bluuebunny/crossref_metadata_2025 huggingface dataset:
The incidence of anxiety and depression in adult cancer outpatients in an area of social deprivation.
Authors: Chapman Hannah Louise , Melcher Lucinda , Shute Justin
Published: March 2020

e20709

Background: Psychological distress is common in cancer patients and negatively impacts patient quality of life. Untreated depression predicts early death in patients with advanced cancer. Anxiety and depression may be unrecognised in cancer patients as symptoms can be mistakenly attributed to the underlying malignancy. We assessed the incidence of anxiety and depression in patients attending two hospitals located in areas of significant social deprivation and ethnic diversity. Methods: Patients attending the oncology department at North Middlesex University Hospital and Princess Alexandra Hospital during a one week period were invited to complete a questionnaire. We collected socio-demographic data. The rest of the questionnaire consisted of the Hospital Anxiety and Depression Scale (HADS). HADS is a 14 question, validated screening tool. Total scores range from 0-42, but can be divided into two subscales: HADS-D for depression and HADS-A for anxiety. Interpretation is based primarily on cut-off scores suggested by the test’s authors. In a previously reported non-clinical sample, mean total HADS was 9.82, HADS-D 3.68 and HADS-A 6.14. Results: 96 patients completed the questionnaire. 64 out of 96 patients (67%) were aged between 50 and 79 years. The majority were of white UK ethnicity. The most common types of cancer were breast and colorectal. Seventy five patients (78%) had a ‘normal’ total HADS (≤14). The mean scores for total HADS, HADS-D and HADS-A were 10.53, 4.61 and 5.93, respectively. On the HADS-A subscale, 14 patients had mild anxiety, 12 had moderate and 2 patients had severe anxiety. Depression scores were slightly lower: 12 patients had mild depression and 4 had moderate depression. No patient had severe depression. Only 6 (6%) patients reported taking anti-depressant medication. Conclusions: We demonstrate lower levels of anxiety and depression in a mixed group of cancer patients than previously reported. We explore the possible causes for this difference. Thresholds set to identify ‘cases’ in a non-clinical population may be too high for cancer patients. HADS is a useful screening tool in oncology patients but should be combined with clinical assessment to improve sensitivity and specificity.
Sorafenib (SFB) low dose in octogenarians with advanced or inoperable (a/i) HCC: Toxicity and efficacy evaluation.
Authors: Carreca Ignazio Ugo ,   A.I.R.O.N.A.-i.a.o.r.g..-S.I.C.O.G.
Published: March 2020

e20719

Background: HCC accounts for approximately 90% of all primary liver cancers, and is the fifth most common cancer in the world. So far prognosis of AHCC is very poor, particularly if consider very elderly pts. Treatment with SFB at standard dose may results in untolerable toxicity especially in very old people with HCC Cancer Aim of the study is to investigate if SFB at reduced dose is efficient and tolerable in octogenarian people with HCC. Methods: 30 patients,16 male and 14 female with AHCC histologically proven were enrolled; mean age was 79. Main Inclusion Criteria: Child-Pugh A or B; adequate liver, hematological, and renal function; informed writed consent acquired. Comprehensive Geriatric Assessment (CGA) according to Balducci’s classification and PFS (ECOG) not greater then 1 were considered as well. Serum CgA, VEGF and αFP were evaluated at baseline. Response evaluation were according to RECIST. Results: Pts received SFB 400 mg p.o., daily until intolerable ADRs or progression disease No discontinuation of treatment was needed for all pts; only 6 pts experienced severe ADRs not discontinued treatment withdrawal was needed. Pts with good OS (median value:11mths) showed also lower values of serum CgA and VEGF better than pts with poor prognosis. This outcome is under investigation. Conclusions: SFB could be administered with “not inferiority criteria vs SFP std treatment. Even if increased age is poor prognostic factor for tolerability, the reduction of dose don’t seem to reduce the efficacy of treatment in this group of patients. On the other hand the minimization of ADRs positively affects the quality of life. Further data were needed to assess how the lower values of serum CgA and VEGF levels, could play a role as new prognostic factors in HCC advanced or inoperable in octogenarian people.
Cognitive function in breast cancer and lymphoma patients receiving chemotherapy: An ongoing nationwide University of Rochester Cancer Center (URCC) Community Clinical Oncology Program (CCOP) observational study with 1,200 patients and controls.
Authors: Janelsins Michelle Christine , Mustian Karen Michelle , Yao Song , Heckler Charles E. , Palesh Oxana , Ontko Mary , Dakhil Shaker R. , Smiskol Paul , Melnik Marianne , Gross Howard M. , Ahles Tim , Ambrosone Christine B. , Morrow Gary R.
Published: March 2020

