bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world characterization of advanced/metastatic non-small cell lung cancer (aNSCLC) patients (pts) with rapid disease progression (RDP).
Authors: Gutierrez Martin , Molife Cliff , Belli Andrew J. , Hansen Eric , Stefaniak Victoria Jennifer , Winfree Katherine B. , Cui Zhanglin Lin , Batus Marta , Clarke Jeffrey Melson , Narayanan Viraj , Manion Chelsea , Norden Andrew David , Bonomi Philip D.
Published: March 2020

e20706

Background: Despite advances in therapy, recent observational data shows that aNSCLC pts with RDP continue to have a poor prognosis. This retrospective, observational study characterizes the demographic, molecular, & treatment profile of pts with RDP. Methods: Adult aNSCLC pts receiving first-line (1L) platinum-based (Pt) therapy between 01/2014 - 12/2018 were identified in the COTA Real-World Evidence database and assigned to RDP (n = 280) & non-RDP (n = 1,212) cohorts based on time to progression during 1L Pt therapy (≤ 12 and > 12 weeks, respectively). Results: Of 1,492 eligible pts, the incidence of RDP was 19%. Mean age (±SD) was 64.6 (10.9) and 66.1 (10.2) in the RDP and non-RDP group, respectively (p = 0.04). Data showed RDP patients had higher percentage of stage IV disease at diagnosis (77 v 72, p < 0.01), higher histologic grade G3/G4 (37 v 29, p = 0.01), and PD-L1 negative (< 1% expression) status (p = 0.01). Table shows molecular profiling across cohorts. No notable difference in treatment patterns across 1L and 2L was observed. Conclusions: This study identifies stage IV disease at diagnosis, higher grade, & PD-L1 negative ( < 1% expression) as potential risk factors for RDP. A better understanding of this poor prognosis cohort may offer an opportunity to better optimize therapies & outcomes. [Table: see text]
Treatment and outcomes for patients (pts) with selected advanced/metastatic cancers by place of care.
Authors: Xu Yihua , Hess Lisa M. , Molife Cliff , Cuyun Carter Gebra , Zhu Yajun Emily , Bunniran Suvapun , Loy Bryan A. , Churchill Collin , Nair Radhika
Published: March 2020

e20717

Background: Place of care may be an important factor affecting treatment & economic outcomes for pts in advanced stages of cancer. This retrospective observational study compared treatment patterns, healthcare resource use & costs, and overall survival (OS) for pts treated for selected cancers in the hospital outpatient department (HO) vs community oncology practices (CP) including physician offices & freestanding ambulatory centers. Methods: Claims data from a large national health plan were used to identify adult pts with newly diagnosed advanced/metastatic non small cell lung cancer (aNSCLC), metastatic breast (mBC) or metastatic colorectal cancer (mCRC) between 07/2012 & 12/2016, who initiated anticancer therapy in HO or CP settings. Pts enrolled in Medicare Advantage Prescription Drug (MAPD) or commercial plans for ≥ 6 months prior & ≥ 30 days after start of first line (1L) (index date) were included. OS was evaluated among pts enrolled in MAPD and costs were evaluated among pts enrolled ≥ 6 months pre- & post-index, by cancer type & by place of care. Outcome analyses were adjusted using multivariable models. Results: Among 8,333 eligible pts, there were 4,618, 2,304 & 1,411 pts with aNSCLC, mCRC & mBC, respectively and each cohort was evenly split by place of care. No notable differences in baseline characteristics or the most commonly used 1L, 2L or 3L regimens were observed by place of care for the 3 cancers. For aNSCLC pts, mean 1L treatment duration was shorter (96 v 102 days, P = 0.02) and time between 1L & 2L was longer (125 v 106 days, P = 0.04) in the HO than the CP setting, respectively. For mBC, mean 1L treatment duration was longer in the HO setting (156 v 190 days, P < 0.01). Adjusted total all cause healthcare costs were higher in HO than CP for mBC ( P < 0.01) & mCRC ( P < 0.01), but no significant difference in median OS was observed between HO & CP settings for the 3 cancer types. Conclusions: This study showed no major differences between HO & CP settings in baseline characteristics, the first 3 lines of therapy, or adjusted median OS for aNSCLC, mCRC, or mBC cohorts. However, total costs were higher in the HO setting for mCRC & mBC pts. These findings may be useful for healthcare decision & policy makers but warrant further evaluation.
Can texture analysis of pre-immunotherapy CT imaging predict clinical outcomes for patients with advanced NSCLC treated with Nivolumab?
Authors: Spieler Benjamin Oren , Saravia Diana , Lopes Gilberto , Azzam Gregory , Kwon Deukwoo , Dal Pra Alan , Yechieli Raphael , Diwanji Tejan , Mihaylov Ivaylo
Published: March 2020

e20720

Background: Targeted therapies are ineffective in most NSCLC patients and response rates remain < 20% for patients with advanced NSCLC on immuno-monotherapy. Predictive models that distinguish responders from non-responders to immunotherapy could help guide clinical practice. Texture analysis is a data-mining tool used to identify intensity patterns in diagnostic imaging. We hypothesized that texture features on pre-immunotherapy CT imaging can be associated with clinical outcomes for patients with advanced NSCLC treated with Nivolumab. Methods: In an IRB-approved database containing 159 patients with advanced NSCLC treated with Nivolumab monotherapy, 20 patients with the longest overall survival (OS) and 20 with the shortest were selected for retrospective analysis. Patient characteristics were compared using paired t-tests. The last pre-immunotherapy PET CT for each patient was transferred to MIM software for segmentation. All FDG-avid intrathoracic tumors were delineated on the CT scan per RTOG contouring guidelines. Ninety-two texture features within each tumor were analyzed for association with the primary endpoint, OS. OS time was dichotomized to less than 1 year vs. more than 1 year. A univariate logistic regression model was used to estimate odds ratio (OR), 95% confidence interval and p-value for each feature. Multiple testing adjustments were performed using false discovery rate. Results: Eleven out of 92 texture features showed significant association with OS time (p-values from 0.009 to 0.044), of which 7 exhibited large effect (OR < 0.5 or > 1.5). Fifteen additional texture features trended toward statistical significance with p-values from .05 to .10. In all, 26 out of the 92 texture features showed significant association or trended toward significance with duration of OS. Conclusions: This preliminary study suggests that texture features on pre-immunotherapy CT imaging may help in predicting OS duration for patients with advanced NSCLC treated with Nivolumab monotherapy. We are in the process of validating a multivariate predictive model. Future directions include expansion of this study across the full database, survival analyses and correlation of texture features with tissue biology.
Personalizing cancer treatment using gene activity scores with the NIH Medical Genetics Summaries.
Authors: Malheiro Adriana J. , Dean Laura Charlotte , Kattman Brandi L.
Published: March 2020

