bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilization of intravenous bisphosphonates (IVBs) in patients with bone metastases (BMets) secondary to breast, lung, or prostate cancer (BC, LC, PC).
Authors: Hagiwara May , Cong Ze , Chung Karen , Delea Thomas E.
Published: March 2020

e20665

Background: Cancer patients with BMets are predisposed to skeletal complications. Bone targeted therapies such as denosumab or IVBs reduce the risk of these complications. The objective of this study was to characterize patterns of IVB use in these patients. Methods: This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial and Medicare databases (9/02 - 6/11). Subjects were all persons with ≥1 claim with a diagnosis (Dx) of BC, LC, or PC and ≥1 claim with a Dx of BMets. The date of first BMet Dx claim was the “index date”. Key exclusion criteria were Dx of other primary cancer, receipt of IVB pre-index, or <6 mos continuous enrollment pre-index. Cumulative incidence of treatment initiation (first IVB claim, death as competing risk), interruption (gap of >60 days between IVB claims, discontinuation as competing risk), and discontinuation (last IVB claim) were analyzed. Results: Cumulative incidence of initiation of IVB at 12 mos post-index was greatest for BC followed by PC and LC (Table). IVB treatment interruption at 12 mos ranged from 16% (LC) to 31% (PC). IVB treatment discontinuation at 12 mos ranged from 46% (BC) to 83% (LC). Cumulative incidence of initiation of IVB at 12 mos declined with age in all tumor types: e.g., in BC, from 62% at age<50 years to 47% at age 75+ years. Conclusions: IVBs are used more frequently in patients with BMets secondary to BC than PC or LC. Many patients interrupt or discontinue IVB therapy within 12 mos. of initiation, potentially impacting effectiveness. [Table: see text]
Toward integration of palliative care into cancer care: A study on profile of psychosocial and clinical complications among attendees of a Nigerian oncological center.
Authors: Olagunju Andrew Toyin , Aina Olatunji Francis , Olagunju Tinuke Oluwasefunmi , Sarimiye Foluke Oladele
Published: March 2020

e20675

Background: The integration of palliative care into cancer management is abysmal in this context and paucity of empirical evidence constitutes constraint for policy formulation and their translation into cancer care. This study assessed psychosocial and clinical complications among Nigerian cancer subjects. We postulated the interplay of psychosocial and clinical factors would constitute evidence for palliative care. Methods: This is an observational study among 200 adult participants with histological diagnosis of cancer recruited using systematic random sampling. Eligible participants were interviewed by the researchers using socio-demographic/clinical profile questionnaire, Centre for Epidemiological Studies Depression Scale Revised (CES-DR) and Schedule for Clinical Assessment in Neuropsychiatry (SCAN). Data analyses were done using SPSS-15. Results: The commonest type of malignancy was breast cancer (51.0%); cervical cancer 29.5%, colorectal and prostatic cancers were 10.5% and 9.0% respectively. Slightly less than half (49.0%) of subjects had advanced cancer. Most subjects (36.5%) had symptoms for over a year at presentation. Two-thirds (66.0%) had pain, 52% had weight loss and 20.0% had external ulcer. Ninety-eight (49.0%) subjects had depressive symptomatology (CES-DR score ≥16), while prevalence of depression based on SCAN was 27.5%. Depression was significantly associated with higher educational status (p=0.003), unemployment (p=Ÿ0.004), unmarried status (p=0.004), advanced cancer stage (p=0.006), longer duration of cancer (p=0.048), pain (p<0.001), physical complications (p<0.001). However, unmarried status, unemployment, pain and duration of cancer still correlated with depression following logistic regression. Conclusions: In this study, preponderance of physical, psychosocial complications, advanced stage illness and high symptoms burden suggest that integration of palliative care into cancer management should be the rule rather than exception. Lastly, further research on palliative care with translation of resulting research based evidence into cancer care is implied.
Application of multiphoton/CARS tomography for detecting early stages of chemotherapeutically induced dermal side effects.
Authors: Lademann Juergen , Patzelt Alexa , Zastrow Leonhard , Chekerov Radoslav , Sehouli Jalid , Weinigel Martin , Koenig Karsten , Darvin Maxim E.
Published: March 2020

e20688

Background: A wide variety of chemotherapeutics is available for systemic cancer therapy. Many of them are known to induce dermal side effects (DSE), although the pathomechanisms often remain unclear. Recently, it was found that pegylated liposomal doxorubicin (PLD) is delivered to the skin via the sweat. The palmar and plantar region provides the highest density of sweat glands and the thickest stratum corneum serving as reservoir, and thus seems to be the predestined area to develop a palmar plantar erythrodysethesia (PPE). Due to its specific fluorescent properties PLD is easily detectable. DSE can also be induced by other chemotherapeutics, however, as there are lacking fluorescence properties, the pathomechanism is difficult to verify. In the present study, a multiphoton/CARS (coherent anti-Stockes Raman scattering) tomograph was used to detect early stages of skin inflammation during therapy with various chemotherapeutics. Methods: The investigations involved 12 patients under chemotherapy with e.g., capecitabin, docetaxel and 5 FU. The patients had a history of 2 to 4 cycles of chemotherapy and were free from clinical signs of DSE at the time of investigation. An internationally unique system was used combining multiphoton tomography permitting cellular structures to be clearly imaged without contrast agents and CARS microscopy which detects lipids. Results: In the present study the lipid structure of patients under chemotherapy was compared to that of healthy volunteers determined in preliminary investigations. While no inflammation was visible on any patient’s skin surface, pathological changes were detected in deeper lipid structures revealing an early stage of DSE. Conclusions: Changes in the lipid structure are independent of the applied chemotherapeutic and imply an early stage of an inflammatory process. Thus, multiphoton/CARS tomography permits early DSE diagnostics before pathological changes manifest themselves on the skin surface. The method is suited to investigate the pathomechanism of DSE of various chemotherapeutics and can help to develop prevention measures such as the topical application of antioxidants during chemotherapy as proposed for PPE.
A new model of early supportive care and symptoms management: The experience of Pisa medical oncology.
Authors: Antonuzzo Andrea , Vasile Enrico , Lucchesi Maurizio , Ginocchi Laura , Galli Luca , Brunetti Isa Maura , Ricci Sergio , Falcone Alfredo
Published: March 2020