TPS9647

Background: Chemotherapy-related cognitive impairment (CRCI) is a major concern for up to 75% of cancer patients that can negatively affect quality of life. Studies which have objectively assessed cognitive function (CF) in patients suggest that chemotherapy is associated with declines in multiple domains. A large, prospective longitudinal study with age- and gender- paired healthy controls is needed to confirm and expand these findings, to identify etiological mechanisms of CRCI, and to identify the best assessment methods for detecting CRCI. Methods: We are conducting a nationwide prospective observational study (N=1,200), conducted through the URCC CCOP Research Base and 23 CCOPs. The primary aim is to test the hypothesis that breast cancer and lymphoma patients receiving chemotherapy will have greater impairments in CRCI over time than a control comparison group. Breast cancer (stage I-IIIc) and lymphoma patients (intermediate/high grade disease) meet the following eligibility: 1) chemotherapy naïve, 2) ≥21 years of age, 3) no CNS disease, 4) scheduled to receive a standard course of chemotherapy, and 5) no concurrent radiation. Healthy control participants meet eligibility criteria 1-3 and are the same gender and age as paired patients. CF is assessed at pre-chemotherapy (Assess. 1), post-chemotherapy (Assess. 2), and 6 months post-chemotherapy in patients; their paired controls are assessed at the same time intervals. CF is measured via: 1) Computer-based CANTAB neuropsychological (NP) battery (assessing memory (primary aim), verbal memory, sustained attention, processing speed, and executive function (secondary aims)), 2) paper-based objective NP assessment (secondary aims), 3) phone-based objective NP assessment (tertiary aims), and 4) Single item, patient-reported CF (tertiary aims). Blood is collected at Assess. 1 and 2 to explore inflammatory and genetic mechanisms. 807 participants have been enrolled in 21 months. Funding: U10CA037420-26 Supp. MCJ; U10CA037420, GRM; & URCC/RPCI Grant, MCJ & CBA. Clinical trial information: NCT01382082.
Evaluating unconscious bias: Speaker introductions at an international oncology conference.
Authors: Duma Narjust , Durani Urshila , Woods Cynthia Brooke , Kankeu Fonkoua Lionel Aurelien , Cook Joselle , Wee Christopher , Fuentes Harry E , Gonzalez-Velez Miguel , Murphy Martina Cathryn , Jain Shikha , Marshall Ariela Lucy , Graff Stephanie L. , Knoll Miriam
Published: March 2020

10503

Background: Gender bias can be reinforced through the use of gender-subordinating language and differences in the forms of address. We examined how professional titles were used during speakers’ introductions at the American Society of Clinical Oncology (ASCO) Annual Meeting. Methods: A retrospective observational study of video-archived speaker introductions at the 2017 and 2018 ASCO annual meetings was conducted. Data were extracted by mixed-gender coders. Professional address was defined as professional title followed by full name or last name. Multivariable logistic regressions were used to identify factors associated with the form of address. Results: 2511 videos were reviewed and 812 met inclusion criteria. Regarding speakers’ characteristics, 530 (65%) were non-Hispanic white (NHW), 743 (92%) held a MD or MD-PhD degree, and 484 (60%) were an associate or full professor. Female speakers were less likely to receive a professional address compared to male speakers (61% vs. 81%, p < 0.001). Female speakers were more likely to be introduced by first name only (17% vs. 3%, p < 0.001). Males were less likely to use a professional address when introducing female speakers compared to male speakers (53% vs. 80%, p < 0.01). No gender differences in professional address were observed for female introducers (p = 0.13). Male introducers were more likely to address female speakers by first name only compared to female introducers (24% vs. 7%, p < 0.01). In a multivariable regression including gender, race, degree, and academic rank, male speakers were more likely to receive a professional address compared to female speakers (OR: 2.67, 95%CI: 1.81-3.94, p < 0.01). Black speakers of both genders were less likely to receive a professional address compared to NHW (OR: 0.10, 95%CI: 0.01-0.53, p < 0.01). Female gender was a predictor for a non-professional form of address (first name only) (OR: 9.50, 95%CI: 4.38-20.62, p < 0.01). Conclusions: When introduced by men, female speakers were less likely to receive a professional address and more likely to be introduced by first name only compared to male speakers. Selective use of forms of address may strengthen gender bias; more research is needed to explore the causes of this disparity and its influence.
The higher school of oncology: An educational program adopting the western oncology experience in Russia.
Authors: Baron Ekaterina , Sittig Michelle , Gushchin Vadim
Published: March 2020

10512

Background: Disparities in current global oncology care are a major concern for many societies. Two-year oncological training in Russia is deficient in evidence-based medicine (EBM) and effective patient communication skills, despite the fact that these dictate the ability to provide optimal cancer care. We report a 3.5-year sustained program aimed at implementing Western-oriented education among young Russian oncologists to combat these educational deficiencies. Methods: The Higher School of Oncology (HSO) is a 5-year national competitive program established to supplement the traditional 2-year Russian oncology curriculum with an emphasis on patient communication, critical appraisal of oncologic articles, multidisciplinary cancer care, and program development. A total of 35 PGY1-4 residents (8-9 residents annually) have enrolled in the program. Expatriate Russian physicians practicing in the US led 140 online educational seminars with journal clubs and clinical case presentations. Communication skills were evaluated by an independent private educational group. Results: Significant improvement of EBM knowledge was marked among HSO residents, from inability to explain basic concepts to practicing and teaching EBM. Beginning in the 3rd year of the program, residents organized educational courses and conducted journal clubs for HSO and non-HSO colleagues. Residents of the program had higher patient communication scores compared to that of residents of standard Russian programs. HSO residents promoted the spread and popularization of EBM and a patient-centered approach among attending physicians, improving the quality of cancer care. The HSO also triggered imitation of similar projects in other residency programs. Conclusions: The HSO project has pioneered EBM training and led to systemic changes in cancer patient care for Russian oncologists. This model has shown success and may be useful in overcoming global medical educational disparities in other specialties and in other countries facing similar challenges.
Implementation of competency-based medical education in a Canadian medical oncology training program: Lessons from our first year.
Authors: Tomiak Anna T. , Linford Geordie , McDonald Micheline , Willms Jane , Hammad Nazik
Published: March 2020

