrospective study of 59 BS performed in 15 ONJ patients treated with BPs (8 with breast cancer,6 prostate cancer,1 renal cell carcinoma). Two Nuclear Medicine specialists reviewed 18 "baseline" BS (before treatment with BP), 14 BS in the 6-12 months prior to diagnosis of ONJ, 13 BS performed at the diagnosis time of ONJ (or within 6 months), 14 BS collected after the diagnosis of ONJ. Results: 6-12 months prior to diagnosis, 10 BS were positive (jaw uptakes in ONJ sites) and 4 negative. At the moment of ONJ diagnosis, 12 out of 13 exams resulted positive and one doubtful. Conclusions: These retrospective data will be used to design a case-control study with different patient groups, inluding ONJ cases, patients treated with BP and not suffering from ONJ, and cancer patients not receiving BPs.
Electronic medical record (EMR) order sets, counseling, and complementary therapy for chemotherapy induced nausea/vomiting (CINV) control.
Authors: Nora Richard E. , Greenlaw Roger , Macy Lori
Published: March 2020

e20698

Background: EMR order sets entry can standardize CINV therapy and reduce errors. EMR CINV control, impact of counseling and use of complementary therapies for nutrition and control of CINV are rarely reported. Methods: Patient interview regarding CINV, nutrition education, weight change, and use of other therapies for nutrition and nausea control. Patients initially medicated with parenteral short T1/2 5HT3 antagonist and dexamethasone and oral prochlorperazine. Antiemetics changed at physician discretion. Medical records review for chemotherapy, antiemetics, and weights. Interviews conducted by a research coordinator who did not counsel, prescribe, or treat the patients. Results: 79 patients participated after minimum 2 and maximum 6 cycles of chemotherapy, 24 males and 55 females, age range 38-87 years. 76/79 received moderately or highly emetogenic chemotherapy. 78/79 reported good control of CINV at the time of interview. 38/79 reported decrease in appetite or dysgeusia associated with chemotherapy. 7 patients had change short to long T1/2 5HT3 antagonist. 9 patients had oral aprepitant added. All patients were prescribed oral prochlorperazine and ondansetron, but home use was not assessed as part of the study. 77/79 recalled dietary counsel, but recollection of source and content was not consistent with curriculum or medical record. 8 patients had weight loss >10 pounds, 4 patients had weight gain >10 pounds during chemotherapy. 18 patients reported weight change at least 10 pounds different from measured change. 28/79 patients used calorie and/or protein supplements. 24/79 used ginger related products. 7/79 reported improvement in dysgeusia or appetite with use of plastic utensils. Conclusions: CINV control can be achieved for most patients with combination antiemetics prescribed by EMR order set. Some patients require additional or alterative therapy. A substantial number of patients access nutritive or complementary therapy for CINV control. Patients’ recall of dietary counseling was poor, possibly related to timing of education. Patient reports and possibly perception of chemotherapy associated weight changes are frequently inaccurate.
Cognitive decline as a result of impaired sleep and glucose levels during chemotherapy treatment in breast cancer patients.
Authors: Moyers-Ruiz Liliana , Hickish Tamas , Mayers Andrew , Thompson Simon
Published: March 2020

e20713

Background: Sleep efficiency might be altered during chemotherapy treatment. Cognitive decline has been associated with sleep disruption, impaired glucose levels, and chemotherapy treatment. We hypothesize that the biological factors considered in this study are playing an important role. Anecdotical reports have shown discrepancy with neuropsychological batteries results, therefore a qualitative interview and memory self-reports will be conducted for the cancer group. Methods: A sample of 32 Breast cancer patients and 29 healthy controls has been recruited in the Dorset area in the UK. The chemotherapy group will be tested three times within de course of their treatment (baseline, mid-treatment, after treatment). The radiotherapy participants will be tested three times within a period of four months, and the healthy control group two times within a four-month period. A subset of chemotherapy participants will be tested six months after chemotherapy. A neuropsychological battery is being used to assess cognitive function, and sleep efficiency is analysed using a sleep monitor and validated self-reports; Furthermore, glucose levels will be analysed for the chemotherapy group, and an online semi-qualitative interview will be conducted for cancer patients for a thematic analysis, along with a Prospective Memory questionnaire. Results: Preliminary data shows that sleep efficiency is disturbed during the course of chemotherapy, although not statistically significant, there is a trend in decreased sleep efficiency percentage when we compared baseline and mid-chemotherapy assessment The strongest tendency is observed on the PSQI self-report, showing an increase in Global PSQI score . Glucose levels show an increase during mid-treatment, although preliminary analyses show no significant effect. Memory data is still under scrutiny and more data will be reported at the poster presentation, along with assessments for times three and four. Conclusions: The inclusion of a semi-qualitative study will add a very important information to this study when test results are compered with anecdotical and self-reports.
NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting (CINV) following repeated chemotherapy cycles: Results of a phase III trial.
Authors: Jordan Karin , Rossi Giorgia , Rizzi Giada , Palmas Marco , Gralla Richard J.
Published: March 2020