e20711

Background: Recent advances in medical oncology research and new possibilities of care create a growing number of treatment-related complications. Due to these clinical relevant toxicities a significative number of patients have to admit to our hospital emergency rooms in the recent years. Data from different institutions in Italy suggest that an integrated model of supportive care dedicated to symptoms management and not only, is more effective for cancer patient’s care. Methods: In the last seven months of 2012 we started the “supportive care-team” activity giving a dedicated-room inside the day hospital offering to the patients a direct and early management of chemotherapy toxicities (mucositis, febrile neutropenia, etc.) and “new drugs” induced toxicities (cutaneous, hypertension/cardiovascular, infective, etc.). The medical and nurse team does receive the patient without appointment, based on the severity of clinical problems and give a mobile phone consult all days in the morning. Patients receive symptomatic therapy, i.v. fluid infusions, collecting of blood samples, corrections of medical therapies (e.g. pain therapy), venous accesses management for one-day or more until resolution and physicians are able to organize further specialists evaluations. Moreover, there are strictly linked specialists such as anesthesiology involved in all cases of severe drugs adverse reactions. Other two ancillary support activities the for patients are offered by the psychologist and chaplain daily inside the day hospital. Results: During all 2012 we have delivered 13.365 courses of anticancer therapies in 1,358 patients. All these were outpatients. During the last 7 months of 2012 we have made 761 unplanned visits (median number/day 6, range 0-13) and the team did respond to 1,138 phone calls (median number/day 9, range 2-24). Conclusions: These analysis does attempt to answer to the main question of reducing hospitalizations and their related costs. Our new organizative model prompt to maintain much more the management of oncologic patients inside the oncologic department and to increase the feasibility of patient’s continuos care, improving symptoms control and patient’s quality of life.
Phase III study of NEPA, a fixed-dose combination of netupitant (NETU) and palonosetron (PALO), versus PALO for prevention of chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC).
Authors: Aapro Matti S. , Rossi Giorgia , Rizzi Giada , Palmas Marco , Grunberg Steven
Published: March 2020

LBA9514

The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Integrating concept maps into a medical student oncology curriculum.
Authors: Brondfield Sam , Seol Allen , Hyland Katherine , Teherani Arianne , Hsu Gerald
Published: March 2020

10506

Background: Proliferating knowledge domains have prompted medical schools to reconsider how best to facilitate multidisciplinary learning. Concept maps promote knowledge retention and integration; however, the feasibility and utility of integrating concept maps into a medical student oncology curriculum as a learning and assessment tool have not previously been described. Methods: In 2015-2016, all 152 second-year University of California, San Francisco (UCSF) medical students in a hematology/oncology course produced a concept map about a single cancer type over four weeks. Two of three graders independently scored each map using a standard rubric. We used linear regression to calculate the Pearson correlation coefficient between graders and between concept map scores and preclinical examination scores, USMLE Step 1 scores, and clerkship grades. We sent course evaluations to 50 randomly selected students (as is typical in the UCSF curriculum) and performed an inductive content analysis of open-ended comments about concept mapping. Results: We graded all 152 concept maps. Inter-rater reliability was excellent ( r = 0.95 or greater between the graders). Concept map scores did not correlate with preclinical or clinical performance. 43 of 50 students (86%) rated the helpfulness of concept mapping on a 5-point agreement scale (1=strongly disagree; 5=strongly agree). The median rating was 3, and the mean (SD) rating was 2.81 (1.44). 22 of 50 (44%) students submitted comments about concept mapping. Some (9 of 22) found concept mapping useful, expressing themes such as “learning the material better” and delving into the “details.” Others (7 of 22) did not, expressing themes such as preferring “other study methods” and feeling that concept mapping was “busy work” or “stressful.” Conclusions: Integrating concept maps into a medical student oncology curriculum was feasible, and we demonstrated reliability evidence as an assessment tool. Future studies should explore whether integrating concept maps earlier in medical school, producing multiple concept maps over time with training and feedback, or developing concept maps collaboratively may increase utility as a learning and assessment tool.
TeamX integrative oncology scholars: Harnessing the potentials of students in shaping oncological care.
Authors: Hung Kin Wai (Tony) , Hui Ka-Kit , Kim Irene S. , Busch Silvia Orvietani
Published: March 2020