10514

Background: As part of a university wide initiative, CBME was implemented in our MO training program in July 2017. Stages, Entrustable Professional Activity (EPA) assessments and Required Training Experiences established by the Royal College of Physicians and Surgeons of Canada were adopted. MedTech Central, the electronic portfolio developed at our university was used for assessment collection. We share here observations and experiences from our first year of implementation. Methods: Assessment metrics were obtained through MEdTech. Ethics was granted by Queen’s University as part of an ongoing research study on feedback. Lessons learned were compiled from discussions between the Program Director, Residents, Program Administrator, CBME Education Consultant and CBME lead. Results: A total of 195 assessments were completed July 2017-November 2018. 81% were EPA assessments and the remainder multisource feedback, rubrics and field notes. The median number of assessments per faculty was 17 (0-42). 52% of assessments included written “Comments” or “Next steps”. A median of 6 assessments per faculty member included specific or actionable feedback. Lessons learned centered on: 1) Faculty and Resident development and engagement (critical before, during and after implementation); 2) Value of sharing work of CBME (CBME Education Consultant, CBME Lead, Academic Advisors, Competence Committee); 3) Importance of effective communication strategy with stakeholders 4) Importance of collaboration with other training programs at institutional and national levels; 5) Culture change (a slow process); 6) Resident concerns regarding lack of global assessment; 7) Assessment plan challenges (How many observations required?); 8) Burden of CBME (Resident driven assessments or a better balance?) ; 9) Limitations of e-portfolio (How to live track and by whom?); 10) Costs 11) Value of continuous quality assurance and improvement. Conclusions: Our first year of implementation was successful in introducing CBME concepts, work based assessments and e-portfolios. Ongoing work is needed, including increasing the number of assessments and quality of feedback.
Choosing oncology as specialization: Medical students' perception after clinical rotation in cancer center.
Authors: Castillo Fernandez Omar Orlando , Lim Maria , Montano Lilian Hayde , Perez-Jimenez Gaspar , Camaño Jhonattan , Mendoza Enrique , Pereira Yamileth
Published: March 2020

10528

Background: Cancer is a leading cause of death worldwide and the demand for oncologist and palliative care specialists is increasing dramatically. Two years ago, The Universidad de Panama incorporated Oncology in the curriculum in order to face the shortage of professionals involved in cancer care. Little information is available concerning young medical students desire to pursue a career in oncology.The aim of this study is to evalute medical students perception about Oncology as a specialization field. Methods: An electronic survey was sent to medical students from Universidad de Panama after finishing Oncology rotation the last 2 years. Chi square and Mann Whitney U tests were used to compare variables. Results: 145 questionnaries were responded (40%). 60% female and 40% male. Median age was 25 years old. Clinical rotation during Oncology practices were: 37% in Medical Oncology, 24% in Surgical Oncology, 21% in Radiation Oncology and 18% in Palliative Care. 20% (29) of students are highly motivated to pursue a career in Oncology. 8 in Radiation Oncology. 8 in Surgical Oncology, 8 in Medical Oncology and 5 in Palliative Care. Variable associated with a oncology preference were: male gender (p=0.007), lack of human resources (p=0.009), contact with patients and family (p=0.005), good experience with mentor (p=0.002), nature and complexity of disease (p<0.001). Potential emotional burden was negatively asssociated (p=0.004) with oncology preference. 66% of students acknowledged that clinical rotation changed positively their perception about cancer patient care and a third of students haved not rule out the possibility to choose Oncology in the near future. Conclusions: Early exposition to medical student to cancer care might help to reduce the global shortage of oncologist and palliative specialists.
STRASS (EORTC 62092): A phase III randomized study of preoperative radiotherapy plus surgery versus surgery alone for patients with retroperitoneal sarcoma.
Authors: Bonvalot Sylvie , Gronchi Alessandro , Le Pechoux Cecile , Swallow Carol Jane , Strauss Dirk C. , Meeus Pierre , van Coevorden Frits , Stoldt Stephan , Stoeckle Eberhard , Rutkowski Piotr , Sangalli Claudia , Honoré Charles , Rastrelli Marco , Raut Chandrajit , Chung Peter , Fiore Marco , Litiere Saskia , Marreaud Sandrine , Gelderblom Hans , Haas Rick L.M.
Published: March 2020

11001

Background: The predominant pattern of failure of retroperitoneal sarcoma (RPS), frequently associated with subsequent death, is locoregional recurrence. Unlike in limbs, the efficacy of radiotherapy (RT) combined with surgery is not established. Methods: STRASS is a randomized, multicentre, international trial. Eligible patients had histologically-proven localized primary RPS, operable and suitable for radiotherapy. Patients were randomized 1:1 to preoperative RT (3D-CRT or IMRT) 50.4 Gy followed by surgery (RT/S group) or surgery alone (S group), stratified by hospital and performance status (0-1 vs 2). Primary endpoint is abdominal recurrence-free survival (ARFS; local relapse after complete resection, peritoneal sarcomatosis, R2 surgery, progressive disease during RT or unresectable disease). IDMC recommended a sensitivity analysis in which local progression on RT is not regarded as an event for patients who subsequently achieve complete surgical resection. Secondary endpoints were recurrence-free survival, overall survival, acute toxicity profile of RT, perioperative and late complications, and QoL. The study was designed to provide 90% power to show an increase of 20% in the 5-year ARFS rate, from 50% to 70% (corresponding to a HR of 0.52) at 2-sided 5% significance level. Results: 266 patients from Europe, USA and Canada were randomized between January 2012 and April 2017; 198 patients (74.5 %) had liposarcoma (LPS). Eighteen patients were designated ineligible. Overall rate of re-operation for any complication was 10.1%: 13 (10.9%) and 12 (9.4%) patients in RT/S versus S groups. 19 pts (14%) progressed during RT, 4 of whom did not undergo surgery. 3-year ARFS was 60.4% (95% Confidence interval (CI) 51.4-68.2%) and 58.7% (49.5- 66.7%) (HR = 1.01, 95%CI 0.71-1.44, p=0.954) in RT/S versus S groups. In the sensitivity analysis, 3-year ARFS was 66.0% (57.1-73.5%) and 58.7% (49.5-66.7%) in RT/S versus S groups (HR = 0.84, 95% CI 0.58-1.21, p=0.340). In the LPS subgroup, 3-year ARFS (sensitivity analysis) was 71.6% (61.3-79.6%) and 60.4% (49.8-69.5%) in RT/S versus S groups (HR = 0.64, 95%CI 0.40-1.01, p =0.049). Conclusion: STRASS failed to demonstrate a benefit of pre-operative RT for RPS. In the exploratory analysis, preoperative RT may benefit the LPS subgroup. Funding Source: EORTC and EUROSARC FP7 278472. Clinical trial information: EORTC 62092.
Results of the first interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma.
Authors: McCabe Martin G. , Moroz Veronica , Khan Maria , Dirksen Uta , Evans Abigail , Fenwick Nicola , Gaspar Nathalie , Kanerva Jukka , Kühne Thomas , Longhi Alessandra , Luksch Roberto , Mata Cristina , Phillips Marianne , Sundby Hall Kirsten , Valverde Morales Claudia Maria , Westwood Andrew J. , Winstanley Mark , Whelan Jeremy , Wheatley Keith ,   Euro Ewing Consortium
Published: March 2020