e20716

Background: NEPA is a fixed-dose combination of netupitant (NETU), a highly selective NK1 receptor antagonist and palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3receptor antagonist. Recent clinical trials have been conducted to definitively establish the superiority of the combination, NEPA, over single agent PALO in the prevention of CINV following a single cycle of highly (HEC) and moderately (MEC) emetogenic CT. This study was designed to examine the tolerability and efficacy of NEPA over multiple cycles of HEC and MEC. Methods: Trial design: multinational, randomized, double-blind, parallel group, phase III study assessing the safety and efficacy of a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) administered only on day 1 of each cycle, and given with concomitant oral dexamethasone on day 1 (with MEC) and days 1-4 (when given with HEC) prior to repeated cycles of HEC or MEC. A standard arm 3-day oral aprepitant + PALO + dexamethasone was included as a control group with an unbalanced 3:1 (NEPA : aprepitant) randomization ratio. There was no limit to the number of chemotherapy cycles allowed. Safety was the primary objective of the study as assessed by adverse events; secondary variables included ECGs, left ventricular ejection fraction, cardiac troponin levels and laboratory tests. Efficacy was assessed as the proportion of patients with complete response (no emesis, no rescue medication). Results: 413 patients were randomized in this study with the last patient visit occurring on 13 September, 2012. The analyses will be completed by March 2013 and will be fully available by ASCO 2013. Conclusions: Few large randomized trials have documented safety and efficacy of antiemetic control with multiple cycles of chemotherapy, and especially with HEC. The in depth safety profile will provide new information for all study arms over multiple cycles. NEPA is designed to provide maximal convenience while providing high degrees of antiemetic control throughout the patient’s full course of chemotherapy. Clinical trial information: NCT01376297.
Cancer in elderly patients (CEP) in Tunisia: Retrospective study about 243 patients collected from 2002 to 2007.
Authors: Boussen Hammouda , Ayadi Mohamed Malek , Ben Nasr Sonia , Labidi Soumaya , Afrit Mehdi
Published: March 2020

e20721

Background: To report the epidemiologic, clinical, extension, treatment and results of CEP in a Tunisian population from a department of medical oncology. Methods: We collected retrospectively cases of CEP (> 70 years) within a cohort treated in a medical oncology department in Tunisia. We analyzed the following data : age, sex, delay to diagnosis(DD), site, histologic type, stage, co-morbidities, treatment and evolution. Results: These CEP collected from 2002 to 2007 represented 16.7% of the 1507 patients treated for cancer during this period. Mean age was 77.7+/- 4.2 years(70 to 86), SR 0.93 and delay to diagnosis 7.8+/6 5,28 months(1 to 48). Lung cancer (49 cases), digestive (46 cases) and Breast cancer (29 cases) represented the most frequent anatomic sites and patients presented co-morbidities in 75 cases. 11 patients (4.5%) developed metachronous second cancers and 40 pts (16.4%) have initial metastases at diagnosis. Treatment included CT in 148 pts (61.3%), S in 85 pts (34%) and RT in 40 pts (17%). Median survival was 24 months for the whole population. Conclusions: CEP represented more than 15% of patients treated for cancer in a Tunisian serie, this age group representing presently around 6% of the Tunisian population where aging modified in the last 20 years the ages pyramid aspect. CEP are characterized by late diagnosis/consultation, frequent co-morbidities, locally advanced and/or metastatic cases and probably less aggressive treatment compared to younger patients.
Metabolic syndrome and breast cancer: Effects of a 16-week combined exercise intervention.
Authors: Dieli-Conwright Christina Marie , Tripathy Debu , Schroeder E. Todd , Mortimer Joanne E. , Bernstein Leslie
Published: March 2020