10516

Background: Teams are critical in delivering patient-centered care amid the challenge of health care workforce shortages. While conventional team-based collaborative care model involves physician and non-physician professionals, roles for pre-professional students in teams are largely educational and arguably underutilized. Methods: In a collaborative effort with the University of California Los Angeles (UCLA) Center for East West Medicine (CEWM), TeamX Health, a 501(c)3 nonprofit organization, designed an innovative, team-based curriculum for pre-professional students with our aims to harness the potentials of students in shaping the present and future delivery of oncological care. Over a 10-week academic quarter, students are challenged to explore the evolving evidence-based specialty of integrative oncology, and delivered as a “capstone project”, a creative solution to problems facing cancer patients today. Results: From April 2018 through October 2018, two 6-student cohorts have completed the curriculum. 10 participants (83%) were undergraduates and 2 (17%) were post-graduate alumni. Participants were selected based on a competitive application process with commitment to engage in the 2-hour weekly learning session. Sessions were taught in team-based learning format, covering topics ranging from cancer prevention, survivorship, symptoms management, nutrition, complementary therapies, integrative medicine models, and informatics. At completion of the curriculum, cohort one launched a health promotion YouTube channel addressing the physical and emotional burden for cancer survivors, and cohort two published a website for patients and caregivers to share their cancer journey serving as a greater social support platform. Conclusions: Redesigning the educational experience for pre-professional students may unlock unexpected possibilities to shape how we learned from and care for our patients. Harnessing the potentials for all levels of stakeholders ought to be part of defining team-based collaborative care.
Creation and development of the National Cancer Control Plan in Russia.
Authors: Petrovsky Alexander , Tjulandin Sergei , Tryakin Alexey , Stilidi Ivan S. , Davydov Mikhail , Avksentieva Maria , Ledovskih Yulia
Published: March 2020

10524

Background: The absence of the National Cancer Control Plan (NCCP) did not allow to develop оncology in Russia. Methods: Since 2015 experts of the N.N. Blokhin Russian National Comprehancive Center and Russian Oncology Association has initiated the creation of a National Anti-Cancer Strategy. Results: In 2016, the working group presented the first version of this Strategy to the professional community for wide discussion, which was transferred to the Russian Ministry of Health after a broad discussion in 2017. This strategy included prevention, screening, early diagnosis, treatment, rehabilitation and palliative care in patients with malignant tumors. In parallel, we created National Clinical Cancer Guidelines, which were approved by the professional community, and then we submited them to the Ministry of Health in 2017. Also in the period of 2017-2018, updated principles of creating clinical and statistical groups (CSG) were developed based on the calculation of the real costs of each type of surgery, radiation therapy and drug treatment. More than 1,000 different standards we established for each case of hospitalization and their cost has been calculated. Then, based on these calculations, we ranked four types of treatment (surgery, radiation therapy, chemotherapy and chemoradiation), each of which has 3, 5, 10 and 6 levels, respectively. These calculations formed the basis of the NCCP approved by the Government and the President starting from 2019 with an unprecedented additional level of funding of almost 1 trillion rubles (an increase of almost two times). The major goal of the Russian NCCP is to decrease mortality level from 202 to 185 (8,5%) per 100 000 population by the year of 2024. Conclusions: The еffort of the professional community with due consideration and consolidation with the Ministry of Health allows implementation of the NCCP on a national level.
Working together in cancer care: An academic community partnership for a diverse patient population.
Authors: Ko Naomi , Burgess Mayah , Demers Lindsay , Sanchorawala Vaishali , Gignac Gretchen , Drake Frederick Thurston , Cassidy Michael Ryan , Baiyee Emily , Lee Stephanie , Moy Beverly
Published: March 2020

10525

Background: The Massachusetts General Hospital Cancer Care Equity Program conducted a qualitative survey health assessment in the inner-city communities of Boston to study Black Bostonian patients’ perceptions of the barriers to cancer care. Findings revealed a level of mistrust toward large cancer centers and a request for more interactions with their trusted community health providers. At a subsequent community forum geared toward soliciting solutions to improve relationships with academic medical centers, community members recommended that academic oncologists increase engagement with their community health center (CHC) clinicians with a cancer lecture series. Methods: Academic oncologists from Massachusetts General Hospital and Boston Medical Center met with the leadership at two CHCs prior to the creation of the cancer lecture series. Feedback on how to best support CHC providers was established and a cancer care lecture series was created with continuing medical education (CME) credit provided. Five in-person lectures were given at each CHC. Topics included: Consultative Hematology, Breast Cancer, Prostate Cancer, Thyroid Cancer, Colon Cancer and Adrenal Masses. Survey evaluations (summative and formative) were distributed to all participants. An online portal was established to provide ongoing CME to providers. Results: Six academic physicians specializing in cancer care provided lectures at two CHCs. Currently, we have 176 surveys completed from both CHCs. Thus far, 98.3% surveys have indicated that the lectures have been “Excellent” or “Above Average,” and all participants have responded that the objectives of each presentation have been met. We have developed a website to provide ongoing CME for the lectures that were given: http://bucme.org/cancercare . Conclusions: This project aims to improve cancer care education and communication between providers from academic cancer centers and primary care providers at CHCs that care for a diverse and vulnerable patient population.
Enhancing evidence-based medicine skills in oncology training with cognitive technology.
Authors: Chen Chun-You , Hung Hui-Chun , Chiu Hsin-Yi , Wei Po-Li , Kuo Pih-Lian , Chiou Jeng-Fong , Preininger Anita , Dankwa-Mullan Irene , Kefayati Sarah , Solomon Metasebya , Jackson Gretchen , Rhee Kyu , Yen Yun
Published: March 2020