11007

Background: 5-year survival of RR-ES is about 15%. Several chemotherapy regimens are used, but without robust evidence. rEECur, the first randomised controlled trial in this setting, is defining a standard of care, balancing efficacy and toxicity. Methods: Patients aged 4 to 50 with RR-ES and fit to receive chemotherapy were randomised 2, 3 or 4 ways between topotecan & cyclophosphamide (TC), irinotecan & temolozomide (IT), gemcitabine & docetaxel (GD) or high-dose ifosfamide (IFOS). Primary outcome measure was objective response (OR) after 4 cycles by RECIST 1.1. Secondary outcomes included PFS, OS and toxicity. A probability-based Bayesian approach was used. The first interim assessment to determine which arm should be closed occurred when 50 evaluable patients had been recruited to 3 arms and evaluated for the primary outcome measure. Results: 242 patients (89% RECIST-evaluable) recruited between 18/12/14 and 21/06/18 were randomised to TC (n=75), IT (71), GD (66) and IFOS (30). Median age was 21 years (range 4 to 49). Patients had: refractory ES (20%), 1st recurrence (63%), >1st recurrence (17%); initial primary disease arose in bone in 60%; disease progression sites were primary site (17%), pleuropulmonary (29%) or other metastatic (54%). Median follow up was 11.3 months. Outcomes in the GD arm were: response rate 11.5% (95% CI: 4.4 to 23%), median PFS 3.0 months (95% CI: 1.6 to 8.0), median OS 13.7 months (95% CI: 10.1 to 23.9). The table shows, for each pairwise comparison of GD with the other arms (randomly labelled A, B, C to maintain blinding of open arms), the probabilities given the observed data that OR, PFS and OS were better for GD than for each other arm (RR: relative risk, HR: hazard ratio). For OR and PFS, all comparisons favoured the other arms. There were fewer grade 3/4 adverse events with GD than with the other arms pooled (58% v. 74%). Conclusions: rEECur has shown that GD is a less effective treatment than TC, IT or IFOS in reducing tumour burden or prolonging PFS in RR-ES. Recruitment continues to the remaining arms. Clinical trial information: ISRCTN36453794. [Table: see text]
A phase II randomized study of CMB305 and atezolizumab versus atezolizumab in NY-ESO-1+ soft tissue sarcoma: Analysis of immunogenicity, tumor control, and patient survival.
Authors: Chawla Sant P. , Van Tine Brian Andrew , Pollack Seth , Ganjoo Kristen N. , Elias Anthony D. , Riedel Richard F. , Attia Steven , Choy Edwin , Okuno Scott H. , Agulnik Mark , von Mehren Margaret , Livingston Michael B. , Keedy Vicki Leigh , Verschraegen Claire F. , Philip Tony , Bohac Gerry C. , Yurasov Sergey , Lu Hailing , Chen Michael , Maki Robert G.
Published: March 2020

11011

Background: CMB305 (C) is an immunotherapy designed to generate an anti-NY-ESO-1 immune response (IR). C consists of a dendritic cell-targeting lentiviral vector encoding NY-ESO-1 gene (LV305), and a TLR-4 agonist NY-ESO-1 recombinant protein plus GLA-SE (G305). A Phase 1 study demonstrated C is safe, generates IR and conveys a median overall survival (mOS) of 23.7 months (15.5, not reached [NR]) for soft tissue sarcomas & 29.2 months (12.2, NR) for synovial sarcoma (SS) (ESMO 2018). We evaluated efficacy and safety of C and atezolizumab (A) vs A alone in NY-ESO-1+ SS and myxoid round cell liposarcoma (MRCL). Methods: A prospective randomized open label phase 2 study of C (LV305 Intradermal Days 0, 14, 42, 70 + G305 Intramuscular Days 28, 56, 84 then q 6wk up to one year (yr)) + A (1200mg IV q3wk) vs A alone in advanced NY-ESO-1+ SS/MRCL. Primary endpoints of OS and progression-free survival (PFS); secondary endpoints of safety, IR, and response rate and post hoc analysis by line of therapy. Results: 88 patients (pts) were enrolled and dosed. Arm C+A: median age 48 yrs, 73% SS, 98% relapsed metastatic, 73% ≥2 prior lines chemotherapy; Arm A: 47 yrs, 67% SS, 84% relapsed metastatic, 53% ≥2 prior lines chemotherapy. Most treatment-related adverse events (TRAE) Grade 1/2, no treatment related deaths. Summary of clinical outcomes. Conclusions: Despite no major differences in PFS and OS between the treatment arms (Arm C+A had more advanced disease and more prior lines of chemotherapy), Arm A +C achieved PRs, a higher level of anti-NY-ESO-1 IR, and pts with IR had numerically superior outcomes. Moreover, the clinical benefit of C+A in earlier lines of therapy warrant further study. Clinical trial information: NCT02609984. [Table: see text]
Interval-compressed vincristine, doxorubicin, cyclophosphamide (VAC), alternating with ifosfamide and etoposide (IE) for adults with Ewing or Ewing-like sarcoma.
Authors: Lu Eric , Ryan Christopher W. , Bassale Solange , Lim Jeong Youn , Davis Lara Emily
Published: March 2020