TPS9648

Background: Current evidence suggests that breast cancer treatments such as chemotherapy lead to excessive weight gain, fatigue, physical inactivity, and negative alterations in components of metabolic syndrome (MetS). MetS is associated with increased risk of cancer recurrence, cardiovascular diseases and type 2 diabetes, and is defined by visceral adiposity, insulin resistance, hyperglycemia, hyperinsulinemia, low serum high-density lipoprotein cholesterol, and hypertension. MetS is highly prevalent and present in 25% of American and European adults and higher in minorities. Given that chemotherapy for breast cancer induces many of the components of MetS, an effort to offset these consequences of cancer therapy using exercise/lifestyle intervention could improve breast cancer, cardiovascular and endocrine outcomes. Methods: Our study seeks to determine whether a 16-week exercise intervention induces changes in prognostic components of MetS (waist circumference, blood pressure, serum levels of glucose, insulin, lipids, C-reactive protein and HbA1c) among breast cancer survivors if initiated within 3 months of completion of chemotherapy or radiation therapy. We are currently recruiting women diagnosed with Stage I-III breast cancer from the USC Norris Comprehensive Cancer Center and Los Angeles County Hospital, which cares for a high proportion of minority/underserved patients. Participants are randomized to either the Control (usual care) or the Exercise group. The Exercise group participates in aerobic and resistance exercise sessions 3 times a week for 16 weeks supervised by an exercise specialist at the USC Clinical Exercise Research Center. At baseline and following the study period, all participants are tested for MetS components, muscle strength, body composition, bone density, cardiorespiratory fitness, quality of life, fatigue and shoulder function. We will recruit an additional 85 patients (at present time n=15) over the next 3 years. It is expected that this intervention will improve components of MetS and physical fitness in breast cancer survivors when compared to the Control group, thus defining intervention and biomarker variables for more definitive trials. Clinical trial information: NCT01140282.
Phase III clinical trials with anamorelin HCl, a novel oral treatment for NSCLC cachexia.
Authors: Abernethy Amy Pickar , Temel Jennifer S. , Currow David , Gleich Lyon L. , Friend John
Published: March 2020

TPS9649

Background: Cancer anorexia/cachexia is a debilitating and life-threatening complication of an underlying malignancy that may develop in up to 80% of terminally ill cancer patients. Cancer cachexia has a multifactorial pathogenesis and is manifested by accelerated losses of skeletal muscle and disproportionate losses of lean body mass (LBM). Anamorelin HCl is a ghrelin receptor agonist that has demonstrated significant increases in LBM, physical strength, and body weight in Phase II trials in patients with cancer cachexia. Through its ghrelin and growth hormone secretagogue activity, it displays both anabolic and appetite stimulating properties – two aspects vital to treating cancer anorexia/cachexia. Methods: HT-ANAM-301 (NCT01387269) and HT-ANAM-302 (NCT01387282), also known as ROMANA 1 and ROMANA 2, are double-blind, placebo-controlled, randomized (2:1 anamorelin HCl vs. placebo) Phase III trials in patients with non-small cell lung cancer (NSCLC) cachexia. Eligible patients must have unresectable Stage III or IV NSCLC and cachexia (weight loss of ≥5% body weight within prior 6 months or BMI <20 kg/m2). Patients receive once daily oral doses of anamorelin HCl (100 mg) or placebo for 12 weeks. Co-primary endpoints are the change from baseline in LBM as measured by DXA and in muscle strength as measured by handgrip strength. Secondary endpoints include change in body weight, overall survival, and quality of life (FACIT-F and FAACT questionnaires). For HT-ANAM-301 only, blood samples are collected at Week 6 for population pharmacokinetics. After 12 weeks of treatment, patients may continue in a separate 12-week safety extension study (HT-ANAM-303 [ROMANA 3] NCT01395914). At their last meeting (August 2012), the Independent Data Monitoring Committee suggested no safety issue and allowed the trials to continue as planned. Clinical trial information: NCT01387269, NCT01387282, NCT01395914.
Management of muscle-invasive bladder cancer with bladder preservation in Russia: A survey-based analysis of current practice and the impact of an educational workshop on clinical expertise.
Authors: Dengina Natalia , Chernich Marina , Usychkin Sergey , Degnin Catherine , Chen Yiyi , Gladkov Oleg , Nosov Dmitry , Tsimafeyeu Ilya , Thomas Charles R. , Tjulandin Sergei , Mitin Timur
Published: March 2020