10532

Background: Evidence-based medicine (EBM) requires applying literature evidence to inform practice. Students from Taipei Medical University Hospital, trained in EBM concepts, participated in a preliminary study using Watson for Oncology (WfO), an evidence-based decision-support system to enhance the EBM skills of medical students. Methods: A class of 50 medical students compared traditional search methods (TSM) and WfO in a workshop divided into 2 sequential sessions on colon and lung cancer, respectively. All students were trained on WfO, and 2 groups of 25 students each were randomly assigned to either TSM or WfO in the first session. Those groups were then assigned to the alternate approach in the second session. Students completed a profile that included their clinical experience with each cancer type. Students used either WfO or TSM to help answer a series of questions related to colon or lung cancer. Students then completed a survey of attitudes towards the technology, followed by a constructed-response learning assessment without the aid of TSM or WfO. Assessments were scored and results compared using a Mann-Whitney U Test; outcomes at two different experience levels, based on student profiles, were compared using a Kruskal-Wallis test. Results: In this preliminary study, more than 70% of students reported limited clinical experience with either cancer. On the colon cancer assessment, students in the WfO group performed significantly better than the TSM group ( p = 0.0001); there was no significant difference detected for lung cancer. Students with more clinical experience felt that TSM was easier to learn than WfO ( p= 0.005); students with less experience felt that WfO was clearer and more understandable than TSM ( p= 0.002). Conclusions: These preliminary results are consistent with better learning outcomes for students using WfO in the colon cancer module. Students with more clinic experience reported that TSM was easier to learn than WfO, however it is unknown if this might be due to a potentially greater familiarity with TSM in this more experienced group. More studies are needed to determine what features, if any, of WfO can facilitate EBM approaches in oncology education.
A phase I/II study of pembrolizumab (Pem) and doxorubicin (Dox) in treating patients with metastatic/unresectable sarcoma.
Authors: Pollack Seth , Redman Mary Weber , Wagner Michael , Loggers Elizabeth Trice , Baker Kelsey K. , McDonnell Sabrina , Gregory Jeffrey , Copeland Vanessa C. , Hammer Kathryn J. , Johnson Rylee , Moore Roxanne , Shahnazari Michael , Townson Steven Matthew , Jones Robin Lewis , Cranmer Lee D.
Published: March 2020

11009

Background: Patients with advanced soft tissue sarcomas (STS) treated with single agent Dox have a median progression-free survival (PFS) of 4.6 months (mo) and response rate (RR) of 14%. Dox sensitizes tumors to Pem through calreticulin release and killing of immunosuppressive cells. Thus we hypothesize that combining Dox + Pem will improve patient outcomes. Methods: A phase I/II trial (NCT02888665) evaluating Dox+Pem was designed for Dox naïve STS and select bone sarcomas with a 1° endpoints of safety (CTCAE v4.03) and response rate (RR) by RECIST 1.1. Patients received one “priming” dose of Pem (200mg IV) prior to starting Dox+Pem Q3wks. Dox+Pem was continued for up to 6 cycles, followed by Pem monotherapy for up to 2 years or progression. The phase I portion used a 3+3 design with 2 Dox doses (45 & 75 mg/m2), followed by a Simon 2-stage expansion. A retrospective study of patients treated at our center on non-ifosfamide containing Dox trials (DoxT) was performed in order to compare our observed PFS with a comparable historic population. Results: Treatment was well tolerated; detailed safety data will be presented. No additional cardiac risk was observed. No DLTs were observed during phase I and 75mg/m2 was selected as the phase 2 Dox dose. The study met criteria for expansion to the 2nd stage. Though the planned enrollment was 41, the study closed after 37 as it was clear that the RR (22% , including phase I patients) would not meet the phase 2 RR target of 29%. However, 59% of patients had stable disease (disease control rate = 81%) with tumor regression in a majority of patients. The median PFS on Dox + Pem was 8.1 mo (95% CI: 6.3, 10.8). Patients treated with Dox + Pem had a significantly longer median PFS compared to the DoxT cohort (4.1 mo, 95%CI 3.0 – 6.6, p < 0.001). Conclusions: Dox+Pem is well-tolerated. While this study failed to meet its 1° RR endpoint, a highly significant improvement in PFS was observed compared with historical controls. This is consistent with findings in other cancers, such as head & neck, where improved clinical outcomes were observed without significant increase in RR by RECIST. A randomized trial of Dox +/- Pem should be carefully considered in light of recent negative trials in STS. Clinical trial information: NCT02888665.
SAINT: Results of a phase 1/2 study of safety/efficacy using safe amounts of ipilimumab, nivolumab, and trabectedin as first-line treatment of advanced soft tissue sarcoma.
Authors: Gordon Erlinda Maria , Chua-Alcala Victoria S. , Kim Katherine , Liu Seiya , Angel Nicole , Baby Rekha , Brigham Don , Tseng William W. , Pollack Seth , Jones Robin Lewis , Federman Noah , Srikureja Amor M. , Jalas John , Chawla Sant P.
Published: March 2020