e22000

Background: Oncology professionals need to access a wide range of genetic tests, including tests for cancer biomarkers, predisposition to hereditary cancers, and pharmacogenetic tests. While pharmacogenetic testing is fundamental to personalized medicine, the adoption of testing has been slow, partly due to a lack of readily accessible information about new developments, such as gene activity scores. Methods: Medical Genetics Summaries (MGS) was created to bridge the translation gap between genetic test results and personalized treatment plans. MGS is a free, regularly updated, peer-reviewed pharmacogenetics resource. The complete set of summaries can be browsed online or saved as PDF (www.ncbi.nlm.nih.gov/books/n/gtrbook). Excerpts of the summaries can be found via PubMed (www.pubmed.gov) and MedGen (www.ncbi.nlm.nih.gov/medgen). Results: Of the 45 drug-gene interactions included so far in MGS, 10 are commonly used cancer drugs. These include capecitabine (Xeloda) and fluorouracil (Adrucil), which are both fluoropyrimidines—antimetabolite drugs used in the treatment of colon cancer and breast cancer. The DPYD gene encodes the rate-limiting enzyme for the breakdown of fluoropyrimidines. Patients with specific variations in the DPYD gene (e.g., DPYD*2A, DPYD*13) have decreased or absent enzyme activity. In these patients, the standard recommended dose of fluoropyrimidine can cause life-threatening bone marrow suppression and neurotoxicity. MGS presents the dosing recommendation for each DPYD phenotype, which are clearly defined using the recently assigned DPYD activity scores, from authoritative professional guidelines such as the National Comprehensive Cancer Network (NCCN) and the Clinical Pharmacogenetics Implementation Consortium (CPIC), in addition to the FDA. MGS also provides an overview of the drug (drug class, mechanism of action, adverse events), an introduction to the gene(s) and significant alleles, and guidance on genetic testing—along with links to the relevant tests in the NIH Genetic Testing Registry (GTR, www.ncbi.nlm.nih.gov/gtr). Conclusions: This presentation will demonstrate how NIH precision medicine resources, with a focus on MGS, can simplify the process of ordering and interpreting pharmacogenetic tests and efficiently tailor care for your patient.
Salvage chemotherapy using irinotecan and temozolamide in pediatric and adult populations with relapsed Ewing sarcoma.
Authors: Salah Samer , To Yat Hang , Ismaeel Taleb , Khzouz Omar , Sultan Iyad Yasin , Yaser Sameer , Alnsour Anoud Zaid , Abuhijlih Ramiz , Shahin Omar , Aldouri Rasha , Lewin Jeremy
Published: March 2020

e22500

Background: Irinotecan and temozolomide (IT) is a widely used regimen for relapsed Ewing Sarcoma (ES), although studies are largely limited to the paediatric population. We aimed to compare the tolerability and efficacy of IT between paediatric and adult patients. Methods: We retrospectively reviewed paediatric (< 18 years) and adult patients treated with salvage IT chemotherapy at two institutions from March, 2010 to June, 2018. Toxicities were graded according to common terminology criteria of adverse events (CTCAE v. 4.03) and compared using the Chi Square test. Responses were interpreted by Response Evaluation Criteria in Solid Tumors (RECIST). The Kaplan-Meyer method was used to estimate progression free survival (PFS); survival comparisons were carried out by the Log-rank test. Results: Fifty-three patients were included ( n= 16 paediatric; n= 37 adult). Median age was 20 (range, 5 – 45 years). A total 236 IT cycles were delivered (median = 4, range:1-7). IT was given as second-line ( n= 34; 64%) or ≥third-line ( n= 19; 36%). There was no difference in ≥grade 3/4 haematologic toxicity between paediatric and adult patients (31% vs. 35% respectively; p= 0.76), whilst febrile neutropenia was observed in two (4%) patients (one adults and one paediatric). The frequency of diarrhoea of any grade was similar (38% in each group). Of 43 patients assessable for response, 12 (28%) had objective response (1 CR, 11 PR), 19 (44%) had disease progression and 12 (28%) had stable disease. Objective response rate did not differ between the two groups (36% in paediatrics vs. 25% in adults; p = 0.47). Median PFS was superior in paediatrics vs. adults (7.4 vs. 2.1 months, p = 0.001). Superior PFS for the paediatric population was observed in both, the second-line (6.2 vs. 2.2 months; p= 0.060) and ≥third-line setting (7.4 vs. 1.2 months, p= 0.014). Conclusions: IT is an effective salvage regimen for ES, with favourable toxicity and equally observed objective responses in paediatric and adult populations. The observed superior PFS for the paediatric cohort requires further confirmation in a larger prospective study.
Toxicity and efficacy of busulfan-melphalan (BuMel) compared to treosulfan-melphalan (TreoMel) high dose chemotherapy (HDCT) consolidation in high-risk Ewing sarcoma (ES): A 12-year monoinstitutional experience.
Authors: Abate Massimo Eraldo , Paioli Anna , Cesari Marilena , Longhi Alessandra , Palmerini Emanuela , Setola Elisabetta , Carretta Elisa , Cammelli Silvia , Ronchi Letizia , Rocca Michele , Manfrini Marco , Scotlandi Katia , Donati Davide Maria
Published: March 2020