11025

Background: In Children’s Oncology Group trial AEWS0031, VAC alternating with IE administered every 2 weeks rather than every 3 weeks resulted in a superior event-free survival (EFS). In the 2-week dosing group, a median interval of 15 days (mean 17.3) was achieved. Only 12% of patients enrolled in the trial were age 18+ and thus the feasibility of interval-compressed VAC/IE in the adult population remains poorly described. We conducted a retrospective analysis of our institutional experience using this regimen. Methods: Pharmacy administration records at Oregon Health and Science University were reviewed to identify patients age 18+ with Ewing and Ewing-like sarcoma who received VAC/IE q2wk, with first dose between January 2011 and March 2018. Results: 24 patients were identified. Median age was 28 (range 18 to 60). At diagnosis, 67% had localized disease. The most common primary sites were extremity (38%) and pelvis (17%); another 25% had extra-osseous primary tumors. Local therapy included surgery in 50% and XRT in 33% of subjects. The median interval between cycles was 16.7 days (mean 17.5). The median number of admissions for toxicity per patient was 2. The median number of dose delays (toxicity prolonging the 2 week interval) per patient was 4. Early treatment discontinuation occurred in 17%. Cumulative doses are outlined in Table. 5-year overall survival was 41%. 5-year EFS was 52% among patients with localized disease and 0% among those with metastatic disease. Conclusions: For adults with Ewing and Ewing-like sarcoma, chemotherapy administered every 2 weeks is a feasible and effective therapy, without significant dose reductions required. Our results are comparable to prior studies involving a primarily pediatric population. [Table: see text]
Neurofibromatosis 1 (NF1) and gastrointestinal stromal tumors (GISTs): Five-year experience from a regional center in United Kingdom.
Authors: Bulusu Venkata Ramesh , Casey Ruth , Giger Olivier , Carroll Nicholas , Maher Eamonn
Published: March 2020

11035

Background: NF1 is an inherited autosomal dominant condition characterised by multifocal neurofibromas, café au lait spots, Lisch nodules, freckling. GISTs are the most common mesenchymal tumour of the gastrointestinal tract occurring in NF1 patients. We present our 5 year experience of NF1 associated GISTs from a regional centre in United Kingdom. Methods: 15 patients with GISTs associated with NF1 syndrome were identified from the database. Clinical, pathological, molecular and treatment outcomes were analysed. Results: N = 15. Male-3 and female-12. Median age 46 years. 33% were multifocal and 67% unifocal. Primary site Stomach-6.6%, duodenum-33%, small bowel-67%, colon 6.6%. Presenting symptoms: Abdominal pain-47%, anemia/bleed-40% and incidental finding-13%. Tumour size 0.5-23 cm, median 9 cm. Mitotic index 0-15, median 4 mitoses/5mm2. Risk stratification-Low/intermediate risk 60% and high risk 40%. Histology was spindle cell in 87% and mixed in 13%. All GISTs were CD117 and DOG-1 +ve. SDHB expression was preserved in all GISTs. No activation mutations were detected in KIT (exons 9, 11, 13, 17), PDGFRA (exons 12, 14, 18) and BRAF. Treatment: 67% had the primary GIST resected. None had adjuvant imatinib. 6 patients had been treated with tyrosine kinase inhibitors. 1 partial response lasting < 3 months was observed with Imatinib. No durable responses were seen with Imatinib or Sunitinib or Regorafenib. All 5 patients with metastatic disease died within one year of diagnosis. Conclusions: GISTs associated with NF1 syndrome are rare. Median age of diagnosis is a decade earlier than KIT/PDGFRA mutated GISTs. We observed that NF1 associated GISTs occur predominantly in small bowel, are mostly spindle cell histology and have female preponderance. No durable responses were noted with Imatinib or Sunitinib or Regorafenib. There is an urgent need for systematic international collaboration to identify druggable pathways/targets in NF1 GISTs. Any trials should be multicentre/ multinational to expedite recruitment.
Identification of genomic alterations by circulating tumor DNA in leiomyosarcoma: A molecular analysis of 73 patients.
Authors: Arshad Junaid , Roberts Ali , Cotta Jared Addison , Trent Jonathan C.
Published: March 2020