11016

Background: Sarcoma cells are most immunogenic earlier in the disease course and prior to treatment when the immune system can recognize and destroy them. Hypothesis: Immune checkpoint inhibitors would be most effective when given as first line therapy. Methods: This is an IRB-approved dose-seeking Phase 1/2 protocol using defined doses of I (1 mg/kg i.v. q 12 weeks), N (3 mg/kg i.v. q 2 weeks) and escalating doses of T (1.0, 1.2, 1.5 mg/m2 i.v. q 3 weeks), employing the “Cohort of Three” design, followed by a Phase 2 using the MTD of trabectedin. Results: Nine subjects were treated in Phase 1 of the study, and 31 subjects in Phase 2. Safety analysis: at Dose 1: Grade 3 treatment-related adverse events (TRAEs) included fatigue (n = 1), increased TSH (n = 1). At Dose 2, Grade 4 TRAEs included thrombocytopenia with bleeding, DLT (n = 1), increased CK (n = 1); Grade 3 TRAEs included anemia (n = 1), myalgia (n = 1), increased TSH (n = 1), decreased TSH (n = 1), increased AST (n = 1). Efficacy analysis (evaluable patients): At Dose 1: Disease Control Rate (DCR = CR, PR, SD) was 67%, median PFS, 18 weeks; median OS, 50 weeks; At Dose 2: PR (n-1), DCR 60%, median PFS, 24 weeks; median OS, > 46 weeks. At Phase 2, MTD Dose 2 (PUPs): Safety analysis (n = 31): Grade 3 TRAEs included fatigue (n = 2), increased ALT (n = 6), increased AST (n = 4), hypernatremia (n = 1), hyponatremia (n = 1), dehydration (n = 1), rash (n = 1), port cellulitis (n = 1), psoriasis exacerbation (n = 1), increased TSH (n = 1), decreased hemoglobin (n = 2), neutropenia (n = 1). Efficacy analysis (N = 23 evaluable): PR (n-5; 2 UPS, 1 synovial sarcoma, 1 liposarcoma, 1 leiomyosarcoma,), BORR 22%, DCR 96%. Median PFS and OS not yet reached. After 4 treatment cycles, one resected tumor showed 80% necrosis and a greater number (30%) of CD8+ killer T cells, in the TME compared to archived pre-treatment tumor. Conclusions: These data suggest that the SAINT protocol (1) is safe with manageable adverse events, with no additive toxicity, and (2) may control tumor growth. Phase 2 of the study is on-going. Clinical trial information: NCT03138161.
Precision oncology in sarcoma drug development: Impact of genomic matching on response, clinical benefit, and survival in sarcoma patients on phase 1 trials.
Authors: Sen Shiraj , Pestana Roberto , Hess Kenneth R. , Hong David S. , Janku Filip , Naing Aung , Falchook Gerald Steven , Conley Anthony Paul , Patel Shreyaskumar , Meric-Bernstam Funda , Subbiah Vivek
Published: March 2020

11018

Background: Genomic analyses have revealed many potentially actionable mutations across sarcoma subtypes. Whether sarcoma patients enrolled on genomically matched early phase trials have improved clinical outcomes over patients enrolled on non-genomically matched trials remains unclear. Methods: We analyzed clinical and next gen sequencing data from sarcoma patients on phase 1 trials at MD Anderson Cancer Center (MDACC) and performed logistic and Cox proportional hazards regression analyses to compare response rate (RR), median time to progression (mTTP), clinical benefit rate (CBR = CR, PR, or SD > 6 months), and median overall survival (mOS) between patients treated on genomically-matched and non-genomically matched trials. Results: Among the 406 patients with advanced sarcomas (321 soft tissue sarcoma [STS], 85 bone sarcomas) treated on phase 1 trials at MDACC from May 2006 to May 2018, median age was 53 (range 11-84), 48% were female, and patients had a median 3 prior lines of therapy (range 0-9). The most commonly treated STS subtypes were leiomyosarcoma (n = 66; 16%), liposarcoma (n = 52; 13%), GIST (n = 44; 11%), and synovial sarcoma (n = 11; 3%) and most commonly treated bone sarcomas were osteosarcoma (n = 34; 8%), chondrosarcoma (n = 28; 7%), and Ewing's sarcoma (n = 25; 6%). 23% (n = 93) of sarcoma patients treated on phase 1 trials were treated on genomically-matched trials. RR on non-genomically matched trials was 6% compared to 11% on genomically-matched trials, OR 1.97 (95% CI 0.88, 4.44), p = 0.10. Responses on genomically-matched trials were seen with novel agents targeting TRK, LRRC15, cMET, mTOR, VEGF, MDM2, KIT/PDGFRA, and FGFR. mTTP on non-genomically matched trials was 2.7 months compared to 3.7 months on genomically-matched trials, HR 0.72 (95% CI 0.57, 0.91), p = 0.0048. CBR on non-genomically matched trials was 19% compared to 41% on genomically-matched trials, OR 2.91 (95% CI 1.77, 4.80), p < 0.0001. mOS on non-genomically matched trials was 15.5 months compared to 22.1 months on genomically-matched trials, HR 0.70 (95% CI 0.50,0.98), p = 0.031. Conclusions: Enrollment on genomically-matched phase 1 trials is associated with an improvement in clinical benefit rate, time to progression, and overall survival in heavily pretreated, metastatic sarcoma patients. While RR remained low, we report the mutations associated with responses on genomically-matched trials. A prospective, biomarker-driven genomically-matched basket trial for these alterations is warranted in advanced sarcomas.
Angiosarcoma of bone: A European Muscoloskeletal Oncology Society (EMSOS) multicenter, retrospective study.
Authors: Palmerini Emanuela , Leithner Andreas , Windhager Reinhard , Gosheger Georg , Boye Kjetil , Laitinen Minna , Hardes Jendrik , Traub Frank , Jutte Paul , Willegger Madeleine , Casanova Jose' , Setola Elisabetta , Righi Alberto , Picci Piero , Donati Davide Maria , Ferrari Stefano
Published: March 2020