e22507

Background: We compared toxicity and outcomes of BuMel and TreoMel HDCT consolidation with stem cell rescue in high-risk ES pts prospectively treated in 5 consecutive trials at the Istituto Ortopedico Rizzoli, Bologna, Italy. Methods: Eligible pts had histologically proven diagnosis of ES, high-risk disease defined as localized disease with poor histological/radiological response to standard chemotherapy or lung/pleural metastases or extra-pulmonary metastases or relapsed disease, were aged < 40. All pts received previous standard chemotherapy (vincristine, ifosfamide, doxorubicin, etoposide, cyclophosphamide actinomycin-D) and surgery and/or radiation therapy (RT) as local treatment. From June 1, 2011, TreoMel was used instead of BuMel to avoid potential severe complications related to busulfan, as in case of previous RT on axial skeleton/pelvis. Pts with lung metastases received lung irradiation 12-15 Gy at least 2 months after HDCT. Results: Between January 1, 2007, and September 30, 2018, 98 pts received BuMel or TreoMel: 52 pts with localized disease (7 TreoMel), 26 pts with lung/pleural metastases (5 TreoMel), 10 pts with extra-pulmonary metastases (4 TreoMel) and 10 pts with relapsed disease (1 TreoMel). Median age was 18 yrs (range 3-39 yrs). 14 out of 17 TreoMel pts received previous RT on axial skeleton/pelvis. Median follow up is 4.2 yrs (range 10 mo. - 12 yrs). Pts treated with TreoMel showed a significant lower incidence of grade 3-4 stomatitis (p = < 0.001) and of all grade ≥ 3 non-hematological toxicities (p = < 0.001). One pt died of BuMel-related toxicity (sinusoidal obstruction syndrome/veno-occlusive disease) and none after TreoMel. For localized ES, the 5yr-EFS was 66.7% (95%CI, 47.9-78) for BuMel pts and 66.7% (95CI%, 19.5-90.4) for TreoMel pts. Conclusions: In high-risk ES, TreoMel is significantly less toxic then BuMel. Combining RT on central/axial sites and TreoMel is feasible. In localized ES, results show similar 5yr-EFS between BuMel and TreoMel. TreoMel could be used instead of BuMel when busulfan is contraindicated.
Creation and characterization of a novel human PDGFRA D842V-mutant GIST cell line.
Authors: Klug Lillian Rose , Abalakov Gleb , Griffith Diana , Town Ajia , McKinley Arin , Grunewald Susanne , Bauer Sebastian , Rink Lori , Heinrich Michael C.
Published: March 2020

e22512

Background: Activating PDGFRA mutations are seen in about 10% of gastrointestinal stromal tumors (GIST). Of these, the majority are one specific PDGFRA mutation, D842V, which confers resistance to all clinically approved tyrosine kinase inhibitors (TKI). Much has been learned about the mechanism by which TKIs work in GIST using cell lines derived from human GIST that bear activating KIT mutations. However, despite enormous effort to develop cell lines derived from human tumors over the past 15 years, there are currently no human cell models of PDGFRA D842V GIST. With the development of potent PDGFRA D842V TKI, such as crenolanib, avapritinib, and DCC2618 it is of interest to understand how these drugs affect PDGFRA-mutant GIST biology. Methods: We sought to convert the KIT-driven GIST-T1 cell line to be PDGFRA-driven by transduction with PDGFRA D842V. Endogenous KIT expression was knocked-out using CRISPR Cas9. Knockout was verified at protein and DNA levels. Clonal KIT knockout cell lines were tested for sensitivity to KIT and PDGFRA TKI both in vitro and in vivo models. Kinase dependence was determined by measuring the effect on viability after KIT and/or PDGFRA knockdown by siRNA. Results: GIST-T1 cells transduced with PDGFRA D842V display highly phosphorylated PDGFRA, imatinib resistance, and PDGFRA dependence. Cell lines that express both endogenous mutant KIT and exogenous PDGFRA D842V maintain some dependence on KIT, but less so than the parental KIT-driven GIST-T1 cell line. Complete knockout of KIT protein expression was achieved in GIST-T1 D842V cells using CRISPR-Cas9. GIST-T1 D842V KITko cell lines demonstrate sensitivity to TKI avapritinib, crenolanib, and DCC2618. Xenografts were established using GIST-T1 D842V KITko cell lines and are sensitive to avapritinib in vivo. Conclusions: The GIST-T1 D842V KITko cell line demonstrates ability to switch kinase allegiance resulting in PDGFRA-dependence and KIT-independence. This GIST-T1 D842V KITko cell line represents a novel model of PDGFRA-mutant GIST and can be used to understand the unique biological aspects of these tumors, particularly the response to new potent PDGFRA kinase inhibitors such as avapritinib which will have immense clinical relevance.
Clinical presentation, natural history and therapeutic approach in patients with solitary fibrous tumor: A retrospective analysis.
Authors: Schoffski Patrick , Timmermans Iris , Hompes Daphne , Stas Marguerite , Boecxstaens Veerle , De Leyn Paul , Coosemans Willy , Van Raemdonck Dirk , Hauben Esther , Sciot Raf , Clement Paul M. , Bechter Oliver Edgar , Beuselinck Benoit , Woei-A-Jin Feng Jung Sherida Harriette , Dumez Herlinde , Wessels Tim
Published: March 2020