10509

Background: Trimodality bladder preservation (BP) is an accepted alternative to radical cystectomy for patients with muscle-invasive bladder cancer (MIBC). The global utilization of BP is variable, and practice patterns have not been previously studied in Russia. During the Russian Annual Oncology Congress, organized by the Russian Society of Clinical Oncology in November 2018, our group has conducted a contouring workshop for Russian radiation oncologists (ROs). We sought to elucidate the contemporary practice patterns in Russia and determine the impact of this workshop on attitudes of Russian ROs towards BP. Methods: Pre- and post-workshop IRB-approved surveys were analyzed to determine baseline clinical experience and patterns of care among Russian ROs. The effect of the contouring workshop on participants’ knowledge and attitudes was performed using tests for paired nominal data. Results: We analyzed 77 pre-workshop and 32 matched post-workshop questionnaires. 56% (43 out of 77) of respondents treated MIBC patients with bladder-directed radiation therapy (RT). Of these, 40% (17 out of 43) treated only inoperable patients, and 60% treated both operable and inoperable MIBC patients. 14% offered RT alone to their patients, while the rest offered concurrent chemoRT. 63% (26 out of 41) offered suboptimal concurrent systemic agents, such as single agents carboplatin or paclitaxel. 63% of respondents felt that BP can only be done in specialized centers with established expertise, but only 10% felt uncomfortable offering an MIBC patient a BP option in their clinic. Prior to workshop, 40% of respondents estimated universal poor bladder and erectile functions after BP. The workshop resulted in dramatic change in participants’ attitudes towards BP long-term urinary (Stuart-Maxwell-test, p < 0.01), and sexual (exact McNemar test, p < 0.01) side-effects. Prior to workshop, only 52% of respondents routinely discussed smoking cessation (SC) with their patients, whereas after workshop almost 90% agreed that SC discussion is mandatory (exact McNemar test, p = 0.04). Conclusions: Bladder preservation is commonly used in Russia in the management of MIBC patients. Our contouring workshop resulted in dramatically improved understanding of long-term BP toxicities and inspired Russian ROs to incorporate smoking cessation counseling into routine clinical practice. International educational efforts are critical to improve multi-disciplinary management of MIBC patients.
Molecular profiling (MP) for malignancies: Knowledge gaps and variable practice patterns among United States oncologists (Onc).
Authors: Singh Bhavana Pendurthi , Britton Susan Lynne , Prins Petra , Yin Chao , Lankford Maria L. , Willey Joanne P. , Buettner Arden , Tiscione Brynn , Scharf Mitchell , Blancato Jan , Marshall John
Published: March 2020

10510

Background: Clinically impactful therapies for malignancies require the identification of specific molecular alterations. Onc must be aware of these targets and how to interpret them to provide optimum care. The use of MP has become the standard of care for many cancers, and is recently FDA approved. Using 2 data sets, we assessed the current awareness and incorporation of MP in the treatment of cancer; comparing data from community based Onc (C) to academic Onc (A). Methods: C consisted of 292 physicians polled using an audience response system during 6 case-based research events across the US. Questions focused on various aspects of molecular testing. Data for A was obtained from a chart review focused on timing and extent of MP in disease specific academic practices (lung, breast, GI) (N = 59). Results: Within C, 257 (88%) were Onc from community-based practices. The frequency at which Onc ordered MP significantly varied depending on tumor type; 33% in lung cancer (LC), 18% in colorectal cancer (CRC) and less commonly in breast cancer (BC) (8%). In A, MP was ordered more frequently; 74% in LC, 27% in CRC and 0% in BC. These results reflect a gap in practice among community versus academic Onc, as C had lower utilization of MP for both LC and CRC. In C, Onc were also asked to match the molecular alteration with the appropriate targeted therapy. Onc incorrectly matched the molecular alteration to the targeted therapy or marked unknown in up to 69%. This reflects a large knowledge gap among community Onc with regards to the correct application of MP to currently FDA approved targeted therapies. Conclusions: Given the significant knowledge and practice gap, we conclude there is an urgent need for focused educational activities that facilitate improved knowledge of MP and corresponding personalized therapeutic strategies for Onc in the US.
Collaborative learning workshops to optimize integration of cancer immunotherapies in the community setting.
Authors: Shivakumar Latha , Perloff Tara , Lucas Lorna
Published: March 2020