11046

Background: Angiosarcoma of bone (B-AS) is an exceedingly rare malignant tumor of vascular origin. The aim of this EMSOS retrospective study is to report on natural history, type of treatment and prognosis of B-AS. Methods: Patient data were collected according to the national rules for observational studies through electronic dataset available on EMSOS WEBsite. Results: 80 patients (51 male and 29 female, median age 54 years, range 17 to 92 years, 56% with localized disease, 44% metastatic) from 8 EMSOS Centers were collected. Surgery of the primary tumor was performed in 76% of patients (amputation in 30%), with intralesional margins in 26%. A surgical complete remission status (SCR) was achieved in 47% of the patients. Radiotherapy (RT) was delivered in 41% of the patients (in 15 patients as definitive local treatment), chemotherapy (CT) in 47% (56% in metastatic and 41% in localized cases). With a median follow-up of 31 months (range 40 to 309 months), 68% of patients died, 16% were disease-free, 12% were alive with disease and 4% dead for other causes. The 5-year overall survival (OS) was 27% (95%CI 16-30): 41% (95%CI 25-56) for localized patients (45% SCR, 17% no SCR, p = 0.03) and 8% (95%CI 0-20) for metastatic patients (p = 0.002). Among metastatic patients, 29/35 have died, with a median time to death of 6 months (1-45), while 6 patients were alive with a median follow-up of 22 months (8-106). Improved survival was observed for male patients (30% vs 8%, p = 0.04), while type of treatment (surgery, chemotherapy, radiation), pattern of metastases and age did not affect outcome. In 18 metastatic patients who underwent chemotherapy partial respo nse (PR) was documented in 1/3 patients after paclitaxel (RR 33%), and stable disease (SD) in 5 patients (2/2 with gemcitabine, 2/8 with doxorubicin/ifosfamide, and 1/4 with osteosarcoma-like chemotherapy). In localized patients, the 5-year OS was significantly better for age ≤ 50 years (68% vs 34%, p = 0.02) and extremity and central tumor as compared with pelvis/sacral location (50% vs 58% vs 0%, p = 0.008), with improved disease-free survival (DFS) after chemotherapy (49% vs 33%, p = 0.04). Conclusions: Metastatic B-AS is a fatal disease and inclusion in experimental trials is warranted. In localized patients, a better probability of survival is expected in younger and surgically treated patients. The use of chemotherapy was associated with improved DFS.
Metagenomic discovery of a distinct inflammatory subtype of human angiosarcoma associated with human herpesvirus 7.
Authors: Chan Jason Yongsheng , Lim Jing Quan , Ravi Vinod , Guan Peiyong , Tay Timothy Kwang Yong , Selvarajan Sathiyamoorthy , Ong Choon Kiat , Huang Dachuan , Jing Tan , Ng Cedric Chuan Young , Sung Ken Wing-Kin , Harunal Rashid Mohamad Farid Rin , Quek Richard Hong Hui , Tan Ngian Chye , Teo Melissa Ching Ching , Rozen Steven , Tan Patrick , Futreal Andrew , Teh Bin Tean , Soo Khee Chee
Published: March 2020

11047

Background: Angiosarcomas are rare, clinically-aggressive endothelial tumors with remarkable heterogeneity in terms of anatomical and etiological origins, amongst which UV-radiation and oncogenic viruses have been implicated. Methods: The genomic and transcriptomic landscapes of human angiosarcomas were examined using whole genome sequencing (n = 18) and RNAseq (n = 14). Results were validated in an extended cohort of FFPE tissue (n = 57) on various platforms. Results: We observed recurrent mutations in known angiosarcoma-associated genes including TP53, KDR, POT1 and PTPRB. The median tumor mutation burden (TMB) was 1.95 mutations per megabase and was highest in a subset of head and neck angiosarcomas (HN-AS, n = 6) harboring UV signatures. The remaining cases, including seven HN-AS, contained a significantly lower TMB (5.04 vs 0.91, p= 0.0007). In corroboration, UV exposures were validated by cyclobutane pyrimidine dimer immunohistochemistry in 15 of 35 (42.9%) HN-AS and cutaneous angiosarcomas, but not in visceral or breast angiosarcomas. Gene set enrichment analysis (GSEA) revealed upregulation of “cell cycle” and “inflammation” pathways in angiosarcomas. Notably, drug inhibition of overexpressed kinases including aurora kinase, polo-like kinase and checkpoint kinase-1 potently reduced viability in two angiosarcoma cell lines, achieving IC50s of < 1µM. Metagenomic analysis detected viral reads mapping to the human herpesvirus-7 (HHV-7) genome, which were verified by PCR and immunohistochemistry. Genomic integration of HHV-7 was demonstrated at its flanking DRR telomeric repeat sequence adjoining the subtelomeric region of chromosome 17p. Overall, HHV-7 was detected in 38 of 57 (66.7%) angiosarcomas and inversely correlated with UV exposure ( p= 0.01). GSEA and Nanostring IO360 profiling showed that “inflammation” pathways were enriched in viral-positive angiosarcomas, while “cell cycle” pathways were enriched in viral-negative cases. Compared with HHV-7 negative cases, HHV-7 positive angiosarcomas were associated with high tumor inflammation scores (TIS ≥ median 6.74) (73.3% vs 25.0%, p = 0.02). Conclusions: We identified distinct subtypes of angiosarcoma characterized by HHV7-positive “inflammation” and UV-associated “cell cycle” phenotypes.
Low-dose chemotherapy with methotrexate and vinblastine for patients with refractory desmoid tumors: A second report of relationship between efficacy and various factors.
Authors: Nishida Yoshihiro , Sakai Tomohisa , Shimizu Koki , Urakawa Hiroshi , Arai Eisuke , Ikuta Kunihiro , Ando Yuichi , Ishiguro Naoki
Published: March 2020