e22522

Background: Solitary fibrous tumor (SFT), a rare variant of soft tissue sarcoma (STS), is characterized by the presence of a NAB2-STAT6 fusion. Given the orphan character of SFT we performed a retrospective analysis. Methods: We retrospectively reviewed all patients (pts) with SFT treated in our institution between 12/1990 - 09/2017. Results: We identified 94 SFT pts (incl. hemangiopericytoma) with a med. follow-up for 4.7 yrs. Common anatomic sites were chest (33%), abdomen (21.3%), brain (12.8%) and extremities (9.6%). The symptomatology at diagnosis was variable. Only 6.4% presented with synchronous metastasis. Hypoglycemia (Doege-Potter syndrome) was seen in 2.1% of cases. A resection of the primary SFT was done in 86 pts (91.5%), their disease-free survival was 35.5 mo and 43% stayed SFT-free during follow-up. Local recurrence occurred in 26.7% of cases, associated with a med. overall survival (OS) of 45.1 mo. Metachronous metastasis was seen in 30.2% of pts, occurring after a med. follow-up of 36 mo. Med. OS after diagnosis of metastasis was 19.0 mo. Systemic therapy was given to 92.9% of pts with inoperable/metastatic disease. The most common 1st line therapy was doxorubicin single agent (57.7% of pts), achieving responses in 13.3% of pts. 2nd line therapies included ifosfamide and pazopanib (31.3% of pts each), 3rd line treatment was very heterogeneous. Conclusions: SFT is an orphan malignancy with a variable clinical course, low incidence of distant spread at first diagnosis but considerable risk of local failure and metachronous metastasis. Surgery is the only curative option at diagnosis, time of relapse and in case of resectable metastasis. Palliative systemic therapy is considered in pts with inoperable/metastatic disease but achieves low response rates. The natural course and survival outcomes of SFT cases treated with palliative intent tend to be better than in non-selected STS pts.
Systemic therapy in advanced dermatofibrosarcoma protuberans: Imatinib and beyond.
Authors: Gupta Anshul , Rastogi Sameer , Kumar C Santosh , Barwad Adarsh , Dhamija Ekta , Panday Rambha , Deo S. V. S. , Shishak Sorun , Aggarwal Aditi , Dutta Rimlee , Manasa Parisa , Kumar Pankaj
Published: March 2020

e22523

Background: Imatinib is the standard treatment of advanced Dermatofibrosarcoma (DFSP). However ideal treatment of advanced DFSP patients, who have progressive disease (PD) on imatinib, remains an unanswered question. Methods: We retrospectively analysed consecutive advanced DFSP patients who presented to AIIMS Sarcoma Medical Oncology clinic between January 2016 and January 2019. Results: There were eleven patients, with median age of 35 years, seven (63.6%) of which were males. Fibrosarcomatous transformation was present in six (54.5%) patients. Four (36.4%) had locally advanced disease, while seven (63.6%) had metastatic disease. Primary site was trunk in eight (63.7%) patients. Three (75%) of the four patients who received neoadjuvant imatinib, underwent complete surgical resection. Initial dose of imatinib was 400mg OD in eight (72.7%) patients, 600 mg OD in two (18.2%) and 800 mg OD in one (9.1%) patient. The best response to imatinib was Partial response (PR) in nine (81.8%) patients, stable disease (SD) in one (9.1%) and primary PD in one (9.1%) patient. Median progression free survival (PFS) was 16 months, after a median follow up of 14 months. Five (45.4%) patients had PD on imatinib. As mentioned in table, strategies used in these patients were pazopanib (n = 3), doxorubicin (n = 2), other chemotherapy (n = 2), dose escalation of imatinib (n = 2) and reintroduction of imatinib (n = 1). One patient had prolonged stable disease on pazopanib, while remaining had PD. Conclusions: Imatinib remains prominent first line therapy in advancved DFSP. Though pazopanib has shown some promise, the treatment outcomes in second line therapy and beyond have largely been dismal and need to be studied prospectively.[Table: see text]
Is PAX3-FOXO1 associated with worse outcome in adults with rhabdomyosarcoma (RMS)?
Authors: Guram Sheena , Dirks Julia , Barot Shivali , Griffin Anthony , Weinreb Ilan , Demicco Elizabeth , Shultz David Benjamin , Abdul Razak Albiruni Ryan , Gladdy Rebecca Anne , Gupta Abha A.
Published: March 2020

e22525

Background: Rhabdomyosarcoma (RMS) is a rare soft tissue sarcoma in adults. The PAX3-FOXO1 fusion gene is associated with alveolar rhabdomyosarcoma. PAX3-FOXO1 results from a stable reciprocal translocation of chromosomes 2 and 13, which fuses in-frame the DNA binding domain of PAX3 with the transactivation domain of FOXO1. Occasionally, PAX7-FOXO1 is expressed. In children, the PAX3-FOXO1 fusion gene is associated with worse outcome. We evaluated the prognostic role of FOXO1 fusion status in adults with RMS treated in a single, large volume sarcoma centre. Methods: A retrospective review of adult RMS patients (pts) diagnosed from 1984 to 2018 was done. Information on demographics, treatment, fusion status and survival was collected. Primary favourable site was defined as tumour arising in orbit, non-bladder/prostate genitourinary system and non-parameningeal head and neck. Factors were compared using Fisher’s Exact test. Event-free survival (EFS) was estimated by the Kaplan-Meier method and compared with log rank test. FOXO1 fusion status was coded as FP (fusion positive) or FN (fusion negative). Results: Of 134 pts identified in our database, fusion testing was performed in 55 (41%). Of these, PAX3 fusion was detected in 22 (40%). PAX7 was not detected. The median age of FP and FN pts was 25 yrs (range 18, 90) and 27 yrs (range 18, 65), respectively. Gender distribution was similar between FP and FN. Favourable site was seen in 13 (60%) FP and 21 (64%) FN. Nodal disease was present in 21 (95%) FP and 21 (64%) FN (p = 0.02). Distant metastases were present in 10 (45%) FP and 9 (27%) FN (n.s.). Treatment received was as follows for FP and FN, respectively: chemotherapy (21(95%), 33(100%)), radiation (14(64%), 22(67%)) and surgery (4(18%), 17(52%)). 5-yr EFS for pts without distant metastases was 27% (CI 22.6-76.6) and 46% (CI 21.5 – 70.5) for FP and FN respectively (n.s.). Conclusions: FP and FN RMS occurs in adults of all ages. Similar to children, adults with FP are more likely to present with nodal disease. Our study did not show that fusion status was associated with poorer EFS in adult RMS, however, larger series are needed to confirm this preliminary data.
Incidence and prevalence of synovial sarcoma in the US: An analysis using SEER*Stat.
Authors: Joseph Nedra , St. Laurent Samantha , Nelson Jeanenne Joy , Zheng Shan , Stirnadel-Farrant Heide
Published: March 2020