10535

Background: The expanding armamentarium of immunotherapies available to treat patients with cancer poses a challenge to community practitioners. They need guidance around the practical issues that they must navigate to provide immunotherapy safely and effectively in their own communities. Methods: The Association of Community Cancer Centers (ACCC) implemented collaborative learning workshops focused on best practices for implementing cancer immunotherapies in the community setting with respect to care coordination, monitoring and management of immune-related adverse events (irAEs), and access to care. The workshops were held between April and June of 2018 in community cancer centers. A multidisciplinary steering committee including two medical oncologists, an oncology nurse, and an oncology pharmacist, led this initiative. The workshops started with a 45-minute open discussion section where the faculty posed questions to the learners to understand their specific institutional challenges. The faculty took cues from the initial discussion and focused the remainder of the education on addressing the challenges and barriers that were uncovered, rather than merely summarizing recent clinical data. The faculty discussed clinical case scenarios and presented clinical evidence for the various treatment decisions. At the end of the workshop, the instructors collaborate with the learners to draft an action plan for incorporating changes into their practice. Participants were surveyed at 3 and 6 months following participation in the workshop to report on the status of their action plans. Results: After participating in the workshops, almost 100% of the participants reported being confident in their ability to make changes in their practice. The responses of the participants to the post-activity assessment revealed a 11% relative increase in knowledge and competence and the participants were up to 14.7% more likely to receive evidence-based management with immunotherapies based on effect size calculations. At the 3-month follow-up, the participating sites had already implemented over 30% of the action items listed in their plans and at the 6-month follow-up, 100% of the action items drafted by learners were implemented as planned. Conclusions: The collaborative learning workshops were successful in inducing changes in knowledge, competence, and performance among the intended target audience of community oncology practitioners.
Phase II trial of gemcitabine (G) with pazopanib (P) or gemcitabine with docetaxel (T) in advanced soft tissue sarcoma (STS).
Authors: Somaiah Neeta , Van Tine Brian Andrew , Hill Elizabeth Goodwin , Milhem Mohammed M. , Schuetze Scott , Meyer Christian Frederick , Reuben Daniel Y. , Elias Anthony D. , Read William L. , Chawla Sant P. , Wahlquist Amy E. , Garrett-Mayer Elizabeth , Kraft Andrew S.
Published: March 2020

11008

Background: P is a multi-tyrosine kinase inhibitor with efficacy in many sarcoma subtypes. We designed a trial to assess the benefit of adding P to G as an alternative regimen to the commonly used combination of G+T in pts with STS (NCT01593748). Methods: We performed an open-label, randomized phase 2 trial enrolling pts with advanced non-adipocytic STS who had received prior anthracycline based therapy. Pts were assigned (1:1 stratified randomization based on leiomyosarcoma and prior pelvic radiation) to receive G 1000 mg/m2 on days 1 and 8 with P 800 mg daily or G 900 mg/m2 on days 1 and 8 and T 100 mg/m2 on day 8, repeated q 3 wks. The primary objectives were estimating median PFS and rate of grade ≥3 adverse events (AEs). Secondary objectives included estimating the hazard ratio (HR) and response rates. Cross-over was allowed for RECIST progression. Sample size of 90 was derived based on the precision of 95% confidence intervals (CI) for reporting toxicity and PFS in each arm. Results: A total of 90 pts enrolled; 45 on each arm. Pt characteristics and results are detailed in Table. Median PFS was 4.1 months for each arm (p= 0.3, based on stratified log-rank test). The clinical benefit rate (PR+SD) was 29% for each arm (p>0.99, based on Fisher’s exact test). The rate of related grade ≥3 AEs were 20.6% with G+T and 19.9% with G+P. Related grade ≥3 AEs (%) occurring in ≥10% of pts (G+T; G+P): anemia (36, 20), fatigue (29; 13), low platelets (56; 51), low neutrophils (20; 49), AST increase (2; 13) and hypertension (2; 20). Conclusions: This study demonstrates comparable efficacy between G+P and G+T, suggesting that G+P can be considered for second-line therapy in advanced non-adipocytic STS. Pt Characteristics and Results. Clinical trial information: NCT01593748. [Table: see text]
A randomized phase II study of nivolumab monotherapy versus nivolumab combined with ipilimumab in advanced gastrointestinal stromal tumor (GIST).
Authors: Singh Arun S. , Chmielowski Bartosz , Hecht J. Randolph , Rosen Lee S. , Chow Warren Allen , Wang Xiaoyan , Brackert Sandra , Adame Carlos , Bovill John , Schink Elena , Douek Michael , Chantharasamee Jomjit , Wong Karlton , Eilber Frederick C. , Glaspy John A.
Published: March 2020