11044

Background: Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. In contrast to many sarcomas, the genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating Tumor DNA (ctDNA) offers a rapid and non-invasive method of next-generation sequencing (NGS) that could be utilized for diagnosis, therapy and detection of recurrence. Methods: ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes utilizing NGS. Blood samples from patients with leiomyosarcoma were analyzed, and results from December 2014-December 2018 were reviewed. Results: Of the 90 samples collected and analyzed, alterations were detected in 73 ctDNA samples. After exclusion of variants of uncertain significance (VUS), 63 ctDNA samples harbored cancer-associated genomic alterations. Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. 76% (45) were female with a median age of 63 (range, 38-87) years. All samples were designated metastatic. The following table shows common alterations and types of mutations. The other alterations included RAF1, ERBB2, MET, PTEN, TERT, APC and NOTCH1. In 24 of the 73 patients (33%) the genomic alterations detected by ctDNA are potentially targetable by an FDA-approved or clinical trial therapy. There were 4 (5%) patients who were found to have incidental germline TP53 mutations. Conclusions: NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma.[Table: see text]
Clinical outcomes of sunitinib (Su) for patients (pts) with desmoid tumors (DT).
Authors: Miano Salvatora tindara , Francini Guido , Civitelli Serenella , Petrioli Roberto , Francini Edoardo
Published: March 2020

11052

Background: The incidence of DT is steadily increasing in pts affected by familial adenomatous polyposis (FAP) and represents the first cause of death for pts who underwent preventive proctocolectomy. Currently, there is no standard therapy for DT and Tamoxifen (20 mg once daily) + Meloxicam (15 mg once daily) (TM) is the most commonly used regimen in clinical routine. We sought to evaluate the efficacy of Su, the most active PDGFR TKI, as first-line therapy for pts with DT. Methods: In this phase II IRB approved prospective study, pts with progressive, symptomatic, or recurrent DT were randomized to receive either Su (52 mg once daily) or TM. The primary end point was progression-free survival, defined as time from treatment start to clinical or radiological progression, whichever came first, at 2 years (2yr-PFS). Secondary endpoints were rates of objective response (OR), evaluated per RECIST criteria version 1.1, time to OR (ttOR), and toxicity. Adverse events (AE) were assessed per NCI-CTCAE version 4.02. Results: Of the 32 pts enrolled, 22 received Su and 10 TM. In both groups, median age at diagnosis was 43.5 years No OR was observed in the TM group. In the Su group, 17 pts had a partial response and 5 stable disease and the ORR was 75% (95% CI, 50 to 100). At a median follow-up of 27 months, the 2yr-PFS was 81% (95% CI, 69-96) and 36% (95% CI, 22-57) in the Su cohort and TM cohort, respectively (HR = 0.13; 95% CI, 0.05- 0.31; P<0.001). The median ttOR among pts who had an OR was 24 months. In the TM group, no toxicity was observed. The most frequently reported AE in the Su group were grade 1 or 2 hypothyroidism (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). (HR: 0.260; p = 0.0035). All AE responded to dose reduction (37.5 mg). Conclusions: In a cohort of pts with progressive, recurrent, or symptomatic DT, Su seems to be well tolerated and improve 2yr-PFS and OR rate compared with TM therapy. Further prospective studies with larger samples are needed to verify these results.
Phase 1 combination therapy with pexidartinib (PEX) and sirolimus (S) to target tumor-associated macrophages in pigmented villonodular synovitis, malignant peripheral nerve sheath tumors, and other soft tissue sarcomas.
Authors: Manji Gulam Abbas , Van Tine Brian Andrew , Lee Shing Mirn , Raufi Alexander , Patwardhan Parag , Blumberg Lauren Esther , Sender Naomi , Wang Jennifer , Otap Daniel , Singh-Kandah Shahnaz V. , Do Khanh Tu , Hirbe Angela C. , Bollag Gideon , Schwartz Gary K.
Published: March 2020

11055

Background: No effective therapy exists for unresectable malignant peripheral nerve sheath tumors (MPNSTs). We previously reported that the combination of PEX and the mTOR inhibitor S synergistically inhibited MPNST growth (CCR 20: 3146, 2014) by depleting M2 TAMs and by inhibiting receptor tyrosine kinases (RTKs), including c-KIT, PDGFR, CSF1R. We characterized the safety, tolerability, recommended phase 2 dose (RP2D) of PEX plus S in all sarcoma sub-types. Methods: Patients (pts) received PEX plus S orally in 28 days cycle as per Table. The RP2D was determined using the time-to-event continual reassessment method (TITE-CRM) in advanced sarcoma who have progressed on standard therapy. DLT was defined as any need for a dose reduction. Results: 24 pts were accrued (Acr) of which 18 were evaluable (MPNST – 6, pigmented villonodular synovitis (PVNS) – 3, leiomyosarcoma – 5, and other – 9). The mean age was 46y, 56% were male, and 67% had greater than 2 prior therapies. Most common ( > 20%) grade 2 or higher TEAEs were anemia (33%), WBC count decrease (28%), fatigue, neutropenia, and lymphopenia (22% each). There were 5 dose limiting toxicities (DLT): 2 for elevated LFTs both of which resolved with dose reduction, 2 for supra-therapeutic S trough levels, and 1 for grade 5 dehydration at dose level (DL) 3. Four subjects experienced a partial response (PR; -44% to -77% by RECIST, 18 – 61 wks on therapy). Seven subjects experienced stable disease (SD; +19.7% to -20.7% by RECIST; 9.4 – 30 wks on therapy). Five subjects progressed on therapy and two subjects experienced early DLTs and did not undergo tumor assessment. The RP2D is DL 3 (S 2mg/PEX 1000mg) with an estimated probability of DLT of 26.7% as determined by TITE-CRM. This recommendation is based on a target DLT rate of 25%. TAMs and immune subtypes from available tissue specimens and historical controls will be presented. Conclusions: 1000mg of PEX in combination with 2mg of S daily has an acceptable safety profile. Objective responses and durable SD was observed in PNVS and MPNST patients justifying proceeding with a multi-center single arm phase 2 study in advanced MPNST. Clinical trial information: NCT02584647. [Table: see text]
ARST1321: Pazopanib neoadjuvant trial in non-rhabdomysarcoma soft tissue sarcomas: A report of major wound complications.
Authors: Scharschmidt Thomas , Chen Yen-Lin , Wang Dian , Chi Yueh-Yun , Kayton Mark , Sorger Joel , Randall R. Lor , Hawkins Douglas S. , Weiss Aaron R.
Published: March 2020