11050

Background: Efficacy of low-dose chemotherapy with methotrexate (MTX) and vinblastine (VBL) for desmoid-type fibromatosis (DF) has been reported and approved by many physicians. However, significant factors including biomarker could not be identified to better predict the efficacy of this chemotherapy. Since 2003, meloxicam, which is a selective COX-2 inhibitor, has been applied consecutively as a first line treatment. We applied the low-dose chemotherapy with MTX+VBL for refractory patients. The aim of this study was to reveal the clinical outcome of low-dose chemotherapy with MTX+VBL, and determine the useful factors to predict the efficacy including CTNNB1 mutation status. Methods: Since 2003, 167 cases were histologically diagnosed as DF. Among them, 36 cases were treated with MTX (30mg/M2) +VBL (6mg/M2) chemotherapy. Treatment interval was basically 2 weeks according to our previous study. Effectiveness was evaluated with MRI and/or CT every 3 months according to Response Evaluation Criteria in Solid Tumors (RECIST). Frozen or FFPE (Formalin-Fixed Paraffin-Embedded) specimens obtained at biopsy or previous surgery were subjected to the analyses for CTNNB1 mutation status by Sanger method. Clinical outcome and factors correlating with the efficacy were analyzed. Results: Among 36 cases with this chemotherapy, male was 13, mean age at the treatment was 36±18 years. Mean maximum diameter of tumor was 15±18 cm. Twenty-nine cases (81%) harbored CTNNB1 or APC mutation. Mean treatment duration and cycles of MTX+VBL were 20 months and 29 cycles, respectively. According to RECIST, PD in 2, PR 1n 15, and SD in 19. According to CTCAE, Grade 3 or more adverse events were observed in only one case. CTNNB1 mutation status, gender, age, size, and location did not affect the outcome of RECIST. Longer treatment duration and cycles of chemotherapy were significantly associated with the outcome (P = 0.002 and 0.004, respectively). In 15 cases of PR, recurrent tumors significantly took longer time to get efficacy (P = 0.027), and tumors arising in trunk and extremities tended to take longer time (P = 0.1). Conclusions: Low-dose MTX+VBL chemotherapy is effective and feasible treatment for refractory DF regardless of CTNNB1 mutation status. Occasionally it takes time to obtain objective response.
Use of cardioprotective dexrazoxane and myelotoxicity in anthracycline-treated soft tissue sarcoma patients.
Authors: Silletta Marianna , Spalato Ceruso Mariella , Napolitano Andrea , Mazzocca Alessandro , Valeri Sergio , Improta Luca , Santini Daniele , Tonini Giuseppe , Vincenzi Bruno
Published: March 2020

11053

Background: Dexrazoxane (DEX) is indicated as a cardioprotective agent for patients receiving doxorubicin, who are at increased risk for cardiotoxicity. Concerns have been raised on the use of DEX, particularly in the adjuvant setting, because of the risk of interference with the antitumor effect of doxorubicin. Two meta-analyses in metastatic breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when DEX is used. No data in soft-tissue sarcoma (STS) patients is available, so far. Here, we retrospectively analyzed a cohort of our Institute database to assess whether the addition of DEX causes more bone marrow suppression in STS patients receiving Anthracycline-Ifosfamide (AI) combination in perioperative and advanced setting. Methods: 133 patients who received AI between January 2006 and December 2017 were included. 46 of them received DEX concurrently with the AI treatment. Hospital records were reviewed and available for all patients (the accessibility of all the data was an inclusion criterion). Compared to the non-DEX group, patients who received DEX were more frequently treated in the context of a perioperative setting (respectively 27.3 vs 38.8%). No other differences in terms basal patient features were recorded. Significantly, all patients received similar post-medication after each cycle. Results: Compared with the non-DEX group, DEX treatment was associated with significantly higher rates of G3/4 hematological side effects: leucopenia (28.7 vs 56.5%, p value=0.0014); neutropenia (35.6 vs 69.6%, p value=0.0002); anemia (28.7 vs 41.3%, p value=0.1758); thrombocytopenia (32.1 vs 54.3%, p value=0.0159). Similarly, compared to the non-DEX group, there were more hospitalizations for febrile neutropenia (37.9 vs 63.0%, p value=0.0066) and dose reductions (19.5 vs 39.1%, p value=0.0221) in the DEX group, above all in perioperative setting (15.6 vs 58.3%, p value=0.0085); but no significant difference in the incidence of treatment delays or interruption. Conclusions: Adding DEX to Anthracycline-based chemotherapy in soft-tissue sarcoma patients leads to higher rates of bone marrow suppression in all blood components, as well as more febrile neutropenia events, and dose reductions.
A phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated Classic Kaposi sarcoma (CKS).
Authors: Zer Alona , Icht Oded , Joseph Lilach , Avram Dana , Jacobi Oded , Fenig Eyal , Shamai Sivan , Shapira Frommer Ronnie , Bernstine Hanna , Weitzen Rony , Bar-Sela Gil , Stemmer Salomon M. , Lotem Michal
Published: March 2020