e22535

Background: Synovial sarcoma (SS) is a rare and aggressive soft tissue sarcoma which primarily affects the extremities of the arms and legs, and can also occur in the head and neck, lungs and pleura, and the trunk. The disease burden of SS is generally extrapolated from overall soft tissue sarcoma (STS) with SS accounting for 4.5% of all STS (587 cases estimated in 2018 in the US) (Noone, 2018; Siegel, 2018). The objective of this study was to provide disease burden estimates specific to SS in the US. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) 18 Registries, Nov. 2017 (2000-2015) were analyzed using SEER*Stat software (v8.3.5). The incidence and prevalence of SS was estimated by utilizing SS-specific International Classification of Diseases for Oncology, V.3 (ICD-O-3) and histology codes. Data from 2011-2015 were used to project incidence rates (age-specific and age-adjusted), 5-year limited duration prevalence, number of incidence and prevalent cases, and the age distribution of synovial sarcoma for 2018. Results: In the US, the age-adjusted incidence rate of SS was 0.177 per 100,000 (estimated 580 incident cases) in 2018. SS is more frequently manifested in patients aged 20-49 years, with the highest occurrence of new cases in patients between 45-49 years (incidence rate 0.26 per 100,000). The prevalence rate of SS across all ages was 0.65 per 100,000 (estimated 2129 prevalent cases) as of January 1, 2018. Conclusions: We described incidence and prevalence rates of SS, including age-specific and age-standardized rates, and characterized the age distribution of SS. This approach provided more precise estimates that are specific to SS without extrapolation from STS, and which are not available in the literature. References: Noone AM, et al. (ed). SEER CSR, 1975-2015, https://seer.cancer.gov/csr/1975_2015/ . Siegel RL, et al. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7–30.
Successful generation of patient-derived xenografts and cell lines as preclinical models for sarcomas.
Authors: Kondo Tadashi , Oyama Rieko , Kito Fusako , Noguchi Rei , Hattori Emi , Takahashi Mami , Ichikawa Hitoshi , Yoshida Akihiko , Kawai Akira
Published: March 2020

e22549

Background: The establishment of patient-derived preclinical models has been a challenge issue in sarcomas, because of the rarity of diseases. We report our successful experience in establishing patient-derived sarcoma xenografts and cell lines. Methods: Tumor tissue samples from sarcoma patients undergoing surgery were collected by a team of orthopedicians and pathologists. Small tumor fragments were subcutaneously transplanted to immunodeficient NOG mice. The other part was used to establish a cell line using serum-containing media. The omics profiling was performed to examine the preservation of molecular backgrounds during the model establishment. Effects of FDA-approved drugs were examined in the established models. Results: Since April 2014, tumor samples from 246 sarcoma cases have been processed. The sample characteristics are summarized in the table. Currently we have established PDXs and cell lines from 39 and 27 cases, respectively. Xenografts and cell lines were established from unique sarcomas such as CIC-DUX4 fusion positive sarcoma, extraskeletal osteosarcoma, primary leiomyosarcoma of bone, and alveolar soft part sarcoma. A take rate of xenografts and cell lines varied among the sarcoma types. Omics profiles considerably changed during the process of model establishment. Anti-cancer drugs with significant tumor suppressive effects were detected. Conclusions: Our patient-derived cancer models will facilitate translational sarcoma research. The original biological features preserved in the xenografts and cell lines should be clarified to optimize the utility of sarcoma models. Currently, our cell lines are available for the academic researchers upon a request.
Apatinib for epithelioid sarcoma: analysis on eight advanced stage cases in a single institute.
Authors: Chen Yong , Sun Wei , Wang Bing , Qu Xing-Long , Zheng Bi-Qiang , Huang Wen-Ding , Sun Zheng-Wang , Wang Chun-Meng
Published: March 2020

e22551

Background: Epithelioid sarcoma (ES) is a rare high grade soft tissue sarcoma with high incidence of lymph node involvement and distant metastasis. It is widely recognized that ES is not sensitive to chemotherapy and radiation, surgical treatment is the only curative option for localized diseases. Tyrosine kinase inhibitors (TKIs) has been proven to be effective in sarcomas, here we report the experience of Apatinib in 8 advanced ES cases. Methods: ES patients treated in Fudan University Shanghai Cancer Center from Dec, 2016 to Aug, 2018 were accrued retrospectively. Those with locally advanced diseases or distant metastasis were treated with orally Apatinib 500mg, daily use for at least 2 months. Assessment of efficacy and side effects were recorded every 2 months and patients were then treated according to reponses to Apatinib. Results: There were 8 patients with locally advanced or late stage ES in a total 20 ES patients during the study period. There were 6 males and 2 females with median age of 55 years (20-73). 3 of the 8 were classical type and 5 were proximal type. 7 of the 8 patients were locally advanced and 1 was with lung metastasis at diagnosis. 4 of the 8 had a partial response to Apatinib and one patient has a downstaged ES which was surgically removed. The other 4 had a stable disease to Apatinib but 2 were not able to tolerate side effects and stopped at first evaluation, the other 2 remains progression free. Main side effects included skin rash, hypertension and diarrhea. Hypertension was the only Grade 3-4 side effect. With median follow-up of 12 months, 6 remains progression free, the 2 patients who didn’t tolerate side effects and stopped Apatinib developed lung metastasis. Conclusions: Apatinib has unproven but promising effect in ES, TKI is an option especially for those not sensitive to cytotoxic agents and radiation.
No relevant activity of olaratumab in patient-derived soft tissue sarcoma xenografts selected for expression of platelet-derived growth factor receptor a.
Authors: Cornillie Jasmien , Van Renterghem Britt , Van Winkel Nathalie , Wellens Jasmien , Gebreyohannes Yemarshet , Debiec-Rychter Maria , Sciot Raf , Hompes Daphne , Wozniak Agnieszka , Schoffski Patrick
Published: March 2020