11059

Background: The care of soft tissue sarcomas is complex and multidisciplinary in nature. Even without radiation or chemotherapy wound complications are common after surgical resection with a reported incidence of 6-42%. Wound complication rates with the use of neoadjuvant chemoradiation for high-grade soft tissue sarcomas has been reported and supported in the literature to be approximately 30%. Relevant to this study, a trial evaluating the use of a VEGF receptor inhibitor (bevacizumab) in combination with radiation pre-operatively in soft tissue sarcomas reported a wound complication rate of 25%. ARST 1321 is a phase II/III study evaluating the tyrosine kinase inhibitor Pazopanib +/- chemotherapy and radiation in select high-grade soft tissue sarcomas. The dose-finding phase has been completed and the objective of this report is to detail the major wound complications observed with this protocol. Methods: Patient enrolled on all arms of the study (Pre-operative radiation, +/- pazopanib, +/- doxorubicin and ifosphamide) were evaluated for wound complications (Grade I/II and Grade III). Patient demographics, tumor characteristics, and complication details were compiled and analyzed. Results: There were a total of 130 evaluable patients (100 patients on chemotherapy arm, 30 on non-chemotherapy arm). There were 38 overall wound complications reported (38/130, 29%). 23/38 (60%) occurred on the chemotherapy arm; therefore that cohort had 23/100 (23%) wound complication rate, while the non-chemotherapy cohort had an overall rate of 50% (15/30). Grade III wound complications represented 23/38 (66%) of all the complications. 30/38 (79%) of the complications were in the lower extremity. 23/38 (60%) patients were aged > 18 years. Conclusions: The overall rate of wound complications observed was 29% (38/130) which remains within the accepted historical rate based upon literature review without the use of a tyrosine kinase inhibitor. The overall major wound complication (grade III) rate was 19% (25/130). Also consistent with the literature is the finding that a majority of the complications occurred in the lower extremity. In conclusion, the addition of a tyrosine kinase inhibitor (pazopanib) has a wound complication toxicity profile comparable to current and historical literature. Clinical trial information: NCT02180867.
Solitary fibrous tumor: A Brazilian cohort analysis.
Authors: Cesca Marcelle Goldner , Mello Celso Lopes , Felismino Tiago , Formiga Maria Nirvana , Nicolau Ulisses Ribaldo , Aguiar Samuel , Maia Joyce Maria L.
Published: March 2020

11068

Background: Solitary fibrous tumor (SFT) is a rare mesenchymal tumor that account for less than 2% of all soft tissue sarcomas. SFT has been identified in multiple anatomic locations and can arise anywhere in the body. Surgical management is the mainstay of treatment for localized disease. However, about 20% will develop locoregional recurrences or distant metastasis with a role for systemic treatment. Methods: A retrospective analysis was carried out in a large cancer center in Brazil. Our primary objective was to evaluate clinical and treatment aspects of metastatic/ locally advanced (Mtx/LA) SFT cohort and secondary to describe clinical characteristics of entire population diagnosed with SFT. Descriptive statistics was used for main results. Survival curves were estimated using Kaplan-Meier. Data were retrieved from electronic patient medical records. Results: From April, 1971 to October, 2017, 82 patients with SFT were treated. Median follow-up was 45.5 months. 67 (81.7%) were alive on the cut-off date. Median age at diagnosis was 51 (14-78). 40.2% men. Most common primary sites (PS) were pleura (19.8%), central nervous system (CNS - 11%) and pelvis (11%). 18 (21.9%) underwent chemotherapy for Mtx/LA disease. In this subgroup, 61.1% were men; PS retroperitoneal (22.2%), extremities (16.7%), CNS (16.7%). 66.7% had pulmonary, 44.4% hepatic, 27.8% bone metastasis and one (5.5%) local recurrence. All patients had at least one adverse prognostic factor (tumor size ≥ 10cm, positive margins, necrosis, ≥ 4/10 mitosis). One (5,5%) had Doege-Potter syndrome. 7 (38.9%) did one, 5 (27.8%) two and 6 (33.3%) ≥ 3 lines of treatment. First line was temozolomide/bevacizumab (TMZ/Bev) in 55.6%, followed by chemotherapy (Ch) in 27.8% and tyrosine kinase inhibitors (TKI) in 16.7%. Median progression-free survival was 3.5 months (95% IC: 0.0-7.4) and overall survival 27.3 months (95% IC: 18.7-36.0). Response rate using RECIST criteria was 12.5% for TMZ/Bev and 62.5% had stable disease. TKI and Ch had no response. Conclusions: SFT is rare and with heterogeneous clinical presentation. In our analysis, patients received a wide range of therapy, reflecting the lack of well-established systemic treatment option. TMZ/Bev showed consistent activity in Mtx/LA scenario.
Sarcopenia (SMI(+)) in patients (pts) with advanced or metastatic soft tissue sarcoma (a/mSTS): Potential parameter for risk prediction during multimodal therapy (MT)?
Authors: Strassmann Dennis , Hensen Bennet , Gruenwald Viktor , Stange Katharina , Eggers Hendik , Länger Florain , Panzica Martin , Zardo Patrick , Christiansen Hans , Reuter Christoph W. , Wacker Frank , Ganser Arnold , Ivanyi Philipp
Published: March 2020