11017

Background: Most GISTs are driven by mutations in KIT and PDGFRa and secondary mutations are felt to confer resistance to TKIs. In advanced/metastatic GIST, the benefit of second line TKIs and beyond is progressively less after imatinib failure. As such, novel non-TKI approaches are important to explore. Here we report interim analyses of safety and efficacy in advanced GIST patients treated with immunotherapy. Methods: Patients with advanced/metastatic GIST refractory to at least imatinib were enrolled on a randomized, parallel group, unblinded Phase 2 trial of either nivo (240 mg Q2wks) or nivo (240 mg Q2wks) with ipi (1mg/kg Q6wks) for up to 2 years. The primary endpoint was the objective response rate(ORR) of nivo alone or nivo + ipi by RECIST 1.1 criteria. Imaging was assessed by investigator and 3 independent radiologists. Patients were randomized 1:1 and were restaged every 8 weeks. With a sample size of 20 per group, an exact binomial test with a nominal 0.050 one-sided significance level will have 82% power to detect the difference between the null hypothesis response rate 1.5% and the alternative response rate of 15%. Secondary objectives are to ascertain the PFS, CBR, RR by Choi criteria and safety. Blood and biopsies are also being collected. Results: At cutoff, 29 patients (27 evaluable) with a median of 3 (1-7) lines of prior therapies have started on trial. In the nivo only arm, 7/15 pts had a best response of SD for a CBR of 46.7% with the median PFS being 8.57 wks. In the nivo + ipi arm, 1/12 patients had a PR and 2/12 have SD for a CBR of 25.0% (95% exact C.I. 5.5%-57.2%) with a median PFS of 9.1 wks. 8 patients have been on therapy for more than 6 months and two patients with a KIT Exon 17 mutation had radiographic disease shrinkage. Most AEs were grades 1-2 with fatigue (37%) being the most common. 4 Grade 3/4 AEs occurred in the nivo and ipi arm (hyperglycemia, weakness, diarrhea x 2) and 4 grade 3/4AEs occurred in the nivo arm (DKA, hyperglycemia, rash, fatigue). Pretreatment biopsies have been obtained in all patients and blood has been collected on all patients for correlative analysis. Conclusions: In a heavily pretreated GIST population, responses and disease control with both nivo and nivo + ipi were observed. To date, the drugs have been well tolerated and no new safety signals have been observed in this disease state. Clinical trial information: NCT02880020.
Pathologic discordance in sarcomas: Prospective comparison of external and sarcoma center pathologic diagnosis.
Authors: Eckardt Mark A. , Graham Danielle S. , Singh Arun S. , Chmielowski Bartosz , Federman Noah , Kalbasi Anusha , Bernthal Nicholas M. , Bukata Susan V. , Hornicek Francis J. , Yanagawa Jane , Levine Benjamin D. , Motamedi Kambiz , Seeger Leanne L. , Eckardt Jeffrey J. , Eilber Frederick R. , Dry Sarah M. , Nelson Scott D. , Eilber Frederick C.
Published: March 2020