e22556

Background: Soft tissue sarcoma (STS) comprises a heterogeneous family of rare tumors of mesenchymal origin. Single-agent doxorubicin (DOX) remains the standard-of-care for advanced and inoperable STS, but response rates are < 15% and survival is generally poor. In 2016, Tap et al. reported impressive results of a phase Ib/II trial combining DOX and the platelet-derived growth factor receptor a (PDGFRA)-directed antibody olaratumab (OLA), suggesting an unprecedented survival advantage of the combination over DOX alone, without providing a mechanistic rationale for the observed activity (Lancet 2016;388:488-97). We decided to evaluate the efficacy of OLA in a panel of patient-derived STS xenografts (PDX). Methods: NMRI nu/nu mice were transplanted bilaterally with tumor tissue of models expressing PDGFRA, including PDX of leiomyosarcoma (UZLX-STS22), malignant peripheral nerve sheath tumor (STS39), myxofibrosarcoma (STS59) and undifferentiated pleomorphic sarcoma (STS84). Mice were randomly divided into 4 treatment groups: (1) control, (2) DOX (3 mg/kg once weekly), (3) anti-PDGFRA [OLA (60 mg/kg twice weekly) + mouse anti-PDGFRA antibody 1E10 (20 mg/kg twice weekly)] and (4) the combination of DOX and anti-PDGFRA (same dose/schedule as single treatment arms). Tumor volume, histopathology and Western blotting were used to assess treatment efficacy. Results: Anti-PDGFRA treatment as single agent did not reduce tumor growth and did not result in significant anti-proliferative or pro-apoptotic activity. Combining DOX and anti-PDGFRA did not reduce tumor burden, though a mild inhibition of proliferation was observed in models STS39 and STS59 and a pro-apoptotic effect was seen in all models except STS22. Antitumor effects on histology were not significantly different comparing DOX and the combination treatment. Anti-PDGFRA treatment, both as a single agent as well as with DOX, did not inhibit downstream MAPK and PI3K/AKT signaling pathways. Conclusions: In vivo findings in PDX models selected for PDGFRA expression support negative findings of the phase III trial NCT02451943 with OLA reported at this meeting.
The ideal amount of physical activity to improve quality of life and symptoms in lung cancer patients: A systematic review.
Authors: Castro Gilberto , Codima Alberto , das Neves Willian , Borges Ana Paula Souza
Published: March 2020

e23158

Background: The symptoms which burden lung cancer patients contribute to a vicious cycle of physical inactivity as the disease progresses. Some studies have shown that exercise is feasible and safe for this population, and it improves their symptoms and quality of life. However, the current recommendations are non-specific, and little is known about the optimal amount and type of exercise in this scenario. Here we aimed to identify a specific recommendation of physical activity that could work more efficiently, benefiting lung cancer patients, in terms of diminishing their symptom burden and improving quality of life. Methods: A systematic review was undertaken through structured searches on PubMed, Medline, Embase, Scopus, Web of Science and SciELO. The search protocol was registered on the Prospero platform. Rayyan QCRI was used for data extraction and determining eligible studies after a blind screening of titles and abstracts by the three authors. The Physiotherapy Evidence Database (PEDro) scale was used for quality assessment of each eligible trial in regards of risk of bias. Trials which had clear eligibility criteria and a summary score equal or superior than 6 were considered to have low risk of bias, and accepted for full text review. Results: From September/1998 to January/2019, a total amount of 1998 studies were returned from the aforementioned databases, and 17 studies were established to be eligible for quality assessment. All the 17 quality-assessed studies were randomized clinical trials. However, two of them did not clearly report the eligibility criteria and were immediately excluded. Five other studies were considered to have high risk of bias. Therefore, we considered only 10 trials to be fully reviewed, including 843 patients. Only 3 trials found significant improvement in the quality of life after their interventions, and included 243 patients. Two studies associated aerobic exercise and resistance training from 10 to 20 weeks post surgery, while the other studied intervention was Tai Chi for 10 days after each chemotherapy cycle. Conclusions: Evidence from this review suggests that exercise may improve quality of life of lung cancer patients. However, we could not identify an ideal amount nor type of physical activity given the limited available data and the heterogeneity of methods. Further studies are warranted.
Severity, implications, and understanding of cancer related fatigue in cancer survivors of South Asian ethnicity.
Authors: Nayyar Harleen Kaur , Hussain Shaik Maheboob , Thakur Ruchika , Sonthwal Neha , Chaturvedi Harit Kumar , Gupta Alok
Published: March 2020