11069

Background: Objective parameters identifying ideal pts for MT from pts with a/mSTS remain scarce. Here, we analysed the impact of sacropenia in a/mSTS pts on treatment outcome of MT, retrospectively. Methods: Pts. with a/m STS treated at our centre (12/98-5/16ere identified. 89/181 pts were evaluable for analysis (CT-scans: -14 days before MT onset). Lumbar skeletal muscle index (SMI) was measured with MeVisLab 2.7 by manually segmentation of preinterventional CTs. SMI cut-off were defined through optimal fitting method (sarcopenia = SMI(+) in male: < 44 , in female: 38). Progression was defined by clinical or radiological judgment. Descriptive statistics, Kaplan-Meier-analysis and Cox-regression were administered. Results: At MT onset 28/89 pts (31%) suffered from sarcopenia, and SMI(+) pts were older than SMI(-) pts (p = 0.025). SMI(+) pts tends to receive lower numbers of medical treatments, received less often surgery, and more frequently radiotherapy, although differences were not significant. Further on, SMI(+) pts tends to profit less from first line medical treatment, compared to SMI(-) pts (objective responses: 14,3% vs. 27.9%, p = .161, clinical benefit rate: 25% vs. 65.6%, p = .032, PFS: 1 (95%-CI:.35-1.65) vs. 16 (95%CI:8.8-23.2) months, p = .002). OS was inferior in SMI(+) compared to SMI(-) pts. (4 (95%CI:2-6) vs. 16 (95%CI:8.8-23.2), p = .002). Multivariable analysis showed a trend for SMI(+) to be associated with PFS (HR: 1.7 (95%CI: 0.9-2.8), p = .067) and were independently associated with OS (HR: 2.53 (95%CI: 1.5-4.2), p < .001). Conclusions: In our cohort sarcopenia tends to be associated with less aggressive therapy in a/mSTS pts. However, sarcopenia tends to be associated with inferior PFS and was identified as independent risk factor for inferior OS. Although this analysis is limited due to its sample size sarcopenia might offer an attractive tool as guidance for treatment intensity modulation in a/mSTS patients, avoiding overtreatment in this cohort with dismal prognosis.
Results of the dose-finding phase of ARST 1321 from the Children's Oncology Group and NRG Oncology: Neoadjuvant chemoradiation or radiation therapy +/- pazopanib in non-rhabdomyosarcoma soft tissue sarcomas.
Authors: Chen Yen-Lin , Weiss Aaron R. , Scharschmidt Thomas , Chi Yueh-Yun , Black Jennifer M. , Choy Edwin , Kao Simon C. , Kayton Mark , Okuno Scott H. , Ostrenga Andrew , Randall R , Terezakis Stephanie Alicia , Zambrano Eduardo , Spunt Sheri L. , Hawkins Douglas S. , Wang Dian
Published: March 2020

11070

Background: Pazopanib is a tyrosine kinase inhibitor approved globally for advanced soft tissue sarcomas. The dose finding phase of this cooperative group trial assessed the dose limiting toxicities (DLT) and the maximally tolerated dose (MTD) of adding pazopanib to neoadjuvant chemoradiation or radiation therapy in children and adults with unresected intermediate/high-risk trunk and extremity non-rhabdomyosarcoma soft tissue sarcomas (NRSTS). Methods: ARST1321, a jointly designed intergroup study lead by Children's Oncology Group and NRG Oncology opened for enrollment in July 2014. Eligible adult and pediatric patients with newly diagnosed, unresected trunk/extremity NRSTS with plans for primary tumor resection were enrolled into either the Chemotherapy Cohort (those with chemosensitive NRSTS > 5 cm, grade 3, including all synovial sarcoma) or the Non-Chemotherapy Cohort (those with chemotherapy insensitive NRSTS of any size, grade 2/3, or any chemosensitive NRSTS for whom no chemotherapy was planned per discretion of patients and treatment teams). In the Chemotherapy Cohort, pazopanib was given with ifosfamide (7.5 grams/m2) and doxorubicin (75 mg/m2) plus 45 Gy preoperative RT starting after cycle 2. Primary tumor was resected at week 13, followed by chemotherapy and pazopanib to week 25. In the Non-Chemotherapy Cohort, pazopanib was given with 50 Gy preoperative RT, primary tumor was resected at week 10, and pazopanib continued to week 25. Feasibility was assessed through week 6 of therapy to determine pazopanib dose escalation/de-escalation based on DLT, total doses of pazopanib, and overall adverse event profile. Results: In the Chemotherapy Cohort, MTD was reached at Dose Level 1 (350 mg/m2 peds; 600 mg adults) with two DLTs (1 grade 3 ALT rise, 1 intolerability to therapy) in 10 patients. In the Non-Chemotherapy Cohort, 11 patients enrolled at Dose Level 1 (350 mg/m2 peds; 600 mg adults) without any observed DLTs and all received ≥75% of prescribed total pazopanib dose; MTD was reached at Dose Level 2 (450 mg/m2 peds; 800 mg adults) with 2 DLTs in ten patients enrolled (1 grade 3 dermatitis and 1 intolerability to therapy) and 9/10 receiving ≥75% of full dose. Conclusions: Pazopanib in combination with chemoradiation or radiation therapy alone was found to be safe in children and adults with NRSTS. Following this finding, ARST1321 opened in both arms using the newly determined pazopanib MTDs. Clinical trial information: NCT02180867.