11020

Background: With more than 80 different histologic subtypes, sarcomas are a unique pathologic challenge. As therapeutic decisions have become histology-specific, obtaining an accurate pathologic diagnosis is critical in guiding treatment decisions. The aim of this study is to determine the discordance between the diagnosis rendered by an external non-specialized pathologist and pathologic re-review by a specialized sarcoma pathologist at a high-volume sarcoma center. Methods: Patients who presented at the UCLA Multidisciplinary Sarcoma Conference (MSC) in 2017 that had a pathologic diagnosis from an outside facility were included in this study. All specimens underwent pathologic re-review at UCLA by an experienced sarcoma pathologist. The pathology was classified as concordant (identical diagnoses), minor discordance (difference with minor impact on prognosis/therapy) and major discordance (difference with significant impact on prognosis/therapy). Results: 1350 patients were presented at the UCLA MSC in 2017. Of the 635 new patients, 196 presented with an outside pathologic diagnosis and underwent pathologic re-review at UCLA. 44% (n = 87) were concordant, 22% (n = 43) had minor discordance, and 34% (n = 66) had major discordance. Major discordance included substantial discrepancies in histologic subtype (n = 24, 36%), benign/malignant mismatch (n = 23, 35%), diagnostic from non-diagnostic (n = 12, 18%) and major grading discrepancy (n = 7, 11%). Major discordance was most often seen in biopsies [needle (n = 27, 32%), incisional (n = 30, 44%)] as compared to resection (n = 9, 21%). Conclusions: 56% of external non-specialized sarcoma pathologic diagnoses were discordant from specialized sarcoma pathologist review, 34% of which were major discordances. Pathologic re-review of a presumed sarcoma by a specialized sarcoma pathologist is critical for both patient care and investigational studies. [Table: see text]
Depletion of mutant IDH1 impairs chondrosarcoma growth by downregulating integrins.
Authors: Li Luyuan , Hu Xiaoyu , Trent Jonathan C.
Published: March 2020

11031

Background: chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers, including chondrosarcomas. These mutations lead to the inability of IDH to convert isocitrate into α-ketoglutarate (α-KG). Instead, α-KG is reduced into 2-hydroxyglutarate (D-2HG), an oncometabolite. We sought to determine the role of IDH1 mutation in the tumorigenesis of human chondrosarcomas by inactivating mutant IDH1 (mIDH1) using genetic approaches. Methods: we employed two human chondrosarcoma cell lines, JJ012 and HT1080 that carry endogenous IDH1 mutations. D-2HG levels were measured by tandem mass spectrometry. mIDH1 was knocked out via the CRISPR/Cas9 technique. Colony-forming ability and cell migration were evaluated using soft agar assay and Transwell assay, respectively. The effect of mIDH1 on chondrosarcoma growth was analyzed in murine xenograft models. RNA-seq from total RNA was performed to identify differentially expressed genes (DEGs) between the parental and knockout cells. The biological functions of DEGs were identified through Ingenuity pathway analysis. Results: we found that mIDH1 knockout almost completely depleted D-2HG production, dramatically inhibited colony formation by 35% - 60% in JJ012 ( p < 0.01) and by 40% - 80% in HT1080 ( p < 0.01), and significantly reduced the migratory cell numbers by around 40% in both cell lines ( p < 0.01). Moreover, we observed that loss of mIDH1 led to a marked attenuation of chondrosarcoma formation, whereby the mean volume of the tumors derived from mIDH1-knockout cells was approximately 30% of that of control tumors, in both cell lines (JJ012 and HT1080) ( p < 0.01). Interestingly, RNA-seq data showed a significant downregulation of integrin genes such as ITGA10, ITGA5 and ITGB5 in response to mIDH1 knockout (adjusted p < 0.001). These results were confirmed by qRT-PCR and Immunoblotting. Conclusions: our findings demonstrate that mutant IDH1 plays a vital role in chondrosarcoma tumor formation through aberrant activation of integrins.
Racial disparity in incidence and survival for gastrointestinal stromal tumors (GIST): An analysis of SEER database.
Authors: Ulanja Mark Bilinyi , Rishi Mohit , Beutler Bryce , Konam Kenneth , Sharma Mokshya , Ambika Santhosh , Gullapalli Nageshwara , Hinojosa Tomas
Published: March 2020