e23177

Background: Cancer Related Fatigue (CRF) is a common debilitating symptom among cancer survivors that interferes with their Quality of Life (QOL). We evaluated incidence, severity, perception and implications of CRF on QOL among cancer survivors of South Asian ethnicity. Methods: Between July & December 2018, cancer survivors who visited cancer follow up clinic were asked to participate in this study by filling CRF questionnaire which focused on evaluating an individual’s assessment of severity, perception of causes and implications of CRF on their QOL as well as the measures taken to overcome CRF. Results: 160 cancer survivors, median age 52 years, 125 female & 34 male with most common diagnosis of breast cancer(60%) participated in the study. All survivors had received ≥2 treatment modalities. Overall, 133(84%) underwent surgery, 144(91%) received chemotherapy, 103(65%) received radiation therapy, 60(38%) received hormonal therapy & 34(21%) received targeted therapy. 36(23%) experienced weight loss and 26(16%) required blood transfusion. 148(93%) survivors reported CRF of any grade. 82(52%) reported moderate intensity CRF(affecting work but not activities of daily living) while 33(21%) reported severe intensity CRF (affecting activities of daily living). CRF was perceived as generalized weakness by 137(86.2%), emotional labiality by 42(26%), diminished concentration/attention span by 36(23%) and decreased motivation/interest in usual activities by 29(18%) survivors. CRF was attributed to treatment of cancer by 137(86%), psychological and social factors by 50(31%), cancer itself by 34(21%) and environmental /genetic factors by 16(10%) survivors. CRF adversely affected various aspects of QOL including activities of daily living in 79(50%), mood in 74(47%), professional work in 46(29%) and interpersonal relationships in 36(23%) survivors. To overcome CRF, 70(44%) survivors increased physical activity, 61(38%) resorted to mind-body interventions, 29 (18%) took pharmacological intervention and 25 (16%) resorted to psychosocial interventions. CRF resolved within 3 months after completion of therapy in 29(18%), 3-6 months in 23(15%), 6-12 months in 23(15%) and > 12 months in 1 survivor. CRF persisted in 78(49%) survivors. Conclusions: Incidence & severity of CRF is high in cancer survivors of South Asian ethnicity. Persistence of CRF beyond treatment completion significantly affects QOL and remains a poorly understood & incompletely addressed health issue among cancer survivors. More research is warranted in this field.
Phase I/II clinical trial of NY-ESO-1-specific TCR-engineered T-cell transfer combined with a novel T-cell stimulator CHP:NE1 for patients with refractory soft tissue sarcoma.
Authors: Ishihara Mikiya , Hattori Hiroyoshi , Arai Eisuke , Nishida Yoshihiro , Takada Kohichi , Emori Makoto , Kawai Akira , Ueda Takafumi , Endo Makoto , Matsumoto Yoshihiro , Sasada Tetsuro , Sato Eiichi , Yamada Tomomi , Matsumine Akihiko , Nagata Yasuhiro , Harada Naozumi , Shiku Hiroshi , Kageyama Shinichi
Published: March 2020

TPS11074

Background: Combination therapy to enhance the efficacy of T cell receptor (TCR)-engineered T cells (TCR-T) has received increasing attention. We found that a combination therapy of TCR-T and a long peptide vaccine with CpG adjuvant without lymphodepletion regimen caused regression of immune checkpoint inhibitor-resistant sarcoma in a preclinical mouse model. Based on this finding, we initiated a clinical trial of TBI-1301 combined with CHP:NE1 without lymphodepletion for the patients with NY-ESO-1-expressing advanced soft tissue sarcoma. TBI-1301 is an NY-ESO-1157–165/HLA-A*02:01- or -A*02:06-specific TCR-T engineered to reduce endogenous TCR mRNA expression. CHP:NE1 is a novel T cell stimulator consisting of NY-ESO-1 long peptide antigen, cholesteryl pullulan (CHP) nanogel, and CpG oligoDNA. CHP nanogel is used for efficient delivery of long peptide antigen into the lymph nodes. CpG oligoDNA is a TLR9 agonist and used as an adjuvant. CHP:NE1 is expected to reinforce TBI-1301 T cells in the lymph nodes. Methods: This is an investigator-initiated multi-institutional first-in-human phase I/II clinical trial. TBI-1301 is infused at 5×109 cells one day after subcutaneous injection of CHP:NE1. CHP:NE1 is injected again 7 days after TBI-1301 infusion. This cycle is repeated once more. Lymphodepletion using cyclophosphamide and/or fludarabine is not performed. Key inclusion criteria include: refractory soft tissue sarcoma with NY-ESO-1 antigen expression, HLA-A*02:01- or HLA-A*02:06- positive, ECOG Performance Status 0 or 1, and adequate organ function. The primary objective is to assess the safety and efficacy in the phase 1 and 2 parts, respectively. The secondary objective is to assess the efficacy and immune response (blood concentration, immunophenotype and activity of TBI-1301) in the phase 1 part and the safety and immune response in the phase 2 part. Enrollment in this study is currently ongoing. Clinical trial information: JMA-IIA00346.
A phase I trial of palbociclib in combination with dexamethasone in relapsed or refractory adult B-cell acute lymphoblastic leukemia (ALL).
Authors: Kasner Margaret T. , Wilde Lindsay , Keiffer Gina , Palmisiano Neil David , Calabretta Bruno
Published: March 2020

TPS7065

Background: c-Myb is a DNA-binding transcription factor that is highly expressed in immature hematopoietic cells. c-Myb and its products are essential in regulating normal hematopoiesis and influencing leukemogenesis. Knockdown of c-Myb causes cell cycle arrest and apoptosis in pre-B-ALL cells. The effects of c-Myb depend on transcriptional regulation of CDK6 and Bcl-2. c-Myb-silenced Ph+ ALL cells exhibit Rb-dependent cell cycle arrest and apoptosis, both of which are rescued by ectopic expression of cyclin D3, CDK6, and Bcl-2 expression. Preclinical studies suggest that the cytotoxic activity of dexamethasone in ALL cells may be due to decreased c-Myb expression and reduced Bcl-2 levels. Thus, the novel combination of palbociclib, a small molecule CDK4/6 inhibitor, and dexamethasone is a logical approach for the treatment of B-cell ALL. Methods: This is a single arm, phase I, dose escalation study with a traditional 3+3 design. Adult patients with relapsed or refractory B-cell ALL are eligible. Patients with Ph+ ALL must be refractory to or intolerant of standard tyrosine kinase inhibitor therapy. Patients receive a 1-week lead-in of palbociclib alone followed by induction with 4 weeks of palbociclib and dexamethasone. If an adequate response is seen, patients move to maintenance therapy, which consists of 1 week of palbociclib plus dexamethasone followed by 3 weeks of palbociclib alone. Treatment continues until disease progression, dose limiting toxicity, or availability of an alternative therapy. The primary endpoints are dose limiting toxicity and maximum tolerated dose of palbociclib and dexamethasone. Correlative studies, which are performed on pretreatment, day +1 and day +8 samples, include RB phosphorylation and FOXM1 expression as measures of palbociclib activity; CD19+ cell gene expression profiling of (1) p21 expression as an indicator of cell cycle activity, (2) S-Phase, Annexin V/Caspase 3 activation as indicators of proliferation and apoptosis and (3) Myb and Bcl-2 expression as indicators of dexamethasone sensitivity. Cohort 1 is currently enrolling. Once a maximum tolerated dose is established, an expansion cohort is planned. Clinical trial information: NCT03472573.
Phase 2, open-label study of pembrolizumab in children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) with slow early response (SER) to frontline chemotherapy: KEYNOTE-667.
Authors: Mauz-Körholz Christine , Kelly Kara M. , Keller Frank G. , Ramchandren Rod , Nahar Akash , Giulino-Roth Lisa
Published: March 2020