11064

Background: CKS is an angioproliferative mesenchymal neoplasm causatively associated with human herpes virus 8 infection. Though recombinant IFNa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation in CKS therapy. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated progressive CKS (NCT03219671). Methods: CKS pts with progressive disease after ≥ 1 line of systemic therapy and measurable disease by PET/CT and/or physical exam received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint was overall response rate (ORR), secondary endpoints include 6-months progression free survival rate (PFS) and safety. Correlative studies in tumor and serum samples are ongoing using an NGS panel for DNA and RNA and proteomic staining (Tempus Labs Inc). A pre-planned interim analysis was conducted after the first ten enrolled patients for efficacy and toxicity evaluation. Results: Ten patients were enrolled and evaluable between April2018 and February2019. Median age 72 (61-79), all male. At a median FU of 3.1 months (1.5-8.1) ORR was 50% (4 patients PR, 1 patient CR, 5 patients SD). Median PFS was not reached however no progression of disease was documented so far. The safety profile was as expected with all patients experiencing G1 toxicity and four patients with G2 toxicity (1 ALT/AST increase, 2 asymptomatic lipase increase). One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in one patient (G2 LFT increase. maintaining CR 4 months after treatment discontinuation). Correlative results are pending. Conclusions: The interim analysis in this prospectively designed phase II study of nivolumab and low-dose ipilimumab demonstrate promising activity in progressive CKS, with 50% ORR and no events of progression thus far. We expect to report the updated efficacy and correlative data. Clinical trial information: NCT03219671.
Using machine learning to predict mortality in older patients with cancer: Decision tree and random forest analyses from the ELCAPA and ONCODAGE prospective cohorts.
Authors: Audureau Etienne , Soubeyran Pierre-Louis , Martinez-Tapia Claudia , Bellera Carine A. , Bastuji-Garin Sylvie , Boudou-Rouquette Pascaline , Rainfray Muriel , Chahwakilian Anne , Grellety Thomas , Hanon Olivier , Mathoulin-Pélissier Simone , Paillaud Elena , Canoui-Poitrine Florence
Published: March 2020

11516

Background: Accurate prognosis is crucial to decision making in oncology, but remains challenging in older patients due to the heterogeneity of this population and the lack of ability of current models to capture complex interactions between oncological and geriatric predictors. We aimed to develop new predictive algorithms based on machine learning to refine individualized prognosis in older patients with cancer. Methods: Data were collected from 3409 patients ≥70 years referred to geriatric oncology clinics for completion of a geriatric assessment (GA), including 2012 and 1397 patients from the ELCAPA (training set) and ONCODAGE (validation set) French prospective cohorts, respectively. Candidate predictors included baseline oncological and geriatric parameters, G-8 score and routine biological data (CRP/albumin ratio). Prognostic models for 12-months mortality were built using Cox regression model, single decision tree (DT) and random survival forest (RSF). Models performance was compared based on externally validated Harrell’s C-indexes. Results: During the 1-year study period, 875 (43%) and 219 (16%) patients died in the training and validation sets, respectively (mean age: 81±6 / 78±5, women 47% / 70%, metastasis 50% / 34%). Cox model identified 9 independent predictors of mortality: tumor site/metastatic status, anticancer treatment, weight loss > 3kg, drugs > 5, renal failure, increased CRP/Albumin, ECOG-PS≥2, ADL≤5 and altered TGUG. DT identified more complex combinations between features, yielding 16 patient groups with highly differentiated survival, notably depending on the G-8 ( < 10 vs. ≥10 as the root node). RFS had the highest C-index (0.86 [RFS], 0.82 [Cox], 0.81 [DT]), identifying the G-8, CRP/albumin and tumor site/metastasis as the most important features. Conclusions: While Cox modeling confirmed known independent prognostic factors, DT revealed more complex interactions between them and random forest achieved superior prognostic performance by better capturing patient’s complexity. The latter model has been implemented into an interactive web interface for easy and direct use in clinical practice. Clinical trial information: NCT02884375.
Comparing outcomes data from dedicated oncology-subspecialist hospitalists to those from a traditional care model on an inpatient oncology service.
Authors: Fanucci Kristina , Yang Andrew Chung , Reinert Steven E. , Niroula Rabin
Published: March 2020

11538

Background: Changes in the complexity and delivery of health care and efforts to contain rising costs gave rise to the hospitalist model of care delivery in the 1990s. More recently some hospitals have begun using the hospitalist model on inpatient oncology floors. Oncology patients are a unique population who require high rates of hospitalization for problems arising from their progressive disease burden and side effects of cancer-directed therapy and have high rates of 30 day readmissions (30DR), an important quality metric. The majority of studies in this area have shown similar outcomes comparing care given by internal medicine hospitalists working full time on an inpatient oncology service compared to multiple oncologists working in rotating shifts on the same inpatient oncology service (Traditional). A new care model using dedicated hematology/oncology subspecialist hospitalists (H-O) to care for patients admitted to the oncology service has been implemented at our academic medical center. Methods: We conducted a retrospective chart review to identify patients with a cancer diagnosis admitted to the oncology service over a six year period. 7/1/2012-6/30/2015 marked the Traditional care model and 7/1/2015-7/1/2018 the H-O model. We compared 30DR, discharge to hospice, length of stay (LOS), and inpatient mortality between these two groups. Results: We identified a total of 3778 patients admitted to the oncology service over this six year period—1932 patients admitted to the Traditional service and 1846 patients admitted to the H-O service. There was a significant difference in 30DR between the Traditional v. H-O service (36.7% v. 29.5%, χ2= 21.1, p < 0.00001) and discharge to hospice (7.6% v. 12.9%, χ2= 29.0, p < 0.0000001). There was no significant difference in LOS between the Traditional and H-O services (6.40 days v. 6.03 days, p = 0.122) or in-hospital mortality (2.6% v. 1.9%, χ2= 2.16, p = 0.14). Conclusions: The shift to dedicated hospitalist-oncologists caring for patients on the inpatient oncology service significantly decreased 30DR at our institution. There were also significantly more patients transferred to hospice care. We found no significant difference between the two groups in LOS or inpatient mortality. This care model may help reduce the cost of caring for oncology patients by decreasing 30DR.