11037

Background: Gastrointestinal tumors (GISTs) represent the most common mesenchymal tumors of the gastrointestinal tract. There has been limited data on GISTs incidence and survival disparities between ethnic groups. We assess disparities in incidence and survival among race in the United States in the era of available GIST histologic codes and treatment. Methods: We queried Surveillance, Epidemiology, and End Results (SEER) database for GIST from 2002 to 2015, with diagnostic code 8936. Results: Of the 7,204 patients identified, 4,928 (68.4%) were White; 1,308 (18.2%) African American (AA) and 968 (13.4%) were classified as Other (American Indian/Alaskan Native, Asian/Pacific Islander). The overall incidence rate (IR) was 0.753 per 100,000. IR was highest among AA at 1.372/100,000, but 0.648/100,000 for Whites, 1.075/100,000 for Asians/Pacific Islanders and 0.276/100,000 for American Indians/Alaskan Natives. The GIST incidence was twice as high for AA as for Whites (Rate ratio [RR]: 2.12; 95% CI: 1.98-2.26; p<0.001). Lower proportion of AA underwent surgery as compared to white and Other. Median overall survival (OS) [116 months] and GIST specific survival (GSS) was significantly lower in AA as compared to White and Other. In multivariate Cox model, belonging to Other had better OS (adjusted hazard ratio [aHR]; 0.81, 95% CI: 0.69-0.95, P=0.011) for GIST, but no difference in prognosis and OS for AA and White [(aHR for whites; 0.93, 95% CI: 0.83-1.04, P=0.187), AA=reference]. Conclusions: Significant racial disparity in incidence and survival for GIST exists, and efforts should be made to bridge this gap and improve outcomes for all races. [Table: see text]
Immune signature and molecular profiling of radiation-induced sarcoma (RIS).
Authors: Malone Eoghan Ruadh , Anderson Nathaniel , Lewin Jeremy Howard , O'Sullivan Brian , Dickson Brendan , Shlien Adam , Abdul Razak Albiruni Ryan
Published: March 2020

11040

Background: RIS is a rare subset of soft tissue sarcoma (STS) with poor prognosis and limited treatment options. We hypothesize that subsets of STS that carry genomic complexity, such as RIS, will have a neoepitope and immune signature that predicts response to immunotherapy as these mutations act as strong antigenic targets for eliciting immune response. Methods: Cases of RIS were identified from an institutional database. Formalin fixed paraffin embedded (FFPE) samples were stained for PD-1, PD-L1, CD3, CD4, CD8. Immune scoring was performed. Tumor-infiltrating lymphocytes (TILs) were assessed using a 4-tiered scale: 0 (no lymphocytes); 1 (1-10/HPF); 2 (11-50/HPF), 3 (51-100/HPF); 4 ( > 100/HPF). TIL staining with PD-1 and PD-L1 was also scored whereby the overall percentage of positive cells on the entire slide was quantified. Tumor DNA was extracted from FFPE samples and underwent whole exome sequencing (WES). Results: FFPE samples from 20 cases of RIS were selected for analysis. PD-1 and PD-L1 expression (threshold set at ≥ 1% positive cells) was seen in 35% and 45% of the cases respectively. CD3+, CD4+, CD8+ T cell infiltration (threshold set ≥ 11 cells /HPF) was seen in 45%, 15% and 20% of cases respectively. 12 exomes of unpaired RIS samples were successfully sequenced. The most common histologies were angiosarcoma (n = 3), undifferentiated spindle cell sarcoma (n = 3), de-differentiated liposarcoma (n = 2) and radiation induced spindle cell sarcoma (n = 2). Provisional analysis did not reveal any pattern to the relative mutational burden between the RIS’s. There does however seem to be relatively higher rate of mutation than that seen in other cancer subtypes. Half the samples had at least one pathogenic or likely pathogenic variant. Different HRAS mutations were seen in two samples (sarcoma NOS and angiosarcoma) and FGFR4 mutation was present in two samples, both spindle cell sarcomas. Conclusions: To our knowledge this is the first study to investigate the immune profile in RIS. Up to 45% of these tumors were positive for PD1/PDL1 expression, as well as presence of tumour infiltrating lymphocytes. Results from WES demonstrate that RIS may benefit from immunotherapy due to a relatively higher mutational burden.