TPS7567

Background: High risk for relapse is observed in cHL patients (pts) with SER to initial chemotherapy and organ toxicities may be higher following dose intensification. Methods: The phase 2 KEYNOTE-667 study will enroll 440 pts aged 3 to 17 (children) or 18 to 25 years (young adults) with newly diagnosed, confirmed stage IA, IB, or IIA cHL without bulky disease (Group 1 [low-risk]) or stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL (Group 2 [high-risk]); measurable disease; and performance status per Lansky Play-Performance Scale ≥50 (age ≤16 years) or Karnofsky score ≥50 (age >16 years). Pts will receive induction with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD; Group 1) or vincristine, etoposide/etoposide phosphate, prednisone/prednisolone, doxorubicin (OEPA; Group 2) for 2 cycles, then early response assessment by PET/CT/MRI. Pts with rapid early response (Deauville score 1-3) will receive standard therapy. Pts with SER (Deauville score 4-5) will receive consolidation with pembro 2 mg/kg Q3W up to 200 mg (children) or 200 mg Q3W (young adults) plus 2 cycles AVD (Group 1) or 4 cycles cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28; Group 2). PET/CT for late response assessment (LRA) will be performed after consolidation. After LRA, Group 1 pts with SER and Group 2 pts with Deauville score 4-5 will receive radiotherapy (RT). All pts will receive maintenance with pembro Q3W concomitantly with RT. Pembro will continue up to 17 administrations, with an option to stop after 24 weeks due to CR, or until progression, unacceptable toxicity, or withdrawal. The primary endpoint is ORR per Cheson 2007 IWG criteria by group in SER pts. Secondary endpoints are SERs with PET negativity after consolidation, 2-yr event-free survival (EFS), OS, and RT frequency and details by group, RERs with PET negativity after ABVD induction, 3-yr EFS by investigator, and OS by risk group, and serum TARC levels at screening in SERs by risk group. ORR with 95% CI will be estimated by Clopper-Pearson method. EFS and OS will be estimated by Kaplan-Meier method. Safety will be assessed in all treated pts. Clinical trial information: NCT03407144.
Phase I/II, open-label, 2-arm study to evaluate safety, tolerability, and clinical activity of GSK2857916 in combination with 2 standard-of-care (SoC) regimens in relapsed/refractory multiple myeloma: (DREAMM 6).
Authors: Costa Luciano J. , Quach Hang , Stockerl-Goldstein Keith , Augustson Bradley , Ferron-Brady Geraldine , Chopra Bikramjit , Moore Allie , Hudson Sophia , Zhou Jiangxiu , Bragulat Veronique , Talekar Mala Kiran , Opalinska Joanna
Published: March 2020

TPS8053

Background: B-cell maturation antigen (BCMA) is a validated therapeutic target in Multiple Myeloma (MM). GSK2857916 is a humanized (IgG1) anti-BCMA monoclonal antibody conjugated to monomethyl auristatin-F via protease resistant maleimidocaproyl linker and produced in afucosylated form to enhance antibody-dependent cellular cytotoxicity. In FTIH study BMA117159, GSK2857916 was well tolerated and showed unprecedented clinical activity [ORR=60%; mPFS 7.9 months (95% CI, 3.1–not estimable)] as monotherapy in heavily pretreated MM patients. GSK2857916 in combination with SoC regimens, could potentially further improve outcomes for patients with relapsed/refractory (RR) MM. Methods: DREAMM 6 is a 2-part study: Part 1 (dose escalation) is evaluating safety and tolerability of 2 doses (2.5 mg/kg and 3.4 mg/kg) of GSK2857916, in combination with SoC regimens in two independent arms: Arm A with Lenalidomide/Dexamethasone, and Arm B with Bortezomib/Dexamethasone. Modified Toxicity Probability Interval design will guide dose escalation and RP2D of GSK2857916 in each arm for Part 2 (cohort expansion). Part 2 will confirm safety, evaluate clinical activity of GSK2857916 RP2D with either combination and collect pharmacokinetic information on GSK2857916, Lenalidomide and bortezomib. Up to 90 subjects previously treated with at least 1 prior line of therapy who have undergone autologous stem cell transplant or are transplant-ineligible will be enrolled; up to 24 in Part 1 and up to 66 in Part 2. Subjects in Arm A will continue combination treatment until progression, intolerance, consent withdrawal or death. Subjects in Arm B will receive up to 8 cycles of GSK2857916 in combination with Bor/Dex and then continue GSK2857916 monotherapy until progression, intolerance, consent withdrawal, or death. Enrolment on study started in October 2018 and is ongoing. Study funded by GlaxoSmithKline; drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. ClinicalTrials.gov Identifier: NCT03544281.